Stimuli Responsive Topical Gels for Mechanically Assisted Wound Debridement

用于机械辅助伤口清创的刺激响应局部凝胶

• 批准号: 8057532
• 负责人: ANJAL C SHARMA
• 金额: $ 32.12万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8057532
• 关键词: Address; Animals; Area; Bacteria; Beds; Behavior; Biocompatible; Burn injury; Chemicals; Chronic; Contracts; Cosmetics; Cost Savings; Debridement; Diabetes Mellitus; Diabetic Foot; Effectiveness; Elasticity; Engineering; Enzymes; Etiology; Evaluation; Excision; Exudate; Fee-for-Service Plans; Filler; Functional disorder; Future; Gel; Goals; Healed; Hydrogels; Israel; Knowledge; Laboratories; Left; Measures; Mechanics; Medical; Medical center; Methodology; Methods; Modality; Modeling; Molecular; Morphology; Nature; Necrosis; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Pain; Patients; Performance; Phase; Phase Transition; Physics; Physiological; Polymers; Preparation; Procedures; Property; Research Design; Science; Secondary to; Small Business Technology Transfer Research; Sterile coverings; Stimulus; Supervision; Surface; Swelling; Techniques; Technology; Temperature; Theoretical model; Time; Tissues; Trauma; Treatment Cost; Water; Wound Healing; base; commercialization; crosslink; cytotoxicity; cytotoxicity test; density; design; diabetic; foot; healing; improved; innovation; medical schools; metal oxide; minimally invasive; nanoparticle; neutrophil; novel; particle; phase 1 study; poly-N-isopropylacrylamide; scale up; secondary infection; sound; technology development; wound; wound cleaning

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.

描述（由申请人提供）： 在应用填充物、敷料或移植物之前，对来自热烧伤伤口和缺血性和坏死性糖尿病足伤口的特定子集的死亡、受损和/或感染组织进行清创是常用的伤口准备方式。现有的伤口清创技术具有严重的问题，例如侵入性和不精确性、疼痛、去除明显的健康区域沿着死亡组织、不可接受的缓慢手术时间以及由于手术创伤或由于表面细菌的更深嵌入而引起的继发感染发作的更大机会。显然，由于仅在美国每年就进行超过500万次清创手术，其中大多数是外科手术，因此这是一个高度医学关注的领域。因此，引入一种新的清创模式，不具有现有方法的局限性，这是必要的，可以引起范式转变，对该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.哈佛医学院的贝丝以色列女执事足部中心是专门为解决上述挑战而设计的。在这项工作中，我们提出了一种新的伤口清创技术，包括一种局部凝胶，该凝胶经过专门设计，可选择性地附着在坏死组织区域上，并在消肿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去除。此外，凝胶去溶胀还有望提供额外的渗出物截留和清除益处，留下干净的伤口床，为进一步治疗做好准备。我们假设，这种类型的微创伤口清创技术的独特性质应该为缺血性和坏死性慢性伤口以及热烧伤伤口的准备提供最大的受益。在该I期STTR工作期间，我们的总体目标是通过追求以下具体目标来提供该伤口清创技术的可行性的概念验证，即（1）制备和表征伤口清创凝胶，（2）开发综合理论模型来解释凝胶体积相变，（3）进行离体细胞毒性评价以证明凝胶的生物相容性，和（4）利用正常和糖尿病兔模型进行初步动物研究，以证明水凝胶可用于伤口清创。这些具体目标的成功完成应证明这种新的伤口清创概念的充分可行性，并将使我们能够在未来的后续第二阶段工作中计划更全面的技术开发和商业化目标。此外，在II期研究期间，我们可能会通过纳入水凝胶相变触发的酶促清创促进剂的缓慢释放来进一步改进基础伤口清创凝胶技术平台。这种新型伤口清创技术的最终商业可用性可能对需要伤口清创的患者群体保持高度积极的影响。 公共卫生关系： 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，并专门设计为我们的刺激响应纳米磨料伤口清创凝胶技术的可行性提供概念验证。该研究如果成功，也将在医疗伤口准备市场上保持较高的商业影响，因为它预计将成为微创伤口清创产品。每年数百万接受清创手术的患者的潜在受益是众多的，包括疼痛减轻、伤口愈合时间更快、从生理学和美容学角度来看愈合效果更好以及治疗成本降低。