A novel photocrosslinked phosphate functionalized Chitosan-Sr<inf>5</inf>(PO<inf>4</inf>)<inf>2</inf>SiO<inf>4</inf> composite hydrogels and in vitro biomineralization, osteogenesis, angiogenesis for bone regeneration application

Abstract

The natural polysaccharide-based hydrogels have gained significant interest to use as 3D scaffolds for bone repair and reconstruction owing to their excellent biocompatibility, biosafety, and biodegradability. Yet, these hydrogels have major obstacles in terms of insufficient properties such as mechanical, osteogenic, angiogenic, and biomineralization. Therefore, this study mainly aims to develop an innovative water-soluble phosphate functionalized chitosan (CSMAP) through consequent modification with methacrylic anhydride (MA), then alteration by phosphonopropionic acid (P). Further, a novel photocrosslinked composite hydrogel was fabricated with a combination of CSMAP and synthesized strontium phosphosilicate (SPS, Sr5(PO4)2SiO4) bioceramic nanoparticles with a photoinitiator under UV irradiation. The various concentrations of nanosized SPS particles (0.5, 2.5, 5, and 10 mg/mL) were incorporated into the CSMAP matrix and the swelling, mechanical, morphological, physiochemical, osteogenic, angiogenic properties were investigated. The CSMAP-SPS composite hydrogels possessed a well-arranged porous network structure. The composite hydrogel was restricted to swell in distilled water with the increased concentration of SPS particles. The compressive strength and modulus of CSMAP hydrogel were improved by the inclusion of SPS particles. The bioactive Sr, P, and Si ions were released from CSMAP-SPS hydrogels in a sustained and controlled manner at a non-toxic level. The composite hydrogels promoted in vitro amorphous apatite deposition, revealing a superior biomineralization activity. In vitro results demonstrated that the composites hydrogels showed no toxicity to preosteoblast MC3T3-E1 cells, induced MC3T3-E1 osteogenic differentiation with detection of bsp, ocn and opn osteogenic genes, and also promoted the endothelial tube formation with increased capillary length, branch points, and angiogenic gene vegf expression. Thus, the obtained results proved that the fabricated novel CSMAP-SPS hydrogel could act as an attractive candidate for bone regeneration.