Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration

The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,nano-hydroxyapatite(n-HA)/resveratrol(Res)/chitosan(CS)composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res.Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release.Notably,microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α,IL-1βand iNOS in RAW264.7 cells in a dose dependent manner.Further,enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth.The ability to enhance osteo-differentiation was supported by up-regulation of Runx2,ALP,Col-1 and OCN,and substantial mineralization in osteogenic medium.When implanted into bone defects in the osteoporotic rat femoral condyles,enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing.The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.