Antimicrobial Hydrogels for Prevention of Surgical Site Infections (SSIs)

描述（由申请人提供）：手术部位感染（ssi）是手术的主要并发症。ssi导致患者发病和死亡，并对医疗保健造成重大负担。尽管有高标准的预防保健，伤口感染仍然是一个严重的问题。手术切口打破宿主防御屏障，增加组织的微生物污染。可直接应用于手术伤口的生物相容性抗菌屏障可显著减少感染。amicrorobe的科学家们与Timothy J. Deming教授（UCLA生物工程）合作，正在开发可以自组装成分层结构的嵌段共肽，以实现这一目标。Amicrobe的主要候选产品是新型嵌段共肽，可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，因此可以在（轻微）变形时流动，填充伤口腔并迅速重新凝胶。我们的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），从而提高疗效和安全性。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，并且与组织具有生物相容性。我们的最终产品将被设计为易于应用，抗菌活性的持续时间，和

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.