Antibacterial Molecular Coatings Pre-Fabricated for Biologic Wound Dressings

描述（由申请人提供）：在美国，与治疗慢性和烧伤伤口相关的医疗负担每年超过250亿美元，涉及860万患者。伤口护理的一个最新进展是开发了含有动物源性成分（如胶原蛋白）的“生物敷料”。生物敷料在烧伤和慢性伤口中具有优异的上级愈合率。然而，与它们的使用相关的是细菌感染的显著率（高达20%），导致愈合时间增加，患者疼痛和治疗费用增加。因此，具有广泛推进伤口护理的潜力的未满足的需求是结合广谱抗菌剂如银的生物敷料的制造。银制剂在医院中广泛用于治疗伤口感染。然而，用于将稳定形式的银掺入常规敷料中的方法不能适用于生物敷料，因为所涉及的化学和物理处理损害了它们的结构和活性。 为了满足这些需求，Embed Biosciences，Inc.正在开发一种平台技术，该技术能够将含有精确负载生物活性剂的分子薄聚合物膜整合到伤口敷料和皮肤替代品上。在第一阶段的提案中，Embed将优化这项技术，将银纳米颗粒整合到生物伤口敷料上（其中的范例将是Biobrane（R），一种领先的生物敷料），这样它们就可以抑制细菌定植，而不会影响细胞的生长和修复。Embed方法的创新包括：（i）纳米厚聚合物膜的工程设计，该聚合物膜浸渍有精确负载的银纳米颗粒，可发挥抗菌活性而无细胞毒性;以及（ii）将含有银纳米颗粒的聚合物膜转移到生物敷料上，而不会损害其结构和生物活性。初步数据显示，Imbed的银纳米颗粒涂层释放的银浓度比传统银敷料释放的浓度低两个数量级，当整合到Biobrane（R）上时，可在24小时内杀死其表面99.999%的细菌（6 log 10），并预防小鼠实验感染伤口中的败血症。在这个项目中，Imbed组建了一个非常有成就的研究团队，他们在生物材料（Agarwal和Abbott）、微生物学（Czuprynski）、动物伤口模型（McAngland和Murphy）和临床伤口护理（McAngland，Murphy和Schurr）方面具有丰富的专业知识。在该提案中，含有银纳米颗粒的聚合物膜将集成在Biobrane（R）上。在目标1中，将优化银载量，使其在体外试验中具有抗微生物活性而无细胞毒性。目的2将通过鉴定不会引起全身毒性、促进正常伤口愈合并促进模型感染伤口愈合的银负载，提供小鼠中的安全性和有效性数据。这些目标的完成将有助于与客户进行进一步的商业化讨论，并为II期研究提供关键的可行性数据（包括更广泛的细菌菌株/伤口模型）。 公共卫生相关性：在美国，伤口管理是一个巨大的经济和医疗负担。SBIR申请中描述的研究将实现一类新的混合伤口敷料，该敷料将生物和抗菌伤口敷料的益处联合收割机结合在一起。新的伤口敷料将加快伤口闭合，减少抗生素的使用，最大限度地减少敷料更换和护理时间，并降低患者疼痛，药物费用和住院时间。

DESCRIPTION (provided by applicant): The health care burden associated with treatment of chronic and burn wounds amounts to more than $25 billion annually in the U.S., involving 8.6 million patients. One recent advance in wound care has been the development of "biologic dressings" that contain animal-derived components such as collagen. Biologic dressings provide superior healing rates in burns and chronic wounds. Associated with their use, however, is a significant rate (up to 20%) of bacterial infection that results in increased healing time, patient pain, and treatment costs. Therefore, an unmet need with the potential to broadly advance wound care is the fabrication of biologic dressings that incorporate broad-spectrum antibacterial agents such as silver. Silver formulations are widely used in hospitals for treatment of wound infections. However, approaches used to incorporate stabilized forms of silver into conventional dressings cannot be adapted to biologic dressings because the chemical and physical processing involved compromises their structure and activity. To address these needs, Imbed Biosciences, Inc. is developing a platform technology that enables integration of molecularly-thin polymer films containing precise loadings of bioactive agents onto wound dressings and skin substitutes. In this Phase 1 proposal, Imbed will optimize this technology to integrate silver nanoparticles onto biologic wound dressings (the exemplar of which will be Biobrane(R), a leading biologic dressing) such that they inhibit bacterial colonization without compromising cellular growth and repair. The innovation in Imbed's approach includes: (i) the engineering of nanometer-thick polymer films impregnated with precise loadings of silver nanoparticles that exert antimicrobial activity without cytotoxicity; and (ii) transfer of polymer films containing silver nanoparticles onto biologic dressings without compromising their structure and bioactivity. Preliminary data shows that Imbed's silver nanoparticle-coating that releases concentrations of silver two orders of magnitude lower than those released from conventional silver dressings, when integrated on Biobrane(R), killed 99.9999% bacteria (6 log10) on its surface within 24 hr and prevented sepsis in experimentally infected wounds in mice. For this project, Imbed has assembled a highly accomplished team of researchers with substantial expertise in biomaterials (Agarwal and Abbott), microbiology (Czuprynski), animal wound models (McAnulty and Murphy) and clinical wound care (McAnulty, Murphy and Schurr). In this proposal, polymer films containing silver nanoparticles will be integrated on Biobrane(R). In Aim 1, silver loadings that lead to antimicrobial activity without cytotoxicity in in-vitro assays will be optimized. Aim 2 will provide safety and efficacy data in mice by identifying silver loadings that do not cause systemic toxicity, facilitate normal wound healing, and promote healing of model infected wounds. Completion of these aims will enable further commercialization discussions with customers and provide critical feasibility data for Phase 2 studies (to include a wider range of bacterial strains/wound models). PUBLIC HEALTH RELEVANCE: Wound management presents a huge economic and healthcare burden in the U.S. The research described in this SBIR application will lead to the realization of a new class of hybrid wound dressings that combine the benefits of biologic and antimicrobial wound dressings. The new wound dressings will expedite wound closure, reduce use of antibiotics, minimize dressing changes and nurse time, and lower patient pain, medication costs and length of hospital stays.