Omics, Gene Editing, and Single-Cell Technologies

Microbiome/Inflammasome/Virology

The human microbiome encompasses the entire microbial community, including bacteria, fungi, protozoa, and viruses associated with humans (Baker et al. 2017). The microbial community has a rich and complicated genetic content (Fischbach 2018), making the microbiome an active player in human health and disease (Proctor et al. 2017).

The oral microbiome is a distinct and diverse group of microbes that inhabit the oral cavity’s hard and soft surfaces (Takahashi 2015). Studies among humans have uncovered its vital role in the two most prevalent oral infectious diseases—dental caries and periodontitis—as well as in a wide range of physiological and pathologic processes essential to overall health (Bowen et al. 2018; Lamont et al. 2018). The oral cavity harbors more microbes than any other part of the body except the gastrointestinal tract. Most of the microbes in the mouth live within biofilms (dental plaque) attached to soft (tongue, gingiva, and oral mucous membranes) and hard (tooth) tissue surfaces.

The mouth provides distinct habitats, including saliva, tongue, mucosal, and tooth surfaces, all colonized by site-specific microbial assemblages (Human Microbiome Project Consortium 2012a). The development of high-throughput DNA sequencing has allowed these distinct groupings to be characterized. Studies have sequenced aspects of genetic regions to obtain an overview of the oral microbiome according to oral health status (Griffen et al. 2012; Gross et al. 2012), presence of systemic disease (Diaz et al. 2013; Starr et al. 2018), environmental exposures and behavioral habits (Mason et al. 2015), heritability (Demmitt et al. 2017), and a variety of genetic defects (Abusleme et al. 2018). Studies in twins show that both heritable and environmental factors shape the oral microbiome (Gomez et al. 2017). Behaviors such as smoking (Mason et al. 2015), genetic mutations (Abusleme et al. 2018), and disease (Griffen et al. 2012; Imabayashi et al. 2016) affect the homeostatic (optimally healthy) balance of the oral microbiome and host tissues.

A web-based human oral microbiome database was established and then enlarged as the expanded Human Oral Microbiome Database (eHOMD) (Escapa et al. 2018). Along with another oral microbiome database, the CORE database (Griffen et al. 2011), eHOMD provides a valuable platform for oral microbiome studies. These tools enable clinically relevant studies to be conducted by identifying new species (Beall et al. 2018a), new metabolic pathways (Verma et al. 2018), or novel biosynthetic gene clusters (Medema et al. 2014) associated with health and disease. A comprehensive road map to oral microbial assembly has emerged, revealing the oral microbiome’s resilience to a variety of environmental challenges (Gomez and Nelson 2017).

Studies of the gut (gastrointestinal) microbiome also are relevant to oral health and have led to the concept of dysbiosis, which is broadly defined as shifts in the microbial community that feature a reduction in the species diversity of microbes, changes in metabolic and signaling activity, and adverse health consequences (Honda and Littman 2016). The increase in biomarker microbe species rather than the acquisition of new species, which is observed in both dental caries and periodontitis patients, supports a current model (the polymicrobial synergy and dysbiosis model) in which imbalances and altered metabolic pathways among microbes already present in the oral cavity cause these two diseases.

The interrelationship of the oral microbiome, gut microbiome, and systemic health has received considerable attention, with several investigations reporting an association between the oral microbiome and systemic diseases with an inflammatory component, such as rheumatoid arthritis (Potempa et al. 2017), colorectal cancer (Kostic et al. 2012), oral cancer (Hayes et al. 2018), and Alzheimer’s disease (Dominy et al. 2019).

Biomaterials

There are many examples of promising new technologies designed to produce better restorative materials that are more durable, stimulate the formation of new tooth-like mineral to repair defects and replace lost tooth structure, have improved aesthetics (better mirror the properties of enamel and dentin), support function (mirror the wear of natural tooth surfaces), repel or kill damaging bacteria to stop the formation of new cavities, and regenerate lost tooth components. Structural and mechanical functions are generally considered the biomaterials’ most valuable functions or properties. However, biological properties, such as biocompatibility and biodegradability, also are important.

Biomaterials are considered to be biocompatible if they are inert and cause no undesired negative effect on the body. In contrast, bioactive materials intentionally regulate biological functions of cells or tissue. Biomimetic materials imitate specific composition, structure, or characteristics of biological materials or systems. Bioinspired materials have specific advanced properties or functions inspired by a biological system. It is critical to remember that the safety of these new materials, not only for the patient, but also for the health care provider and the environment, must be studied.

A large portion of the biomaterials used today in dental or oral health treatment are biocompatible, inert materials. However, development of bioactive materials—such as bioceramics, bioglass, and biocomposite materials—used in dental and craniofacial bone repair and restoration has been increasing. The bioactive components in these biomaterials are mainly inorganic materials, including bioceramics (crystalline) and bioglass (noncrystalline). Calcium phosphates, such as hydroxyapatite and tricalcium phosphate, are widely used bioceramics with structures similar to the minerals in bone and teeth (Chu et al. 2001; Hench 2015) and have been made into porous scaffolds for bone and dental tissue regeneration (Hench and Polak 2002; Denry and Kuhn 2016). To overcome their shortcomings, many biocompatible materials have been made into composite materials with polymers to enhance processability and mechanical properties. Such bioactive composite materials are biomimetic (designed to mimic components of natural bone and dentin) and bioinspired (inspired by the structure of biological materials).

Nanotechnology

Nanotechnology is the control of materials at dimensions between 1 and 100 nanometers. It involves imaging, measuring, modeling, and manipulating matter at this scale. Applications of nanotechnologies in dentistry include the development of tools that enable probing and imaging of biological systems with high precision, as well as designing and manufacturing preventive and restorative dental biomaterials. As a result, dental biomaterials have become more bioinspired and biomimetic (Jefferies 2014), which enhances some of their properties in comparison to the same materials at larger scales. Nanomaterials are now a part of the majority of restorative dental composites (Ferracane 2011), remineralizing agents (Hannig and Hannig 2012), and antimicrobial systems (Cheng et al. 2017).

Biodegradable Polymers and Nanofibrous Scaffolds

Biodegradable polymers, such as polylactic acid, polyglycolic acid, and their copolymers (polylactic-co-glycolic acids) have good biocompatibility, controllable biodegradability, excellent processability, and desirable initial mechanical properties. They are widely used to fabricate highly porous scaffolds, but there are other ways to make nanofibrous materials. Electrospinning is a popular technique to generate nanofibrous materials from various polymers (Doshi and Reneker 1993; Boland et al. 2001). In addition to tissue-engineering scaffolds, biodegradable polymers can be used to fabricate microparticles or nanoparticles for controlled release of drugs or molecules. For example, antibiotics have been incorporated into dissolvable particles to treat periodontitis (Williams et al. 2001), and various kinds of extracellular matrixes have been used for soft-tissue regeneration around teeth (in tooth recession defects) or around dental implants in situations involving reduced tissue thickness or implant exposures (Tavelli et al. 2020).

Periodontal Regenerative Medicine

Clinicians are currently using techniques and products created for periodontal regeneration (Larsson et al. 2016). Guided tissue regeneration (GTR), the most well-documented technique, employs a barrier membrane to promote the selective repopulation of periodontal defects using tissues capable of reattaching, such as alveolar bone and periodontal ligament (Karring et al. 1993). Attempts also have been made to use bioactive molecules, such as enamel matrix derivative and platelet-derived growth factor, to promote periodontal regeneration (Giannobile and Somerman 2003; Nevins et al. 2013). Results have been comparable to those obtained with GTR, although complete regeneration remains elusive in the vast majority of clinical cases.

Orofacial Muscle Regenerative Medicine

The face is a highly organized mixture of elements, composed of an underlying bone and cartilage framework that supports muscle and subcutaneous and skin tissue (See Figure 1, Section 3A) (Susarla et al. 2011). These components are attached to one another with ligaments and interact dynamically within a neurovascular network that allows the face’s complex animation. Each subregion of the face constitutes an aesthetic unit, so that reconstruction has to be considered on the basis of the unit (Rose 1995; Mureau and Hofer 2009). Hence, reconstruction of the maxillofacial region is challenging. Current treatments of extensive craniomaxillofacial defects include static reconstruction, free vascularized muscle transfer (Tate and Tollefson 2006; Ghali et al. 2011), and composite tissue allografting (Siemionow 2017). Tissue-engineering strategies that employ inductive scaffolds or scaffolds combined with growth factors or cells have been broadly applied to generate functional skeletal muscle (Larkin et al. 2006; Passipieri and Christ 2016). Because of the greater inflammatory and fibrotic response associated with common degradable synthetic polyesters, the field has been focusing on materials of biological origin such as alginate, gelatin or collagen, and fibrin (Passipieri and Christ 2016). The loading of specific growth factors into scaffolds has been shown in multiple cases to induce the desired response of increased angiogenesis (new blood vessels), myogenesis (new muscle tissue), or neurogenesis (new nerve cells), or in some cases, a reduction of fibrosis (scar tissue) (Passipieri and Christ 2016). In summary, orofacial regenerative medicine holds great promise for improving patients’ health. Technologies in this area will reduce the number of procedures requiring autologous (self-transplant) donor tissue, which result in significant patient morbidity. They will provide less invasive and less costly treatments without donor harvest and with targeted (personalized) replacement constructs that can lead to more predictable treatments for patients.

Stem Cell Biology

Stem cells are undifferentiated cells in embryonic and adult tissues in the body that can self-renew and differentiate into different types of cells. Mesenchymal stem cells (MSCs) have been extensively studied in craniofacial regenerative applications involving stem cell therapy. The unique properties of MSCs—namely, their ability to differentiate into multiple cell types, produce bioactive factors involved in tissue regeneration, travel to distant sites of injury, and escape the body’s immune response—have made them a desirable population for stem cell therapies. MSC therapies currently are under preclinical and clinical investigation and are being administered to specific sites to replace damaged or deficient hard (bone, cartilage) and soft (gingiva, dental pulp) tissues, promote tissue neovascularization, or reduce inflammation (Polymeri et al. 2016). Because of their therapeutic potential, identification of MSCs from craniofacial and oral tissues has created excitement in the field of regenerative dentistry.

Genetics- and Genomics-Based Precision Medicine

Specific gene variations have been linked to more than 10,000 human diseases (World Health Organization 2020). Powerful research approaches and large, multidisciplinary research efforts are improving our understanding of the genetic basis of health and disease (Collins and Varmus 2015; Cheifet 2019). Defining diseases by their genetic and environmental drivers and identifying the biological pathways involved will profoundly affect disease classification as well as provide the ability to develop diagnostic tests, determine susceptibility, and create variant-specific treatment intervention strategies. Until recently, genetic information has been most useful in diagnosing relatively rare Mendelian genetic disorders, rather than parsing the complex genetic origins of more common diseases, such as heart disease, diabetes, and periodontitis.

Thousands of genetic diseases manifest symptoms in the oral cavity or craniofacial complex. Major clinical findings for a number of these conditions, such as amelogenesis imperfecta or isolated cleft palate, are found in the oral cavity. For others, such as dentinogenesis imperfecta and syndromic forms of orofacial clefting, symptoms may manifest both orally and in the vascular system, bones, and kidneys. In some conditions, dental symptoms are the most prominent; therefore, a dentist may be the first to recognize the need for further testing to confirm a genetic condition (Pallos et al. 2001).

Laser- and Light-Based Imaging Technologies

Dental carious lesions are routinely detected using visual methods coupled with radiography and, when needed, complemented with tactile exploration methods. Despite their common use, these methods are insufficiently sensitive or specific for diagnosing early noncavitated carious lesions. Radiographic methods lack the sensitivity to detect early dental decay, particularly occlusal lesions, and, by the time the lesions are radiolucent, they often have progressed well into the dentin, making surgical intervention necessary. If carious lesions are detected early enough, nonsurgical means such as fluoride therapy, antibacterial therapy, or dietary changes can reverse or arrest them.

Two different fluorescence-imaging systems have been introduced commercially. The first method, commonly called quantitative light fluorescence, uses blue or ultraviolet light with green fluorescence. The loss of fluorescence from the underlying sound tissue owing to increased light scattering by demineralization is the mechanism for increased contrast between the lesion and sound areas (Ten Bosch and Angmar-Mansson 1991). Fluorescence images provide increased contrast between sound and demineralized tooth structure, but the method is limited because stains and plaque fluoresce strongly and make detection difficult (Stookey 2005). A second approach relies on the red fluorescence from bacterial-produced porphyrins (Konig et al. 1999; Lussi et al. 2004). Porphyrins accumulate in highly porous subsurface lesion areas in dentin, causing hidden occlusal lesions to fluoresce (Lussi et al. 2004). However, this method has some drawbacks. Because the dental decay-causing bacterium S. mutans does not contain porphyrins, this approach is not an effective way of monitoring cariogenic bacteria. Moreover, it has poor sensitivity for lesions confined to enamel because porphyrins do not accumulate there (Shi et al. 2000). Several clinical devices that measure both red and green fluorescence currently are commercially available.

Digital Dentistry, Computer-Aided Design/Computer-Aided Manufacturing, and 3D Bioprinting

Dental medicine widely employs digital dental technology, including intraoral scanning, 3D imaging, reconstructive processing using CAD/CAM, and artificial intelligence (AI). This boom in technology in the areas of CAD/CAM and the expanded use of 3D bioprinting to create synthetic and natural dental tissues have made the production of dental restorations faster and simpler, and often less expensive.

CAD/CAM technologies for fabricating dental restorations have rapidly spread worldwide (van Noort 2012). To date, the most commonly used CAD/CAM methods in dentistry are subtractive, such as computer-controlled milling machines that drill a block of material to achieve a desired shape. Dentistry has profited greatly from this technology (Alghazzawi 2016), which makes it possible to create accurate restorations while saving time (Bindl and Mormann 2005). Using solid blocks of material results in fewer internal defects, which are common in handmade restorations and compromise their strength (Belli et al. 2017). Significant strides have been made in the field of 3D bioprinting—an additive manufacturing process—of regenerative scaffolds and cell-laden craniofacial structures, which are being developed as the next generation of bone, vascular, periodontal, and dental grafts (Murphy and Atala 2014).

Chemotherapeutics/Drugs in Dentistry

There are many types of medications, supplements, and other chemotherapeutics available in the marketplace that are promoted as preventing or managing dental diseases. However, the majority have not been approved by the FDA. Dental drugs that have been approved by FDA since the 2000 Surgeon General’s report include, but are not limited to, (in alphabetical order): Arestin, Articaine, Atridox, Colgate’s Total, Cuvposa, Evoxac, Oraqix, Oraverse, Kepivance, Kovanaze, Orabloc, PerioChip, Periostat and Salagen. FDA has determined a number of over-the-counter (OTC) drugs for oral health as generally recognized as safe and effective for the general population without the need to seek treatment from a health professional. The most common examples of OTC drugs employed in dentistry are those used to prevent dental caries, including sodium fluoride, stannous fluoride, and sodium monofluorophosphate. Dentists can dispense or provide products with higher levels of fluoride than those available OTC, as well as prescribe chlorhexidine as an intraoral antimicrobial rinse. Noninvasive diagnostic tools with improved sensitivity and specificity in detecting active dental caries lesions are needed, as are new drugs for treating periodontitis.

The National Center for Complementary and Integrative Health defines complementary and alternative medicine as non-mainstream approaches used together (complementary) or in place of (alternative) conventional medicine. These two approaches are brought together by integrative medicine, with the aim of caring for the whole person rather than just treating disease (National Center for Complementary and Integrative Health 2021). Most complementary and alternative medicine systems in oral health care are biologically based, such as botanical products and holistic medical systems such as (e.g., Ayurveda, homeopathy, Chinese medicine). Most complementary and alternative medicine systems have insufficient clinical evidence for their safety or efficacy (Shi and Heber 2013; Rigassio Radler 2014).

Electronic Health Records

The implementation of EHRs is a strategy for reducing errors and improving health care delivery and outcomes (Song et al. 2011; Gold and McLaughlin 2016). Advances in the understanding of the connections between oral and total body systems and a shift toward individualized care have created a demand for an integrated medical and dental health care delivery system. The integrated medical and dental EHR has created new opportunities to exchange medical and dental information electronically, leverage resources, and improve patients’ oral and overall health care. EHRs have made it possible to develop an oral health care system that is better integrated with our country’s medical and behavioral health care systems (Acharya 2016; Faiola and Holden 2017; Shimpi et al. 2019a). Recognizing strategies to reduce the incidence of chronic diseases and improve the effectiveness and efficiency of care through the application of informatics is of paramount importance (Liu and Rubin 2012; Glurich et al. 2019; Shimpi et al. 2019b; Shimpi et al. 2019c). Unfortunately, an integrated EHR does not yet exist for most of the U.S. population.

Teledentistry

Telehealth includes telemedicine (the use of technology to deliver health care services at a distance) as well as patient and health professional education and public health and administrative activities (Daniel et al. 2015). Telemedicine has been introduced in rural and remote communities and in federal health programs to improve access to care. Various medical specialties and subspecialties in the United States and in other parts of the world now employ the technology supporting telehealth (Kvedar et al. 2014; Daniel et al. 2015). In addition to documented improvements in the flexibility of health services and high levels of acceptance among patients and providers, the benefits of telehealth include increased accessibility, improved quality of care, multidisciplinary collaboration, and education (Gilman and Stensland 2013; Banbury et al. 2014; Wade et al. 2016; Powell et al. 2017).

Although teledentistry has been slower to spread, it is now becoming more widely utilized across the country and in other parts of the world (Kopycka-Kedzierawski et al. 2008; Irving et al. 2018). The arrival of the COVID-19 pandemic has further fueled its use. See Section 4 for more information on the uses and practices of teledentistry.

Learning Health Systems

Efforts to create learning health systems (LHSs) at various levels of scale—organizations, networks of organizations, states and regions, and entire nations—promise to transform human health. The general idea is that a systems problem needs a systems solution. The National Academy of Medicine (National Academy of Engineering 2011) defines LHS as an integrated health system in which “progress in science, informatics, and care culture align to generate new knowledge as an ongoing, natural by-product of the care experience, and seamlessly refine and deliver best practices for continuous improvement in health and health care.”

The core building blocks of LHSs are learning cycles, which begin when communities share a common passion around a specific individual or population health problem and form a learning community targeting that problem. Learning communities typically consist of multiple stakeholders, including researchers, care providers, and patients and their families, and draw on expertise from diverse disciplines. From a national perspective, a large-scale learning community may consist of several entities (Figure 2).

FIGURE 2

National perspective of an ultra-large scale learning health system.

Learning cycles proceed in three stages: capturing health experience in computable forms, learning from the data to generate new knowledge, and mobilizing new knowledge to inform decisions and change performance (Friedman et al. 2017). The right knowledge must be delivered to the right person, at the right time, in the right dose, through the right route, in the right form, with the right documentation, and for the right reason (Federico 2015). Each new cycle of learning begins where the previous one leaves off, making health improvement repeated and continuous in nature as exemplified in Figure 3.

FIGURE 3

View from the ground: How learning happens: “Virtuous cycles” of study and change.

Evidence-Based Approaches to Introduce New Technologies into Clinical Applications

One important aspect of implementation science is evidence-based practice. Providers’ adoption of evidence-based dental practices is expanding due to the growing emphasis on improving population health, controlling cost of care, and delivering value for patients and care purchasers. Long lag times between the dissemination of evidence and its eventual adoption into routine practice limited the initial development of evidence-based practice in the 1990s. For example, even after compelling scientific evidence had accumulated in 2001 that fluoride varnish was superior to other modes of fluoride administration, 6 years later only 15.7% of general dentists and 30.8% of pediatric dentists in Texas reported that fluoride varnish was the topical fluoride they used most often (Bansal et al. 2012). Providers’ failure to change their practice patterns in response to scientific evidence demonstrates that scientific evidence alone is not sufficient to change these patterns.

Practice-Based Research Networks

Practice-based research networks (PBRNs) are an important component of NIDCR’s implementation science portfolio. A PBRN is a consortium of practitioners, clinical scientists, and health organizations focused collectively on conducting research to improve the health of their patients and communities. PBRNs link clinicians with health services and clinical researchers to improve the transfer of science to practice. This improvement is accomplished by fostering quality improvement through participation in research, addressing questions of high priority to the practitioners, and translating new knowledge into everyday clinical practice. Although medical PBRNs began in the 1970s, no oral health-focused PBRN existed in the United States before 2002. Because PBRNs can make substantial, unique improvements to clinical practice, they have continued to grow in number and breadth and now comprise a diverse array of health care practitioners.

PBRNs have as their foundation the understanding that the experience, insight, and practical wisdom of everyday practitioners and their patients, coupled with rigorous scientific studies, are powerful forces to advance population health. The oral health care system can play an active role in these advances, showing that knowledge transfer takes place not only from research to practice, but also from practice to research.

NIDCR funding has kept the National Dental PBRN in continuous operation since 2005 and has productively engaged thousands of clinicians in the research process.

Sixty studies have been conducted as of 2021, leading to more than 175 peer-reviewed scientific publications in 58 different journals, many with clinicians as coauthors. Examples of topics include risk factors for osteonecrosis of the jaw, dental material selection for crowns, and the use of rubber dams during root canal treatments. Practitioners from diverse settings are willing to engage in the excitement of discovery and to partner with fellow practitioners and academicians to improve daily clinical practice.

The National Dental PBRN also conducts studies of drug or device effectiveness as well as studies to test methods of evidence dissemination and implementation. The network continues to make significant contributions to research priorities and to help close the research-to-practice gap (Gilbert et al. 2013). In addition to exploring optimal means for disseminating evidence (Melkers et al. 2019), the network has conducted research to expand the scope of dental practice and to foster studies at the intersection of dentistry and medicine. These studies have been related to osteonecrosis of the jaw, cessation of tobacco use, blood glucose screening, human papillomavirus screening, opioid prescription patterns, and medical risk screening.

Education and Training for Oral Health Scientists

Major advancements in knowledge in the oral health sciences have made it increasingly important to train the next generation of leaders on how to translate basic science innovations into clinical practice. Oral health scientists include PhD basic scientists, clinical research scientists, and those trained in health services and dental public health. Scientists who focus on oral health come from many diverse disciplines—sometimes with a clinical emphasis, but often without. All make essential contributions to the basic, applied, developmental, and implementation levels of research to inform clinical practice, population health management, and policy development as well as serve as educators of the workforce pipeline. Traditional dental education begins with an early focus on foundational and biological sciences and progresses to clinical focus in later years, a path that does not always lead to an appropriate level of exposure to population health issues. Integrating research experience into the predoctoral curriculum sets a foundation of critical thinking and inquiry that has value for evidence-based clinical decision-making. An ideal dental school graduate would be a highly skilled clinician with a deep understanding of the scientific foundation of dentistry, an appreciation of population health issues, and the compassion to serve. In the first 2 years of most dental schools, the vast majority of education consists of didactic instruction and simulation. Although the final 2 years are spent primarily in providing patient care, the likelihood is that most programs offer sparse instruction on understanding the health and social needs of low-income and underserved minority populations. Few dental programs offer supplemental public health electives.

To understand population-based research, oral health professionals need a basic understanding of epidemiology and biostatistics, health policy and management, health and wellness promotion, evidence-based dentistry, risk assessment at the individual and population levels, behavioral and social determinants, and health literacy. In addition, exposing future oral health professionals to real-world conditions—which can be accomplished through clinical rotations in community health centers, public health units, and other settings—provides them with experience treating low-income and underserved minority populations. Such exposure might also take place if they later enroll in Advanced Education in General Dentistry and General Practice Residency programs, which frequently serve these populations. In addition to these postdoctoral training programs, others can pursue public health training through a combined DDS and Master of Public Health or PhD program, thereby gaining valuable tools for research in underserved populations.

Imperative for preparing the next generation of scientists in oral health are core elements that the National Academies of Sciences, Engineering, and Medicine (2018a) recommend for all doctoral-level education. These include the cultivation of scientific and technologic literacy, the conduct of original research, and the development of leadership, communication, and professional competencies. PhD candidates should acquire deep, specialized expertise through the kind of original research that requires rigorous standards of investigation, as well as ethical responsibilities for the design and dissemination of science. They also should develop the ability to work collaboratively across scientific disciplines and be integral members of team science efforts (Hall et al. 2018).

Omics/Gene Editing/Single-Cell Technologies

Single-cell technology was a conceptual vision in 2000 but has expanded into many areas of biomedical research in the past 5 years. Although oral and craniofacial research has lagged behind other types of research, some advances have been made. In the case of oral infectious diseases, the single cell sequencing of genomic amplicons (pieces of DNA or RNA that are the source or product of amplification or replication events) has been exploited to correlate the presence of uncultured bacterial species with oral health (Campbell et al. 2013; Beall et al. 2018b), and to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various sites of the oral cavity (Huang et al. 2021), both of which open new pathways for salivary diagnostics. In looking at the levels of single-cell gene expression in patients with head and neck cancer, molecular heterogeneity among the same types of cells warrants attention because it can influence the effectiveness of an individual’s treatment strategy (Stucky et al. 2017). A single-cell analysis linked expanded salivary gland T cells to glandular dysfunction (Joachims et al. 2016) and revealed a higher frequency of activated T helper 17 cells (an immune cell population) in patients with Sjögren’s syndrome (Voigt et al. 2018).

Genome-wide association studies (GWAS) of oral and craniofacial diseases may show limited concordance among them due to random and systematic errors incorporated during study implementation (Agler and Divaris 2020). For example, in periodontal tissue studies, inherent genetic differences between the study populations, as well as inconsistencies in the precise definition of periodontitis cases and controls across studies, may be a problem. Given the multifactorial nature of periodontitis and the decisive roles of environmental factors such as bacterial exposures and cigarette use, it is reasonable to conclude that genetic information will explain only part of the variance of the disease at the population level. In the current post-genomic era, our inadequate understanding of crucial epigenetic mechanisms and transcriptional controls that regulate gene expression is slowing progress (Barros and Offenbacher 2014; Larsson et al. 2015).

To date, the majority of published single-cell techniques have been in embryology, neurology, and oncology. Although the applications of single-cell technology show promise, they have barely touched the mechanisms involved to affect applications in oral health and personalized dentistry.

Microbiome/Inflammasome/Virology

Microbiome research has grown significantly because of the availability of polymerase chain reaction (PCR) methods mentioned in the 2000 Surgeon General’s report on oral health. Over the past 20 years, there has been an evolution in methods and a revolution in knowledge. One of the greatest advances in oral health is the greatly expanded knowledge of the diversity and biology of the microorganisms found in the oral cavity.

Microbiome studies have evolved from the use of bacterial-specific probes (Dewhirst et al. 2010) to the characterization of the entire microbiome community (Escapa et al. 2018). Such in-depth characterization has led to greater understanding of the microbial community, its interactions with the host, and its contributions to health and disease. Technologic advances are revolutionizing the traditional concepts of microbial virulence and pathogenesis (Lamont et al. 2018; Al-Hebshi et al. 2019). Oral pathogens, long regarded as key contributors to the development of dental caries and periodontitis, have now been recognized as mediators in tuning microbe-host interactions and in tipping the balance between microbial synergy and dysbiosis (Lamont et al. 2018). Human microbiome studies that selectively target specific organisms are revealing conserved biochemical activities and signaling cascades (Olsen and Potempa 2014; Garcia et al. 2017), which have led to promising compounds that make precision therapy possible.

Regenerative Medicine and Dental Repair

Continuing challenges regarding existing biomaterials include a relatively high incidence of recurring decay around bonded dental restorations; a higher than desirable rate of fracture of dental composite fillings because of their limited strength; a lack of ideal aesthetics for the highest strength ceramic materials, such as zirconia; and a higher than desirable incidence of infection around dental implants that may lead to premature failure. Other key challenges include the development of materials that have biological effects, such as inhibiting bacterial adhesion and colonization at sensitive tooth-adhesive interfaces, and materials that promote the production of new tooth mineral to replace lost tooth structure. The development of a material that can replace infected pulp tissue to avoid endodontic therapy or tooth extraction could be critical for saving severely damaged teeth. Despite the great success of dental implants, problems leading to failures and implant loss still occur. One area of intense interest is to better understand the incidence of peri-implantitis, in which tissues become inflamed where the implant emerges from the bone and is in contact with the gingival tissues (Berglundh et al. 2019).

Perhaps the area that appeared the most promising 20 years ago but has seen relatively little practical advancement because of its tremendous complexity is the in situ regeneration of new teeth (Monteiro and Yelick 2017). Natural-appearing teeth have been grown in small animals (Yelick and Vacanti 2006) and in larger mammals (Wu et al. 2019), but the implantation of such teeth, or the regeneration of new, anatomically correct hard tooth structure within a human mouth, remains a more distant goal.

Dental Adhesives and Dental Composites

Today, adhesive and composite materials have mostly replaced dental amalgam as the primary restorative materials. Dental adhesives and dental composites are similar polymer-based materials that restore lost tooth structure by bonding to and sealing the tooth to maintain its integrity and resist further tooth decay (Bedran-Russo et al. 2017; Pfeifer 2017). New dental adhesives and composites represent a true revolution in dental treatment as a result of intense research and product development, especially for the resin component (Fugolin and Pfeifer 2017). As a result of significant advances in the past 20 years, current materials may last for decades when placed appropriately and in patients with good oral health (van de Sande et al. 2013). Research into advanced formulations of the materials has mostly solved the situation of excessive wear on posterior teeth from chewing, a major problem 20 or more years ago (Ferracane 2006).

Many clinical studies have shown average lifetimes for restorations that approach 15–20 years or more in both anterior and posterior teeth (Bayne et al. 2019). However, other studies have shown much lower rates of success and the need for earlier intervention, possibly within 6–7 years of placement (Kopperud et al. 2012; Rho et al. 2013). The reason for this discrepancy is at least threefold. First, the most common reason for failure was secondary dental caries. Second, the adhesive and composite materials have characteristics that require a demanding, multistep placement technique that can lead to premature failures. Third, composites also shrink during curing, which may produce stresses that challenge the adhesive’s bond to the tooth. One approach to address this issue is the development of new resin formulations with reduced contraction stress (Meereis et al. 2018). Many commercial products have been produced, including easier to place bulk-fill composites (Veloso et al. 2019). Another approach has been the development of adhesives that directly bond to the tooth but do not require the tooth to be pretreated with an acid solution to promote bonding. Some of these self-etch adhesives have shown favorable clinical results (Peumans et al. 2010; van Dijken 2010). Another important factor influencing premature restoration failure is that many patients’ diets and oral habits predispose them to recurrent dental caries. In the future, it is critical that research focuses on the production of materials that are more robust, simpler to use, and inherently effective against the attachment of bacterial plaque.

Dental Ceramics

Dentists are familiar with the use of and indications for metal alloys, which have provided stable and durable restoration of tooth structures for more than 100 years (Donovan et al. 2004). Although predominantly gold-based alloys have been the primary material for dental crowns and bridges that replace one or more teeth, dental ceramics (such as dental porcelain) have emerged as a viable and sought-after option to minimize or eliminate the use of metals in the mouth (Zhang and Kelly 2017).

Dramatic advances in materials that provide strong and tough ceramics, such as lithium disilicate and zirconia, have revolutionized the replacement of broken and severely decayed teeth with materials that are durable and resemble natural teeth (Denry and Kelly 2014; Zhang and Lawn 2018). These new materials, especially lithium disilicate, are highly aesthetic and strong, although their use in heavy dental occlusion is still limited. Increased use of zirconia ceramic, which is nearly twice as strong as any other dental ceramic and requires less tooth reduction, has had a noted impact in dental care (Ghodsi and Jafarian 2018).

Dental Implants

In the past, tooth loss was treated by placing a dental bridge, which requires cutting away the two sound adjacent teeth to prepare them as abutments to hold the bridge with the replacement tooth crown. In the past 20 years, however, dental implants, which offer distinct advantages over dental bridges, have become a normal part of dental treatment (Howe et al. 2019). Dental implants typically are made from titanium because of its strength and excellent biological response, although new high-strength ceramics, such as zirconia, are increasingly being used in areas where metal may partially show in the mouth because of their high biocompatibility and improved aesthetics. Dental crowns or bridges are placed on the implant. The survival of tooth-supported and implant-supported three-unit fixed dental prostheses has been shown to be similar (Pol et al. 2018). The key to the greater success of the dental implant is that it becomes solidly anchored through the growth of new and supportive bone around the device, a process called osseointegration (Bosshardt et al. 2017). Several factors have been shown to affect this process. Effort is now focused on better understanding the optimal implant surface texture, such as roughening on the micro- or nanometer scale, to create an optimal tissue response at the implant surface (Albrektsson and Wennerberg 2019). Implant characteristics, together with local and systemic host factors, may affect susceptibility to peri-implantitis, which remains one of the most common biological complications of functional implants (Rakic et al. 2018; Hashim and Cionca 2020).

Biological factors offer significant potential for tissue regeneration around teeth and for dental implant site development (Larsson et al. 2016). Enamel matrix derivative (EMD) is the earliest-studied biologically active product for periodontal regeneration (Koop et al. 2012). EMD is available commercially as an injectable gel solution containing enamel matrix proteins (amelogenins and other enamel proteins) and a carrier, propylene glycol alginate. Systematic reviews have shown that EMD delivers improved clinical outcomes compared to open-flap debridement (Esposito et al. 2009; Koop et al. 2012). Recombinant human platelet-derived growth factor-BB, combined with β-tricalcium phosphate, is another commercially available product that has shown promising results for addressing regenerative intrabony and furcation (bone loss in the area where the tooth branches off from the root) defects in periodontal treatment (Nevins et al. 2013). Other growth factors, such as fibroblast growth factor 2, have been under clinical development and have demonstrated promising results in human clinical trials (Cochran et al. 2016).

Nanotechnology

The safety of nanoscale materials is a continuing challenge. Nanoparticle toxicology is still an emerging field, with inconsistencies in the published literature. Tests to determine nanoparticle toxicity have not reached consensus (Webster 2009). Furthermore, although many nanomaterials have been claimed to lead to unprecedented improvements in efficacy—in terms of physical properties, biological interactions, and control—dental materials and technologies that rely on nanoscale systems have yet to deliver paradigm-shifting outcomes. Improvements have mostly been incremental and on par with those from many traditional microscale technologies.

Stem Cell Biology

Over the last 2 decades, advanced molecular biology tools and bioinformatic capabilities have become available that use machine learning algorithms to rigorously characterize different stem cell populations on the basis of their molecular signatures. This deeper understanding of stem cells’ unique molecular profiles will enable more targeted therapies for specific applications.

In 2000, the fields of tissue engineering and regenerative medicine were just emerging, stem cell therapy for craniofacial regeneration was merely a concept, and bone marrow was the only known source of MSCs. Since that time, tremendous technologic, clinical, and scientific advances have led to a deeper understanding of MSC biology, including how MSCs interact with other cells, how to isolate them from different tissues, how to control their behavior with different signals and microenvironments, and how to deliver them to local and distant sites. A new paradigm has been proposed for the mechanisms of action of MSCs in the laboratory, on the basis of their potent immunomodulatory, anti-inflammatory, and multifaceted trophic (stimulatory or growth) effects, such as proangiogenic, tissue-remodeling, antioxidant, and antiapoptotic effects (Shi et al. 2018).

MSCs can migrate to injured and inflammatory sites, actively sense the signals or cues from damaged cells, and communicate with other types of cells, particularly immune cells. Once activated, MSCs respond with increased proliferation activity, including secretion of several biological factors to modulate immune cell functions, promote blood vessel growth, suppress cell death, and reduce reactive oxygen species (also sometimes called free radicals), thus establishing a regenerative microenvironment.

To date, more than 800 clinical trials using MSCs have been registered with ClinicalTrials.gov; in those trials, MSCs of different origins are being tested for their therapeutic effects on a wide spectrum of autoimmune, inflammatory, and degenerative diseases (Shi et al. 2018). Although there are a number of MSC products being used to treat patients with dental, oral, and craniofacial conditions under the practice of medicine, there are no MSC products yet approved by the U.S. Food and Drug Administration (FDA) (U.S. Food and Drug Administration 2020b).

Despite their potential to differentiate into cells of all three germ layers, the clinical use of embryonic stem cells (ESCs) faces several major challenges. There are critical ethical challenges, difficulties involved in the differentiation of transplanted ESCs into mature and physiologically functional cell types capable of integrating into the relevant damaged tissues, long-standing issues of immunogenicity, and potential tumorigenicity as a result of genomic instability (Guhr et al. 2018; Prentice 2019).

The use of MSCs of different tissue origins as therapeutic products in regenerative medicine presents many biological, manufacturing, and clinical challenges (Martin et al. 2019). More stringent methods of characterizing these heterogeneous cell populations are needed to elucidate the mechanisms underlying cell variability (Huang et al. 2009; Bianco et al. 2013). Another challenge is to determine the best modality in which to deliver stem cells. Different rigid and injectable polymers have been used as scaffolds, but information has been insufficient to drive clinical efficacy. Overcoming these challenges with robust, well-designed clinical trials utilizing fully characterized source materials is instrumental for gaining FDA approval.

Cost-effective reimbursement models and protocol logistics for the isolation, expansion, and delivery of stem cells need to be established to bring technologies to clinical adoption. Stem cell manufacturing that meets the appropriate regulatory and safety standards likely will be expensive and increase the costs for the clinician and the patient. In addition, current reimbursement by dental insurers provides insufficient coverage for regenerative therapies in dentistry. As a result, these approaches may widen health disparities. Despite a considerable market for bone (an estimated US$750 million) and dental pulp (an estimated US$200 million) regeneration, many companies are cautious about committing resources because of existing limitations and inadequacies of third-party reimbursement for new treatment procedures. Academic partnerships with industry will need to be fostered to establish cost-effective models for autologous stem cell production.

Discussions of stem cell biology would be incomplete without mentioning the progress during the past 20 years in understanding cancer stem cells’ role in the development, progression, and therapeutic resistance of cancer (Baillie et al. 2017). Cancer stem cells can self-renew and proliferate, have been identified in head and neck cancer, and are highly capable of forming tumors. Advances in their identification and characterization have stemmed from the cell and molecular technologies developed and explored during the past 20 years and are currently being expanded with new technologies such as single-cell approaches (Qi et al. 2019).

Genetics- and Genomics-Based Precision Health

As the costs of sequencing DNA have decreased during the past 20 years, the use of whole-exome (the part of the genome that codes for proteins) and whole-genome (the entire 3 billion base pairs of DNA) sequencing has increased. These tests have revealed genetic mutations underlying dental conditions, such as amelogenesis imperfecta (Smith et al. 2019), tooth agenesis (Salvi et al. 2016), and latent transforming growth factor-betabinding protein 3 (LTBP3)-related disorders (Intarak et al. 2019). LTBP3 pathogenic variants are associated with amelogenesis imperfecta, short stature, and predisposition to thoracic aortic aneurysms and dissections (Guo et al. 2018). Many dental genetic variants are associated with more severe conditions. Dental findings, including radiolucencies (defects that appear as darkened areas on radiographs), have been associated with some types of mucopolysaccharidosis and Gaucher disease (Saranjam et al. 2013). Oligodontia (an absence of six or more teeth) can be associated with colon cancer (Lammi et al. 2004). One genetic variant of amelogenesis imperfecta with gingival hyperplasia is associated with nephrocalcinosis (an increase of calcium levels in the kidneys). These findings suggest that persons with these oral signs should be referred for a renal workup (Koruyucu et al. 2018).

The advent of new approaches, such as clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 and the expanded capabilities for gene editing, including ex vivo cell therapy and in vivo gene editing (Raaijmakers et al. 2019), as well as DNA vaccines, chimeric antigen receptor therapies, pharmacoepigenetic approaches to manipulate targeted genomic expression, and gene replacement therapies show promise for improved clinical strategies in genetic conditions.

In contrast with disorders caused by a single genetic variant, most chronic diseases are complex and caused by the interactions of multiple genes, environmental exposures, and lifestyle factors. These multifactorial origins characterize conditions such as diabetes, heart disease, hypertension, and common cancers.

Environmental factors can modify DNA or the histone proteins in chromatin, altering gene regulation and expression and influencing disease (Berdasco and Esteller 2019).

Factors other than the actual nucleotide sequence play a role in gene expression. Changes that do not affect the actual DNA sequence are epigenetic in nature and involve methylation of DNA or histone modifications. The environment can cause epigenetic modifications, for example, through diet, smoking behaviors, exposure to microbial agents, gender, aging, drugs, and toxins (Niller and Minarovits 2016; Berdasco and Esteller 2019). Such environmental exposures are important in the development of many conditions dentists encounter, such as dental caries, periodontal disease, and oral cancers. Many pathologies of the oral cavity are linked to systemic conditions such as diabetes, heart disease, and obesity, which also have epigenetic components in their development.

Advances in understanding genomic architecture and the role of RNA biology have altered our perception of how the genome functions and interacts with genetic and environmental factors to regulate health and disease, yet much is still unknown (Jukam et al. 2019). To fully participate in these genomics initiatives, the dental community will need to overcome barriers to the integration of all health care records and interprofessional training (Regier and Hart 2016; Weitzel et al. 2016).

Pharmacogenetics, which is increasingly playing a role in dental care, uses information about an individual’s genome to choose drugs and drug doses likely to work best for that person’s unique genetic profile—a departure from the one-drug/one-dosage-fits-all approach. Pharmacoepigenomics target pharmacologic treatments that may reduce or reverse epigenetic effects in diseases. Clinical applications of pharmacoepigenomic interventions have increased and show promise for treating oral and craniofacial diseases that result from a combination of genomic, metabolic, epigenomic, and environmental factors (Teijido and Cacabelos 2018; Jones et al. 2019). An example of progress in which genetic strategies may be particularly valuable is a targeted approach aimed at the tumor suppressor p53 protein, which shows promise in sensitizing head and neck cancer stem cells to chemotherapy (Rodriguez-Ramirez and Nör 2018).

One of the most revolutionary advances in medicine in the last 20 years has been the incorporation of genetic information into clinical care. The dramatic reduction in the cost of acquiring genomic information and the use of information technology to understand clinically useful relationships among genomic data, health, and disease are accelerating the process. Genomic data linked to extensive phenotypic and health information are being collected on millions of individuals across ethnic groups, enabling clinical research in data biobanks and creating the possibility of asking more complex genetic questions (Tyler-Smith et al. 2015; Stark et al. 2019; Verma et al. 2019), which will help characterize healthy states and disease-associated conditions, identify robust predictive associations (clinical validity), and facilitate evaluation of clinical utility (Ioannidis and Khoury 2018). Careful clinical characterization, including longitudinal data, will facilitate identification of disease-associated genetic variants in humans. Despite promise, the genetic information revolution has had very limited impact on dental care, with yet untapped potential for managing oral health in the future.

A continuing challenge to the dental community is the integration of increasingly available genomic information into clinical practice in valid and useful ways. Barriers need to be overcome, including data collection, recording, and interpretation. Surmounting these barriers will likely require changes to health records and introduction of multidisciplinary health teams. Regulatory challenges and determination of evidence for clinical utility need to be addressed. Dental education and training will need to incorporate genetics education and interprofessional collaboration (Johnson et al. 2008).

Although big data has a role in precision medicine, certain risks do exist. Ethical, legal, and social tenets of genomics need to be applied to ensure privacy and confidentiality (Dolley 2018). Maximizing the utility of genomic information in clinical care requires integration of health records and the incorporation of genomics into EHR systems (Ohno-Machado et al. 2018). Standards for best practices in analysis and interpretation of clinical genomic information are needed (Brownstein et al. 2014; Lu et al. 2018). Because genomic factors affect many diseases across the life span and across clinical disciplines, no single professional group encompasses the entirety of this field, reinforcing the need for genomics education and interprofessional practice (Schully et al. 2015).

Diagnostics

Three-Dimensional Bioprinting and Additive Manufacturing

Developments in the past 20 years are shifting trends in dental reconstruction away from conventional impression technologies and toward digital imaging. Cone beam computed tomography (CBCT) and intraoral scanners are now used to design and produce dental prostheses and surgical guides that can be fabricated using additive manufacturing, as well as the more traditional subtractive manufacturing technologies (Abduo 2019). Additive manufacturing, or additive layer manufacturing, is the production name for 3D printing in which a computer-controlled process creates 3D objects by layering materials. Technologies of this type have made complex treatment feasible for most dentists and have decreased manufacturing time. Potential challenges include consistent dimensional accuracy and material suitability.

A wide selection of platforms, printable materials, and applications now is available in medical 3D printing (Tappa and Jammalamadaka 2018). Materials include most major classes: thermoplastics, thermosets, gels, ceramics, and metals. Each material requires specific processing strategies and precursor materials—for thermosets, a liquid resin; for metals, specially prepared powders. Because biomaterials have a variety of advantages and disadvantages, this lends them to specific or potential uses in health care (Table) (Tappa and Jammalamadaka 2018).

Perhaps the most widely adopted technology in dentistry is vat polymerization, in which a light source (such as a laser) is directed onto a photocurable resin to build it up layer by layer. Examples of the products of this technology include orthodontic aligners, mouthguards, and surgical guides. Several metal printers have been advocated for dental use to fabricate fixed and removable partial-denture frameworks as well as to fabricate custom implantable devices (Forrester et al. 2019). Several variations of vat photopolymerization, including continuous liquid interface production, digital light projection, and stereolithography, are used by many laboratories to print patterns for fixed partial-denture frameworks for conventional casting methods. The availability of aligner software for orthodontic movement of teeth and fabrication of provisional restorations has increased demand for faster printers (Abduo 2019; Gonzalez Guzman and Ohara 2019).

Conventional tissue engineering approaches have limitations for fabricating vascularized and functional tissues and organs (Ozbolat and Hospodiuk 2016). In the last decade, advances in stem cell biology, biomaterials science, tissue engineering, and 3D bioprinting technology have significantly advanced the fabrication of implantable artificial tissue complexes for regeneration of both soft and hard tissues (Gomes et al. 2017). Bioprinting is a computer-driven, rapid prototyping technology that utilizes computer-aided design software to generate blueprints for highly accurate biomimetic tissue constructs (Kang et al. 2016). This state-of-the-art platform for fabricating complex biomimetic tissues using biocompatible bioinks mimics the chemical, physical, and physiological properties of native tissues. Various types of synthetic or natural polymers, different types of cells, and growth factors have been implemented as the cellular and noncellular components for 3D bioprinting for regenerative purposes (Nagarajan et al. 2018). Because of their ability to become different types of cells and their regenerative potential, MSCs have been extensively explored as the seed cells for generation of tissue engineering and regenerative medicine products, including 3D bioprinting of biomimetic tissue constructs (Snyder et al. 2015).

Despite advantages, the use of printed objects in dentistry is still limited. Definitive restorations (e.g., crowns, bridges) cannot yet be manufactured because of the lack of suitable materials. In subtractive manufacturing, the most commonly used materials for definitive restorations are reinforced ceramics, metals, and composite resins. In additive manufacturing, some polymer prototypes and metals are starting to find their way into clinical practice, although 3D-printed ceramics for dental applications are still struggling to be accepted (Dehurtevent et al. 2017). Metal is commonly used for conventional prosthodontic treatment, and promising clinical outcomes have been reported with posterior single-unit metal-ceramic crowns (Abou Tara et al. 2011; Atzeni and Salmi 2015). Despite its good mechanical properties, metal is not suited for modern microinvasive and aesthetic treatments, whereas 3D-printed reinforced polymers show better potential for final restorations, but they need further development.

Table

Biomaterials classification with their advantages, disadvantages, and applications.

Complementary, Alternative, and Integrative Medicine in Dental and Oral Care

The use of complementary, alternative, and integrative medicine is extensive, but limited by issues of safety, research and evidence, and regulation. These approaches may include nutritional (e.g., herbs, dietary supplements), psychological (e.g., meditation, hypnosis) and/or physical (e.g., acupuncture, massage) interventions (National Center for Complementary and Integrative Health 2021).

Herbal preparations are commonly used by U.S. adults (Wu et al. 2014). Because herbs are regarded as food products, they are not subject to the same scrutiny and regulation as conventional medications. Various herbal supplements have been reported or are suspected to interact with certain dental drugs. The use of some herbal supplements is associated with oral manifestations including aphthous ulcers, lip and tongue irritation, swelling with fever, tongue numbness, dry mouth, oral and lingual dyskinesia, and salivation (Tachjian et al. 2010).

Big Data and Health Information Technology Systems

The generation of evidence using real-world data sources in the past 20 years has created the opportunity to transform dental care and redefine dentistry’s role within the health care system. Parallel developments include the significant strides made in analyzing genomic information and the discovery of physical, functional, and biochemical biomarkers for disease. These developments offer new approaches for diagnosing and managing diseases instead of relying exclusively on symptoms and clinical assessment. Moreover, the increasing use of electronic devices to track daily activities, such as sleep, physical activities, and diet, is generating previously unavailable data regarding lifestyle behaviors.

The Patient Protection and Affordable Care Act of 2009 and the 21st Century Cures Act of 2016 (National Institutes of Health 2020b) have resulted in dramatic progress toward increasing electronic documentation of patient care in dentistry and medicine and improving provider, patient, and researcher access to electronic health information. Access to electronic health data has led to the development and evaluation of clinical decision support systems, an appreciation for new imaging modalities such as CBCT to monitor disease progression and treatment outcomes, and a better understanding of the natural history of diseases. However, the full potential of these advances can only be accomplished through evaluating and monitoring the quality of their data.

The dental profession has been mostly solo or small group practices. Consequently, there are as many different ways of recording patient encounters as there are practices, and there has been no consensus on a standardized method of data entry into EHRs. Furthermore, data are entered differently at each dental school, and how information is gathered across schools varies, which makes data mining challenging. A data-sharing framework has yet to be developed that allows oral health professionals to send their data to a curated data warehouse.

The choice of EHR has had a limited impact on the way dental medicine is practiced. To date, 72% of U.S. dental practices use an EHR to capture at least some clinical information (Acharya et al. 2017). Momentum for improved utilization of EHRs is building as the dental profession begins to see the advantages gained from using big data in medicine. However, the need remains for a critical paradigm shift with respect to dental data, with more effective and structured pooling of data and consistent use of diagnostic codes.

Most oral health providers cannot imagine a world without EHRs, yet clinicians often struggle with the lack of user-friendliness of available programs (Jha et al. 2018). Dentists are faced with many unmet information needs when using EHRs, such as timeliness of access to information; quality of visual representations of dental problems; access to patient-specific, evidence-based information; and the accuracy, completeness, and consistency of patient records (Song et al. 2010).

Furthermore, there are unmet needs related to access to medical records, genetic data, proteomics data, microbiome data, and biospecimen data. Issues around privacy of medical and dental information also pose daunting challenges to effective data utilization.

Researchers who want to use the vast amounts of data collected in EHRs face other challenges: Clinical notes cannot easily be queried, and there are data quality issues, such as incomplete and missing information or inaccurate and inconsistent data (Song et al. 2013). Although there are many efforts in medicine to address the problem of data fitness for research projects (Zozus et al. 2014), dentistry has lagged behind when it comes to the adoption of standardized diagnostic terminologies (White et al. 2011) and the use of standardized risk assessment tools (Ismail et al. 2013).

Integrated Electronic Health Records

Progress with EHRs has been fueled by technologic developments, allowing for enhanced system features, as well as by greater depth of knowledge and the urgent need for these records. Specifically, today’s systems can provide tools for integrated care and quality care metrics across practice locations to meet growing population needs.

Following publication of the 2000 Surgeon General’s report on oral health, the Health Resources and Services Administration began to prioritize and fund medicine-focused federally qualified health centers (FQHCs) to initiate or expand dental operations; part of this expansion included funding for development of integrated EHRs. The following health informatics initiatives provide examples of translational research using EHRs to improve patient outcomes and advance the delivery of high quality, integrated care.

FQHCs are uniquely suited to serving large populations with oral health disparities because they understand the advantages of better integration across the medical, behavioral, and oral health domains and because their staffs have spent decades honing skills to eliminate barriers to care and conducting outreach to communities in support of population health objectives. Moreover, utilizing EHRs and a referral management module in FQHCs has the advantage of providing early patient triage and referral to cross-disciplinary providers.

Point-of-Care Clinical Decision Support Systems in the Electronic Health Record

Secondary use of data routinely collected at point-of-care settings in an integrated medical and dental care environment has improved understanding of oral and systemic associations (Acharya et al. 2018). For example, a growing evidence base supports a relationship between diabetes and periodontal disease driven by underlying inflammatory activity (Mealey 2006; Eke et al. 2012; Glurich et al. 2013). Few of the health systems that have EHRs have developed strategies and tools to support integrated care delivery models that might offer better outcomes for patients with diabetes (Shimpi et al. 2016; Glurich et al. 2018; Shimpi et al. 2018; Shimpi et al. 2019d). In the absence of glycemic index monitoring in the dental setting, engaging predictive modeling and artificial intelligence (AI) to create a clinical decision support tool has offered a solution for identifying at-risk individuals. Once integrated into the EHR, this tool sorts available clinical data and identifies at-risk patients in need of triage for further clinical evaluation.

Several challenges still exist for an integrated health care model. Oral health professionals sometimes struggle to fully understand patients’ underlying medical conditions because medical and dental records remain largely separate from one another. Physicians also miss critical diagnostic information when they ignore the craniofacial complex. Integrated medical and dental records help dental clinicians use medical information more effectively and make it much easier for all health care providers to understand a patient’s health and history at the point of care, which can lead to fewer errors and more individual-centered care (Figure 5). Health disparities in oral health are pervasive and compromise the ability to elevate health for all.

Figure 5

Integrated electronic health record (EHR).

Finally, greater exploration of the effectiveness of care delivery models that integrate oral health risk assessment tools, alerts, and reminders into medical settings is warranted. This may include integration of dental services within oncology practices to support patients’ oral health needs before, during, and following exposure to chemotherapy or radiation therapy; integration within pediatric practices to reduce the incidence and prevalence of dental caries through dental assessment and the placement of sealants and fluoride varnish applications; and integration into obstetrics to improve prenatal dental care. Health disparities in the context of oral health delivery present complex problems that rely on critical, multilevel analyses as described in the National Institute on Minority Health and Health Disparities Research Framework (National Institute on Minority Health and Health Disparities 2018).

Development of Quality Metrics and Dental Quality Dashboards

Using an EHR supports the development of quality metrics within a dental quality dashboard (Hegde et al. 2017). A dashboard’s summary format presents relevant patient data that respond to the needs of cross-disciplinary providers for patient management (e.g., diagnoses, treatment history, recent health events and procedures, medication exposure, insurance status, compliance with preventive care appointments).

A Dental Quality Analytics Dashboard (DQAD) is a web-based tool that has potential to facilitate data-driven performance reviews for use by dental providers and administrators. Its near-real-time visual analytic platform allows users to monitor, compare, and analyze key clinical, operational, and provider performance and productivity data to identify trends, set goals, and inform improvement activities across multiple providers or clinics. The application may also provide a summary view of the practice population, which may include information on socio-demographic characteristics and medical conditions. An example of an operational DQAD is shown in Figure 6, where sealant applications are tracked against a benchmark to help improve caries prevention activities across clinics (Nycz et al. 2020).

FIGURE 6

Screenshot from the Dental Quality Analytics Dashboard (DQAD).

Data Modeling

Health data analytics have grown exponentially during the last decade as electronic data have become available and accessible, and computing power has become cheaper. Today, there is no shortage of machine learning algorithms and deep learning models capable of analyzing large volumes of data of any type within a few seconds.

Multilevel models for health care data promote effective and interoperable biomedical information systems and services. For example, the Unified Medical Language System (UMLS) of the National Library of Medicine gathers several health and biomedical vocabularies as well as related items to facilitate interoperability between computer systems (National Library of Medicine 2021d). Additionally, it supports some widely used database models and multiple relational database management algorithms, including MySQL (open source) and Oracle. Computer modeling of data types contained in EHRs (biospecimen, imaging, clinical, genomic, and metadata) now includes descriptive data modeling for data processing and predictive data modeling for in-depth analytics.

Descriptive data modeling offers a system for data analytic strategies. Logical and physical data modeling defines and implements the structures of the different data elements of oral health information, setting the relationships and dependencies between them, such as functional, connectivity, and traceability relationships. The descriptive data modeling output explains the data using a structured form such as clustering or network analysis.

Descriptive modeling studies have suggested exciting associations between oral health and disease and phenotypic measures, but these findings often are not generalizable to other samples. Categorizations using descriptive models of oral conditions—temporomandibular disorders and facial pain; cleft lip, cleft palate, or both; dental caries; periodontal disease; and oral and pharyngeal cancer—often fail to achieve stated objectives because of the complex nature of clinical presentations and clinical progression, which can make the responses to therapeutic interventions unpredictable (Slavkin 2018).

Geometric or spatial descriptive models are used to represent craniofacial geometric or spatial relationships. Such 3D surface and volumetric texture models are used in dentistry to diagnose and plan treatment, assess treatment outcomes, and create physical models for 3D bioprinting of anatomy, appliances, maxillofacial grafts, and tissue engineering scaffolds. Three-dimensional geometric models that correlate facial morphology with genomic data show great promise in revealing underlying pathology. Utilizing a meta-analysis of genome-wide association studies, a complex pattern of coordinated genomic variants has emerged that governs variation in facial structures (White et al. 2021). Large-scale statistical modeling is required to control for multiple comparisons so that these studies can help provide a better understanding of the links between facial morphology and the genome.

Expert diagnostic systems driven by algorithms, that is, AI, may enhance diagnostic processes when utilized for decision support (Cabitza et al. 2017). It is imperative that researchers, clinicians, and the public engage in dialogue to explore data science’s ethical challenges and the interpretability and applicability of the underlying algorithms (Obermeyer et al. 2019). Unambiguous interpretation of the algorithms used in health care data gathering and analysis can ensure that individuals are treated equitably regardless of their race, gender, or ethnicity. Algorithms that determine treatment options, resource allocation, and prognosis of disease must be transparent to facilitate bioethical considerations and to promote public acceptability.

Teledentistry

An overview of U.S. teledentistry (Nichols 2019) describes the progress of this technology. The emergence of COVID-19 in the United States in 2020 and the resulting limitations on in-person care have demonstrated the value of telehealth, resulting in additional policies and applications being rapidly adopted. Most teledentistry functions as a public health service meant to address access-to-care issues, with a focus on risk assessment and prevention. The Center for Democracy and Technology now has specific codes for teledentistry that facilitate filing claims. By the last quarter of 2018, 49 states offered reimbursement for live video encounters, and 11 states reimbursed for store-and-forward (in which video interaction is recorded and viewed later, rather than live). A number of states now have policies allowing public health insurance reimbursement (Medicaid) for teledentistry: Arizona, California, Georgia, Minnesota (for children, pregnant women, and adults [limited benefits]), New York, North Carolina (synchronous only), Tennessee, and Washington (Center for Connected Health Policy 2020).

Teledentistry faces challenges before it can become a viable and widespread adjunct to mainstream clinical dentistry, however. These challenges include dissimilarities and conflicts in state and federal laws, reimbursement limitations, and concerns about data quality and security. Because technology can cross state borders, interstate provider licensure transferability is a key issue. Ensuring privacy and data security has become increasingly important.

Learning Health Care Systems

A learning health system (LHS) is a health care system that “learns.” In a LHS, knowledge generation is so embedded into health care practice that it becomes a natural product of the health care delivery process, leading to continual improvement in care (Institute of Medicine 2007). The LHS concept was virtually unknown in 2000. The LHS vision is more than a concept; organizations, networks, regions, and nations are actively working to become LHSs. Prominent health care systems (Ovretveit et al. 2016) and academic health centers (Pronovost et al. 2017) are launching LHS initiatives across the United States, and organizations are routinely coming together to form learning and improvement networks (Califf et al. 2016) with support from recognized public and private funders (Selby et al. 2013).

At a national level, the federal Office of the National Coordinator for Health Information Technology has made it an objective to connect LHSs across the country into a nationwide LHS by 2024 (DeSalvo and Galvez 2015). Initiatives at the Agency for Healthcare Research and Quality (Bindman 2017) and the Patient-Centered Outcomes Research Institute (Selby et al. 2013) complement and amplify this work. Globally, other countries are declaring their intentions to form nationwide LHSs (The Learning Healthcare Project 2021; Boes et al. 2018), and international networks continue to proliferate as well (Ethier et al. 2017).

The ethical, legal, and social implications of LHSs require increased attention (Platt et al. 2018), but daunting challenges exist related to cultivating the data, disseminating the knowledge, and acknowledging their benefits. A major benefit of national-scale LHSs is rapid and effective pharmacovigilance. For example, in a network the size of the U.S. population, post-marketing drug safety signals could be rapidly detected in a few weeks rather than multiple years, preventing unnecessary morbidity and deaths (Friedman et al. 2015). The underutilization of the ability of data to inform best practices and maintain optimal patient safety is an ongoing concern.

Evidence-Based Approach to Introduction of New Technologies into Clinical Applications

The transition from a clinic-centric, business-driven model to one that is patient-centered, that is, more focused on individualized approaches to patient care, is influencing current trends in clinical research. The National Institute of Dental and Craniofacial Research (NIDCR) supports research in implementation science through National Institutes of Health (NIH)-wide and institute-specific dissemination and implementation funding opportunity announcements. Funded provider-related studies have addressed, for example, the use of a clinical decision support tool to aid in prescribing opioid and non-opioid analgesics for pain management following dental extractions (U.S. National Library of Medicine 2018); Rindal et al. 2021); the use of sealants to arrest noncavitated carious lesions (de Assunção et al. 2014); the use of an EHR system to enhance care provided to an ethnic minority population (Northridge et al. 2018); and engagement in an organizational change model to decrease appointment no-show rates (U.S. National Library of Medicine 2017).

Many illnesses have symptoms that present in the mouth. This means dentists and hygienists can help recognize early signs of disease, as well as spot life-threatening conditions such as diabetes and oral cancers at the earliest stage because they see many patients on a routine, rather than problem-driven, basis. Early detection improves the patient’s prognosis and helps control costs. For example, one medical insurance company conducted a 3-year retrospective study of 23,441 insured women, analyzing pregnancy outcomes and dental care using the health system’s combined medical-dental database. Mothers who received preventive dental treatment while pregnant had 25% lower preterm birthrates and 34% fewer incidents of low birth weight (Albert et al. 2011). However, this conflicts with the results of another NIDCR-funded study examining women in the second trimester of pregnancy that found no effect (Offenbacher et al. 2009).

The 21st Century Cures Act (U.S. Food and Drug Administration 2020c) has significantly modernized the field of clinical research. This Act recognizes the need to expedite the development of investigational medical products (drugs, biologic products, and medical devices) and implement faster and more efficient approaches to patient care. The Act provides the legal framework enabling the FDA to include patients’ perspectives in developing investigational medical products.

Implementation science as a field has seen significant growth in the past 2 decades (Norton et al. 2017), including development of guidelines and assessment tools for interventions appropriate for diverse populations, as well as models of community partnership and stakeholder engagement to ensure use of evidence-based practices (Damschroder et al. 2009; Barrera et al. 2013; Stirman et al. 2013; Anderson et al. 2015; Napoles and Stewart 2018). Innovative study designs that test components of complex interventions (Collins et al. 2016) were developed as well as system science approaches that examine the effectiveness of evidence-based practices at the population level (Green 2006). Finally, research methods such as hybrid effectiveness-implementation designs (Curran et al. 2012; Landes et al. 2019) have been developed to accelerate progress through the research pipeline from efficacy through implementation research when used appropriately.

Practice-Based Research Networks

To catalyze the development of dental practice-based research networks (PBRNs), NIDCR funded three regional dental PBRNs from 2005 to 2012 and is supporting a single, unified PBRN (the National Dental PBRN) through 2026. By the end of their initial funding period, the regional PBRNs had conducted numerous studies with thousands of patients and hundreds of practitioners. Studies investigated numerous topics using a broad range of study designs, demonstrated rigor and impact on clinical practice, and showed that dental practitioners could effectively contribute to every step of the research process.

The National Dental PBRN has made meaningful progress in better understanding clinical issues related to oral cancer, sensitive teeth, and root canal treatment, among other oral health conditions. For example, a study of cracked tooth syndrome in 2,858 individuals revealed that a large proportion of these teeth are asymptomatic and may remain stable, with little progression of cracks or symptoms during a year of follow-up (Hilton et al. 2020).

Delays in study implementation as a result of institutional review board requirements and slow initial recruitment of practitioners were early challenges in the development of oral health PBRNs. Many lessons were learned to inform future recruitment (Gilbert et al. 2011; Mungia et al. 2018). Oral health PBRNs have since demonstrated that practitioners from a broad array of practice settings and geographic regions will readily contribute research ideas and participate in studies. Whether and how regional networks of clinicians interface with dental trainees and faculty and whether this transfer of knowledge in clinically relevant areas is integrated into dental research environments are additional challenges the National Dental PBRN faces. Although the nature of PBRN research presents many challenges, these can clearly be overcome when managed appropriately for the improvement of practices and care of patients.

Considerations and Challenges in Clinical Research

Important advances have been made over the past decades through the benefit of large clinical research trials. Such trials are typically supported by private companies (mostly pharmaceutical), government, nongovernment organizations, or are self-funded (e.g., universities). The potential for advances can be tempered by the expense of engaging in clinical trials when sponsorship for large trials is mostly limited to some private entities or governmental funding opportunities. Because the cost of a trial is closely related to the length and number of follow-up visits occurring within a trial, it is important to support robust, well-designed, and well-powered studies to yield useful information for clinical care. Additional strategies to ensure stewardship of support are human participant safety oversight, clinical study monitoring, transparency, and timely reporting of findings.

It can be challenging to recruit participants to studies, and study generalizability may be limited by the lack of representativeness on the basis of, for example, age, race/ethnicity, gender, and even other demographic characteristics such as socioeconomic factors and location of residence. In order to identify causative underpinnings of oral and craniofacial diseases and develop new therapeutics for the treatment of chronic conditions affecting this region, longitudinal studies that are incredibly demanding in terms of years of investigational investment are needed.

Education and Training

A number of activities in the past 20 years have addressed strengthening and sustaining a robust and diverse research workforce in oral health science. The NIH Common Fund was initiated in 2004 to address emerging scientific opportunities and pressing challenges in biomedical research and research training, including the development of clinician-scientists. The Common Fund includes programs to enhance training opportunities for early-career scientists to prepare them for a variety of career options. The Common Fund’s Diversity Program Consortium aims to enhance diversity in the biomedical research workforce by engaging, training, and mentoring students; enhancing faculty development; and strengthening institutional research training infrastructure to enhance the participation and retention of individuals from diverse backgrounds in biomedical research careers (National Institutes of Health 2021a).

During the past 20 years, academic dentistry has undergone several major reforms promoted by the American Dental Education Association (ADEA) that have focused on improving health care providers’ overall effectiveness. Exposing future oral health professionals to research can have an impact on their educational experiences. However, related outcomes are not well measured, and approaches vary among institutions (Polverini and Krebsbach 2017). Various training schemes supported by NIDCR and other stakeholders and institutions, such as combined Doctor of Dental Surgery (DDS) and Doctor of Philosophy (PhD) programs and targeted research development programs, are designed to promote entry into academia, but these have fallen short of anticipated outcomes, as shown in Figure 7 (D’Souza and Colombo 2017).

FIGURE 7

Physician-Scientist Workforce training pipeline.

The current demand for dental school faculty and research scientists is not being met. The ADEA task force report on the dental school faculty workforce showed that the number of vacant, budgeted, full-time faculty positions rose from 181 in 1993 to 374 in 2005 (Wanchek et al. 2015). A subsequent decrease to 252 in 2014 was primarily the result of permanent elimination of vacant positions (Garrison et al. 2014) as dental schools managed the shortage by adjusting curricula, increasing the teaching load of existing faculty, and hiring additional adjunct faculty. If faculty retirements and a faculty turnover rate of 33% every 5 years are factored in, it has been suggested that dental schools across the country need 208–218 new faculty members each year (Kennedy 1990). There is a critical need to create and sustain a viable pipeline of dental faculty (Wanchek et al. 2015).

Dental schools currently fail to attract more than 0.3% of their graduating seniors to academic careers (Istrate et al. 2021). Although some programs have been addressing this issue at a local level (Horvath et al. 2016), dental education in the United States now depends on the influx of foreign-trained academics to replace aging faculty. Forty percent of faculty at academic dental institutions are more than 60 years of age (Contreras et al. 2018). U.S. dental public health residency programs admit qualified international dental school graduates and have high percentages of foreign-trained dental graduate applicants and residents. During the 2019–2020 academic year, 62% of all dental public health residents were foreign trained (American Dental Association 2020).

The NIH Physician-Scientist Workforce Working Group Report identified challenges for clinically trained investigators in pursuing research careers, including educational debt as a result of high educational costs, as well as a long period of clinical and research training, which create a vulnerable transition period between research training and independent academic research careers (National Institutes of Health 2014). Competition for prestigious NIH funding has become increasingly intense (Ginther et al. 2011). The average age of first receipt of a major NIH independent research grant (the R01) rose from 36 years old in 1980 to 45 years old in 2013 (Daniels 2015), which can lead to several challenges facing younger researchers in academic settings.

The consensus study report, The Next Generation of Biomedical and Behavioral Sciences Researchers, of the National Academies of Sciences, Engineering, and Medicine, prepared in 2018 by the Committee on the Next Generation Initiative Board on Higher Education and Workforce Policy and Global Affairs, defined the core challenges that undercut the vitality, promise, and productivity of the biomedical sciences (National Academies of Sciences, Engineering, and Medicine 2018a). The percentage of tenure-track opportunities among all positions in academic dentistry has declined steadily (Chmar et al. 2006). Given that vacant faculty positions averaged 257 per year between 1994 and 2015, graduates from the existing 22 oral sciences PhD programs who entered U.S. academic institutions could have filled only 3.6% of the annual vacant dental faculty positions during this time period (Herzog et al. 2018). If the annual number of graduates continues at this low rate, the United States is at risk for a significant compromise in the size of the available academic workforce.

There are no analytic data on trends in enrollment for PhD programs or the placement of their graduates. This lack of program-specific data for oral sciences PhD programs has made it difficult to gauge how many students optimally should be trained to support the dental profession’s education and research mission. The report, Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016, was the first attempt to summarize oral sciences PhD program outcomes. According to that report, oral sciences doctoral programs have enrolled more women (54.7%) than men (44.5%). Race or ethnicity among these enrollees was reported as White (39.1%), Asian (34.7%), Hispanic (7.1%), Middle Eastern (5.2%), Black (2.9%), Indian (2.4%), and unknown or not reported (8.6%) (Herzog et al. 2018). Clearly, diversity in these programs is less than optimal. Both the growth in student debt and the widening income gap between dental practitioners and academic professionals make recruiting and retaining dental faculty challenging. Although there is a small group of dental students interested in teaching, very few structured mentoring programs exist to guide them in pursuing academic career goals.

The financial pressures on dental schools often lead them to increase emphasis on clinical revenue generation and decrease their emphasis on research (Wanchek et al. 2015). Consequently, the pool of research faculty available to act as mentors for early-career dentist-scientists has diminished. In addition, the amount of student debt upon graduation likely presents a barrier to dentists pursuing careers in academic dentistry.

NIDCR maintains strong partnerships with dental schools and other institutions that have a vital role in educating and training oral health researchers (Feinberg et al. 2015; Ferland and Winstanley 2017; Herzog et al. 2018). However, the institute’s total investment in dental schools decreased during the past 15 years (Ferland and Winstanley 2017). These data align with long-standing concerns about dental institutions’ diminished research and research training capacities, especially in training the dentist-scientist research workforce (D’Souza and Colombo 2017). This decrease in support compromises dental schools’ abilities to generate new science to prevent and treat dental, oral, and craniofacial diseases (Feinberg et al. 2015; Polverini and Lingen 2017; Formicola et al. 2018). When adjusted for inflation, there also has been a steady decrease in NIH funding since the doubling of the NIH budget (Kaiser 2019). One of the consequences of these decreases is a hypercompetitive environment that has too many researchers vying for limited resources and discourages students and postdoctoral scientists from continuing academic research careers (Alberts et al. 2014).

Faculty impediments to conducting research include the paucity of protected time for research and inadequate formal mentoring and career guidance programs for early-stage faculty. Disciplinary silos continue to determine requirements and curricula, with little opportunity for interdisciplinary exploration, creation of scientific networks, and experience with diverse methods and working styles in research groups. In addition, little time and few opportunities exist for development of professional skills on scientific writing, public communication of science, leadership, or learning how to manage projects and staff.

Redoubling Commitments to Diversity and Inclusion

In addressing the preparation of the future scientific workforce, committed action to diversity is essential. In 2018, more than half of first-time graduate students (master’s and doctoral level) were women (Okahana and Zhou 2019), and women received more than half of the doctoral degrees in 2017, in fields related to biological and biomedical sciences, health sciences, and public health (National Academies of Sciences, Engineering, and Medicine 2018a). In contrast, reports indicate that in a number of fields related to science, technology, engineering, and mathematics (STEM), including the physical sciences and engineering, no real progress has been made in recruiting underrepresented minority students (National Academies of Sciences, Engineering, and Medicine 2018b; National Science Foundation 2019), and the number of minority doctorate recipients is far below minorities’ representation in society (National Science Foundation 2019).

Critically, the National Center for Science and Engineering Statistics lists hundreds of fields and subfields of study, yet it does not include dentistry or oral health sciences among them, making it difficult to estimate the progress, or lack thereof, in developing a diverse cadre of scientists in this area. A 2019 article in The Atlantic noted that “in more than a dozen academic disciplines—largely STEM related—not a single Black student earned a doctoral degree in 2017” (Harris 2019). If this trend continues, the diversity and inclusiveness of faculties and leadership will continue to fall. Creating safe and inclusive environments for individuals of different racial and ethnic groups, genders, and socioeconomic status, as well as those with disabilities is an ongoing challenge that requires strategic consideration and fresh approaches to diversifying the academic workforce in oral health.

NIH also has funded efforts to support diversification of the scientific workforce (National Institute of General Medical Sciences 2021a). Examples include the Building Infrastructure Leading to Diversity (BUILD) initiative and the National Research Mentoring Network (NRMN). The BUILD initiative consists of linked grants issued to undergraduate institutions to implement and study innovative approaches to engaging and retaining students from diverse backgrounds (National Institute of General Medical Sciences 2021b). The NRMN is a nationwide network of mentors and mentees from all biomedical disciplines relevant to the NIH mission of providing support to individuals spanning undergraduate education to early-faculty careers.

A special advisory group to the NIH director on diversity in the biomedical workforce was convened in 2011 (Working Group on Diversity in the Biomedical Research Workforce 2012). In addition, the topic of diversity and inclusion in the dental research workforce within the United States was covered in a special issue of Advances in Dental Research and discussed by D’Souza and colleagues (D’Souza et al. 2017; Ioannidou et al. 2019). Promising advances in these programs led to new initiatives in 2018 to sustain progress and identify methods and interventions to support sustainable models for enhancing diversity in biomedical research.

Omics/Gene Editing/Single-Cell Technologies

Emerging clinical innovations have already begun to employ the tools of the omics era. Notably, there have been a number of successful genome-wide association studies of phenotypes, including orofacial clefting (Leslie et al. 2016; Leslie et al. 2017; Haaland et al. 2018), dental caries (Wang et al. 2012; Haworth et al. 2018), periodontitis (Divaris et al. 2013; Haworth et al. 2018), tooth eruption and development (Geller et al. 2011; Fatemifar et al. 2013), and orofacial pain (Randall et al. 2017). There also is a long tradition of researchers utilizing microbiomics (Dewhirst et al. 2010; Escapa et al. 2018), metabolomics (Foxman et al. 2016), and metagenomics, notably focusing on dental caries and periodontal disease.

There is a major international effort to develop databases to integrate genomics into health care (Stark et al. 2019) by linking nationwide electronic health records (EHRs) and obtaining DNA samples. At least 14 countries have begun such vital endeavors (Stark et al. 2019). In the United States, the program is known as the All of Us Research Program (National Institutes of Health 2021b) and has a goal of engaging 1 million volunteers to reflect the nation’s diversity, including all life stages, health statuses, racial and ethnic groups, and geographic regions. All of Us and other endeavors, such as the National Cancer Institute’s Cancer Moonshot (National Cancer Institute 2020) and the 21st Century Cures Act (National Institutes of Health 2020b), hold great promise for the development of innovative prevention strategies, treatments, and data sharing. It is critical to integrate dental, oral, and craniofacial health phenotypes into these initiatives.

Applications of Genome Editing to Human Cells

We are in an era with access to a variety of highly versatile editing technologies that allow genetic material to be added, removed, or altered at locations across the genome. These technologies offer exciting routes to new therapeutic development by potentially allowing for correction of underlying genetic deficits that exist in a number of human diseases, as well as in microorganisms that compromise health. Several genome editing technologies may influence oral disease and congenital malformations, including zinc-finger nucleases, transcription activator-like effector nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein systems, and RNA editing (Baysal et al. 2017; Yu et al. 2019).

In the field of oral health, single-gene disorders, which are caused by mutations in a single gene, are targets of genome-editing technologies for research and therapeutic applications (Figures 8 and 9) (Patil et al. 2014). Many of these disorders feature craniofacial anomalies that can be prevented or reversed with replacement therapies that involve proteins as well as agonist small molecules and antibodies (Jia et al. 2017a; Jia et al. 2017b). Advances in genome editing technologies have raised hope for improving the clinical diagnosis, treatment, and outcomes for patients with craniofacial malformations associated with single-gene disorders (Neben et al. 2016; Yu et al. 2019).

Figure 8

Working classification of single gene disorders with oral manifestations.

Figure 9

Single gene disorders with common oral manifestations.

In light of advances in human genome editing, it also is important to consider the potential of microbial genome editing. Although still in its infancy, this field has had some early proof-of-principle studies, including the design of a self-targeting CRISPR system in Streptococcus mutans—a primary causative agent of human dental caries—that could reduce the bacteria’s pathogenicity. Limited genetic tractability in many bacterial species is being addressed on multiple fronts with newer technologic advances in genetic engineering of bacteria (Cuiv et al. 2015; Johnston et al. 2019).

Microbiome/Inflammasome/Virology

The human microbiome has become an attractive drug discovery platform for new therapeutics (Milshteyn et al. 2018). There is increased recognition of the vast numbers of unidentified molecules produced by oral microorganisms that are likely to affect the oral microbiome (Edlund et al. 2017). Promising strategies to engineer and manipulate these communities are emerging. Several prebiotics, which are substances that potentially modulate the microbiome, are being investigated. For example, identifying individuals whose oral microbiomes are exceptionally robust and efficient at reducing lactic acid to protect against tooth decay could provide insight into unique preventive microbial communities. Scientists could identify persons who are genetically prone to periodontal infection but could potentially be protected by a healthy oral microbiome that keeps inflammation in check or limits keystone pathogens (Lamont et al. 2018). Such case studies would provide opportunities to uncover new therapeutic molecules made by unique biosynthetic gene clusters (Donia et al. 2014).

Basic and clinical research should incorporate evaluation of the microbiome, including clinical trials to evaluate new therapeutic regimens and engage scientists and dentists who have a wide range of expertise (Human Microbiome Project Consortium 2012a; 2012b). There also is a need to understand complex microbe-microbe interactions (Mark Welch et al. 2016; Stacy et al. 2016) and microbe-host interactions (Lamont et al. 2018).

Development of new tools would go far to advance microbiome applications. Gnotobiotic mice (animals in which all microorganisms are either known or excluded) colonized with a select group of human gut microbiota have been instrumental in determining the contribution of those microbiota to disease (Fitzgerald 1968; Kashyap et al. 2013; Smits et al. 2016). The establishment of a similar model would provide a powerful tool for evaluating contributions of the oral microbiome, help uncover new keystone players, and facilitate the development of more relevant microbiota-targeted therapeutics. Engineering of the microbiome in the oral cavity in situ remains challenging. Such microbiome engineering (Ronda et al. 2019) should enable the precision delivery of novel genetic and biochemical traits into the oral cavity and open a new frontier in synthetic biology.

Antimicrobial Materials

The addition of antimicrobial materials to existing dental materials offers an opportunity to improve their longevity and promote better oral health. Materials are being developed that incorporate antimicrobial agents to kill potentially harmful bacteria on contact or prevent them from forming biofilms (Cocco et al. 2015; Stewart and Finer 2019). One example is a biomaterial that releases fluoride into surrounding areas (Hafshejani et al. 2017). Commercial products have been developed for restorations that provide a contact-kill mechanism to keep bacteria from colonizing the area between the restoration and remaining tooth where cavities are thought to begin (Imazato 2009; Makvandi et al. 2018). Continued research into such materials is likely to lead to improved dental restoratives that preserve tooth structure and reduce the need for later intervention.

Remineralizing Materials

New remineralizing materials hold great promise for reducing restorative failure and improving oral health. Many materials have become commercially available that have the potential to promote mineral formation in the oral cavity, either through the addition of fluoride or the incorporation of calcium phosphate, calcium silicate compounds, or bioactive glasses (Taha et al. 2017). Some new materials are designed with nanotechnology-based materials that simultaneously promote remineralization and demonstrate antibacterial effects (Cheng et al. 2015; Zhang et al. 2017). These types of materials currently are primarily used for lining the deeper portions of a dental restoration for direct pulp capping (Paula et al. 2018). Promising results have been shown in promoting dentin material using new and already existing materials, such as calcium hydroxide and mineral trioxide aggregate (Didilescu et al. 2018). Continued work in this area will undoubtedly result in a host of commercial products that can be used throughout dentistry to provide more predictable responses to decayed tooth tissue treatment.

Regenerative Materials for Tooth Replacement and Alveolar Bone Repair

The use of advanced scaffold designs that can guide the spatiotemporal requirements for periodontal regeneration, which is key for new periodontal attachment formation, has the potential to significantly improve therapeutic outcomes (Ivanovski et al. 2014; Vaquette et al. 2018). In regenerative endodontics, there is strong potential in materials, typically built on resorbable polymer scaffolds (Fukushima et al. 2019; Patel et al. 2019), that can be implanted into the removed, damaged tooth pulp to restore healthy form and function. Investigators are exploring the development of materials from three-dimensional (3D)-bioprinted scaffolds implanted with undifferentiated stem cells that can generate vasculature, nerves, and structural cells capable of functioning in much the same way as a natural, healthy tooth (Athirasala et al. 2017).

3D Bioprinting and Additive Manufacturing

Emerging research into the use of 3D bioprinting technologies (also known as additive manufacturing) in dentistry includes the development of bioinspired microstructural arrangements, such as topology optimization (TO). This process maximizes physical performance by optimizing the structural arrangement within the design of an object composed of one or more materials (Bendsoe and Sigmund 2004). Initially, TO was used to modify the macroscopic geometries of objects designed using homogeneous materials (Sigmund 1994), but it is now possible to work at a much higher resolution when combining different materials into designs that incorporate specific microstructures suited to a desired performance.

Use of 3D printing is growing rapidly across many sectors. This innovation encompasses a suite of technologies for fabricating parts directly from 3D digital models. The technology’s power lies in its ability to produce high-value, complex, and individually customized parts. The integration of the different types of printable materials, as well as better software and hardware, has dramatically expanded the potential for these approaches (Ligon et al. 2017; Harun et al. 2018).

The quality of 3D products, in terms of speed of production, dimensional control, strength, and biocompatibility, is increasingly meeting the needs of dentistry. At the same time, the capabilities of scanners to generate, digitize, store, and manipulate 3D patient data in a cost-effective fashion continue to grow. In the future, dental offices will be able to produce patient-customized specific parts, such as implants and dentures, by combining the digital powers of 3D scanners and 3D printers (Figure 10) (Galante et al. 2019). This shift will have implications for clinical practice, researchers, materials producers, and equipment manufacturers—with ultimate benefit to the patient (Bhargav et al. 2018; Oberoi et al. 2018).

FIGURE 10

3D Printed denture teeth processed and seated on supporting dental implants. Notes: Digital denture designed with CAD/CAM software and denture teeth 3D printed. Dentures can be designed in less than 20 minutes and printed in as little as 30 minutes.

Nanotechnology

The utilization of nanotechnologies in dentistry is in a young, yet promising, stage of emerging discoveries and breakthroughs. One encouraging new direction uses intracellular nanodelivery tools, such as polymeric or lipid nanoparticles, nanoneedles, electroporation, and other similar methods, including inorganic nanoparticles, to manipulate cellular behavior in situ (Stewart et al. 2016). This will form the basis for the development of next-generation vaccines, precision therapies, and patient-specific regenerative strategies that take advantage of cell reprogramming, differentiation, and tissue engineering and regenerative medicine. Another area of development is nanotheranostics, which employs minimally invasive techniques using nanoscale materials simultaneously for early-stage disease diagnostics and therapy (Cheng et al. 2017). Two more areas that deserve attention are the rapidly emerging fields of nanofabrication and nanorobotics in medicine, as well as exosome engineering (Yim et al. 2016).

Stem Cell Biology

Innovative stem cell approaches should allow first-in-human clinical trials in dentistry for repair of bone defects around teeth, dental implants, cleft and orofacial repairs, and regenerative endodontics. A promising area of development is allogeneic stem cell therapy, which can use stem cell banks as ready sources for stem cells on an as-needed basis. Better coordination among scientists, clinicians, industry, federal regulatory agencies, and reimbursement entities would accelerate the potential for stem cell biology to provide clinical advances.

Genetics- and Genomics-Based Precision Health

Technologic advances have profoundly decreased the cost of sequencing genomes, potentially enabling genetic information to be generally available to guide clinical care (Chiu and Miller 2019). During the next 10 years, genetic and genomic information will increasingly have an impact on dentistry, as they have in medicine, and will be used with other data, including diet and lifestyle, to inform clinical prevention and treatment decisions. Genomic information about an individual will increasingly be used to inform clinical care decisions (for susceptibility, diagnostic, or therapeutic decision-making) as development of national genome-medicine initiatives continue to integrate genomic, epigenomic, environmental, behavioral, and other information in a meaningful way to fulfill the promise of precision health care (Stark et al. 2019). These projects’ capacities to integrate data from millions of individuals will provide the power to identify and validate clinically useful data.

Advances in Laser- and Light-Based Imaging Technologies

Higher-performance imaging devices operating at longer wavelengths beyond 1,000 nanometers (nm) will likely become commercially available in the near future as the prices of germanium and indium gallium arsenide sensors continue to decrease. The highest contrast of demineralization on tooth surfaces occurs at longer near-infrared (IR) wavelengths greater than 1,000 nm, owing to reduced scattering in sound tissues and higher water absorption (Chung et al. 2011; Fried et al. 2013). Higher water absorption also can be exploited to yield high contrast of demineralization and dental calculus on root surfaces at wavelengths beyond 1,450 nm (Yang et al. 2018). Stains can easily be differentiated from actual demineralization, which is not possible at wavelengths less than 1,200 nm (Chung et al. 2011). At wavelengths greater than 1,300 nm, near-IR imaging is more sensitive than radiography for the detection of lesions on both occlusal and proximal tooth surfaces in vivo (Simon et al. 2016).

Optical coherence tomography (OCT), a noninvasive technique for creating cross-sectional images of internal biological structures (Bouma 2002), can be used to measure the reflectivity within dental hard tissues to a depth of up to 3–5 millimeters (mm) in enamel and 1–2 mm in dentin, with an axial (depth) resolution exceeding 10 micrometers. Commercial OCT systems are on the horizon to monitor demineralization (Fried et al. 2002; Louie et al. 2010). High-speed OCT systems are now available that can make an image of a tooth in less than a second. In the near future, systems will likely have scanning rates 10–100 times faster than today. Dedicated dental OCT imaging systems are under development and should be available in the next few years.

Neuroimaging-Based Technologies for Managing Orofacial Pain

Researchers have started to analyze the neurologic signatures of pain using neuroimaging. Portable neuroimaging devices with technical benefits similar to functional magnetic resonance imaging (fMRI) have been developed. Functional near-infrared spectroscopy (fNIRS) detects concentration variations of oxyhemoglobin and deoxyhemoglobin, such as blood-oxygen-level-dependent signal in fMRI, by measuring the absorption of near-IR light at wavelengths between 700 and 1,000 nm. fNIRS, akin to fMRI, can be used to study functional brain activity in the clinical environment. The fNIRS device has the portability, interface, and compatibility necessary for ferromagnetic and electrical environments, so it can be used in many clinical settings to monitor patients’ functional brain activity (hemodynamic responses) and functional connectivity. Future dental offices may have the opportunity to localize orofacial pain with much greater accuracy using less invasive techniques and smaller, easier to use devices to improve diagnoses related to oral pain.

New Therapeutic Approaches in Dentistry

Biomarker studies have led to the discovery of new drug targets such as microbiome-modulating compounds (C16G2) or anti-inflammation reagents (resolvins and lipoxins) to treat and prevent dental caries and periodontitis. Various new microbiome-reengineering approaches, such as probiotics, prebiotics, and phage therapy, have promise.

Innovative technologies have been reported for dental caries reduction through an oral microbiome-based preventive approach, such as topical use of the amino acid arginine (Bijle et al. 2019). Another new direction is the application of silver diamine fluoride to a decayed dental surface to stop the progression of a carious lesion (Horst and Heima 2019). Although the use of silver diamine fluoride to inhibit dental caries is not a new therapeutic approach and has been extensively used in other countries, there has been renewed interest in the United States in this product.

Areas that hold great promise for the treatment of head and neck cancers include immunotherapeutics that expand tumor-specific T cell mechanisms and radiation sensitizers that utilize DNA-damage repair agents (Heath et al. 2019; Manukian et al. 2019). Diagnostic and therapeutic precision approaches in the treatment of head and neck cancers also are under intensive investigation on the basis of the delineation of key signaling pathways, and they offer promising therapeutic opportunities (D’Silva and Gutkind 2019). New strategies for stem cell based anticancer therapies are on the horizon that build on the key concepts of precision health (Wang and Aguirre 2018).

Big Data and Electronic Health Records

Big data gleaned from EHRs and other databases should be analyzed electronically to project attributable risk for disease emergencies using data-mining approaches to develop predictive models (Glurich et al. 2017; Hegde et al. 2017). Moreover, integration of oral and craniofacial health with general health through an integrated EHR is critical and will support advances in understanding the physiological interactions between oral and systemic health and disease.

The creation of a collaborative environment across disciplines using EHRs supports high quality health care, research, and education and connects hospitals and health care organizations. Moreover, EHRs have substantial research potential through monitoring health events and evaluating outcomes using data generated from integrated health care systems. This, in turn, can synergistically improve our understanding of the relationships between oral health and overall health and well-being within real-world environments.

Dentists will increasingly help other medical professionals provide primary care to their patients. In many dental offices, recording of vital signs is routine. Screening for diabetes, atrial fibrillation, obesity, vaccinations, mental illness, risk of falls, substance abuse, domestic abuse, and other conditions normally screened for by primary care providers also could be routinely obtained within a dental office environment. The resulting data, residing in an integrated EHR, would be updated and acted upon in a more frequent, regular, and efficient manner. A unified record has a positive impact on population-based research by making it easier to conduct longitudinal studies with greater data fidelity. The study of various oral disease processes will be better understood in the context of the larger whole.

Using EHRs to create a collaborative environment across disciplines contributes to the common goal of providing access to state-of-the-art, high quality, and holistic health care for all segments of the population. One example of an integrated model pairs a large community center (Marshfield Clinic, see Section 4) with a center-dedicated research team. This model expands access to dental care and promotes improved quality of care by generating new knowledge and creating decision support tools that can be quickly translated into practice or used to guide future planning (Acharya et al. 2012). It holds great promise for advancing oral health and integrating oral, medical, and behavioral health in ways that accelerate progress toward improved oral and general health for the patients and communities served. Encouraging national promotion of this model would be beneficial for improving patient outcomes (Acharya 2016; Shimpi et al. 2016; Shimpi et al. 2019a). The Institute for Healthcare Improvement (2003) employs a model for improvement that includes plan-do-study-act cycles for rapid tests of change to emphasize multidisciplinary innovation and learning under an umbrella of improvement science. Such an approach could prove valuable on a platform of an integrated EHR.

Data Science

Oral health data science continues to evolve as an integral contributor to emerging technologies that advance treatment for oral diseases and disorders. However, few institutions have explored the potential for utilizing EHR data to study oral health problems that may cause or co-occur with other medical conditions.

Applying mathematical and computational approaches to complex and multidimensional data can lead to a deeper understanding of dental, oral, and craniofacial health and ultimately transform how oral health care is delivered. This outcome will involve a more comprehensive integration of basic, clinical, and population science to devise new tools and approaches. Understanding the spectrum of information and data science requires that oral health data scientists be skilled in applying advanced data-mining approaches for analyses of large amounts of data (Figure 11).

FIGURE 11

Data management life cycle.

Teledentistry

Teledentistry offers substantial potential for improving the oral health of underserved populations. The application of telehealth and teledentistry also creates opportunities for distance learning that improve dental science and oral health literacy. Similarly, mobile health care services and the use of mobile technology, such as smartphone apps and text messages to manage and track dental health conditions or promote healthy behaviors, have substantial promise for further expanding the effective utilization of teledentistry in both the private and public health sectors. Clearly, teledentistry provides a feasible choice for remote screening, diagnosis, consultation, treatment planning, and education in dentistry (Irving et al. 2018). One successful application of teledentistry to improve access to oral health specialty care for high risk rural children is the partnership among the Eastman Institute for Oral Health, the Finger Lakes Migrant HealthCare Project, the Community Health Center of the North Country, and others (Box 1).

Promising partnerships and programs such as these can serve as models for others to improve the oral health of underserved populations living in rural areas. Another example of a promising new direction in teledentistry is use of the Institute for Healthcare Improvement’s plan-do-study-act cycle to rapidly institute a teledentistry helpline at the start of the COVID-19 pandemic (Weintraub et al. 2020).

Learning Health Systems

Recognition of the roles learning health systems (LHSs) can play in eliminating health disparities, including oral health disparities, has been growing. Organizations and networks working to improve the health of underserved individuals and communities have embraced the concept and are advancing it in ways that are broadly inclusive and participant-driven.

For example, an LHS approach could be employed to address gaps in evidence and evidence-based practice by forming a multi-stakeholder learning community with shared interest in learning about and improving treatments for chronic periodontal disease. A key first step would be to capture relevant data from real-world patient care and experiences to study the problem of interest (e.g., assessing what adjuncts to supplement scaling and root planing work best for different types of patients). This could include patients’ observations of symptoms and self-reports of health-related behaviors as well. Next, analytics could be used to generate new knowledge from the data (e.g., an algorithm to predict which adjuncts are most likely to benefit different types of patients). The knowledge could then be mobilized in actionable forms to clinicians (as well as patients) and implemented into clinical practice, perhaps in the form of user-friendly applications built into clinical decision support and subsequently integrated into EHR systems. In turn, successive cycles of data capture, analyses to generate knowledge, and implementation would begin to enable continuous learning and improvement. The knowledge would be refined, optimized, and updated. Such an approach holds the potential to transform how treatment decisions are made.

Status of Research in Dental Educational Programs

Within the last 5–7 years, much study and discussion have addressed science, technology, engineering, and mathematics workforce needs and doctoral education (Human Microbiome Project Consortium 2012a; 2012b; National Academies of Sciences, Engineering, and Medicine 2018a). By placing increased emphasis on skills needed for working both within and beyond academic institutions, graduate education will benefit from increased focus on interdisciplinary science, collaborative team science, and technology and data science.

Comprehensive research universities, including member institutions within the Association of American Universities (AAU), prepare 70–80% of all Doctor of Philosophy graduates. Schools of dentistry are represented in about one-third of AAU member institutions. At the same time, new schools of dentistry have emerged without visible, productive research programs and lack the collaborative strengths of medical and public health sciences found in comprehensive research universities. Reports and research represented in the Bailit and Formicola (2017) project, “Advancing Dental Education in the 21st Century,” address needed changes to ensure sustainable commitments to contemporary research.

How the profession comes together to realize the future for graduate and professional education is key to sustaining these advances and making improvements in clinical care accessible. The students admitted to dental schools today, whether pursuing science or clinical care, will be working well into the second half of the 21st century. Most of this future work could very well be related to advancing science in oral-systemic connections and discovering appropriate interventions to improve oral and craniofacial health. Such work will require collaborations across medicine, engineering, and dentistry in multidisciplinary areas of precision health care, big data, systems biology, stem cell biology, biomaterials, and tissue engineering (Polverini and Krebsbach 2017).

Supporting Oral Health Science Training

Dental institutions have shared the vision of shaping dentistry’s future leaders to sustain the mission of advancing health through education, service, research, and discovery. It is time to focus on the early stages of the pipeline, with enhanced training and constant stewardship to sustain an optimal support system for young scientists and clinician-scientists.

Academia is a major pathway for oral health scientists, but recruitment alone without increasing the pool of candidates will have limited impact on solving the dental faculty workforce shortage. Evidence suggests that formal training programs that provide students with necessary skills and basic knowledge about academia enhance awareness and facilitate the development of an academic career after graduation (Roger 2008; Gironda et al. 2013; Horvath et al. 2016). Dental institutions and professional organizations have developed programs to actively promote the recruitment and retention of future faculty. ADA, the American Dental Education Association (ADEA), and the American Association for Dental, Oral, and Craniofacial Research (AADOCR) (formerly the American Association for Dental Research) offer dental careers and professional development fellowships to dental students and educators that include structured mentoring, career insights, and hands-on experiences in research, teaching, and other aspects of an academic career. ADEA’s Academic Dental Careers Fellowship Program recommends that institutions improve the climate for academic careers, promote academia’s value, and increase robust interactions among students, faculty, and the institution (Palatta 2016).

Mentoring programs in dental schools and professional organizations also will help strengthen grant-writing skills, improve young faculty retention and advancement in academic careers, and enhance workforce diversity. A national mentoring program involving many institutions will be essential to diminishing disparities among institutions and to enhancing diversity in the faculty workforce (Jones et al. 2017). Cultivating partnerships and collaborations with NIH and professional dental organizations such as ADA, ADEA, and AADOCR; enhanced utilization of the NIH Loan Repayment Program to address educational debt; and developing research training programs targeted to the unique needs and challenges of dentist-scientists would enhance their abilities to successfully compete for research funding from NIH and other federal and nonfederal sources to sustain their research careers.

Several organizational efforts are attempting to increase and diversify the oral health scientific workforce. These include the National Institute of Dental and Craniofacial Research (NIDCR) Award for Sustaining Outstanding Achievement in Research, the NIH Scientific Workforce Diversity Office, and the NIH Policy Supporting the Next Generation Researchers Initiative. NIDCR funds such programs as the Director’s Postdoctoral Fellowship to Enhance Diversity in Dental, Oral, and Craniofacial Research; the Summer Dental Student Award; the Dentist Scientist Career Transition Award for Intramural Investigators (K22); and the Dual Degree Dentist Scientist Pathway to Independence Award (K99/R00), created in 2008. These programs, along with all research training, should be monitored in partnership with the community of stakeholders to assess their effectiveness.