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

基本信息

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
项目类别：
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

项目摘要

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 Imbed Biosciences 要求不得向他人透露的专有/特权信息政府以外的范围，但出于审查和评估目的除外。概括在美国，每年与治疗慢性伤口相关的医疗费用超过 250 亿美元。生物膜被认为是导致愈合延迟的关键因素。许多伤口具有复杂的表面。清创可能具有挑战性，留下的生物膜碎片仍然对抗菌治疗有抵抗力，作为生物膜复发的病灶，目前尚无有效的市售局部制剂。 Imbed Biosciences 的研究由 NIH 和私募股权投资资助，开发出了具有独特形状因数的超薄伤口接触基质。是一种 20-25 µm 厚的生物可吸收聚合物多层薄膜，可以无痛地放置在伤口中，并且可以超薄基质可在几天内溶解，与底层轮廓紧密贴合。 Imbed 最近获得了 FDA 的许可，可提供生物活性分子的局部和长期释放。基于该平台的 Microlyte® Ag 伤口基质的清除，其中基质浸有银原位形成的纳米颗粒已成功用于治愈数千名患者的慢性伤口。美国它可以有效地杀死体外和小鼠感染伤口模型中的多种细菌。在我们最近发表的研究中，我们证明了它不能有效杀死生物膜中的细菌。基于这些科学发现和成功的临床，银和镓 (Ga3+) 离子消除生物膜的作用。在医院采用 Microlyte® Ag 矩阵超薄外形，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，可以在伤口上发挥银和镓的协同作用第二阶段研究的第一年确定了 10 µg/cm2 银纳米颗粒和 140 或 210 µg/cm2 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 48 小时成熟的铜绿假单胞菌生物膜中提供 > 4 log10 CFU 减少，并且 > 3 小鼠伤口模型中 CFU 减少了 log10，并且 (2) 根据 ISO 10993 指南具有生物相容性。这些结果证明了我们放大镓和银离子对抗生物膜的协同作用的科学前提通过将细菌呈现在微型基质中，在第二年完成第二阶段研究将导致最终确定一种生物相容性原型，可有效杀死猪伤口模型中的多种生物膜根据我们的 FDA 预分会议，该 CRP 研究提案旨在建立质量。控制、验证产品设计、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 510k de Novo 对于该项目，Imbed 组建了一支在该领域拥有丰富专业知识的研究人员团队。生物材料（Agarwal、Pranami、Dalsin 和 Abbott）、微生物学（Czuprynski）、动物伤口模型（McAnulty）和临床伤口护理（McAnulty 和 Schurr）。