LAUSR

Toad bone not only rich in cartilage-like matrix components including collagen II and glycosaminoglycans but also presents low immunogenicity because of its much less developed evolution. It was inferred that decellularized matrix of toad cartilage (dBECM) may provide the more profitable osteoinductive microenvironment for mesenchymal stem cells (MSCs) to promote the repair of critical-size bone defects. Herein, a hollow bone-inspired tube was firstly prepared by using the bone matrix component, hydroxyapatite (HA) and poly (γ-glutamic acid) (PGA), and then MSCs/dBECM hydrogel was uniformly filled its central cavity to construct a biomimetic bone (dBECM+MSCs-PGA+HA). Firstly, in vitro scratch and transwell experiments showed that dBECM hydrogel not only could effectively promote migration and proliferation of MSCs but also induce their osteogenic differentiation presented by higher expression of ALP, Collagen I and OCN after 28 days of treatment. Moreover, the less inflammatory macrophages were infiltrated at 3rd day after subcutaneously injecting dBECM hydrogel into the skin of rat, indicating its low potential for inflammatory attack. The hollow bone-inspired tube with ratio of PGA/HA at 80% (w/w) presented the slowest degrading rate and the highest compressive modulus of 370 MPa, which was very beneficial to maintain its central dBECM/MSCs hydrogel for a long time. After implanting dBECM+MSCs-PGA+HA to critical radius defect of rabbit, X-ray and CT imaging showed that the cortex was effectively regenerated and the medullary cavity recanalization was completed at 20 weeks. Moreover, the expression of Collagen Ⅱand OCN were obviously increased in the defect zone after treatment with dBECM+MSCs-PGA+HA, indicating both of the endochondral ossification and intramembranous ossification had been involved in the bone repairing. The therapeutic mechanism for dBECM+MSCs-PGA+HA were highly associated with the enhanced angiogenesis, as indicated by VEGF and CD31 staining. Collectively, the biomimetic dBECM+MSCs-PGA+HA scaffold might be a promising strategy to improve radius defect healing efficiency. This article is protected by copyright. All rights reserved.