Constructing advanced electrospun nanofiber/hydrogel composite scaffolds loading with nano hydroxyapatite and puerarin for promoting osseointegration and osteanagenesis in a rat cranial defect model

ABSTRACT In this study, one advanced composite scaffold was designed. Its characteristics, effect on repairing large-sized bone defects and related mechanisms were explored. Methods In vitro , a bi-layered composite scaffold constructing with one layer of electrospun poly (3-hydroxybutyrateco-3-hydroxyvalerate) (PHBV) nanofiber membrane and one layer of UV-crosslinked methacrylated gelatin (MeGel) hydrogel were fabricated. Moreover, two types of bio-components including nano hydroxyapatite (nHAP) and puerarin (Pur) were encapsulated into the MeGel hydrogel layer to impart the composite scaffolds with multiple biofunctions. In vivo , the calvarial defect models with Sprague Dawley rats were created to ascertain the impact of PHBV/MeGel, PHBV/MeGel-HAP, and PHBV/MeGel-HAP-Pur composite scaffolds. Results The in vitro studies demonstrated that all the composite scaffolds loading with or without nHAP and Pur exhibited great water swelling and retention properties, as well as excellent rheological and mechanical properties. Furthermore, the PHBV/MeGel-nHAP-Pur composite scaffolds could facilitate the osteogenesis and vascularization, but inhibit osteoclast formation. Also, hydrogel layer could provide a benificial micro-environment for the cell infiltration. In vivo study demonstrated that the PHBV/MeGel-nHAP-Pur composite scaffolds obviously promote the healing of rat cranial defect with large injury size, and the healing rate was roughly 99.25% after 8 weeks of treatment. Conclusion Our present study suggests that the bi-layered PHBV/MeGel-nHAP-Pur composite scaffolds with multiple bio-functions show huge potential for the repair and regeneration of large-sized bone defects.