Regulation of osteoimmune microenvironment and endogenous bone regeneration by versatile injectable nanocomposite hydrogel

Irregular-shaped bone defects are commonly encountered in clinical practice, and various biomaterials have been developed to address these issues. Injectable in situ forming hydrogels not only effectively fill irregular-shaped defects but also provide a suitable growth environment for host cells. In this study, we developed an injectable nanocomposite hydrogel, which includes chitosan oligosaccharides (COS), DL-α-Glycerol phosphate magnesium salt hydrate (Mg-GP), 4-arm PEG-Succinimidyl Carbonate (4-arm-PEG-SC), and mesoporous polydopamine (MPDA) nanoparticles loaded with bone morphogenetic protein-2 (BMP-2). The injectable hydrogel demonstrates excellent physical properties, including injectability, self-healing, photothermal property, appropriate swelling (182%) and degradation rates (59%), sufficient mechanical strength (280 kPa) and adhesion (10 kPa). Additionally, the injectable hydrogel exhibits multiple biological effects, including controlled release of BMP-2 (59.1%) and magnesium ions (55.1%), antioxidant and antibacterial properties, promotion of cell proliferation and migration, regulation of immune microenvironment, and stimulation of osteogenesis and angiogenesis. In summary, both in vitro and in vivo experiments demonstrate that the injectable nanocomposite hydrogel may represent a promising minimally invasive solution for endogenous bone regeneration.