Inspired by lubricin: a tailored cartilage-armor with durable lubricity and autophagy-activated antioxidation for targeted therapy of osteoarthritis

Abstract

Osteoarthritis (OA), which disables articular cartilage, affects millions of people. The self-healing capacity is inhibited by internal oxidative stress and external lubrication deficiency and enzymatic degradation. To overcome these challenges, a tailored cartilage-armor is designed to ameliorate the inflamed cartilage, which is implemented by a novel collagen type II (Col II)-binding peptide conjugated zwitterionic polymer (PSB-b-PColBP, PSP). By mimicking natural lubricin, PSP specifically targets the cartilage surface and forms an in situ hydration armor. This engineered cartilage-armor can prevent enzymatic cartilage degradation (nearly 100% resistance to catabolic enzymes) and provide durable lubrication properties (COF < 0.013 for 500 cycles). An autophagy-activation process, absent in previous biomimetic lubricants, enhances the enzymatic activity of the tailored cartilage-armor, offering effective anti-oxidant properties to suppress oxidative stress. By inhibiting the PI3K-Akt/NF-κB signaling pathway, chondrocytes protected by the tailored armor can secrete a cartilage matrix even in inflammatory microenvironments. In OA rat models, osteophyte formation and the inflammatory response have been inhibited by the cartilage-armor, demonstrating a therapeutic effect comparable to most drug-loaded systems. This study underscores the potential of tailoring cartilage-armor with the cartilage targeting and autophagy-activating properties in integrating offensive–defensive mechanisms for cartilage remodeling. This represents an alternative strategy for clinical OA therapy.