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具有长期内在抗菌性能的半互穿水凝胶促进感染伤口愈合。

Semi-Interpenetrating Hydrogel with Long-Term Intrinsic Antibacterial Properties Promotes Healing of Infected Wounds .

机构信息

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.

Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030000, China.

出版信息

ACS Appl Bio Mater. 2024 Oct 21;7(10):7051-7061. doi: 10.1021/acsabm.4c01218. Epub 2024 Oct 10.

Abstract

Bacterial infections significantly deteriorate the process of wound healing. The wound dressings loaded with antimicrobials are widely used to reduce bacterial infections. However, release-based sterilization may increase the risk of drug resistance of bacteria and complicate translation. Thus, the development of long-term intrinsic antibacterial wound dressings is highly desirable. In this study, an intrinsic antibacterial hydrogel (PVA/PPG-HBPL) consisting of poly(vinyl alcohol) (PVA), poly(polyethylene glycol methyl ether methacrylate--glycidyl methacrylate) (PPG), and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The mechanical properties of the PVA/PPG-HBPL hydrogel were enhanced by hydrogen bonding and semi-interpenetrating networks. It also possessed a favorable ability to absorb the wound exudates. The release of antibacterial HBPL was significantly decreased by the methods of cyclic freeze-thawing and covalent cross-linking during hydrogel fabrication, enabling the PVA/PPG-HBPL hydrogel with intrinsic and long-term antibacterial performance. The PVA/PPG-HBPL hydrogel dressing killed 99.9% of methicillin-resistant (MRSA) cultured on its surface without observable cytotoxicity . It observably shortened the healing process by 2 orders of magnitude of colonies compared with the control in the MRSA-infected full-thickness skin wound of rats even after being soaked in phosphate-buffered saline (PBS) for 21 days (PBS was changed every 3 days). The antibacterial hydrogels could kill wound bacteria in a timely manner, significantly reduce inflammatory cell infiltration, and promote neovascularization and collagen deposition.

摘要

细菌感染会显著恶化伤口愈合过程。负载抗菌剂的伤口敷料被广泛用于减少细菌感染。然而,基于释放的灭菌可能会增加细菌产生耐药性的风险并使翻译复杂化。因此,开发长效内在抗菌伤口敷料是非常需要的。在这项研究中,设计并制备了一种由聚乙烯醇(PVA)、聚(聚乙二醇甲基醚甲基丙烯酸酯-甲基丙烯酸缩水甘油酯)(PPG)和超支化聚-l-赖氨酸(HBPL)组成的内在抗菌水凝胶(PVA/PPG-HBPL)。PVA/PPG-HBPL 水凝胶的机械性能通过氢键和半互穿网络得到增强。它还具有吸收伤口渗出物的良好能力。通过在水凝胶制备过程中循环冷冻-解冻和共价交联的方法,显著降低了抗菌 HBPL 的释放,使 PVA/PPG-HBPL 水凝胶具有内在和长期的抗菌性能。PVA/PPG-HBPL 水凝胶敷料在其表面培养的耐甲氧西林金黄色葡萄球菌(MRSA)上杀死了 99.9%,而没有观察到细胞毒性。与对照组相比,它显著缩短了 MRSA 感染的全层皮肤伤口大鼠的愈合过程,甚至在浸泡于磷酸盐缓冲盐水(PBS)中 21 天后(每 3 天更换一次 PBS)。抗菌水凝胶可以及时杀死伤口细菌,显著减少炎症细胞浸润,并促进新生血管形成和胶原蛋白沉积。

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