Contractile Hydrogel Dressing for Primary Wound Closure

用于闭合原发伤口的收缩性水凝胶敷料

• 批准号: 8000269
• 负责人: ANJAL C SHARMA
• 金额: $ 31.73万
• 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: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8000269
• 关键词: Acute; Address; Adhesives; American; Amputation; Animal Model; Animals; Area; Beds; Biocompatible; Biodegradation; Cell Adhesion; Cells; Characteristics; Chemicals; Chronic; Contracts; Cosmetics; Diabetes Mellitus; Diabetic Foot; Diabetic Foot Ulcer; Elasticity; Engineering; Ensure; Etiology; Evaluation; Fee-for-Service Plans; Functional disorder; Future; Gel; Goals; Growth Factor; Healed; Hospitalization; Hydrogels; Impaired wound healing; Israel; Knowledge; Laboratories; Lower Extremity; Measures; Medical; Medical Staff; Modeling; Molecular; Mus; Nature; New Zealand; Oryctolagus cuniculus; Outcome; Pain; Patients; Phase; Phase Transition; Physics; Physiological; Polymers; Preparation; Property; Quality of life; Ramp; Readiness; Research Design; Science; Small Business Technology Transfer Research; Staging; Sterile coverings; Stretching; Supervision; Swelling; Technology; Thick; Time; Treatment Cost; Ulcer; Wistar Rats; Work; Wound Healing; antimicrobial; commercialization; crosslink; cytotoxicity; density; design; diabetic; diabetic patient; foot; healing; improved; inhibitor/antagonist; innovation; novel; phase 1 study; physical property; poly-N-isopropylacrylamide; polypeptide; public health relevance; scale up; sound; technology development; wound

DESCRIPTION (provided by applicant): Acute and chronic wounds such as diabetic foot ulcers represent a major area of medical concern. With roughly 27 million patients suffering from these types of partial thickness wounds, representing substantial billions in medical expenses, a means to rapidly close such acute and chronic wounds with minimal medical staff involvement would be a major new breakthrough, capable of sustaining extremely high impact in the 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 dressing technology, consisting of a contractile biocompatible hydrogel which may form adhesive bonds at the molecular level with cells in the wound bed. The hydrogel dressing will be engineered to de-swell upon application to the wound resulting in an applied contractile force felt throughout the wound bed. As the hydrogel contracts, it will stretch the wound edges inwards to stimulate primary wound closure. The hydrogel dressing will also contain biodegradable crosslinking to not only ensure that the average contractile force felt at the wound edges stays dominant even when the wound contracts over time but to also allow the dressing to be naturally excluded due to cell turnover towards the latter stages of healing. Since wound healing is impaired in the diabetic patients, including the primary wound contraction mechanisms responsible for natural wound closure; we hypothesize that this type of wound dressing technology should provide the greatest benefit to the healing of such chronic wounds. During this Phase I STTR effort, our overall goal is to provide proof-of-concept for the feasibility of this wound dressing by pursuing the following specific aims, namely (1) prepare and characterize contractile hydrogels, (2) optimize the contractile properties of the hydrogel, (3) optimize the biodegradability of the hydrogel, (4) perform ex-vivo cytotoxicity evaluation to demonstrate the biocompatible nature of the hydrogels, (5) perform preliminary animal studies utilizing normal and diabetic rabbit and murine models to demonstrate that the hydrogels are useful to accelerate wound closure. The successful completion of these specific aims should demonstrate ample feasibility of this new wound dressing technology, 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 contractile hydrogel dressing technology platform by including hydrogel phase transition triggered slow release of growth factors, antimicrobials and mmp inhibitors. The eventual commercial availability of such a novel wound dressing technology is likely to sustain high positive impact in the quality of life within the patient populace suffering from chronic wound types. PUBLIC HEALTH RELEVANCE: This proposed study will sustain high positive impact in the field of accelerated chronic and acute wound healing and is specifically devised to provide proof-of-concept for the feasibility of our contractile hydrogel dressing technology. The study if successful will also sustain high commercial impact in the medical wound dressing marketplace as it is expected to be a multifunctional wound healing product. The potential benefits to the approximately 27 million citizens suffering from DFU 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）： 诸如糖尿病足溃疡等急性和慢性伤口是医学关注的主要领域。大约有 2700 万患者患有此类部分厚度伤口，相当于数十亿美元的医疗费用，一种在最少医务人员参与的情况下快速闭合此类急性和慢性伤口的方法将是一个重大的新突破，能够对医疗保健产生极高的影响。领域。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敷料技术，该技术由可收缩的生物相容性水凝胶组成，可以在分子水平上与伤口床中的细胞形成粘合键。水凝胶敷料将被设计成在应用于伤口时消溶胀，从而在整个伤口床中感受到施加的收缩力。当水凝胶收缩时，它将向内拉伸伤口边缘以刺激初级伤口闭合。水凝胶敷料还将含有可生物降解的交联，不仅确保即使伤口随着时间的推移收缩，伤口边缘感受到的平均收缩力仍然占主导地位，而且还允许敷料由于细胞更新到后期而自然地被排除。康复。由于糖尿病患者的伤口愈合受到损害，包括负责伤口自然闭合的主要伤口收缩机制；我们假设这种类型的伤口敷料技术应该为此类慢性伤口的愈合提供最大的益处。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，为这种伤口敷料的可行性提供概念验证，即（1）制备和表征收缩水凝胶，（2）优化其收缩特性水凝胶，（3）优化水凝胶的生物降解性，（4）进行离体细胞毒性评估以证明水凝胶的生物相容性，（5）利用正常和糖尿病兔和小鼠模型进行初步动物研究证明水凝胶可用于加速伤口闭合。这些具体目标的成功完成应该证明这种新的伤口敷料技术具有充分的可行性，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，我们可能会进一步完善基本的收缩性水凝胶敷料技术平台，包括水凝胶相变触发的生长因子、抗菌剂和mmp抑制剂的缓慢释放。这种新型伤口敷料技术的最终商业化可能会对患有慢性伤口类型的患者群体的生活质量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加速慢性和急性伤口愈合领域产生高度积极的影响，并且专门为我们的收缩水凝胶敷料技术的可行性提供概念验证。该研究如果成功，还将对医用伤口敷料市场产生巨大的商业影响，因为它有望成为一种多功能伤口愈合产品。对于大约 2700 万患有 DFU 的公民来说，潜在的好处有很多，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。