Multifunctional Hydrogel Platform Overcoming Clinical Limitations of Traditional Hydroxyapatite Scaffolds for Hard Tissue Engineering

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Abstract Critical-sized bone defects remain a major clinical challenge due to the brittleness and poor surgical handling of conventional hydroxyapatite (HA) scaffolds. Herein, we report a multifunctional composite hydrogel designed to overcome these limitations for bone tissue engineering. The hydrogels were fabricated through a rapid and biocompatible strategy by integrating ovalbumin-derived proteins, poly(vinyl alcohol), oxidized alginate, borax, and tunable concentrations of HA (0–80 wt %). The resulting hydrogels exhibited remarkable elasticity, malleability, and intrinsic self-healing behavior, enabling easy shaping during surgical application while maintaining mechanical stability. Structural characterization (FTIR, X-ray diffraction, and field emission scanning electron microscopy) confirmed homogeneous HA incorporation within a porous interconnected network favorable for bone in-growth. Physicochemical properties, including swelling, degradation, and wettability, were effectively tuned by HA loading, with the 80 wt % HA hydrogel showing optimal cross-linking density and controlled degradation. In vitro studies demonstrated excellent cytocompatibility (>90% viability) with NIH3T3 fibroblasts and MC3T3 preosteoblasts, along with strong cell adhesion and proliferation. Enhanced osteogenic potential was confirmed by significantly higher calcium mineralization in HA-loaded hydrogels using Alizarin Red staining after 14 days of culture. The hydrogels also showed excellent hemocompatibility (<5% hemolysis), antioxidant, antibacterial, and anti-inflammatory activities, together with a strong pro-angiogenic response marked by 8–10-fold vascular endothelial growth factor upregulation. These synergistic properties highlight the potential of this multifunctional hydrogel platform for advanced bone regeneration.

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