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水凝胶微球包载溶菌酶/MXene 用于光热增强的抗菌活性和感染伤口愈合。

Hydrogel microspheres encapsulating lysozyme/MXene for photothermally enhanced antibacterial activity and infected wound healing.

机构信息

Center for Orthopaedic Science and Translational Medicine, Department of Orthopaedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 301 Yanchang Road, Shanghai 200072, PR China.

Center for Orthopaedic Science and Translational Medicine, Department of Orthopaedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 301 Yanchang Road, Shanghai 200072, PR China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 201102, PR China.

出版信息

Int J Biol Macromol. 2024 Nov;279(Pt 4):135527. doi: 10.1016/j.ijbiomac.2024.135527. Epub 2024 Sep 10.

Abstract

The high mortality and enormous economic burden of bacterially infected wounds remains a huge challenge for human health. The development of ideal wound dressings with desirable antibacterial and good wound healing properties still remains a major problem affecting the regeneration of bacterially infected wound tissue. Herein, we present novel alginate-based hydrogel microspheres containing lysozyme and MXene (i-Lyso@Alg), in which the positively charged lysozyme is immobilized on the negatively charged MXene by electrostatic interaction. Due to the presence of MXene, i-Lyso@Alg exhibits good thermal effect, drug release behavior and strong antibacterial activity under near-infrared (NIR) irradiation. The synthesized i-Lyso@Alg can realize not only improvement of lysozyme stability but also photothermal responsive up-regulation for biocatalysis of lysozyme. The excellent antibacterial activities of i-Lyso@Alg were attributed to the photothermally enhanced lysozyme activity, assisted by bacterial death caused by local thermal effect of photothermally activated MXene and the physical damage due to the MXene. In addition, in the infected skin wounds of rats, i-Lyso@Alg + NIR significantly accelerates the wound healing process by inhibiting the expression of inflammatory factors and bacterial (Staphylococcus aureus) infection, and inducing the expression of pro-angiogenic factors and tissue remodeling. Overall, the results of this study introduce a pioneering approach by integrating the unique photothermal properties of MXene with the enzymatic action of lysozyme within an alginate-based hydrogel microsphere. This synergistic system not only advances the frontier of antibacterial wound dressings but also represents a significant step towards effective management of infected wounds, which possesses great potential in clinical treatment of infected wounds.

摘要

细菌感染伤口的高死亡率和巨大经济负担仍然是人类健康的巨大挑战。开发具有理想抗菌性能和良好伤口愈合性能的理想伤口敷料仍然是一个主要问题,影响着细菌感染伤口组织的再生。在此,我们提出了一种新型的基于海藻酸钠的水凝胶微球,其中含有溶菌酶和 MXene(i-Lyso@Alg),其中带正电荷的溶菌酶通过静电相互作用固定在带负电荷的 MXene 上。由于 MXene 的存在,i-Lyso@Alg 在近红外(NIR)照射下表现出良好的热效应、药物释放行为和强大的抗菌活性。合成的 i-Lyso@Alg 不仅可以提高溶菌酶的稳定性,而且可以光热响应上调溶菌酶的生物催化活性。i-Lyso@Alg 的优异抗菌活性归因于光热增强的溶菌酶活性,辅助作用来自光热激活的 MXene 的局部热效应引起的细菌死亡和 MXene 引起的物理损伤。此外,在大鼠感染皮肤伤口中,i-Lyso@Alg+NIR 通过抑制炎症因子和细菌(金黄色葡萄球菌)感染的表达以及诱导促血管生成因子和组织重塑的表达,显著加速伤口愈合过程。总的来说,这项研究的结果通过将 MXene 的独特光热特性与海藻酸钠水凝胶微球内的溶菌酶的酶促作用相结合,引入了一种开创性的方法。该协同系统不仅推进了抗菌伤口敷料的前沿,而且为有效管理感染性伤口迈出了重要一步,在感染性伤口的临床治疗中具有巨大潜力。

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