Nano MgO loaded thermosensitive HPCH@HA hydrogel accelerates in situ bone repair through osteoimmunomodulation while enhancing angiogenesis and osteogenesis

Bone defect repair is a complex physiological process, starting with early modulation by the inflammatory immune system, and involves multiple physiological events, including angiogenesis, osteogenic differentiation, and mineralization. Biomaterial can regulate inflammatory responses through relevant immune cells in the local immune microenvironment of the implant-bone interface which is a hot topic in the field of regenerative medicine. Currently, Mg²⁺ regulates immune cells in the bone microenvironment to promote osteogenesis and angiogenesis mainly focuses on macrophages,but there is relatively little research on T cells.At the same time, the effective delivery and release of Mg²⁺ remains a challenge. To address these issues, we designed a new thermosensitive hyaluronic acid-hydroxypropyl chitin hydrogel (HPCH@HA) that has good affinity for Mg²⁺ and can sustained release it. In vitro, nano MgO loaded complex hydrogels effectively induced macrophage polarization from M0 phenotype to M2 phenotype and simultaneously activate T lymphocytes which also promoted human adipose-derived stem cells (hADSCs) osteogenic differentiation and mineralization and human umbilical vein endothelial cells (HUVECs) angiogenesis. In vivo, at the early stage of repair, the composite hydrogel has a good repair effect on mouse skull critical defect. All these results show that our designed composite hydrogels can effectively regulate the immune microenvironment of bone tissue and promoting the formation of mature bone in large bone defects and supporting in situ bone regeneration without the use of exogenous cells or inducers. It's a promising candidate as immunomodulatory biomaterials for bone tissue engineering purposes.