Biomimetic bone scaffold functionalized with traditional Chinese medicine ingredients and collagen-binding IGF-1 for bone regeneration

Abstract Many active ingredients from traditional Chinese medicine (TCM) have been applied in bone tissue engineering. However, the fuzzy mechanism of these ingredients limits their application. In this study, a novel biomimetic bone scaffold functionalized with two TCM ingredients, nano deer bone meals (nBM) and neferine (Nef), as well as collagen-binding IGF-1 (CBD-IGF-1) was fabricated via a combination of phase inversion and particle leaching methods. The biomimetic CIGF1&Nef@PLGA/nBM scaffold mimicked cancellous bone in terms of its porous structure and bone matrix composition rich in collagen. Both Nef contained in the scaffold and CBD-IGF-1 bound to collagen matrix could be slowly released from the scaffold, exerting long-term and safe bioactivity. In vitro tests showed that the CIGF1&Nef@PLGA/nBM composite significantly enhanced the adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells on the material. Nef and IGF-1 in CIGF1&Nef@PLGA/nBM scaffold exerted a synergistic effect on IGF-1-mediated osteogenic differentiation via IGF-1R axis to ensure the osteogenic activity of the biomimetic scaffold. In vivo skull defect repair experiment confirmed that CIGF1&Nef@PLGA/nBM could promote the neocortical bone formation and osseous maturation, further accelerating the bone defect repair. The findings of this research demonstrated that the biomimetic CIGF1&Nef@PLGA/nBM scaffold is a promising implantation in bone defect therapy.