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-alpha, IL1 beta and 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 nHA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.

Automated summary

This study developed nano-hydroxyapatite/resveratrol/chitosan composite microspheres for promoting bone formation and inflammation reduction. The controlled release of resveratrol improved cell adhesion, proliferation, and osteogenic differentiation, leading to enhanced bone regeneration and fracture healing in osteoporotic conditions, indicating promising multifunctional fillers for osteoporotic bone defect/fracture treatment.