Abstract: Objective · To construct the dual-functional organic/inorganic composite hydrogel with osteoinductivitycombined organic medicinal therapy with inorganic nanoparticle treatment into make hydrogel more functional in clinical application and more efficient for bone regeneration research. Methods · Liposomes simultaneously loaded with organic drug vitamin D3 and inorganic calcium phosphate nanoparticles were prepared, and dynamic light scattering (DLS), transmission electron microscopy(TEM), scanning electronmicroscopy (SEM), hightperformance liquid chromatography (HPLC) were utilized to explore the particle size, zeta potential, morphology and release property of these composite nanocarriers. Further, composite hydrogels (VD3&CaP-Lip@Gel) with the ability of osteoinductivity were fabricatedincorporating these composite nanocarriers with gelatinmethacrylic (GelMA) hydrogel, and the morphology, drug release property, mineralization, cytocompatibility, cell adhesion and osteogenic differentiation of these compound hydrogels were investigatedSEM, HPLC, CCK-8 kit, live&dead staining, alkaline phosphatase (ALP) activity assay,ALPstaining, alizarin red S staining and alizarin red S quantitative analysis. Results · The VD3&CaP-Lip@Gel was successfully constructed. According to the results of drug release, the hydrogel could continuously release vitamin D3 for 17 days in situ. The results of morphology exhibited that these hydrogels possessed excellent morphological characteristics and could promote mineralization in simulated body fluid (SBF) solution. Comparing with the negative control group, positive control group and GelMA group, the composite hydrogel revealed remarkable capability in cytocompatibility and osteogenic differentiation in vitro experiments. Conclusion · The dual-functional organic/inorganic osteogenetic hydrogel has been successfully constructed with the ability in long-term release of drug and inorganic nanoparticles in situ, which is able to promote bone regeneration in vitro.

Key words: hydrogel, liposome, bone regeneration, calciumphosphate nanoparticle (Cap)