改善生物相容性的电纺丝酸中和纤维

Yanbing Shen, T. Tu, Bingcheng Yi, Xianliu Wang, Han Tang, Wei Liu, Yanzhong Zhang
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引用次数: 0

摘要

可生物降解的脂肪族聚酯,特别是聚乳酸(PLA)、聚乙醇酸(PGA)及其共聚物聚乳酸-共乙醇酸(PLGA)是组织工程和再生医学领域最具代表性和应用最广泛的合成聚合物。然而,这些聚酯在植入后往往会引起其酸性降解产物引发的无菌性炎症问题。本文提出了具有酸中和能力的壳核结构的壳聚糖/聚乳酸-羟基乙酸酯单向纤维(即CTS/PLGA),以解决上述问题,从而提高生物相容性。结果表明,在8周的降解过程中,壳聚糖的壳层具有独特的碱性中和酸的特性,明显阻碍了plga核降解导致的pH降低。在模拟酸性环境下对人真皮成纤维细胞的测试中,壳聚糖激活的酸性中和可以显著减少体外炎症因子的分泌,下调成纤维细胞中相关炎症基因,如白细胞介素-6 (IL-6)和白细胞介素-8 (IL-8)的表达。随后,体外生物相容性评价表明,CTS/PLGA纳米纤维的细胞粘附能力比PLAG纳米纤维差,但具有细胞相容性,促进了细胞迁移和胶原的分泌。此外,体内皮下埋植2周和4周后发现,CTS/PLGA纳米纤维显著减少了炎症细胞的募集和异物巨细胞(FBGCs)的形成。因此,本研究证明壳聚糖包被层对减轻plga核的酸性降解产物引起的炎症反应具有良好的酸中和作用。我们的高度排列的CTS/PLGA纳米纤维,作为一种具有酸中和能力的准“ph中性纤维”,可能潜在地应用于那些结构各向异性组织(如肌腱/韧带)的工程,以提高再生效率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Electrospun Acid-Neutralizing Fibers for Improved Biocompatibility
Biodegradable aliphatic polyesters, especially polylactide (PLA), polyglycolide (PGA), and their copolymer poly(lactide-co-glycolide) (PLGA), are the most representative and widely used synthetic polymers in the field of tissue engineering and regenerative medicine. However, these polyesters often give rise to the aseptic inflammation problem triggered by their acidic degradation products after implantation. Here, shell-core structured unidirectional fibers of chitosan/poly(lactide-co-glycolide) (i.e., CTS/PLGA) with acid-neutralizing capability were proposed for addressing the noted issue so as to achieve improved biocompatibility. Our results showed that during a period of 8-week degradation, the shell-layer of chitosan with its unique alkaline nature for acid-neutralization obviously hindered pH decrease as a result of the degradation of PLGA-core. In a mocked acidic environment testing with the human dermal fibroblasts, chitosan-enabled acidity neutralization could significantly reduce in vitro the secretion of inflammatory factors and down-regulate the expression of related inflammatory genes, such as Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in the fibroblasts. Thereafter, biocompatibility assesments in vitro showed that CTS/PLGA nanofibers had poorer cell adhesion capacity than PLAG nanofibers, but were cytocompatible and promoted the cell migration and secretion of collagen. Moreover, two and four weeks of subcutaneous embedding in vivo revealed that the CTS/PLGA nanofibers significantly reduced the recruitment of inflammatory cells and the formation of foreign body giant cells (FBGCs). This study thereby demonstrated the excellent acid-neutralizing effect of the chitosan-coating layer on alleviating the inflammatory response caused by the acidic degradation products of the PLGA-core. Our highly-aligned CTS/PLGA nanofibers, as a kind of quasi ‘pH-neutral fibers’ with acid-neutralizing capability, may be potentially applied for engineering those architecturally anisotropic tissues (e.g., tendon/ligament) toward improved efficacy of regeneration.
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