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

• 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
• 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

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(申请人提供)：烧伤、创伤和手术伤口的临床感染是巨大的经济和医疗负担。在美国，外科创面的感染率为2-5%，烧伤创面的感染率高达20%。目前的护理标准是密集和昂贵的，包括频繁地局部应用抗菌药(每天两次)，并痛苦地更换敷料。含有抗菌剂的昂贵高级敷料会沉积有毒浓度的抗菌剂(通常为每天100μg/cm~2的银)，从而损害伤口愈合。当与生物敷料一起使用时，这些护理标准仍然会导致高达20%的感染率。有一种严重的未得到满足的制剂需求，这些制剂提供：长期释放抗菌剂而不会在伤口中形成有毒物质；支持先进敷料的广泛治疗使用；以及减少频繁的敷料更换。IMBED生物科学公司第一阶段研究的成功完成导致了一种独特的银质伤口敷料产品概念的发明和开发，该产品概念基于IMBED正在申请专利的纳米膜技术：具有独特稳定的银纳米颗粒的可溶解微膜伤口接触式敷料。缩微胶片敷料的一个主要特点是它含有少量的银，使活性银与伤口床更紧密地接触，对伤口毒性较小，使用起来更温和。微缩薄膜敷料符合伤口床的微轮廓，以提供活性银离子的“局部”和“长期”释放。低成本的制作和低成本使缩微胶片敷料成为与昂贵的银敷料配合使用的高性价比的替代品(节省60%)，用于湿润和生物伤口敷料。一期研究结果表明，缩微胶片银敷料(1)杀灭包括MRSA在内的几种细菌的4log10CFU，(2)提供至少4天的杀菌银的持续释放， (3)未显示可检测到的体外细胞毒性或体内全身毒性，(4)允许通过重新上皮化实现正常的伤口愈合，(5)显著减少微生物定植，并在生物合成敷料下加速受污染小鼠伤口的愈合。与其他银敷料的比较表明，微缩薄膜敷料释放的银比大多数现有敷料少100倍，具有同等或更好的抗菌活性，并允许正常的伤口再上皮化，不像一些银敷料。基于这些来自第一阶段研究的充满希望的数据，以及临床医生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、优化和验证用于高通量制造(Aim 1)、广谱抗菌活性(Aim 2)、生物兼容性(Aim 3)和猪伤口愈合(Aim 4)的缩微胶片银敷料产品概念。我们已经组建了一支由材料科学家、微生物学家、兽医和医学外科医生组成的团队，他们有着成功的合作历史。第二阶段研究的完成将为微缩胶片敷料提供优化的设计和数据集，这是生产放大和监管批准人体临床试验所需的。