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多功能双纳米 MOF 修饰脱细胞小肠黏膜下层膜加速感染性创面愈合。

Multifunctional Dual Nano-MOF-Modified Decellularized Small Intestinal Submucosa Membrane Accelerates Healing of Infected Wound.

机构信息

Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.

Department of Pediatric Surgery, Division of Orthopedic Surgery, Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.

出版信息

ACS Appl Mater Interfaces. 2024 Nov 20;16(46):63368-63388. doi: 10.1021/acsami.4c16218. Epub 2024 Nov 11.

Abstract

The treatment of complex or chronic skin wounds caused by burns, trauma, surgery, and genetic disorders has been a worldwide challenge. Small intestinal submucosa (SIS) is a biological material that is widely used in wound healing. How to further expand the wound healing application of SIS, especially in repairing infected wounds, remains a hot research topic for many tissue engineering and biomaterial scholars focusing on skin regeneration. This study uses nanometal-organic frameworks (nano-MOFs), which have not been applied to modify the SIS membrane before, to construct multifunctional dual nano-MOFs @ SIS membrane (dnMOF@SISm). Nano-MOFs are functionalized onto the nanofiber of SIS via self-assembly under mild reaction conditions without any toxic reagent or complex instruments. The dnMOF@SISm can release Co, Zn, and bioactive factors, participating in the whole stage of the repair of infected wounds. , it can regulate the biological activities of various functional cells such as fibroblasts, endothelial cells, and macrophages and shows good antibacterial ability. In the infected full-thickness skin defect rat model, dnMOF@SISm can release metal ions and ligands, killing pathogenic bacteria colonized on the wound surface at the first stage, and then trigger and accelerate the skin repair process via angiogenesis, immune regulation, and collagen deposition. Above all, an efficient, nontoxic, mild self-assembly strategy realizes the functionalization of dual nano-MOFs on the nanofiber of SIS to expand its clinical application scenarios, especially in infected wounds.

摘要

治疗烧伤、创伤、手术和遗传疾病引起的复杂或慢性皮肤伤口一直是全球性的挑战。小肠黏膜下层(SIS)是一种广泛应用于伤口愈合的生物材料。如何进一步扩大 SIS 的伤口愈合应用,特别是在修复感染性伤口方面,仍然是许多专注于皮肤再生的组织工程和生物材料学者的热门研究课题。本研究使用纳米金属-有机骨架(nano-MOFs),以前从未应用于修饰 SIS 膜,构建多功能双纳米 MOFs@SIS 膜(dnMOF@SISm)。在温和的反应条件下,通过自组装将纳米 MOFs 功能化到 SIS 的纳米纤维上,无需任何有毒试剂或复杂仪器。dnMOF@SISm 可以释放 Co、Zn 和生物活性因子,参与感染性伤口修复的整个阶段。它可以调节成纤维细胞、内皮细胞和巨噬细胞等各种功能细胞的生物活性,并且具有良好的抗菌能力。在感染性全层皮肤缺损大鼠模型中,dnMOF@SISm 可以释放金属离子和配体,在第一阶段杀死定植在伤口表面的致病菌,然后通过血管生成、免疫调节和胶原蛋白沉积触发并加速皮肤修复过程。总之,一种高效、无毒、温和的自组装策略实现了双纳米 MOFs 在 SIS 纳米纤维上的功能化,扩大了其临床应用场景,特别是在感染性伤口方面。

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