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研究一种新型的双层 PCL/PVA 静电纺丝纳米纤维,其中包含壳聚糖-LL37 和壳聚糖-VEGF 纳米颗粒,作为一种先进的抗菌细胞生长促进型伤口敷料。

Investigation of a novel bilayered PCL/PVA electrospun nanofiber incorporated Chitosan-LL37 and Chitosan-VEGF nanoparticles as an advanced antibacterial cell growth-promoting wound dressing.

机构信息

Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.

Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran; Department of Microbiology, School of Medicine, Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.

出版信息

Int J Pharm. 2024 Aug 15;661:124341. doi: 10.1016/j.ijpharm.2024.124341. Epub 2024 Jun 14.

Abstract

Chronic wounds have become a growing concern as they can have a profound impact on individuals, potentially resulting in mortality. It is crucial to prevent and manage bacterial infections, particularly drug-resistant ones. Antimicrobial peptides, such as LL-37, can firmly eliminate pathogens. Additionally, the process of angiogenesis, facilitated by growth factors like VEGF, is essential for tissue repair and wound healing. To enhance the stability and bioavailability of therapeutic agents, targeted delivery strategies utilizing Chitosan-based carriers have been employed. Electrospun biopolymers in advanced wound dressings have revolutionized wound care by providing a more effective and efficient solution for promoting tissue regeneration and speeding up the healing process. The present investigation utilized Chitosan nanoparticles to encapsulate the recombinant LL37 peptide and VEGF. An in-depth investigation was carried out to analyze the biophysical and morphological traits of the LL37-CSNPs and VEGF-CSNPs. The first support layer consisted of PCL electrospun nanofiber, followed by the electrospinning of PVA/CsLL37, PVA/CsVEGF, and PVA/CsLL37/CsVEGF onto the PCL layer. An in vitro examination assessed the fabricated nanofibers' morphological, mechanical, and biological characteristics. The antimicrobial effects were tested on methicillin-resistant Staphylococcus aureus (MRSA). The in vivo experiments assessed the antibacterial and wound-healing capabilities of the nanofibers. The findings validated the continuous release of LL37 and VEGF. The composite material PCL/PVA/CsLL37/CsVEGF demonstrated potent bactericidal and antioxidant characteristics. The cytotoxic assay demonstrated the biocompatibility of the fabricated nano mats and their potential to accelerate fibroblast cell proliferation. The efficacy of PVA/CsLL37/CsVEGF in promoting wound healing was confirmed through an in vivo wound healing assay. Furthermore, the histological analysis provided evidence of faster epidermal formation and improved antibacterial activity in wounds covered with PVA/CsLL37/CsVEGF. Adding LL37 and VEGF to the composite material improves the immune response and promotes blood vessel formation, accelerating wound healing and decreasing inflammation.

摘要

慢性伤口已成为一个日益严重的问题,因为它们会对个人产生深远的影响,甚至可能导致死亡。预防和管理细菌感染,特别是耐药菌感染至关重要。抗菌肽,如 LL-37,可以有效地消除病原体。此外,血管生成过程,由 VEGF 等生长因子促进,对于组织修复和伤口愈合至关重要。为了提高治疗剂的稳定性和生物利用度,利用壳聚糖载体的靶向递药策略已经被应用。在先进的伤口敷料中使用电纺生物聚合物已经彻底改变了伤口护理,为促进组织再生和加速愈合过程提供了更有效和高效的解决方案。本研究利用壳聚糖纳米粒来包封重组 LL37 肽和 VEGF。深入分析了 LL37-CSNPs 和 VEGF-CSNPs 的生物物理和形态特征。第一层支撑层由 PCL 电纺纳米纤维组成,然后在 PCL 层上依次电纺 PVA/CsLL37、PVA/CsVEGF 和 PVA/CsLL37/CsVEGF。体外检查评估了所制备的纳米纤维的形态、机械和生物学特性。对耐甲氧西林金黄色葡萄球菌(MRSA)进行了抗菌效果测试。体内实验评估了纳米纤维的抗菌和伤口愈合能力。实验结果验证了 LL37 和 VEGF 的持续释放。复合材料 PCL/PVA/CsLL37/CsVEGF 表现出强大的杀菌和抗氧化特性。细胞毒性试验表明所制备的纳米垫具有生物相容性,并且有可能加速成纤维细胞增殖。通过体内伤口愈合试验证实了 PVA/CsLL37/CsVEGF 在促进伤口愈合方面的功效。此外,组织学分析表明,在覆盖有 PVA/CsLL37/CsVEGF 的伤口中,表皮形成更快,抗菌活性提高。在复合材料中添加 LL37 和 VEGF 可以改善免疫反应,促进血管形成,加速伤口愈合,减少炎症。

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