Biomimetic Hydroxyapatite–Biopolymer Scaffolds with Tunable Architecture for Potential Bone Regeneration and Angiogenesis

Replicating the hierarchical structure and biological functionality of native bone remains a central challenge in bone tissue engineering. Here, porous scaffolds were developed from bovine bone-derived hydroxyapatite (BNHAp) using the polyurethane foam replica method with varying pore densities (15–60 pores per inch, PPI) and subsequently functionalized with collagen–gelatin. Structural analyses confirmed phase-pure hydroxyapatite with uniform biopolymer coating, while microstructural observations revealed well-interconnected porosity. Scaffold mechanics were strongly influenced by pore density, with compressive strength ranging from 0.11 (15 PPI) to 0.43 MPa (60 PPI). All scaffolds exhibited porosities above the threshold for bone regeneration (41–64%) and demonstrated high protein adsorption, excellent hemocompatibility (<2% hemolysis), and cytocompatibility (>70% NIH3T3 viability with progressive proliferation). Controlled degradation was achieved, with higher porosity scaffolds degrading more rapidly, while mineralization assays showed robust hydroxyl carbonate apatite formation, particularly in the 15 PPI group. In vivo chick embryo assays further confirmed significant pro-angiogenic potential, with the 15 PPI scaffold inducing the greatest vessel branching. Together, these results demonstrate that BNHAp–collagen/gelatin scaffolds provide tunable mechanical integrity and biological activity, with low-density scaffolds favoring mineralization and angiogenesis and high-density scaffolds enhancing strength. This balance highlights their promise as biomimetic candidates for bone tissue regeneration.