Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium

整个研究计划包含嵌入生物科学请求的专有/特权信息，这些信息不会向个人发布 政府以外的机构，但审查和评估的目的除外。 标题：银镓超薄可溶抗菌膜创面接触敷料 摘要 年，与治疗慢性和烧伤伤口有关的医疗保健费用每年超过250亿美元。 美国的生物膜被认为是慢性伤口延迟愈合的关键因素。许多 伤口具有复杂的表面，清创可能具有挑战性，留下的生物膜碎片 对抗菌治疗有抵抗力，是生物被膜复发的病灶。这突出了未被满足的 需要一种性价比高、无细胞毒性的抗生物膜创面敷料。目前还没有商业上的 临床上用于在伤口床上扩散生物膜的可用伤口敷料。嵌入 生物科学公司开发了一种独特的含银的微缩胶片伤口接触敷料并将其商业化 名为MicroLyte Ag的纳米颗粒，基于其专利的聚合物多层纳米膜技术， 符合伤口床的微观轮廓，提供与活性物质的亲密和持续接触 与伤口床配合使用，所需的银离子浓度比传统敷料低100倍 以达到无细胞毒性的治疗效果。MicroLyte Ag高效杀灭浮游细菌 并已证明在抑制生物被膜形成方面有效。然而，下一个挑战是创建一个 伤口敷料将刺激伤口中已建立的生物膜的扩散。我们的初步数据显示， 当通过聚电解质多层纳米膜输送时，Ag+和GA3+生物膜的性能提高了1000倍 与相应的局部配方相比，生物被膜CFU的减少。这项研究项目将检验这一假说 抗生物膜镓对生物膜中微生物的敏化将使非细胞毒性水平 抗菌银，杀灭被生物膜包裹的细菌。目前没有商业化的伤口敷料或 使用镓作为抗生物膜剂的局部配方。我们的初步实验表明 在48h的铜绿假单胞菌生物膜中，MicroLyte Ag-Ga原型可以实现高达4log10 CFU的减少 并在体外分散90%的≥生物膜质量，尽管释放的Ag+水平比商用的低5-10倍 抗菌敷料没有表现出任何显著的抗生物被膜活性。这项建议旨在推进 含银抗菌下一代抗菌创面敷料的研制 镓。这一阶段可行性研究的目标是：(目标1)确定银和镓的载量 MicroLyte Ag-Ga对铜绿假单胞菌和沙门氏菌的单种和多种生物膜具有抗菌活性。 无体外细胞毒性的金黄色葡萄球菌和，(AIM 2)评价MicroLyte Ag-Ga在预制棒中的分散效果 小鼠夹板伤口上的生物膜。为了这个项目，IMBED组织了一个研究团队， 在生物材料(Agarwal、Dalsin、Pranami和Abbott)、微生物学(Czuprynski)、动物方面具有丰富的专业知识 伤口模型(麦克安纳蒂)和临床伤口护理(麦克安纳蒂和舒尔)。第一期工程圆满完成 这项研究将为研究多种细菌生物膜扩散的第二阶段项目提供可行性数据 小鼠/猪创伤模型中的菌株。

The entire Research Plan contains proprietary/privileged information that Imbed Biosciences requests not be released to persons outside the Government, except for purposes of review and evaluation. Title: Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium Summary The health care costs associated with treatment of chronic and burn wounds exceeds $25 billion annually in the U.S. Biofilms are implicated as a key factor responsible for delayed healing in chronic wounds. Many wounds have complex surfaces and debridement can be challenging, leaving biofilm fragments that remain resistant to antimicrobial therapy and act as a nidus for recrudescence of biofilms. This underscores the unmet need for a cost-effective and non-cytotoxic antibiofilm wound dressing. There is currently no commercially available wound dressing that is clinically indicated for dispersal of biofilms in a wound bed. Imbed Biosciences Inc. has developed and commercialized a unique microfilm wound contact dressing with silver nanoparticles, named MicroLyte Ag, based on its patented polymeric multilayer nanofilm technology, that conforms to the micro-contours of a wound bed, provides an intimate and sustained contact of active agents with the wound bed, and requires 100x lower concentration of silver ions (compared to conventional dressings) to achieve therapeutic efficacy without cytotoxicity. MicroLyte Ag is highly effective in killing planktonic bacteria and has demonstrated efficacy in suppression of biofilm formation. However, the next challenge is to create a wound dressing that will stimulate dispersal of established biofilms in wounds. Our preliminary data shows that Ag+ and Ga3+ biofilm, when delivered through polyelectrolyte multilayer nanofilm, achieved 1000x greater reduction in biofilm CFU than a corresponding topical formulation. This research project will test the hypothesis that sensitization of microbes in biofilms by antibiofilm gallium would enable non-cytotoxic levels of antimicrobial silver to kill biofilm-encased bacteria. There is currently no commercial wound dressing or topical formulation that employs gallium as an antibiofilm agent. Our preliminary experiments have shown that MicroLyte Ag-Ga prototypes can achieve up to 4 Log10 CFU reduction in 48 h old P. aeruginosa biofilms and disperse ≥ 90% of biofilm mass in vitro, despite releasing 5-10x lower levels of Ag+ than commercial antimicrobial dressings that did not exhibit any significant antibiofilm activity. This proposal seeks to advance development of a next-generation antimicrobial-antibiofilm wound dressing containing silver and gallium. The goal of this Phase 1 feasibility research is to: (AIM 1) Identify silver and gallium loadings in MicroLyte Ag-Ga that exert antibiofilm activity against single and multispecies biofilms of P. aeruginosa and S. aureus without in vitro cytotoxicity and, (AIM 2) Evaluate efficacy of MicroLyte Ag-Ga in dispersal of preformed biofilms in splinted murine wounds. For this project, Imbed has assembled a team of researchers with substantial expertise in biomaterials (Agarwal, Dalsin, Pranami, and Abbott), microbiology (Czuprynski), animal wound models (McAnulty) and clinical wound care (McAnulty and Schurr). Successful completion of Phase 1 research will provide feasibility data for a Phase 2 project to study dispersal of biofilms of multiple bacterial strains in murine/porcine wound models.