Self-Locomotive Antimicrobial Micro-Robot (SLAM) Enhancing Biofilm-Infected Wound Healing

自移动抗菌微型机器人 (SLAM) 增强生物膜感染伤口愈合

• 批准号: 10612835
• 负责人: Hyunjoon Kong
• 金额: $ 42.52万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612835
• 关键词: 3-Dimensional; Aging; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteria; Blood; CD34 gene; Cell Wall; Cell secretion; Cells; Cessation of life; Chronic; Clinical; Collaborations; Collagen; Complex; Cytoprotection; Debridement; Deposition; Dermatologist; Diatoms; Disease; Disinfectants; Disinfection; Edema; Enzymes; Excision; Exhibits; FGF2 gene; Female; Fibroblast Growth Factor; Fracture; Gelatinase B; Goals; Growth; Growth Factor; Hematopoietic Stem Cell Mobilization; Human body; Hydrogen Peroxide; Immune system; Impaired wound healing; Infection; Inflammation; Invaded; Irrigation; Liquid substance; Locomotion; MMP9 gene; Malignant - descriptor; Matrix Metalloproteinases; Metabolic; Metalloproteases; Methods; Microbial Biofilms; Microbubbles; Modeling; Monitor; Multi-modal optical imaging; Mus; Oxygen; PTPRC gene; Patients; Polymers; Porosity; Procedures; Pseudomonas aeruginosa; Recombinants; Recurrence; Regenerative Medicine; Residual state; Scheme; Self Efficacy; Services; Site; Skin; Structure; Surveys; Thick; Time; Tissues; Toxic effect; Translating; United States; United States National Institutes of Health; Vancomycin; Vascularization; Water; Wound Infection; antimicrobial; antimicrobial drug; bioimaging; cost; disability; efficacy evaluation; epithelial wound; extracellular; imaging system; improved; inhibitor; innovation; invention; keratinocyte growth factor; male; mechanical energy; methicillin resistant Staphylococcus aureus; microbial; microrobot; nanosheet; neovascularization; prevent; skin regeneration; stem; stem cells; success; traumatic event; treatment duration; wound; wound biofilm; wound healing; wound treatment

Project Summary Biofilm, a protective extracellular-polymeric substance that surrounds bacterial colonies, is associated with more than 80% of microbial infections. In the United States, the management cost for biofilm- associated infections reaches 94 billion US dollars and is responsible for 0.5 million deaths annually. In particular, millions of wound patients suffer from biofilm-associated infections that lead to persistent inflammation and edema, and ultimately hinder wound healing. Biofilm bacteria are 1,000 times more resistant to antibiotics than free-floating bacteria. In a clinical setting, it is common to remove biofilm from the wound with debridement or enzymes. However, these methods do not remove biofilm in space deep in the wounded tissue, thus allowing biofilm recurrence. To this end, we recently invented a self-locomotive, antimicrobial micro-robot (SLAM) that can invade and remove biofilm. The SLAM is prepared by activating diatom biosilica doped with MnO2 nanocatalysts (MnO2-diatom) to generate oxygen microbubbles using a 3 % hydrogen peroxide solution. The activated MnO2-diatoms propel themselves to enter the biofilm. Within the biofilm, the activated MnO2-diatoms continue to generate microbubbles that fuse and produce mechanical energy high enough to fracture biofilm. It takes 10 minutes for the activated MnO2-diatoms to remove more than 99.9 % of 0.8 mm-thick P. aeruginosa biofilm with similar depth to full-thickness skin. No adverse toxic effects are observed after cleaning. With this success, our overall goals are to improve biofilm removal from the infected wound using SLAM and, in turn, to promote skin regeneration in the wound. We hypothesize that the activated MnO2-diatoms would detach biofilm from wounds and, in turn, increase access of antibiotics to residual biofilm bacteria. The subsequently enhanced wound disinfection would serve to improve the efficacy of regenerative medicine to skin regeneration in wounds. We will examine this hypothesis by using the vancomycin and a pair of keratinocyte growth factor (KGF)-2 and fibroblast growth factor (FGF)-2 as a model antibiotic and regenerative medicine, respectively. Our specific aims are to: (1) evaluate the efficacy of activated MnO2-diatoms to remove biofilm in wounds, (2) examine if activated MnO2- diatoms improve the efficacy of vancomycin to prevent biofilm re-growth, and (3) investigate the extent that activated MnO2-diatoms increase the KGF2/FGF2 efficacy in stimulating skin regeneration. We will conduct each aim study using the P. aeruginosa or methicillin-resistant S. aureus biofilm-infected excisional wound of male and female CD1 mice. We will assess the biofilm removal and skin regeneration in wounds using a multimodal optical imaging system through collaboration with the Boppart group with expertise in bioimaging. We will also determine the matrix metalloproteinase-9 and tissue inhibitor to metalloproteinase levels in the wound fluid, CD34+/CD45- stem cell mobilization, pro-inflammation and edema, and minimal toxicity of SLAM under guidance by Dr. Neitzel, a dermatologist. Overall, this proposed study will significantly impact efforts to treat non-healing, biofilm-infected wounds using innovative SLAMs. In the end, this study will save wound patients from disability and death.

生物膜是一种包裹细菌菌落的保护性细胞外聚合物质