title: 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.
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, and ‡Cartilage Engineering + Regeneration Laboratory, Department of Health Sciences and Technology, ETH Zürich , Zürich, Switzerland.
authors.forename: Giulia
authors.initials: G
authors.lastname: Morgese
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, and ‡Cartilage Engineering + Regeneration Laboratory, Department of Health Sciences and Technology, ETH Zürich , Zürich, Switzerland.
authors.forename: Emma
authors.initials: E
authors.lastname: Cavalli
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, and ‡Cartilage Engineering + Regeneration Laboratory, Department of Health Sciences and Technology, ETH Zürich , Zürich, Switzerland.
authors.forename: Mischa
authors.initials: M
authors.lastname: Müller
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, and ‡Cartilage Engineering + Regeneration Laboratory, Department of Health Sciences and Technology, ETH Zürich , Zürich, Switzerland.
authors.forename: Marcy
authors.initials: M
authors.lastname: Zenobi-Wong
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, and ‡Cartilage Engineering + Regeneration Laboratory, Department of Health Sciences and Technology, ETH Zürich , Zürich, Switzerland.
authors.forename: Edmondo M
authors.identifier: 0000-0002-5657-5714
authors.initials: EM
authors.lastname: Benetti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002356:Cartilage / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D010080:Oxazoles; C577913:poly(2-oxazoline)
keywords: cartilage engineering; graft-copolymers; nanofilms; osteoarthritis; surface assembly