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Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6954-6963. doi: 10.1073/pnas.1819246116. Epub 2019 Mar 18.

Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

Author information

1
Department of Bioengineering, Rice University, Houston, TX 77030.
2
Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030.
3
Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030.
4
Department of Otorhinolaryngology, The University of Texas Health Science Center at Houston, Houston, TX 77030.
5
Synthasome, Inc., San Diego, CA 92019.
6
Department of Biomaterials, Radboud University Medical Center, 6525 EX Nijmegen, The Netherlands.
7
Department of Bioengineering, Rice University, Houston, TX 77030; mikos@rice.edu.

Abstract

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.

KEYWORDS:

bioreactor; bone; craniofacial; in vivo; tissue engineering

PMID:
30886100
PMCID:
PMC6452741
[Available on 2019-10-02]
DOI:
10.1073/pnas.1819246116

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