Abstract
Injectable hydrogels show great promise for bone tissue engineering applications due to their high biocompatibility and drug delivery capabilities. The bone defects in osteoporosis are usually characterized by an oxidative and inflammatory microenvironment that impairs the regeneration capability of bone tissues. To attenuate the reactive oxygen species (ROS) and promote bone regeneration, an anti-oxidative hydrogel with osteogenic capacity was developed in this study. The poorly water soluble, natural antioxidant, resveratrol, was encapsulated in thiolated Pluronic F-127 micelles with over 50-times-enhanced solubility. The injectable hydrogel was facilely formed because of the new thioester bond between the free thiol group in modified F-127 and the arylate group in hyaluronic acid (HA)-acrylate. The resveratrol-loaded hydrogel showed good viscoelastic properties and in vitro stability and was cyto-compatible with bone-marrow-derived mesenchymal stem cells (BMSCs). The hydrogel allowed for a sustained release of resveratrol for at least two weeks and effectively enhanced the osteogenic differentiation of BMSCs by the up-regulation of osteogenic markers, including ALP, OCN, RUNX-2, and COL1. Moreover, the hydrogel exhibited anti-oxidative and anti-inflammatory abilities through the scavenging of intracellular ROS in RAW264.7 cells and inhibiting the gene expression and secretion of pro-inflammatory cytokines TNF-α and IL-1β under LPS exposure. In summary, the results suggest that our multifunctional hydrogel loaded with resveratrol bearing osteogenic, anti-oxidative, and anti-inflammatory actions is easily prepared and represents a promising resveratrol delivery platform for the repair of osteoporotic bone defects.