Dendritic Mesoporous Silica-Modified Decellularized Bone Matrix Scaffold for Sustained Teriparatide Delivery in Bone Defect Repair: Characterization, Drug Release, and In Vitro Biological Performance

Objectives: Critical-sized bone defects continue to represent a substantial challenge in orthopedic clinical practice. Decellularized bone matrix (DBM) possesses favorable osteoconductive properties due to its retention of native extracellular matrix architecture and collagen components. However, its limited osteogenic bioactivity restricts its application in complex bone defect repair. This study aimed to construct a dendritic mesoporous silica (DMSN)-modified DBM composite scaffold loaded with teriparatide (DBM-DMSN@TPTD) and to systematically evaluate its physicochemical properties, drug release behavior, biocompatibility, and osteogenic differentiation-promoting capacity. Methods: A DBM scaffold was prepared from bovine femoral cancellous bone via a combined freeze–thaw and chemical detergent decellularization method. DMSNs were synthesized through a sol–gel method, amine-functionalized with APTES, and covalently grafted onto the DBM surface via EDC/NHS crosslinking. Teriparatide was loaded onto the composite scaffolds at three concentrations (1, 10, and 100 nmol/L). The scaffolds were characterized via SEM, TEM, BET, EDS and XPS. Decellularization efficacy was assessed by DAPI staining and nucleic acid quantification. Drug release behavior was evaluated through in vitro release studies, while biocompatibility and osteogenic differentiation of rat BMSCs were examined using Live/Dead staining, phalloidin/DAPI cytoskeletal staining, CCK-8 assays, ALP staining, and RUNX2/OCN immunofluorescence. Results: DMSNs demonstrated a dendritic mesoporous architecture, featuring a specific surface area of 390.44 ± 1.78 m2/g and pore diameters within the range of 15–20 nm. DBM showed effective removal of immunogenicity, with well-preserved collagen architecture. Drug release displayed a biphasic pattern, with 56.03% released within the first 72 h and 83.23% by day 16. None of the tested scaffolds showed obvious cytotoxicity under the experimental conditions. The DBM-DMSN@TPTD-M group (10 nmol/L) produced the strongest effects on BMSC proliferation and osteogenic differentiation, as indicated by the highest ALP activity and elevated RUNX2 and OCN expression (p < 0.05). Conclusions: The DBM-DMSN@TPTD scaffold offers a native bone microenvironment, sustained drug release, and osteogenic activity in vitro. These features may support BMSC proliferation and osteogenic differentiation. Accordingly, this scaffold warrants further investigation as a potential strategy for bone defect repair.