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: 8253391
• 负责人: Ankit Agarwal
• 金额: $ 32.65万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253391
• 关键词: Address; Agar; Analgesics; Animals; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Area; Bacteria; Bacterial Infections; Beds; Biocompatible Materials; Biological Assay; Biological Dressings; Burn injury; Caring; Chemicals; Chronic; Clinic; Clinical; Clinical Trials; Collagen; Data; Dermal; Development; Diabetic mouse; Diffusion; Drug Formulations; Engineering; Excision; Family suidae; Film; Generic Drugs; Healed; Healthcare; Hospitals; Human; Hybrids; In Vitro; Infection; Lead; Legal patent; Length of Stay; Licensing; Manufacturer Name; Mechanics; Medical Device; Methods; Microbiology; Modeling; Molecular; Mus; Nurses; Pain; Patients; Peptides; Performance; Phase; Polymers; Process; Pseudomonas aeruginosa; Relative (related person); Research; Research Personnel; Safety; Saline; Sepsis; Silver; Skin Substitutes; Small Business Innovation Research Grant; Staphylococcus aureus; Sterile coverings; Structure; Surface; Technology; Testing; Thick; Time; Tissues; Toxic effect; Translations; Treatment Cost; Wound Healing; Wound Infection; antimicrobial; antimicrobial drug; bactericide; base; care burden; cell growth; commercialization; cost; cytotoxicity; healing; health care economics; in vitro Assay; innovation; killings; methicillin resistant Staphylococcus aureus; nanometer; nanoparticle; phase 2 study; physical process; pre-clinical; prevent; repaired; scaffold; tissue regeneration; wound; wound cleaning

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.

描述（由申请人提供）：在美国，与慢性和烧伤伤口治疗相关的卫生保健负担每年超过250亿美元，涉及860万患者。伤口护理的一个最新进展是“生物敷料”的发展，这种敷料含有动物来源的成分，如胶原蛋白。生物敷料在烧伤和慢性伤口中提供优越的愈合率。然而，与它们的使用相关的是细菌感染的显著率（高达20%），导致愈合时间延长，患者疼痛和治疗费用增加。因此，一个未满足的需求与潜在的广泛推进伤口护理是制造生物敷料纳入广谱抗菌剂，如银。银制剂在医院广泛用于治疗伤口感染。然而，用于将稳定形式的银纳入传统敷料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会损害其结构和活性。为了满足这些需求，Imbed Biosciences, Inc.正在开发一种平台技术，可以将分子薄的聚合物薄膜集成到伤口敷料和皮肤替代品上，其中包含精确装载的生物活性剂。在这个第一阶段的提案中，Imbed将优化这项技术，将银纳米颗粒整合到生物伤口敷料中（其范例将是生物膜(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影响细胞的生长和修复。Imbed方法的创新包括：(i)纳米厚聚合物薄膜的工程设计，其中浸染了精确负载的银纳米颗粒，可以发挥抗菌活性而不产生细胞毒性；（ii）将含银纳米粒子的聚合物薄膜转移到生物敷料上，而不影响其结构和生物活性。初步数据表明，Imbed的银纳米颗粒涂层释放的银浓度比传统银敷料释放的银浓度低两个数量级，当与生物膜(R)结合在一起时，在24小时内杀死其表面99.9999%的细菌（6 log10），并防止实验感染小鼠伤口的败血症。为了这个项目，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（McAnulty和Murphy）和临床伤口护理（McAnulty、Murphy和Schurr）方面具有丰富的专业知识。在这个提议中，含有银纳米粒子的聚合物薄膜将集成在生物膜(R)上。在Aim 1中，将优化银负载，使其在体外测定中具有抗菌活性而不具有细胞毒性。Aim 2将通过鉴定不引起全身毒性、促进正常伤口愈合和促进模型感染伤口愈合的银负载，提供小鼠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，并为二期研究（包括更广泛的细菌菌株/伤口模型）提供关键的可行性数据。