Faculty of Medicine, University of Coimbra, Coimbra 3000-354, Portugal.
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-517, Portugal.
ACS Appl Mater Interfaces. 2022 Jun 1;14(21):24213-24228. doi: 10.1021/acsami.2c06601. Epub 2022 May 18.
No effective therapeutic dressings are currently available in the market that can prevent bacterial infection and simultaneously promote skin regeneration in diabetic patients. The lack of re-epithelization, prevalence of inflammation, and high risk of infection are hallmarks of non-healing wounds. Here, we have evaluated the antimicrobial and pro-regenerative effect of a relatively non-leaching LL37 peptide immobilized in polyurethane (PU)-based wound dressings (PU-adhesive-LL37 dressing). The PU-adhesive-LL37 (63 μg LL37NPs/cm) dressing killed Gram-positive and Gram-negative bacteria in human serum without inducing bacterial resistance after 16 antimicrobial test cycles in contrast to commercially available dressings with the capacity to release antimicrobial Ag ions. Importantly, type II diabetic mice ( mice) treated with the PU-adhesive-LL37 dressing for different periods of time (6 or 14 days) showed enhanced wound healing and re-epithelialization (i.e., high keratin 14/5 levels) and lower macrophage infiltration in the wounds compared to animals treated with PU. The wounds treated with PU-adhesive-LL37 dressings showed also low expression of pro-inflammatory cytokines such as TNF-α and IL6 after 6 days of treatment, indicating that they act as an anti-inflammatory dressing. Additionally, PU-adhesive-LL37 dressings do not induce acute inflammatory responses in the peripheral blood mononuclear cells (PBMCs) after 3 days of exposure, in contrast to controls. Taken together, PU-adhesive-LL37NP dressings might prevent the bacterial infections and facilitate wound healing by tissue contact, inducing re-epithelialization and anti-inflammatory processes in diabetic conditions.
目前市场上没有有效的治疗性敷料，既能预防细菌感染，又能促进糖尿病患者的皮肤再生。缺乏再上皮化、炎症流行和感染风险高是难愈合伤口的特征。在这里，我们评估了相对非浸出性 LL37 肽固定在聚氨酯（PU）基伤口敷料（PU-黏附-LL37 敷料）中的抗菌和促再生作用。与具有释放抗菌 Ag 离子能力的市售敷料相比，PU-黏附-LL37（63 μg LL37NPs/cm）敷料在 16 次抗菌试验循环后，在人血清中杀死革兰氏阳性和革兰氏阴性细菌，而不会诱导细菌耐药性。重要的是，用 PU-黏附-LL37 敷料治疗不同时间（6 天或 14 天）的 II 型糖尿病小鼠（mice）与用 PU 治疗的动物相比，伤口愈合和再上皮化（即角质蛋白 14/5 水平升高）增强，伤口中巨噬细胞浸润减少。与用 PU 处理的伤口相比，用 PU-黏附-LL37 敷料处理的伤口在治疗 6 天后还表现出较低水平的促炎细胞因子，如 TNF-α 和 IL6，表明其具有抗炎作用。此外，与对照组相比，PU-黏附-LL37 敷料在暴露 3 天后不会引起外周血单核细胞（PBMCs）的急性炎症反应。综上所述，PU-黏附-LL37NP 敷料通过组织接触可能预防细菌感染并促进糖尿病条件下的伤口愈合，诱导再上皮化和抗炎过程。
