Radical-Scavenging and Subchondral Bone-Regenerating Nanomedicine for Osteoarthritis Treatment.

Osteoarthritis (OA) is characterized by cartilage degradation and subchondral bone remodeling. However, most available studies focus on either cartilage degradation or subchondral bone lesion, alone, and rarely pay attention to the synergy of these two pathological changes. Herein, a dual-functional medication is developed to simultaneously protect cartilage and achieve subchondral bone repair. Black phosphorus nanosheets (BPNSs), with a strong reactive oxygen species (ROS)-scavenging capability and high biocompatibility, also present a notable promoting effect in osteogenesis. BPNSs efficiently eliminate the intracellular ROS and, thus, protect the inherent homeostasis between cartilage matrix anabolism and catabolism. RNA sequencing results of BPNSs-treated OA chondrocytes further reveal the restoration of chondrocyte function, activation of antioxidant enzymes, and regulation of inflammation. Additional assessments solidly confirm that BPNSs inhibit cartilage degradation and prevent OA progression. Meanwhile, histological evaluation and microcomputed tomography (micro-CT) scanning analysis verify the satisfying disease-modifying effects of BPNSs on OA. Additionally, the excellent biocompatibility of BPNSs enables them as a competitive candidate for OA treatment. This distinct disease-modifying treatment of OA on the basis of BPNSs provides an insight and paradigm on the dual-functional treatment strategy focusing on both cartilage degradation and subchondral bone lesion in OA and explores a broader biomedical application of BPNS nanomedicine in orthopedics.