Antimicrobial Hydrogels for Prevention of Surgical Site Infections (SSIs)

描述(由申请人提供)：手术部位感染(SSI)是外科手术的主要并发症。SSIS导致患者发病率和死亡率，并给医疗保健带来重大负担。尽管预防性护理的标准很高，但伤口感染仍然是一个严重的问题。外科手术切口打破了宿主的防御屏障，增加了组织中的微生物污染。可以直接应用于手术伤口的生物相容抗菌屏障可以极大地减少感染。微生物科学家与加州大学洛杉矶分校生物工程学教授蒂莫西·J·戴明合作，正在开发自组装成分层结构的嵌段共聚肽，以实现这一目标。Amicrobe的主要候选产品是新型嵌段共聚肽，它们自组装成独特的抗菌水凝胶。值得注意的是，这些物理水凝胶不是共价交联的，因此，在(轻微)变形时可以流动以填充伤口空洞并迅速重新凝胶化。我们方法的一个优点是能够设计化学和物理特性(例如分层结构)，这可能会提高疗效和安全性。初步数据表明，我们的铅水凝胶具有广泛的抗菌作用，在SSI模型中有效，并与组织生物相容。我们的最终产品将设计为易于使用，抗菌活性持续时间，以及 支持伤口愈合。在手术缝合前直接应用于创面空洞可以显著减少浅部和深部切口SSI和器官间隙SSI的数量。Amicrobe的水凝胶产品还可以帮助预防创伤伤口和慢性伤口的感染，如糖尿病足部溃疡。这些第一阶段研究的目标是选择和制定一个可供进一步开发的主要候选产品。具体地说，我们正在扩大对三名密切相关候选人的综合，以便在遴选过程中进行批判性研究。将分析化学性质，并将在多种浓度和配方下评估物理性质。选定的制剂将在预防伤口感染的SSI模型的试点研究中进行测试。将选择一种先导化合物。预计第二阶段的研究将集中在大规模合成、额外的SSI模型和毒理学上。 公共卫生相关性：手术部位感染(SSI)导致患者发病率和死亡率，并给医疗保健系统带来重大负担。外科手术切口打破了宿主的防御屏障，增加了组织中的微生物污染。为了预防感染，Amicrobe正在开发一种新型的生物兼容水凝胶，它将补充当今的护理标准，并在手术部位提供抗菌屏障保护。Amicrobe的独特产品还可能有助于防止创伤伤口以及糖尿病足部溃疡等慢性伤口的感染。

DESCRIPTION (provided by applicant): Surgical site infections (SSIs) are a leading complication of surgery. SSIs cause patient morbidity and mortality, and place a significant burden on healthcare. Despite high standards of preventive care, wound infections are a serious problem. Surgical incisions break host defense barriers and increase microbial contamination of tissues. Biocompatible antimicrobial barriers that can be applied directly in the wound of surgery could dramatically reduce infections. Amicrobe scientists, working in collaboration with Professor Timothy J. Deming (UCLA Bioengineering), are developing block copolypeptides that self-assemble into hierarchical structures to accomplish this objective. Amicrobe's lead product candidates are novel block copolypeptides that self-assemble into unique antimicrobial hydrogels. Notably, these physical hydrogels are not covalently cross-linked and, therefore, can flow upon (mild) deformation to fill wound cavities and rapidly re-gel. An advantage of our method is the ability to engineer chemical and physical characteristics (e.g. hierarchical structures) that may improve efficacy and safety. Preliminary data suggest that our lead hydrogels are broadly antimicrobial, effective in SSI models, and biocompatible with tissues. Our final product will be designed for ease of application, duration of antimicrobial activity, and support of wound healing. Direct application to wound cavities prior to surgical closure could significantly reduce the number of superficial and deep incisional SSIs and organ-space SSIs. Amicrobe's hydrogel product may also help prevent infections in traumatic wounds and chronic wounds such as diabetic foot ulcers. The goal of these Phase I studies is to select and formulate a lead product candidate for further development. Specifically, we are scaling up synthesis of three closely related candidates to enable critical studies in the selection process. Chemical properties will be analyzed, and physical properties will be assessed at multiple concentrations and formulations. Selected preparations will be tested in pilot studies of SSI models for prevention of wound infection. A lead compound will be chosen. It is anticipated that Phase II studies will focus on large-scale synthesis, additional SSI models, and toxicology. PUBLIC HEALTH RELEVANCE: Surgical site infections (SSIs) cause patient morbidity and mortality, and place a significant burden on the healthcare system. Surgical incisions break host defense barriers and increase microbial contamination of tissues. To prevent infection, Amicrobe is developing a novel biocompatible hydrogel that would complement today's standards of care and provide antimicrobial barrier protection at the site of surgery. Amicrobe's unique product may also help prevent infections in traumatic wounds, as well as chronic wounds such as diabetic foot ulcers.