Novel Janus-type Antimicrobial Dressings for the Treatment of Biofilms in Chronic Wounds

用于治疗慢性伤口生物膜的新型 Janus 型抗菌敷料

• 批准号: 10212426
• 负责人: GUANGSHUN WANG
• 金额: $ 52.91万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212426
• 关键词: 3-Dimensional; Affect; Aftercare; Alanine; Amputation; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacteria; Biopolymers; Cells; Cellular Infiltration; Cessation of life; Communities; Custom; Databases; Debridement; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetic mouse; Diffusion; Disease; ESKAPE pathogens; Electrospinning; Engineering; Expenditure; Failure; Foot Ulcer; Gelatin; Genes; Geometry; Health; Health Care Costs; High Pressure Liquid Chromatography; Human; Immobilization; Immune response; In Vitro; Individual; Infection; Inflammation; Leg Ulcer; Legal patent; Liquid substance; Membrane; Methods; Microbial Biofilms; Microscopic; Molds; Molecular; Monitor; Morphology; Operative Surgical Procedures; Patients; Peptide Hydrolases; Peptides; Performance; Porosity; Process; Protocols documentation; Pseudomonas aeruginosa; Quality of life; Refractory; Resistance; Scanning Electron Microscopy; Sepsis; Spectrum Analysis; Staphylococcus aureus; Sterile coverings; Streptococcus; Structure; Surface; Testing; Tissues; Treatment outcome; Type 2 diabetic; Ulcer; United States; Venous; Wound Infection; antimicrobial; antimicrobial dressing; antimicrobial peptide; base; biomaterial compatibility; chronic infection; chronic wound; cost; cytokine; decubitus ulcer; density; design; diabetic patient; diabetic wound healing; effective intervention; effective therapy; efficacy testing; immunoregulation; improved; in vivo; invention; mortality; nanofiber; novel; novel therapeutics; pathogen; pathogenic bacteria; peptide analog; prevent; screening; skin wound; standard care; ultraviolet; wound; wound care; wound healing; wound treatment

Infections of chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Biofilms are microscopically identifiable in up to 90% of chronic wounds. For example, diabetes mellitus affects 23.6 million people in the United States and approximately 20-25% of diabetic patients will develop foot ulceration during the course of the disease. Among them, 63.4% of diabetic patients develop infections. The direct annual expenditure toward managing these ulcers is $9 billion to $13 billion in the United Sates alone. Bacteria in biofilms are more likely to cooperate and exchange their genes resulting in much higher antibiotic resistance than planktonic bacteria. The composition and organization of biofilms limits diffusion of molecules, including antibiotics, through the structure and into the biofilm or out to the bulk fluid. Consequently, bacteria in a biofilm are refractory to host response and antibiotic treatment. The poor treatment outcomes result in high healthcare cost, amputations, a decreased quality of life, and an increased mortality. There is an urgent need to develop novel therapies for effective treatment of biofilms in chronic wounds. The primary objective of this proposal is to develop a Janus-type antimicrobial dressing by immobilizing dissolvable microneedle arrays to the surface of three-dimensional (3D) nanofiber foams to effectively treat biofilms and promote diabetic wound healing. This proposed study is framed on important inventions made by both PIs, allowing us to generate a unique platform to treat biofilm in chronic wounds. To prove the concept, we have recently demonstrated that Janus-type antimicrobial dressings are indeed effective against the biofilms of resistant pathogens ex vivo and in vivo. Based on the findings, we hypothesize that the Janus-type dressings, consisting of microneedle arrays and 3D nanofiber foams with incorporation of molecularly engineered peptides, can physically penetrate biofilms and release peptides both inside and outside biofilms to effectively eradicate biofilms in chronic wounds and promote cellular infiltration and wound healing. To test the hypothesis and accomplish the objective, we propose the following specific aims: 1) Establish methods for fabrication and characterization of novel Janus-type dressings; 2) Assess the antibacterial efficacy, biocompatibility and antibiofilm mechanism of engineered peptides and their Janus-type dressings in vitro; and 3) Test the efficacy and immune regulation of optimized Janus-type dressings against biofilms in type 2 diabetic mice wounds and ex vivo human skin wounds. We expect completion of these aims to generate an effective intervention with great commercial potential that could effectively treat biofilms, improve quality of wound care, decrease costs, avoid amputations, and most importantly save lives of patients.

慢性伤口的感染，包括糖尿病足溃疡、压力性溃疡和静脉性腿部溃疡，构成了主要的 对伤口处理的挑战。在高达90%的慢性伤口中，生物膜可在显微镜下识别。为 例如，在美国，糖尿病影响2360万人，并且大约20-25%的糖尿病患者患有糖尿病。 病人在病程中会出现足部溃疡。其中，63.4%的糖尿病患者 发展成感染。在美国，管理这些溃疡的直接年度支出为90亿至130亿美元。 美国单独。生物膜中的细菌更有可能合作和交换它们的基因， 抗生素耐药性高于嗜热菌。生物膜的组成和组织限制了扩散 分子，包括抗生素，通过结构进入生物膜或进入大量液体。因此，委员会认为， 生物膜中的细菌对宿主反应和抗生素治疗是难治的。治疗结果不佳 高医疗费用、截肢、生活质量下降和死亡率增加。目前迫切 需要开发用于有效治疗慢性伤口中的生物膜的新疗法。的主要目的 该方案是通过固定可溶解微针阵列来开发Janus型抗菌敷料 以有效地处理生物膜并促进糖尿病伤口 治愈这项拟议的研究是在两个PI的重要发明的框架，使我们能够产生一个 治疗慢性伤口生物膜的独特平台。为了证明这一概念，我们最近证明， Janus型抗菌敷料确实能有效对抗体外耐药病原体的生物膜， in vivo.基于这些发现，我们假设由微针阵列组成的Janus型敷料 和3D生物泡沫与分子工程肽的结合，可以物理穿透生物膜， 并在生物膜内外释放肽以有效地根除慢性伤口中的生物膜， 促进细胞浸润和伤口愈合。为了验证假设并实现目标，我们建议 具体目标如下：1）建立用于制造和表征新型Janus型 2）评估工程敷料的抗菌效果、生物相容性和抗菌膜机制 肽及其Janus型敷料的体外试验;以及3）测试优化的 针对2型糖尿病小鼠伤口和离体人类皮肤伤口中生物膜的Janus型敷料。我们 预期这些目标的完成将产生具有巨大商业潜力的有效干预， 有效处理生物膜，提高伤口护理质量，降低成本，避免截肢，最重要的是 挽救病人的生命。