Stimuli Responsive Topical Gels for Mechanically Assisted Wound Debridement

描述(由申请人提供)： 在应用填充物、敷料或移植物之前，清创来自热烧伤创面的死亡、受损和/或感染的组织以及某些子集的缺血和坏死性糖尿病足创面是一种常用的创面准备方式。现有的伤口清创技术存在严重的问题，如侵袭性和不严谨性，疼痛，切除可察觉的健康区域和死亡组织，手术时间慢得令人无法接受，以及由于程序创伤或表面细菌埋深而导致更大的继发感染机会。显然，由于每年仅在美国就进行了500多万例清创手术，其中大部分是外科手术，这是一个高度医学关注的领域。因此，采用一种不受现有方法限制的新的清创方式是必要的，也是必要的，以引起范式转变，对这一领域产生高度持续和积极的影响。这项拟议的第一阶段STTR工作涉及Lynntech，Inc.和哈佛医学院贝丝以色列女执事足部中心的合作伙伴关系，专门为应对上述挑战而设计。在这项工作中，我们提出了一种新的伤口清创技术，由一种专门设计的局部凝胶组成，这种凝胶选择性地闭锁在坏死组织区域上，并在脱水的同时提供纳米研磨作用，以轻轻地将这些区域从伤口床上移除。此外，凝胶脱胀还有望提供渗出物包裹和去除的额外好处，留下一个干净的伤口床，为进一步治疗做好准备。我们推测，这种微创创面清创技术的独特性质应该为制备缺血性和坏死性慢性创面以及热烧伤创面提供最大的好处。在这项第一阶段的STTR工作中，我们的总体目标是通过追求以下具体目标来为这种伤口清创技术的可行性提供概念验证：(1)制备和表征伤口清创凝胶，(2)开发一个全面的理论模型来解释凝胶体积的相变，(3)进行体外细胞毒性评估，以证明凝胶的生物相容性，以及(4)利用正常和糖尿病兔模型进行初步的动物实验，以证明水凝胶对伤口清创是有用的。这些具体目标的成功完成应该证明这一新的伤口清创概念具有充分的可行性，并将使我们能够在未来的第二阶段工作中规划更全面的技术开发和商业化推进。此外，在第二阶段的努力中，我们可能会进一步完善基础创面清创凝胶技术平台，包括水凝胶相变引发的酶清创促进剂的缓慢释放。这种新的伤口清创技术的最终商业应用可能会对需要伤口清创的患者人群产生很大的积极影响。 公共卫生相关性： 这项拟议的研究将在热和慢性伤口愈合领域保持高度积极的影响，并专门为我们的刺激响应性纳米磨料伤口清创凝胶技术的可行性提供概念证明。这项研究如果成功，还将在医疗伤口准备市场上保持较高的商业影响，因为它有望成为一种微创伤口清创产品。每年接受清创手术的数百万患者的潜在好处是多方面的，包括减轻疼痛、更快的伤口愈合时间、从生理和美容角度看更好的愈合结果以及降低治疗成本。

DESCRIPTION (provided by applicant): Debridement of dead, damaged and/or infected tissue from thermal burn wounds and a certain subset of ischemic and necrotic diabetic foot wounds is a commonly utilized wound preparation modality before the application of fillers, dressings or grafts. The existing wound debridement techniques have serious issues such as invasiveness and impreciseness, painfulness, removal of appreciable healthy areas along with dead tissue, unacceptably slow procedure time and a greater opportunity for secondary infection onset due to procedural trauma or due to deeper embedment of surface bacteria. Clearly since over 5 million debridement procedures are conducted per year in the USA alone, the majority of them being surgical in nature, this is an area of high medical concern. Therefore, the introduction of a new debridement modality that does not have the limitations of the existing methodologies is warranted and necessary to cause a paradigm shift for a highly sustained and positive impact on this field. This proposed Phase I STTR effort which involves a collaborative partnership between Lynntech, Inc. and Beth Israel Deaconess Foot Center at Harvard Medical is specifically designed to address the above challenge. In this effort, we propose a new wound debridement technology, consisting of a topical gel which is specifically engineered to selectively latch onto necrotic tissue areas and provide nanoabrasive action while deswelling to gently remove these areas from the wound bed. In addition, the gel deswelling is also expected to provide the additional benefit of exudate entrapment and removal to leave behind a clean wound bed ready for further treatment. We hypothesize that the unique nature of this type of minimally invasive wound debridement technology should provide the greatest benefit to the preparation of ischemic and necrotic chronic wounds as well as thermal burn wounds. During this Phase I STTR effort, our overall goal is to provide proof-of-concept for the feasibility of this wound debridement technology by pursuing the following specific aims, namely (1) prepare and characterize wound debridement gels, (2) develop a comprehensive theoretical model to explain the gel volume phase transition, (3) perform ex- vivo cytotoxicity evaluation to demonstrate the biocompatible nature of the gels, and (4) perform preliminary animal studies utilizing normal and diabetic rabbit models to demonstrate that the hydrogels are useful for wound debridement. The successful completion of these specific aims should demonstrate ample feasibility of this new wound debridement concept, and will allow us to plan more comprehensive technology development and commercialization thrusts in a future follow-on Phase II effort. In addition, during the Phase II effort, we may further improve the basic wound debridement gel technology platform by including hydrogel phase transition triggered slow release of enzymatic debridement promoting agents. The eventual commercial availability of such a novel wound debridement technology is likely to sustain high positive impact for the patient populace that requires wound debridement. PUBLIC HEALTH RELEVANCE: This proposed study will sustain high positive impact in the field of thermal and chronic wound healing and is specifically devised to provide proof-of-concept for the feasibility of our stimuli responsive nanoabrasive wound debridement gel technology. The study if successful will also sustain high commercial impact in the medical wound preparation marketplace as it is expected to be a minimally invasive wound debridement product. The potential benefits to the millions of patients undergoing debridement procedures annually are numerous including lowered pain, faster wound healing times, better healing outcomes from both a physiological as well as a cosmetic standpoint and lowered cost of treatment.