CIITP-modified collagen hydrogel delivers gold nanoclusters, promoting cartilage repair and anti-inflammation in osteoarthritis

Osteoarthritis (OA) is a debilitating degenerative joint disease marked by chronic inflammation and progressive cartilage loss. Current treatments primarily manage symptoms, as disease-modifying therapies remain elusive. A significant challenge in developing effective OA treatments is the avascular nature of cartilage, which hinders drug delivery and retention. Furthermore, promising nanomaterials often suffer from rapid clearance and poor targeting within the complex joint microenvironment, necessitating innovative strategies for localized and sustained therapeutic delivery.

Researchers developed a peptide-modified, reactive oxygen species (ROS)-responsive collagen hydrogel, named CSH-AuNCs-CIITP, for targeted osteoarthritis therapy. This injectable system encapsulated gold nanoclusters (AuNCs) functionalized with a type II collagen-targeting peptide (CIITP) within a ROS-cleavable disulfide-crosslinked collagen hydrogel (CSH). The hydrogel was designed for enhanced mechanical integrity and enzymatic stability, achieving ROS-triggered, on-demand release of therapeutic nanoclusters specifically within the OA microenvironment. In vitro experiments assessed the hydrogel's ability to promote bone marrow mesenchymal stem cell (BMSC) chondrogenesis and macrophage M2 polarization. In vivo studies evaluated its capacity for cartilage integration and repair.

The engineered CSH-AuNCs-CIITP hydrogel demonstrated significant therapeutic potential by coupling environmental adaptability with molecular precision. The system achieved ROS-triggered, on-demand release of its therapeutic gold nanoclusters within the inflammatory OA microenvironment. In vitro results indicated that this hydrogel system effectively promoted BMSC chondrogenesis, suggesting its capacity to support cartilage tissue formation. Furthermore, it induced macrophage M2 polarization, a crucial shift towards an anti-inflammatory and pro-healing phenotype. These cellular effects translated to promising in vivo outcomes: > The hydrogel facilitated preliminary integration and repair of cartilage, leading to robust matrix restoration. This targeted delivery platform achieved precise cartilage targeting and prolonged intra-articular retention, culminating in superior anti-inflammatory and chondroregenerative outcomes.