Biomaterial Scaffolds for Bone Regeneration

Abstract

Critical-sized bone defects -- those exceeding the intrinsic regenerative capacity of bone tissue -- require scaffold-mediated repair to bridge the defect gap and guide new bone formation. This study systematically developed and compared four biomaterial scaffold systems -- hydroxyapatite/beta-tricalcium phosphate biphasic calcium phosphate (BCP), polycaprolactone/hydroxyapatite composite (PCL/HA), silk fibroin/nano-hydroxyapatite (SF/nHA), and 3D-printed titanium alloy (Ti-6Al-4V) with hydroxyapatite coating -- for critical-sized femoral defect repair in a rat model. Scaffolds were characterised for porosity (micro-CT), compressive strength, degradation kinetics, and in vitro osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) over 28 days, followed by 12-week in vivo evaluation in 8 mm rat femoral defects (n = 10/group). BCP scaffolds achieved the highest bone volume fraction (BV/TV = 42.8 +- 4.6%) at 12 weeks by micro-CT, significantly exceeding PCL/HA (34.2 +- 3.8%; p < 0.001) and SF/nHA (28.4 + 4.2%; p < 0.001). Ti-6Al-4V scaffolds provided superior mechanical support (compressive strength 148.4 +- 12.8 MPa) but lower bone ingrowth (BV/TV = 24.8 +- 3.4%) due to stress shielding. In vitro, SF/nHA produced the highest alkaline phosphatase activity (3.84-fold over control at day 14) and osteocalcin expression (4.42-fold at day 28), confirming superior osteoinductive capacity. These results establish BCP as the optimal scaffold for maximising bone regeneration volume and SF/nHA as the preferred platform for osteogenic differentiation fidelity in bone tissue engineering.