Magnetically functionalized zein-alginate hydrogel coatings enhance angiogenesis-driven bone regeneration and implant...

Poor osseointegration and inadequate vascularisation remain major challenges limiting the long-term success of titanium implants. In this study, a bioactive zein-sodium alginate hydrogel incorporating superparamagnetic iron oxide nanoparticles (SPIONs) was developed as a multifunctional coating to enhance osteogenesis, angiogenesis, and implant integration. The composite hydrogel exhibited good stability, uniform nanoparticle distribution, and excellent cytocompatibility. In vitro evaluation using MG63 osteoblast-like cells demonstrated enhanced cell adhesion, metabolic activity, alkaline phosphatase activity, matrix mineralisation, and upregulation of osteogenic markers, particularly at optimized SPION concentrations. In vivo zebrafish models revealed accelerated scale regeneration, fracture healing, cranial bone repair, and vertebral mineralisation, accompanied by increased expression of stem cell recruitment markers. Angiogenic potential assessed using the chick chorioallantoic membrane assay showed significantly increased vessel density, length, thickness, and branching, along with elevated expression of angiogenesis-related genes in SPION-loaded hydrogels. Furthermore, rabbit tibial implantation studies confirmed enhanced peri-implant bone formation, higher bone-implant contact, and significantly increased removal torque values for hydrogel-coated implants compared to controls. Overall, the zein-SPIONs-sodium alginate hydrogel creates a pro-osteogenic and pro-angiogenic microenvironment, demonstrating strong potential as a bioactive coating to improve osseointegration and mechanical stability of dental and orthopedic implants.