Antibacterial molecular coatings pre-fabricated for biologic wound dressings

用于生物伤口敷料的预制抗菌分子涂层

基本信息

批准号：
8648458
负责人：
Ankit Agarwal
金额：
$ 77.52万
依托单位：
IMBED BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8648458
关键词：
Analgesics Anions Anti-Bacterial Agents Antibiotics Beds Biological Dressings Burn Trauma Burn injury Caring Cessation of life Chlorhexidine Clinical Clinical Trials Collaborations Data Data Set Deposition Dermal Development Drug Formulations Economics Exudate Family suidae Feedback Frequencies Gel Healed Health Healthcare Human Impaired wound healing In Vitro Infection Infection prevention Ions Lead Legal patent Length of Stay Marketing Mechanics Medical Microbe Microfilm Microfilming Molecular Mus Nanotechnology Nurses Ointments Operative Surgical Procedures Pain Patients Phase Polymers Process Property Proteins Recording of previous events Research Savings Scientist Sepsis Silver Small Business Innovation Research Grant Solutions Staining method Stains Sterile coverings Surface Surgeon Surgical wound Technology Therapeutic Uses Thick Time Tissue Stains Tissues Topical Antibiotic Topical application Toxic effect Translational Research Trauma Water Wound Healing Wound Infection antimicrobial bactericide base biomaterial compatibility care burden cost cytotoxic cytotoxicity design healing health care economics health economics improved in vivo irritation killings manufacturing scale-up methicillin resistant Staphylococcus aureus microbial colonization nanoparticle pathogen prevent standard of care tissue regeneration topical antiseptic wound

项目摘要

DESCRIPTION (provided by applicant): Clinical infections in burn, trauma and surgical wounds represent a huge economic and health care burden. In the U.S., there is a 2-5% infection rate in surgical wounds and up to a 20% rate in burn wounds. The current standard of care is intensive and expensive, involving frequent topical application of antimicrobials (twice daily) with painful dressing changes. Expensive advanced dressings with antimicrobials impair wound healing by depositing toxic concentrations of antimicrobials (typically >100 μg/cm2 of silver/day). When used with biologic dressings, these standards of care still result in up to 20% infection rate. There is a critical unmet need for formulations that provide: long-term release of antimicrobials without toxic build up in wounds; support broad therapeutic use of advanced dressings; and reduce frequent dressing changes. Successful completion of Phase 1 research at Imbed Biosciences has resulted in the invention and development of a unique silver wound dressing product concept based on Imbed's patent-pending nanofilm technology: dissolvable microfilm wound contact dressing with uniquely stabilized silver nanoparticles. A key feature of the microfilm dressing is that it contains a small quantity of silver that provides more intimate contact of active silver with the wound bed, which is less toxic to the wound and gentler to use. The microfilm dressing conforms to the micro-contours of the wound bed to provide 'localized' and 'long-term' release of active silver ions. Inexpensive fabrication and low cost of goods makes the microfilm dressing a cost-efficient alternative (>60% savings) to expensive silver dressings for use with moist and biologic wound dressings. Results of Phase I research demonstrated that the microfilm silver dressing (1) kills 4 log10 CFU of several bacterial species, including MRSA, (2) provides sustained release of bactericidal silver for at least 4 days, (3) does not show detectable in-vitro cytotoxicity or in-vivo systemic toxicity, (4) allows normal wound healing by re-epithelialization, and (5) significantly reduces microbial colonization and expedites wound closure under biosynthetic dressings in contaminated murine wounds. Comparison to other silver dressings showed that the microfilm dressing releases up to 100x less silver than most available dressings, provides equivalent or better antibacterial activity, an allows normal wound re-epithelialization unlike some silver dressings. Based on this promising data from Phase 1 research, and enthusiastic feedback from clinicians and potential commercial partners, Phase II research aims to further develop, optimize, and validate the Microfilm Silver Dressing product concept for high-throughput fabrication (Aim 1), broad-spectrum antimicrobial activity (Aim 2), biocompatibility (Aim 3), and porcine wound healing (Aim 4). We have assembled a team of material scientists, microbiologists, and veterinary and medical surgeons, with a history of successful collaboration. Completion of Phase II research will provide optimized design and data sets for microfilm dressings required for manufacturing scale-up and regulatory approval for human clinical trials.

描述（由申请人提供）：烧伤、创伤和手术伤口的临床感染带来了巨大的经济和医疗负担。在美国，手术伤口的感染率为 2-5%，烧伤的感染率高达 20%。目前的护理标准是密集且昂贵的，频繁局部使用抗菌药物（每天两次），昂贵的高级抗菌敷料会沉积有毒浓度的抗菌药物，从而损害伤口愈合。（通常 >100 μg/cm2 的银/天）与生物敷料一起使用时，这些护理标准仍会导致高达 20% 的感染率，而对于能够长期释放抗菌剂的配方来说，这一需求尚未得到满足。不会在伤口中积累毒性；支持先进敷料的广泛治疗使用；并减少频繁更换敷料的情况，Imbed Biosciences 成功完成了基于银伤口敷料产品概念的发明和开发。 Imbed 正在申请专利的纳米薄膜技术：具有独特稳定的银纳米颗粒的可溶性微薄膜伤口接触敷料。微薄膜敷料的一个关键特点是它含有少量的银，可以使活性银与创面床更紧密地接触。对伤口无毒且使用更温和。微胶片敷料贴合伤口床的微轮廓，可“局部”和“长期”释放活性银离子，且制造成本低廉。商品成本使得微胶片敷料成为昂贵的银敷料的经济替代品（节省 60% 以上），与湿性和生物伤口敷料一起使用，第一阶段研究的结果表明，微胶片银敷料 (1) 可杀死 4 log10 CFU。包括 MRSA 在内的多种细菌，(2) 可持续释放杀菌银至少 4 天， (3) 没有表现出降低可检测的体外细胞毒性或体内全身毒性，(4) 通过上皮化使伤口正常愈合，(5) 在受污染的小鼠伤口中，在生物合成敷料下显着微生物定殖并加速伤口闭合。与其他银敷料相比，微缩胶片敷料释放的银比大多数可用敷料少 100 倍，提供同等或更好的抗菌活性，并允许正常伤口与某些银敷料不同的是，基于第一阶段研究的有希望的数据以及来自封建和潜在商业合作伙伴的热情反馈，第二阶段研究旨在进一步开发、优化和验证微电影银敷料产品概念以实现高通量。制造（目标 1）、广谱抗菌活性（目标 2）、生物相容性（目标 3）和猪伤口愈合（目标 4）我们组建了一个材料科学家团队，具有成功合作历史的微生物学家、兽医和外科医生，完成第二阶段研究将为人体临床试验的生产规模扩大和监管批准提供优化的设计和数据集。