Biofabrication and application of decellularized bone extracellular matrix for effective bone regeneration

Abstract

In order to promote effective healing of a bone defect, various bone grafts have been widely implanted into defect sites. However, several drawbacks, such as immunologic rejection, insufficient tissue healing, or secondary damage to the donor site, are still concerns. These limitations of the current bone grafts can be overcome by use of a natural ECM that can influence basic cellular behaviors, such as proliferation, migration, and differentiation. Herein, we introduce a novel bone decellularized ECM (bdECM) material extracted from bovine bones via demineralization and decellularization. This sequential process enabled us to prepare raw material possessing higher contents of native BMP-2 and BMP-7, and a fibrous microarchitecture resembling the collagen bundle in the ECM was maintained. Furthermore, residual calcium and phosphate originated from the bovine bone were considerably removed, and contamination by residual DNA was significantly reduced during the fabrication process. These features enabled the scaffold successfully promote mineralization of the cultured primary osteoblasts in vitro, which was significantly better than those from the bone powder or demineralized bone matrix. In a mouse calvarial defect, new bone formation was improved in the bdECM group and the density of those was also higher than other groups.