Positive Effects of Three-Dimensional Collagen-Based Matrices on the Behavior of Osteoprogenitors

Zhikai Lin; Cristina Nica; Anton Sculean; Maria B Asparuhova

doi:10.3389/fbioe.2021.708830

Positive Effects of Three-Dimensional Collagen-Based Matrices on the Behavior of Osteoprogenitors

Front Bioeng Biotechnol. 2021 Jul 21:9:708830. doi: 10.3389/fbioe.2021.708830. eCollection 2021.

Authors

Zhikai Lin^{1

2

3}, Cristina Nica^{1

2}, Anton Sculean², Maria B Asparuhova^{1

2}

Affiliations

¹ Laboratory of Oral Cell Biology, Dental Research Center, School of Dental Medicine, University of Bern, Bern, Switzerland.
² Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland.
³ Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.

Abstract

Recent research has demonstrated that reinforced three-dimensional (3D) collagen matrices can provide a stable scaffold for restoring the lost volume of a deficient alveolar bone. In the present study, we aimed to comparatively investigate the migratory, adhesive, proliferative, and differentiation potential of mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells in response to four 3D collagen-based matrices. Dried acellular dermal matrix (DADM), hydrated acellular dermal matrix (HADM), non-crosslinked collagen matrix (NCM), and crosslinked collagen matrix (CCM) did all enhance the motility of the osteoprogenitor cells. Compared to DADM and NCM, HADM and CCM triggered stronger migratory response. While cells grown on DADM and NCM demonstrated proliferative rates comparable to control cells grown in the absence of a biomaterial, cells grown on HADM and CCM proliferated significantly faster. The pro-proliferative effects of the two matrices were supported by upregulated expression of genes regulating cell division. Increased expression of genes encoding the adhesive molecules fibronectin, vinculin, CD44 antigen, and the intracellular adhesive molecule-1 was detected in cells grown on each of the scaffolds, suggesting excellent adhesive properties of the investigated biomaterials. In contrast to genes encoding the bone matrix proteins collagen type I (Col1a1) and osteopontin (Spp1) induced by all matrices, the expression of the osteogenic differentiation markers Runx2, Alpl, Dlx5, Ibsp, Bglap2, and Phex was significantly increased in cells grown on HADM and CCM only. Short/clinically relevant pre-coating of the 3D biomaterials with enamel matrix derivative (EMD) or recombinant bone morphogenetic protein-2 (rBMP-2) significantly boosted the osteogenic differentiation of both osteoprogenitor lines on all matrices, including DADM and NCM, indicating that EMD and BMP-2 retained their biological activity after being released from the matrices. Whereas EMD triggered the expression of all osteogenesis-related genes, rBMP-2 upregulated early, intermediate, and late osteogenic differentiation markers except for Col1a1 and Spp1. Altogether, our results support favorable influence of HADM and CCM on the recruitment, growth, and osteogenic differentiation of the osteoprogenitor cell types. Furthermore, our data strongly support the biofunctionalization of the collagen-based matrices with EMD or rBMP-2 as a potential treatment modality for bone defects in the clinical practice.

Keywords: bone regeneration; gene expression; growth factors; osteogenesis; periodontal regeneration; three-dimensional biomaterials; transcription; xenografts.