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 在政府以外的地方，但作检讨和评估之用除外。 好了！ 摘要 在美国，与治疗慢性伤口相关的医疗费用每年超过250亿美元。 生物膜被认为是延迟愈合的关键因素。许多伤口的表面很复杂 清创可能是具有挑战性的，留下对抗菌治疗仍然具有抗药性的生物膜碎片 作为生物膜复发的病灶。目前还没有商业上可用的有效局部制剂 伤口内生物膜的扩散。由NIH和私募股权投资资助的嵌入式生物科学公司的研究， 导致了一种具有独特形状系数的超薄伤口接触矩阵的开发。MicroLyte®矩阵 是一种20-25微米厚的可溶解聚合物多层膜，可以无痛地放置在伤口上，可以 设计成可以在几天内溶解。超薄的矩阵紧密地符合下面的轮廓 提供局部和长期释放生物活性分子的伤口床。Emed最近获得了FDA 基于该平台的MicroLyte®Ag缠绕基质的清除，其中基质浸银 纳米颗粒在原位形成。它已经成功地用于修复数以千计的患者的慢性伤口 它在体外和小鼠感染伤口模型中有效地杀灭了广泛的细菌。然而， 它在杀灭包裹在生物膜中的细菌方面并不有效。在我们最近发表的研究中，我们展示了协同效应 银和镓(GA3+)离子在消除生物膜方面的作用。基于这些科学发现和成功的临床 MicroLyte®Ag基质超薄外形因数在医院中的应用，本SBIR项目的目标是开发一种 经济、易于放置、可溶解的伤口接触矩阵，可在 伤口表面以消除生物膜。第一阶段可行性研究的结果证明，MicroLyte Matrix，当 在聚合物多层膜中战略性地浸渍无毒的银纳米颗粒和镓，是 能够在体外将4log10cfu的细菌分散在混合生物膜中。在延迟伤口愈合模型中 在小鼠身上，这种基质在治疗3天内消除了预先建立的坚固生物膜中90%的细菌。 这些结果证明了我们放大镓和银离子配对抗生物膜协同作用的科学前提。 通过将细菌呈现在微尺度的矩阵中。阶段1的结果为追求阶段提供了强有力的支持 2优化MicroLyte基质设计，使其能够更快地去除伤口床中的生物膜。 第二阶段研究的目标是：(1)Tailor MicroLyte矩阵，用于更高的负载和延长银的释放 和镓，(2)筛选基质中银和镓的生物相容性极限，(3)筛选剂量响应 体外抗混合生物膜，(4)优化生物膜在小鼠夹板伤口中的分散 以及(5)评价感染生物膜的猪伤口模型的愈合效果。对于此项目，嵌入 组建了一支在生物材料(Agarwal、Pranami、Dalsin和 雅培)、微生物学(Czuprynski)、动物伤口模型(McAnty)和临床伤口护理(McAnty和 Schurr)。成功完成第二阶段研究将产生稳定的MicroLyte Ag/Ga矩阵 安全性和有效性数据，可以很容易地转化为人类临床研究，供FDA批准。 好了！

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 dissolvable 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. Results of Phase 1 feasibility study documented that MicroLyte Matrix, when strategically impregnated with non-toxic loadings of silver nanoparticles and gallium in polymeric multilayers, is able to disperse >4 log10 CFUs of bacteria in a mixed species biofilm in vitro. In a delayed wound healing model in mice, such a matrix eliminated >90% of bacteria in a pre-established robust biofilm within 3 days of treatment. 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. Phase 1 results provide strong support for pursuing a Phase 2 study to optimize the MicroLyte Matrix design that can obtain faster elimination of biofilms in the wound bed. The goals of Phase 2 research are: (1) Tailor MicroLyte Matrix for higher loadings and extended release of silver and gallium, (2) Screen biocompatibility limits of silver and gallium in the matrix, (3) Screen dose response against mixed species biofilms in vitro, (4) Optimize loadings for dispersal of biofilms in a murine splinted-wound model, and (5) Evaluate effect on healing in a porcine wound model infected with biofilms. 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). Successful completion of Phase 2 research will result in a shelf-stable MicroLyte Ag/Ga matrix with safety and efficacy data that can be readily translated into human clinical studies for FDA clearance. !