The osteoinductive and osseointegration properties of decellularized extracellular matrix bone derived from different sites.

Abstract

Aims: This study aimed to examine the differences in bone induction and osseointegration performance of acellular extracellular matrix bone at different sites.

Methods: We decellularized bone from bovine epiphysis near the marrow cavity (NMC), the middle of the cancellous bone (MCB), and near the cartilage (NC). The characterization, physicochemical properties, and effectiveness of the decellularization process of decellularized extracellular matrix (dECM) were analyzed. The proliferation, adhesion, seeding efficiency, and osteogenic differentiation properties of bone marrow mesenchymal stem cells (BMSCs) on decellularized extracellular matrix were investigated. The osteogenicity and osteointegration of dECM from different sources were verified in vivo by animal experiments, and the compatibility of dECM in vivo was also verified.

Results: The NC group had the most significant compressive properties, where the compressive strength was about 1.62 times higher than that of the MCB group (p = 0.022) and 1.34 times higher than that of the NMC group (p < 0.001). dECM scaffolds had good histocompatibility and supported the adhesion and proliferation of BMSCs. In vitro, compared with the remaining two groups, the MCB group significantly upregulated the expression of osteogenic genes (alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), osteopontin (OPN), collagen type 1 (COL1), and bone morphogenetic protein 2 (BMP2)) and marker proteins (ALP, BMP2), whereas the NC group showed the weakest osteoinductive properties. In vivo, we confirmed that the MCB group possessed the most significant osteogenic and osseointegrative properties, followed by the NMC group, and the NC group proved to be the weakest. In particular, the MCB group possessed the ability to endogenously immunomodulate macrophage M1 phenotype to M2 phenotype polarization, creating the most favourable immune microenvironment for osteogenesis.

Conclusion: Our data indicated that the xenogenic dECM scaffolds in MCB position possess the most significant biocompatibility and in vitro and in vivo induced osteogenesis and osseointegration properties. This study provides a more complete basis for the selection of dECM scaffolds in bone defect repair. In future studies of dECM composites applied to bone tissue engineering (BTE), utilizing the middle part of cancellous bone may be the best solution.