Restoring the lubrication properties of degenerated cartilage with tissue-reactive graft-copolymers

Lubrication within articular joints is mediated by macromolecular complexes of glycoproteins and polysaccharides, which act as boundary lubricants at the cartilage surface, providing very low coefficients of friction and ensuring no wear over decades. The progressive depletion of these macromolecules, accompanied by extracellular matrix (ECM) degradation, are phenomena associated with the occurrence of degenerative diseases of the joint, such as osteoarthritis (OA). Due to the non-vascularized nature of cartilage and the consequent inhibition of self-healing processes, OA progression results irreversible and a need for treatments to restore its original lubrication properties is increasingly urged. Inspired by the structure and properties of natural biolubricants, we developed an injectable, fully synthetic formulation for both protecting the degraded tissue and restoring its lubrication properties. This relies on brush-forming graftcopolymers featuring a tissue reactive, aldehyde-bearing polyglutamic acid (PGA) backbone, and poly-2-methyl-2- oxazoline (PMOXA) side grafts. The designed graft-copolymers can readily bind on the degenerated cartilage tissue through Schiff-base formation and generate a bioinert and highly lubricious polymer brush layer. A systematic tuning of the molar mass, density and chain-topology of the PMOXA grafts allow to reproduce the low coefficient of friction characteristic of the healthy cartilage, protect the degraded tissue from protein contamination and prevent further damage. All these attractive properties, combined with their high biocompatibility, make these graft-copolymers promising candidates for the development of treatments to halt or slow down cartilage degeneration.