Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Ningbo Institute, Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an 710072, China; School of Flexible Electronics (SoFE) and Henan Institute of Flexible Electronics (HIFE), Henan University, 379 Mingli Road, Zhengzhou 450046, China.
Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Ningbo Institute, Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an 710072, China; School of Flexible Electronics (SoFE) and Henan Institute of Flexible Electronics (HIFE), Henan University, 379 Mingli Road, Zhengzhou 450046, China; Chongqing Technology Innovation Center, Northwestern Polytechnical University (NPU), Chongqing 401120, China.
Acta Biomater. 2024 Oct 15;188:169-183. doi: 10.1016/j.actbio.2024.09.017. Epub 2024 Sep 17.
Biofilm infection and impaired healing of chronic wounds are posing tremendous challenges in clinical practice. In this study, we presented a versatile antimicrobial hydrogel capable of delivering nitric oxide (NO) in a controllable manner to dissipate biofilms, eliminate microorganisms, and promote the healing of chronic wounds. This hydrogel was constructed by Schiff-base crosslinking of oxidized dextran and antimicrobial peptide ε-poly-lysine, further encapsulating photothermal nanoparticles bearing NO donor. This hydrogel could continuously and slowly release NO, effectively dissipating biofilms, and promoting the proliferation of mouse fibroblasts and the migration of endothelial cells. Upon exposure to NIR laser irradiation, the hydrogel generated hyperthermia and rapidly released NO, resulting in the efficient elimination of a broad spectrum of drug-resistant Gram-positive/negative bacterial and fungal biofilms through the synergistic effects of NO, photothermal therapy, and the antibacterial peptide. Notably, the hydrogel demonstrated exceptional in vivo therapeutic outcomes in accelerating the healing process of mice diabetic wounds infected with methicillin-resistant Staphylococcus aureus by successfully eliminating biofilm infection, regulating inflammation, and facilitating angiogenesis and collagen deposition. Overall, this proposed hydrogel shows great promise in accommodating the various demands of the complex repair process of chronic wounds infected with biofilms. STATEMENT OF SIGNIFICANCE: The presence of biofilm infections and underlying dysfunctions in the healing process made chronic wound become stuck in the inflammation stage and difficult to heal. This work developed a NIR laser-modulated three-stage NO-releasing versatile antimicrobial hydrogel (DEPN) exhibiting good therapeutic efficacy for chronic wound. This DEPN hydrogel could inherently and slowly released NO to disperse biofilm. Upon NIR laser irradiation, the DEPN hydrogel generated hyperthermia and induced a rapid burst release of NO effectively eliminating a broad spectrum of drug-resistant bacterial and fungal biofilms. Subsequently, the DEPN hydrogel continually release NO slowly to promote the tissue remolding. This DEPN hydrogel displays great potential in treatment of chronic wounds infected with biofilm.
生物膜感染和慢性伤口愈合受损给临床实践带来了巨大挑战。在本研究中，我们提出了一种多功能抗菌水凝胶，能够以可控的方式输送一氧化氮 (NO) 来消散生物膜、消除微生物并促进慢性伤口愈合。该水凝胶是通过氧化葡聚糖和抗菌肽 ε-聚赖氨酸的席夫碱交联构建的，进一步包封了携带 NO 供体的光热纳米颗粒。该水凝胶可以持续缓慢地释放 NO，有效消散生物膜，并促进小鼠成纤维细胞的增殖和内皮细胞的迁移。在近红外激光照射下，水凝胶产生热，并迅速释放 NO，通过 NO、光热治疗和抗菌肽的协同作用，高效消除广谱耐甲氧西林革兰氏阳性/阴性细菌和真菌生物膜。值得注意的是，该水凝胶在加速感染耐甲氧西林金黄色葡萄球菌的糖尿病小鼠伤口愈合方面表现出出色的体内治疗效果，成功消除生物膜感染、调节炎症、促进血管生成和胶原沉积。总之，该水凝胶在适应慢性感染生物膜的复杂修复过程的各种需求方面具有广阔的应用前景。
生物膜感染和愈合过程中的功能障碍使慢性伤口滞留在炎症阶段，难以愈合。本工作开发了一种近红外激光调节的三阶段 NO 释放多功能抗菌水凝胶（DEPN），对慢性伤口具有良好的治疗效果。这种 DEPN 水凝胶可以内在地、缓慢地释放 NO 来分散生物膜。在近红外激光照射下，DEPN 水凝胶产生热并诱导快速的 NO 爆发释放，有效消除广谱耐药细菌和真菌生物膜。随后，DEPN 水凝胶持续缓慢地释放 NO 以促进组织重塑。这种 DEPN 水凝胶在治疗感染生物膜的慢性伤口方面具有巨大潜力。
