Dual-function injectable fibrin gel incorporated with sulfated chitosan nanoparticles for rhBMP-2-induced bone regeneration

Abstract

Bone fractures commonly occur in the aging patients, and exhibit slow fracture healing rates and high complication rates even with the best treatment strategies available. Additionally, aging patients always suffer from immunosenescence, and thus induce the dysfunction of macrophages to delay the bone repair. Although exogenous bone morphogenetic protein-2 (BMP-2) is verified that can efficiently promote bone regeneration, the supraphysiologic usage is always associated with abnormal heterotopic ossification and inflammatory response. Here, we have developed a dual-function injectable fibrin gel (Fg) with semisynthetic sulfated chitosan (SCS) nanoparticles (NPs) that significantly improves the recombinant human BMP-2 (rhBMP-2)-induced osteogenesis and down-regulates the inflammatory response at the fracture site. The prepared fibrinogen and sulfated chitosan nanoparticles (SCS NPs) efficiently prolong the delivery of rhBMP-2 and decrease the volume of bone callus. Moreover, SCS incorporated Fg regulates the macrophage polarization from pro-inflammatory M1 macrophage to anti-inflammatory M2 macrophage with a significant decrease of inflammatory-related cytokines. Finally, this dual-function injectable gel can also efficiently treat bone fractures well in postmenopausal mice with osteoporosis. Thus, this pro-osteogenic gel offers a translational potential for biomaterial-based bone healing.