A biodegradable chitosan-nano-hydroxyapatite aerogel promotes angiogenesis and osteogenesis for skull defect repair

The course of the skull defect is long, with multiple factors involved. Traditional treatment methods are not sufficient to completely restore the skull defect in a short period. Biomaterial scaffold could replace traditional approaches to bone reconstruction. A major challenge in designing a scaffold for cranial defect repair is to be non-toxic, low swelling, biodegradable, and pro-osteogenic. Herein, a biodegradable aerogel scaffold composed of methylcellulose (MC), thiolated chitosan (TCS), Zn^2 + and nano hydroxyapatite (nHA) was designed for repairing the skull defect. MC/TCS-nHA aerogel was formed by the ionic cross-linking of hydroxyl, amino and thiol groups with Zn²⁺. The prepared scaffolds exhibited a uniform pore structure and structural stability. Interestingly, TCS was used to enhance biocompatibility and biodegradability, Zn²⁺ to enhance antibacterial properties and nHA to enhance pro-osteogenicity. In vivo and in vitro tests confirmed that chitosan-based aerogel could promote macrophage polarization into the M2 phenotype and promote angiogenesis and osteogenesis. The micro-CT characterization analysis and immunofluorescence analysis after 12 weeks indicated that MC/TCS-nHA aerogel could accelerate skull defect repair. Therefore, the chitosan-based aerogel showed great promise as an implant material for medical applications involving the repair of the skull.