Development and optimization of electrophoretically deposited octacalcium phosphate–collagen film as bone analogues

The hierarchical architecture of bone, characterized at the nanoscale, is defined by mineralized collagen fibrils with a disordered, hydrated, carboxylate-rich mineral surface, presenting a complexity often absent in conventional hydroxyapatite (HA) models. Here, we report the design of biomimetic octacalcium phosphate (OCP)-collagen films that reproduce both the crystalline mineral core and the citrate-rich disordered surface of native bone. Phase-pure OCP and citrate-incorporated OCP (OCP-CIT) were synthesized via pH-regulated hydrolysis of α-tricalcium phosphate (α-TCP) under physiological conditions, with citrate inducing structural heterogeneity analogous to natural bone mineral. Electrophoretic deposition facilitated the integration of these minerals into collagen films, aided by hyaluronic acid (HyAc), which stabilized colloidal suspensions by adjusting the zeta potential from -5 to -25 mV and dialysis against DI water by lowering conductivity from ∼30 to 0.01 mS/cm. The resulting films exhibited a collagen-mineral composite composed predominantly of apatitic orthophosphates (74% by ³1P nuclear magnetic resonance (NMR) spectroscopy), with citrate-directed mineral nucleation and HyAc-promoted collagen mineralization. Solid-state NMR rotational-echo double resonance (REDOR) experiments highlighted the essential function of HyAc in establishing proximity between mineral and collagen, absent in citrate-only systems, thereby emulating bone's interfacial organization. The work establishes a scalable film-based strategy for creating physiologically relevant bone analogues, with implications for advancing bone graft materials and disease models.