ROS-scavenging bioactive scaffold orchestrates bone regeneration for osteoporotic bone defect repair

The repair of osteoporotic bone defects, particularly those with irregular shapes, remains a significant challenge due to insufficient bone regeneration and an abnormal level of reactive oxygen species (ROS), which impairs the balance of bone remodeling. Materials that intrinsically regulate ROS to rebalance the activation of osteoblasts and osteoclasts represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Inspired by the tea polyphenols and natural extracellular matrix of bone tissue, a novel biomimetic composite scaffold, the epichlorohydrin-crosslinked hydroxyethyl cellulose/soy protein isolate/polydopamine-coated hydroxyapatite composite sponge (EHSS/PHA) scaffold was designed to orchestrate bone-forming bone marrow mesenchymal stem cells (BMSCs) and bone-resorbing osteoclasts for the rejuvenation of osteoporotic bone defect repair. Benefiting from the distinctive capabilities of the EHSS/PHA, including scavenging active oxygen and osteoinduction, we found that the EHSS/PHA could inhibit the formation of osteoclasts and promote osteogenesis of BMSCs by up-regulating the ratio of Opg/Rankl and activating the β-catenin signaling pathway in an oxidative stress environment. With its antioxidant ability, osteogenic, and self-deploying capability, EHSS/PHA effectively promoted the repair of tibial defects in osteoporotic rats by removing excess reactive oxygen species at the defect site. Taken together, this work presents the EHSS/PHA with multifunctional properties that provide new insight into osteoporotic bone defects.