Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium

整个研究计划包含Embed Biosciences要求不得向个人发布的专有/特权信息 政府以外的，但为审查和评估的目的除外。 总结 在美国，与治疗慢性伤口相关的医疗保健费用每年超过250亿美元。 生物膜被认为是延迟愈合的关键因素。许多伤口表面复杂 并且清创术可能具有挑战性，留下的生物膜碎片仍然对抗菌治疗具有抗性， 作为生物膜复发的病灶。没有市售的局部制剂有效地用于 伤口中生物膜的分散。由NIH和私募股权投资资助的嵌入式生物科学公司的研究， 已经导致了具有独特形状因子的无创接触矩阵的发展。Microlyte®基质 是一种20-25 μ m厚的生物可吸收聚合物多层膜，可无痛放置在伤口中， 可以在几天内溶解该矩阵密切符合基本轮廓 以提供生物活性分子的局部和长期释放。最近获得FDA 基于该平台的Microlyte® Ag缠绕基质的清除率，其中基质浸渍有银 纳米粒子在原位形成。它已被成功地用于治疗数千名患者的慢性伤口， 美国它在体外和小鼠感染伤口模型中可有效杀灭广谱细菌。然而，在这方面， 它不能有效地杀死包裹在生物膜中的细菌。在我们最近发表的研究中， 银和镓（Ga 3+）离子在消除生物膜中的作用。基于这些科学发现和成功的临床 在医院采用Microlyte® Ag基质微球形状因子，该SBIR项目的目标是开发一种 经济、易于放置、可溶解的伤口接触基质，其可以在一个或多个表面上部署银和镓的协同作用。 伤口表面，以消除生物膜。第2阶段研究的第1年确定了10 μg/cm 2的银纳米颗粒， 140或210 µg/cm 2镓作为Microlyte Matrix的最佳生物相容性负载，并表明这些 原型-（1）在体外在48小时的铜绿假单胞菌成熟生物膜中提供> 4 log 10 CFU减少， 小鼠伤口模型中的log 10 CFU减少，和（2）根据ISO 10993指南具有生物相容性。 这些结果证明了我们的科学前提，放大协同配对镓和银离子对生物膜 将它们呈现在微尺度基质中。在第二年完成第二阶段的研究将导致 最终确定一种生物相容性原型，其在猪伤口模型中有效杀死多物种生物膜 加速愈合根据我们的FDA预提交会议，该CRP研究提案旨在建立质量 控制，确认产品设计，制造工艺，建立电子束灭菌方案并收集GLP 在质量控制下生产的产品的临床前性能数据，用于加速FDA 510 k de Novo 应用程序.为了这个项目，嵌入式已经组建了一个研究人员团队，他们在以下方面具有丰富的专业知识： 生物材料（Agarwal、Pranami、Dalsin和Abbott）、微生物学（Czuprynski）、动物伤口模型 （McAngland）和临床伤口护理（McAngland和Schurr）。

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. SUMMARY The health care costs associated with treatment of chronic wounds exceeds $25 billion annually in the U.S. Biofilms are implicated as a key factor responsible for delayed healing. 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. There is no commercially available topical formulation effective in dispersal of biofilms in wounds. Research at Imbed Biosciences, funded by NIH and private equity investments, has resulted in the development of an ultrathin wound contact matrix with a unique form factor. Microlyte® Matrix is a 20-25 µm-thick bioresorbable polymeric multilayer film that allows painless placement in wounds and can be engineered to dissolve over several days. The ultrathin matrix conforms intimately to the underlying contours of a wound bed to provide localized and long-term release of bioactive molecules. Imbed recently obtained FDA clearance for Microlyte® Ag wound matrix based on that platform, where the matrix was impregnated with silver nanoparticles formed in situ. It has been used successfully to heal chronic wounds in thousands of patients in U.S. It is effective in killing a broad spectrum of bacteria in vitro and in infected wound models in mice. However, it is not effective in killing bacteria encased in biofilms. In our recently published study, we demonstrated synergy of silver and gallium (Ga3+) ions in eliminating biofilms. Based on those scientific findings and successful clinical adoption of Microlyte® Ag matrix ultrathin form factor in hospitals, objective of this SBIR project is to develop an economic, easy to place, dissolvable wound contact matrix that can deploy synergy of silver and gallium on a wound surface to eliminate biofilms. Year 1 of Phase 2 research identified 10 µg/cm2 silver nanoparticles and 140 or 210 µg/cm2 gallium as optimal biocompatible loadings for Microlyte Matrix and showed that these prototypes- (1) provided > 4 log10 CFU reduction in 48 h old mature biofilms of P. aeruginosa in vitro and > 3 log10 CFU reduction in a mice wound model, and (2) were biocompatible in accordance to ISO 10993 guidelines. These results proved our scientific premise of amplifying synergy in pairing gallium and silver ions against biofilm bacteria by presenting them in a microscale matrix. Completion of Phase II research in Year 2 will result in finalizing one a biocompatible prototype that is effective in killing multispecies biofilm in porcine wound models and accelerate healing. Based on our FDA pre-sub meeting, this CRP research proposal aims to establish quality controls, validate the product design, fabrication process, set up e-beam sterilization protocol and collect GLP preclinical performance data on product manufactured under quality control, for accelerate an FDA 510k de Novo application. For this project, Imbed has assembled a team of researchers with substantial expertise in biomaterials (Agarwal, Pranami, Dalsin, and Abbott), microbiology (Czuprynski), animal wound models (McAnulty) and clinical wound care (McAnulty and Schurr).