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.
Highlights
Augmentation of bone defects remains a major challenge in reconstructive orthopedic, periodontal, and maxillofacial surgeries
We have demonstrated that four commercially available 3D collagen-based matrices of porcine origin can be efficiently loaded with enamel matrix derivative (EMD) or recombinant growth factors such as the transforming growth factor-β1 (TGF-β1), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor-BB (PDGFBB), growth and differentiation factor-5 (GDF-5), or the bone morphogenetic protein-2 (BMP-2) (Nica et al, 2020)
Two types of osteoprogenitors of mouse origin were used throughout the study: bone marrow-derived mesenchymal stromal ST2 cells were obtained from the RIKEN Cell Bank (Tsukuba, Japan) and calvaria-derived pre-osteoblastic MC3T3-E1 cells were obtained from the ECACC collection (Sigma, Buchs, Switzerland)
Summary
Augmentation of bone defects remains a major challenge in reconstructive orthopedic, periodontal, and maxillofacial surgeries. The ideal biomaterial for the purpose of bone regeneration should be biocompatible, volume stable (space-making), osteoconductive, and osteoinductive (Yamada and Egusa, 2018). It should possess a predictable pattern of biodegradability, be easy for manufacturing and handling, and highly cost effective. The combination of 3D collagen matrices with bone substitute materials (Basudan et al, 2016; Papi et al, 2021) or bioactive substances (Herford and Cicciù, 2012; Herford et al, 2012; Ramseier et al, 2012; Jin and Giannobile, 2014; Edelmayer et al, 2020; França-Grohmann et al, 2020) for the repair of periodontal hard tissue loss and severe alveolar ridge deficiencies have appeared as promising strategies
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