Nanoassemblies of Tissue-Reactive, Polyoxazoline Graft-Copolymers Restore the Lubrication Properties of Degraded Cartilage

Abstract

Osteoarthritis leads to an alteration in the composition of the synovial fluid, which is associated with an increase in friction and the progressive and irreversible destruction of the articular cartilage. In order to tackle this degenerative disease, there has been a growing interest in the medical field to establish effective, long-term treatments to restore cartilage lubrication after damage. Here we develop a series of graft-copolymers capable of assembling selectively on the degraded cartilage, resurfacing it, and restoring the lubricating properties of the native tissue. These comprise a polyglutamic acid backbone (PGA) coupled to brush-forming, poly-2-methyl-2-oxazoline (PMOXA) side chains, which provide biopassivity and lubricity to the surface, and to aldehyde-bearing tissue-reactive groups, for the anchoring on the degenerated cartilage via Schiff bases. Optimization of the graft-copolymer architecture (i.e., density and length of side chains and amount of tissue-reactive functions) allowed a uniform passivation of the degraded cartilage surface. Graft-copolymer-treated cartilage showed very low coefficients of friction within synovial fluid, reestablishing and in some cases improving the lubricating properties of the natural cartilage. Due to these distinctive properties and their high biocompatibility and stability under physiological conditions, cartilage-reactive graft-copolymers emerge as promising injectable formulations to slow down the progression of cartilage degradation, which characterizes the early stages of osteoarthritis.

Chemical Design of Non‐Ionic Polymer Brushes as Biointerfaces: Poly(2‐oxazine)s Outperform Both Poly(2‐oxazoline)s and PEG

“…Poly(2-alkyl-2-oxazoline)s (PAOXAs), in particular the hydrophilic variants poly(2-methyl-2-oxazoline) (PMOXA) and poly(2-ethyl-2-oxazoline) (PEOXA), have been emerging as very promising alternatives to PEGs in av ariety of biotechnological applications,s howing comparable physicochemical properties,b iocompatibility,a nd stealth properties. [21][22][23][24][25][26][27] Moreover,P AOXA films on organic and inorganic supports showed similar biopassivity to their PEG counterparts, [28][29][30][31] and as ignificantly higher resistance towards oxidation. [32] Following these pioneering reports,the need for ageneral, comparative study of the properties of different PAOXA brushes and their PEG analogues has emerged, stimulating the present work.…”

Chemical Design of Non‐Ionic Polymer Brushes as Biointerfaces: Poly(2‐oxazine)s Outperform Both Poly(2‐oxazoline)s and PEG

“…Poly(2-alkyl-2-oxazoline)s (PAOXAs), in particular the hydrophilic variants poly(2-methyl-2oxazoline) (PMOXA) and poly(2-ethyl-2-oxazoline) (PEOXA), have been emerging as very promising alternatives to PEGs in a variety of biotechnological applications, showing comparable physicochemical properties, biocompatibility, and stealth properties. [21][22][23][24][25][26][27] Moreover, PAOXA films on organic and inorganic supports showed similar biopassivity to their PEG counterparts, [28][29][30][31] and a significantly higher resistance towards oxidation. [32] Following these pioneering reports, the need for a general, comparative study of the properties of different PAOXA brushes and their PEG analogues has emerged, stimulating the present work.…”

Investigation of design parameters in generating antifouling and lubricating surfaces using hydrophilic polymer brushes

“…Among several successfully grafted hydrophilic natural biopolymers and synthetic polymers, poly(ethylene glycol)‐ and poly(2‐oxazoline)‐based films in brush configuration have shown the ability to enhance biopassivity and lubricating properties of the surface . For example, the synthetic graft copolymer of poly( l ‐lysine)‐ graft ‐poly(ethylene glycol) (PLL‐g‐PEG) has been widely employed to anchor a densely packed PEG polymer brushes on several metallic and ceramic substrates via electrostatic interactions with polyelectrolyte l ‐lysine backbone .…”