Osteoarthritis is a chronic and degenerative condition that results in a structural and functional failure of synovial joints. In particular, a loss in the glycosaminoglycan (GAG) content takes place, together with a consequent reduction of wear-resistance in the cartilage tissue. To develop a treatment that could restore the lubrication properties of an injured joint, we took inspiration from the natural components of the synovial fluid. Among these, hyaluronic acid and glycoproteins, such as lubricin, were shown to play a major role. The latter shows a central brush-like region extensively modified by O-linked oligosaccharide side chains. Furthermore, it binds to the cartilage surface and protects it from adsorption of proteins and cells. In orded to mimic the structure and activity of lubricin we developed new biomimetic graft-copolymers featuring a biodegradable polyglutamic acid (PGA) backbone with poly-2-(methyl-2-oxazoline) (PMOXA) and aldehyde-bearing side chains. In particular, PMOXA forms a biopassive and lubricating brush film at the interface. In addition, the aldehyde functions react with aminolized, degenerated cartilage tissues via Schiff-base formation. A series of PGA-α-PMOXAx-β-aldehyde copolymers with different side-chain lengths (x) and PMOXA(α)/aldehyde(β) grafting densities were successfully synthesized and adsorbed on bovine cartilage tissues (Figure). Depending on the adsorption conditions and on the graft-copolymer architecture enhanced antifouling properties resulted for the films featuring higher surface density of MOXA units. In addition, very low coefficients of friction were observed for the coatings with increased mass of copolymer for surface unit. The combination of selective anchoring to aminolized surfaces with high lubricating properties, biocompatibility and protein resistance makes PGA-α-PMOXAx-β-aldehyde graft-copolymers promising biolubricants for cartilage tissues.
Tissue-reactive polymethyloxazoline-based graft-copolymers as promising biolubricants for articular cartilage
Benetti E
2016
Abstract
Osteoarthritis is a chronic and degenerative condition that results in a structural and functional failure of synovial joints. In particular, a loss in the glycosaminoglycan (GAG) content takes place, together with a consequent reduction of wear-resistance in the cartilage tissue. To develop a treatment that could restore the lubrication properties of an injured joint, we took inspiration from the natural components of the synovial fluid. Among these, hyaluronic acid and glycoproteins, such as lubricin, were shown to play a major role. The latter shows a central brush-like region extensively modified by O-linked oligosaccharide side chains. Furthermore, it binds to the cartilage surface and protects it from adsorption of proteins and cells. In orded to mimic the structure and activity of lubricin we developed new biomimetic graft-copolymers featuring a biodegradable polyglutamic acid (PGA) backbone with poly-2-(methyl-2-oxazoline) (PMOXA) and aldehyde-bearing side chains. In particular, PMOXA forms a biopassive and lubricating brush film at the interface. In addition, the aldehyde functions react with aminolized, degenerated cartilage tissues via Schiff-base formation. A series of PGA-α-PMOXAx-β-aldehyde copolymers with different side-chain lengths (x) and PMOXA(α)/aldehyde(β) grafting densities were successfully synthesized and adsorbed on bovine cartilage tissues (Figure). Depending on the adsorption conditions and on the graft-copolymer architecture enhanced antifouling properties resulted for the films featuring higher surface density of MOXA units. In addition, very low coefficients of friction were observed for the coatings with increased mass of copolymer for surface unit. The combination of selective anchoring to aminolized surfaces with high lubricating properties, biocompatibility and protein resistance makes PGA-α-PMOXAx-β-aldehyde graft-copolymers promising biolubricants for cartilage tissues.
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