纳米组装接枝共聚物可有效恢复退化软骨的润滑性能
骨关节炎引发关节液成分改变,并导致关节软骨摩擦增加及渐进性不可逆损坏。对此,医疗领域热切期待建立一种有效的,长期的治疗方法使损伤的软骨恢复润滑以缓解这种退化性疾病。
最新,瑞士苏黎世联邦理工学院的研究人员开发了一系列的接枝共聚物PGA-α-PMOXA(x)-β-HBA,能够选择性附着于退化软骨,重新铺贴,恢复组织天然的润滑性能。这种材料包括聚谷氨酸(PGA)为成型枝干,侧链连接增强表面润滑功能的2-甲基-2-恶唑啉(PMOXA),以及可锚定于软骨表面的乙醛基团结构。通过优化接枝共聚物的结构(即功能侧链的密度和长度)使退化的软骨表面均匀钝化。接枝共聚物处理后的软骨关节液可以有效降低的摩擦系数,提高天然软骨的润滑性能。由于这些独特的性能及其生理条件下的高度生物相容性和稳定性,使得这些接枝共聚物成为极具前景的减缓软骨退化进程(尤其针对早期骨关节炎)的注射制剂。
论文作者:Giulia Morgese, Emma Cavalli, Mischa Müller, Marcy Zenobi-Wong, and Edmondo M. Benetti
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.
Keywords:cartilage engineering; graft-copolymers; nanofilms; osteoarthritis; surface assembly
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