交联电纺pH敏感纳米纤维吸附Temporin-Ra以促进伤口愈合。
Cross-Linked Electrospun pH-Sensitive Nanofibers Adsorbed with Temporin-Ra for Promoting Wound Healing.
发表日期:2023 Mar 20
作者:
Fatemeh Koohzad, Ahmad Asoodeh
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
生物响应性纳米药物输送系统在组织工程应用方面具有极大的潜力。多阴离子和多阳离子生物聚合物为设计pH敏感性药物输送系统提供了卓越平台。在此方面,通过优化制备过程,产生了质量和可重复性都很高的透明质酸-壳聚糖-聚乙烯醇复合纳米纤维。此外,合成的复合纳米纤维具有66.82 kN/mm的韧度、200%的肿胀率和60%的孔隙率,表现出满足理想敷料要求的优异性能。绿色交联剂柠檬酸阻止了纳米纤维在长时间浸泡在生物溶液中后的破坏。ζ电位研究表明,合成纳米纤维在生理pH值下具有负表面电荷(〜-30)。Temporin-Ra肽的pKa约为10,在生理条件下,肽分子具有净正电荷。因此,将肽分子固定在合成支架上,基于表面吸附。体内评估证明,伤口床具有碱性环境,有利于肽从纳米纤维支架中释放。电纺纳米纤维可以模仿细胞外基质结构,加速伤口愈合。体外研究显示,在负载肽的纳米纤维样品上,比其他组更好的附着、增殖、迁移和成纤维细胞生长。在小鼠模型中对全层厚度伤口进行的体内研究表明,所设计的纳米纤维逐渐被吸收,不会导致干燥或感染。在第6天,与对照组(17%)相比,负载肽的纳米纤维显示出60%的伤口闭合。此外,根据组织学研究,复合纳米纤维展示出出色的组织修复能力,因此这些活性纳米纤维垫可以成为现有伤口敷料的良好替代品。基因表达研究表明,抗微生物肽通过加速肿瘤坏死因子-α 细胞因子反应,缩短了伤口愈合炎症阶段的时间框架。
Bioresponsive nanodrug delivery systems have excellent potential in tissue engineering applications. Poly-anionic and poly-cationic biopolymers have provided a superior platform for designing pH-sensitive drug delivery systems. In this regard, hyaluronic acid-chitosan-polyvinyl alcohol complex nanofibers with high quality and reproducibility were produced by optimizing the solution preparation process. In addition, the synthesized composite nanofiber, with 66.82 kN/mm toughness, 200% swelling ratio, and 60% porosity, exhibited excellent properties to meet the requirements of the ideal wound dressing. Green cross-linking with citric acid prevented the destruction of the nanofiber even after prolonged immersion in biological solutions. ζ potential studies demonstrated that the synthesized nanofiber has a negative surface charge (∼-30) at physiological pH. The pKa of the temporin-Ra peptide is about 10, and as a result the peptide molecules have a net positive charge in physiological conditions. Therefore, peptide molecules immobilized on the synthesized scaffold based on surface adsorption. In vivo evaluation has proven that the wound bed has an alkaline environment, facilitating peptide release from the nanofiber scaffold. Electrospun nanofibers can imitate the architecture of the extracellular matrix for accelerating wound healing. In vitro investigation showed better adhesion, proliferation, migration, and fibroblast cell growth on peptide-loaded nanofiber samples than other groups. In vivo studies on full-thickness wounds in the mouse model indicated that the designed nanofiber was gradually absorbed without causing dryness or infection. On day 6, the peptide-loaded nanofiber revealed 60% wound closure compared to the control group (17%). In addition, based on histological studies, the composite nanofiber demonstrated excellent tissue repair ability, hence these active nanofiber mats can be a good alternative to existing wound dressings. Gene expression studies show that the antimicrobial peptide promotes the inflammatory phase of wound healing in a shorter time frame by accelerating the tumor necrosis factor-α cytokine response.