Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium

含银镓的超薄可溶性抗菌膜伤口接触敷料

• 批准号: 10259892
• 负责人: Ankit Agarwal
• 金额: $ 40.51万
• 依托单位: IMBED BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259892
• 关键词: Adoption; Animals; Antibiotics; Antimicrobial Resistance; Bacteria; Biocompatible Materials; Biological Sciences; Chronic; Clinical; Complex; Data; Debridement; Development; Devices; Discipline of Nursing; Economics; Effectiveness; Engineering; Evaluation; Family suidae; Film; Formulation; Frequencies; Funding; Gallium; Government; Guidelines; Health Care Costs; Healthcare; Hospitals; Impaired healing; In Situ; In Vitro; Investments; Ions; Length of Stay; Life; Microbial Biofilms; Microbiology; Mus; Operative Surgical Procedures; Oral cavity; PF4 Gene; Pain; Painless; Patients; Performance; Persons; Phase; Polymers; Preparation; Privatization; Process; Protocols documentation; Pseudomonas aeruginosa; Publications; Publishing; Quality Control; Rattus; Recrudescences; Reproducibility; Research; Research Personnel; Research Proposals; Resistance; Safety; Silver; Small Business Innovation Research Grant; Source; Sterile coverings; Sterilization; Surface; Thick; Time; Tissues; Topical Antibiotic; Treatment Cost; Treatment Efficacy; United States National Institutes of Health; Validation; Work; Wound Infection; Wound models; antimicrobial; base; biodegradable polymer; biomaterial compatibility; burn wound; chronic wound; design; effectiveness validation; experience; fighting; healing; improved; in vivo; meetings; microbial; nanoparticle; physical property; polymicrobial biofilm; pre-clinical; prototype; skin wound; standard of care; synergism; systemic toxicity; wound; wound bed; wound biofilm; wound care; wound closure; wound healing; wound treatment

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).

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。 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微米厚的可生物吸收的多层聚合物薄膜，可以无痛地放置在伤口上，可以 被设计成在几天内溶解。超薄的矩阵与下面的轮廓紧密一致 伤口床提供局部和长期的生物活性分子释放。Emed最近获得了FDA 基于该平台的Microlyte®Ag缠绕基质的清除，其中基质是浸银的 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 在医院采用Microlyte®Ag基质超薄外形因数，此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。第二阶段研究的第一年确定了10微克/平方厘米的银纳米颗粒和 140或210微克/平方厘米的镓作为Microlyte基质的最佳生物相容性载量，并表明这些 原型-(1)提供了体外培养48h的成熟铜绿假单胞菌生物膜的&gt；4log10 CFU减少和&gt；3 小鼠创伤模型中的log10CFU减少，以及(2)符合ISO 10993指南的生物相容性。 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。在第二年完成第二阶段研究后， 敲定一种在猪创伤模型中有效杀死多种生物膜的生物相容性原型 并加速愈合。基于我们的FDA预分会，这份CRP研究提案旨在建立质量 控制、验证产品设计、制造过程、建立电子束灭菌规程并收集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 510k de Novo 申请。为了这个项目，IMBED组建了一支研究团队，他们拥有丰富的专业知识 生物材料(Agarwal、Pranami、Dalsin和Abbott)、微生物学(Czuprynski)、动物创伤模型 和临床伤口护理(麦克阿纳尔蒂和舒尔)。