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

基本信息

批准号：
10030925
负责人：
GUANGSHUN WANG
金额：
$ 48.8万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/10030925
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

项目摘要

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，压疮和静脉腿溃疡挑战伤口管理。在高达90％的慢性伤口中，生物膜在显微镜上可识别。为了例如，糖尿病在美国影响2360万人，约有20-25％在疾病过程中，患者会出现脚步溃疡。其中有63.4％的糖尿病患者发展感染。管理这些溃疡的直接年度支出为90亿美元至130亿美元联合国一个人。生物膜中的细菌更有可能合作并交换其基因，从而导致很多抗生素耐药性高于浮游细菌。生物膜的组成和组织限制扩散通过结构并进入生物膜或散装流体的分子，包括抗生素。最后，生物膜中的细菌是宿主反应和抗生素治疗的难治性。不良的治疗结果高度医疗保健成本，截肢，生活质量降低以及死亡率增加。有紧急需要开发新的疗法，以有效治疗慢性伤口的生物膜。主要目标该提议是通过固定可溶解的微针阵列来开发Janus型抗菌味到三维（3D）纳米纤维泡沫的表面有效治疗生物膜并促进糖尿病伤口康复。这项拟议的研究是基于两个PI的重要发明的，使我们能够产生一个在慢性伤口中治疗生物膜的独特平台。为了证明这个概念，我们最近证明了 Janus型抗菌敷料确实有效地针对抗性病原体的生物膜，并且体内。根据调查结果，我们假设Janus型敷料，由微针阵列组成和3D纳米纤维泡沫，并掺入分子工程肽，可以物理穿透生物膜并释放内部和外部生物膜的肽，以有效地消除慢性伤口和促进细胞浸润和伤口愈合。为了检验假设并实现目标，我们提出了以下具体目的：1）建立新型Janus类型的制造和表征的方法调味料； 2）评估工程的抗菌功效，生物相容性和抗体机制肽和他们的Janus型敷料在体外； 3）测试优化的功效和免疫调节 2型糖尿病小鼠中针对生物膜的Janus型敷料伤口和体内人体皮肤伤口。我们预计这些目标的完成将产生具有巨大商业潜力的有效干预措施有效治疗生物膜，提高伤口护理的质量，降低成本，避免截肢，最重要的是挽救患者的生命。