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基于α-乳白蛋白的支架用于感染性伤口愈合和组织再生。

α-Lactalbumin based scaffolds for infected wound healing and tissue regeneration.

机构信息

College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310012, China.

College of Textile and Clothing Engineering, Soochow University, Suzhou 215123 China.

出版信息

Int J Pharm. 2024 Sep 30;663:124578. doi: 10.1016/j.ijpharm.2024.124578. Epub 2024 Aug 15.

DOI:10.1016/j.ijpharm.2024.124578
PMID:39153643
Abstract

Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options.

摘要

多药耐药菌感染导致的伤口愈合中断对全球医疗保健系统来说是一个有害的问题,由于抗菌药物耐药性的存在,常规治疗方法可能无法解决这一问题。因此,需要开发具有内在伤口愈合特性的支架来对抗细菌感染的伤口。受α-乳白蛋白(Lalb)促进胶原蛋白合成能力的启发,我们在此将拉巴尔与头孢氨苄(CPL)和表没食子儿茶素没食子酸酯(EP)共纺以生产纳米纤维(CE-Lalb NF)来解决这个问题。CE-Lalb NF 是通过静电纺丝技术制备的,并进行了理化特性、体外和体内评估。CE-Lalb NF 促进成纤维细胞迁移、增殖和胶原蛋白合成,而 CPL/EP 则能消灭耐甲氧西林金黄色葡萄球菌(MRSA)和大肠杆菌(E. coli)感染。理化特性证明了 CE-Lalb NF 的成功制备和掺杂。抗菌试验和部分抑菌浓度指数(FICI)表明 CE-Lalb NF 对 MRSA 和 E. coli 具有协同抗菌活性。体内和免疫组织化学数据证明了其在伤口愈合方面的特殊潜力,能促进生长因子、胶原蛋白合成,并减少疤痕形成。在伤口部位存在成熟的胶原蛋白、较少的炎症细胞因子、增加的血管表达和低水平的 IL-6 表达支持了体外和体内的结果。在我们看来,定制支架是个性化伤口敷料的下一步,通过提供非侵入性和易于操作的治疗选择,可以满足患有感染性伤口的患者的未满足需求。

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