Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907-2057, United States.
School of Materials Engineering, Purdue University, West Lafayette, Indiana 47907-2045, United States.
ACS Appl Bio Mater. 2021 Jul 19;4(7):5405-5415. doi: 10.1021/acsabm.1c00087. Epub 2021 Jun 15.
Chronic nonhealing wounds are a growing socioeconomic problem that affects more than 6 million people annually solely in the United States. These wounds are colonized by bacteria that often develop into biofilms that act as a physical and chemical barrier to therapeutics and tissue oxygenation leading to chronic inflammation and tissue hypoxia. Although wound debridement and vigorous mechanical abrasion techniques are often used by clinical professionals to manage and remove biofilms from wound surfaces, such methods are highly nonselective and painful. In this study, we have developed a flexible polymer composite microneedle array that can overcome the physicochemical barriers (i.e., bacterial biofilm) present in chronic nonhealing wounds and codeliver oxygen and bactericidal agents. The polymeric microneedles are made by using a facile UV polymerization process of polyvinylpyrrolidone and calcium peroxide onto a flexible polyethylene terephthalate substrate for conformable attachment onto different locations of the human body surface. The microneedles effectively elevate the oxygen levels from 8 to 12 ppm once dissolved over the course of 2 h while also providing strong bactericidal effects on both liquid and biofilm bacteria cultures of both Gram-positive () and Gram-negative () bacterial strains commonly found in dermal wounds. Furthermore, the results from the ex vivo assay on a porcine wound model indicated successful insertion of the microneedles into the tissue while also providing effective bactericidal properties against both Gram-positive and Gram-negative within the complex tissue matrix. Additionally, the microneedles demonstrate high levels of cytocompatibility with less than 10% of apoptosis throughout 6 days of continuous exposure to human dermal fibroblast cells. The demonstrated flexible microneedle array can provide a better approach for increasing the effectiveness of topical tissue oxygenation as well as the treatment of infected wounds with intrinsically antibiotic resistant biofilms.
慢性难愈性伤口是一个日益严重的社会经济问题，仅在美国每年就有超过 600 万人受到影响。这些伤口被细菌定植，这些细菌通常会形成生物膜，生物膜充当治疗和组织氧合的物理和化学屏障，导致慢性炎症和组织缺氧。尽管临床专业人员经常使用伤口清创和剧烈的机械磨损技术来管理和去除伤口表面的生物膜，但这些方法高度非选择性且疼痛。在这项研究中，我们开发了一种灵活的聚合物复合微针阵列，可以克服慢性难愈性伤口中存在的物理化学屏障（即细菌生物膜），并同时递送氧气和杀菌剂。聚合物微针是通过使用聚维酮和过氧化钙的简便 UV 聚合过程在柔性聚对苯二甲酸乙二醇酯基底上制造的，以便于贴合人体表面的不同位置。微针在 2 小时内溶解时，有效地将氧气水平从 8ppm 提高到 12ppm，同时对皮肤伤口中常见的革兰氏阳性（）和革兰氏阴性（）细菌菌株的液体和生物膜细菌培养物均具有强大的杀菌作用。此外，在猪伤口模型的离体试验结果表明，微针成功插入组织，同时在复杂的组织基质内对革兰氏阳性和革兰氏阴性菌均具有有效的杀菌性能。此外，微针与人真皮成纤维细胞连续接触 6 天，其细胞存活率超过 90%，细胞凋亡率小于 10%，表现出高细胞相容性。该柔性微针阵列可提供一种更好的方法，以提高局部组织氧合的效果，并治疗具有内在抗生素耐药性生物膜的感染性伤口。
