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

基本信息

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
项目类别：
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

项目摘要

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，清创来自热烧伤伤口和某些缺血性和坏死性糖尿病足伤口的死亡、受损和/或感染组织是常用的伤口准备方式。现有的伤口清创技术存在严重的问题，例如侵入性和不精确性、疼痛、去除相当多的健康区域以及死亡组织、手术时间慢得令人无法接受以及由于手术创伤或由于表面细菌更深的嵌入而导致继发感染的机会更大。显然，仅在美国每年就进行超过 500 万例清创手术，其中大多数是外科手术，因此这是一个备受医学关注的领域。因此，引入一种不受现有方法限制的新清创方式是必要的，也是必要的，以引起范式转变，从而对该领域产生高度持续和积极的影响。这一拟议的第一阶段 STTR 工作涉及 Lynntech, Inc. 和哈佛医学院贝斯以色列女执事足部中心之间的合作伙伴关系，专门为解决上述挑战而设计。在这项工作中，我们提出了一种新的伤口清创技术，由一种局部凝胶组成，该凝胶经过专门设计，可以选择性地锁定坏死组织区域，并在消肿的同时提供纳米研磨作用，以轻轻地从伤口床上去除这些区域。此外，凝胶消肿还有望提供渗出液截留和清除的额外好处，从而留下干净的创面床以备进一步治疗。我们假设这种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益处。在第一阶段 STTR 工作中，我们的总体目标是通过追求以下具体目标，为这种伤口清创技术的可行性提供概念验证，即 (1) 制备和表征伤口清创凝胶，(2) 开发一种全面的伤口清创凝胶。理论模型来解释凝胶体积相变，（3）进行离体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该证明这种新的伤口清创概念具有充分的可行性，并使我们能够在未来的后续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，在第二阶段的工作中，我们可以通过加入水凝胶相变触发的酶清创促进剂的缓慢释放来进一步改进基本的伤口清创凝胶技术平台。这种新颖的伤口清创技术的最终商业可用性可能会对需要伤口清创的患者群体产生巨大的积极影响。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，还将在医疗伤口准备市场上产生巨大的商业影响，因为它有望成为一种微创伤口清创产品。每年数百万接受清创手术的患者的潜在好处很多，包括减轻疼痛、加快伤口愈合时间、从生理和美容角度来看更好的愈合效果以及降低治疗成本。