Proteoglycan-Mimetic Bottle-Brush Polymer Brushes for Osteoarthritis Therapy: Lubrication Enhancement and Multifunctional Disease Modulation.

Lubrication is essential for maintaining joint health and enabling smooth articulation. In healthy joints, natural lubricants such as proteoglycans endow articular cartilage with an exceptionally low coefficient of friction. Notably, proteoglycans possess a characteristic bottle-brush architecture that generates robust hydration layers at the cartilage surface, thereby facilitating effective lubrication. In osteoarthritis (OA), degradation of extracellular matrix components, depletion of proteoglycans, and increased friction and wear at inflamed joint interfaces collectively accelerate disease progression. Therefore, restoring joint lubrication has emerged as a promising strategy to reduce friction-induced damage and delay OA progression. In recent years, extensive efforts have been devoted to developing biomimetic lubricants, particularly proteoglycan-mimetic polymer brushes inspired by natural proteoglycan architectures. These systems are designed to replicate the bottle-brush architecture and hydration lubrication mechanism of native proteoglycans. In this review, we summarize the fundamental lubrication mechanisms of articular cartilage, with emphasis on boundary and hydration lubrication mediated by proteoglycans, and discuss the design principles and representative material systems of proteoglycan-mimetic polymer brushes. By linking native lubrication mechanisms with biomimetic brush design and translational considerations, this review highlights proteoglycan-inspired polymer brushes as promising disease-modifying candidates for OA treatment.