Antibacterial molecular coatings pre-fabricated for biologic wound dressings

描述（由申请人提供）：烧伤、创伤和手术伤口中的临床感染代表了巨大的经济和卫生保健负担。在美国，在外科伤口中有2-5%的感染率，在烧伤伤口中高达20%。当前的护理标准是密集且昂贵的，涉及频繁局部应用抗菌药物（每天两次）以及痛苦的敷料更换。含有抗菌剂的昂贵高级敷料通过沉积毒性浓度的抗菌剂（通常>100 μg/cm 2的银/天）损害伤口愈合。当与生物敷料一起使用时，这些护理标准仍然导致高达20%的感染率。对于提供以下内容的制剂存在关键的未满足的需求：长期释放抗菌剂而不会在伤口中产生毒性;支持先进敷料的广泛治疗用途;以及减少频繁的敷料更换。在Embed Biosciences成功完成第一阶段研究后，发明和开发了一种独特的银伤口敷料产品概念，该产品概念基于Embed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敷料。微膜敷料的一个关键特征是它含有少量的银，这提供了活性银与伤口床的更紧密接触，这对伤口的毒性更小，使用更温和。微膜敷料符合创面的微轮廓，以提供活性银离子的“局部”和“长期”释放。廉价的制造和低成本的商品使得微膜敷料成为与湿性和生物伤口敷料一起使用的昂贵的银敷料的具有成本效益的替代品（节省>60%）。第一阶段研究的结果表明，微膜银敷料（1）可杀死4 log 10 CFU的多种细菌物种，包括MRSA，（2）可持续释放杀菌银至少4天， (3)没有显示出可检测的体外细胞毒性或体内全身毒性，（4）允许通过再上皮化的正常伤口愈合，和（5）在污染的鼠伤口中，在生物合成敷料下显著减少微生物定植并加速伤口闭合。与其他含银敷料的比较表明，微膜敷料释放的银比大多数现有敷料少100倍，提供等同或更好的抗菌活性，并且与某些含银敷料不同，允许正常的伤口上皮再生。基于1期研究的这些有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，II期研究旨在进一步开发、优化和验证Microfilm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）。我们组建了一个由材料科学家、微生物学家、兽医和外科医生组成的团队，拥有成功合作的历史。II期研究的完成将为微膜敷料提供优化的设计和数据集，这些设计和数据集是人体临床试验的生产规模扩大和监管批准所需的。

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.