Multifunctional Semi-IPN Hydrogel Scaffolds Reinforced with Tannic Acid-Coated Hydroxyapatite for Enhanced Osteogenesis

Granular hydroxyapatite (HA) is a common bone substitute material, but it tends to migrate from irregular defects and offers scant protection against postoperative oxidative stress or infection. Here, we report a multifunctional semi-interpenetrating polymer network (semi-IPN) hydrogel─PAM/SA/TA@HA─engineered to secure HA and modulate the local microenvironment. The hydrogel combines a dense polyacrylamide/sodium alginate (PAM/SA) matrix that immobilizes HA particles with a tannic acid (TA) coating that anchors them through Ca2+–phenolate coordination, improving dispersion and interfacial bonding. The phenolic-rich TA affords intrinsic antioxidant and broad-spectrum antibacterial activity, countering reactive oxygen species and bacterial invasion at the defect site. Optimal HA loading produced a uniformly distributed particle phase, significantly enhanced compressive strength, and generated a hierarchical porous architecture favorable for cell infiltration. In vitro coculture with bone marrow–derived mesenchymal stem cells demonstrated excellent biocompatibility, promoting both proliferation and osteogenic differentiation. By simultaneously providing structural reinforcement, particle stabilization, and microenvironmental protection, the PAM/SA/TA@HA hydrogel overcomes the limitations of conventional HA grafts and emerges as a promising scaffold for oral bone tissue regeneration.