Contractile Hydrogel Dressing for Primary Wound Closure

描述(由申请人提供)： 糖尿病足部溃疡等急慢性伤口是医学界关注的一个主要领域。由于约有2700万患者患有这种类型的部分厚度伤口，相当于数十亿美元的医疗费用，因此，在医务人员参与最少的情况下迅速愈合这种急慢性伤口的手段将是一项重大的新突破，能够在实地维持极高的影响。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创面敷料技术，由一种可收缩的生物相容水凝胶组成，它可以在分子水平上与伤口床中的细胞形成粘附键。水凝胶敷料将被设计成在应用于伤口时消肿，从而在整个伤口床上感受到施加的收缩力量。当水凝胶收缩时，它会向内拉伸伤口边缘，以刺激伤口一期闭合。水凝胶敷料还将包含可生物降解的交联物，以不仅确保伤口边缘感受到的平均收缩力即使在伤口随着时间的推移而收缩时保持主导地位，而且还允许敷料由于细胞在愈合后期的更替而自然被排除在外。由于糖尿病患者的伤口愈合受损，包括导致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对此类慢性伤口的愈合提供最大的好处。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为这种伤口敷料的可行性提供概念验证：(1)制备和表征可收缩水凝胶，(2)优化水凝胶的收缩性能，(3)优化水凝胶的生物可降解性，(4)进行体外细胞毒性评估，以证明水凝胶的生物相容性，(5)利用正常和糖尿病的兔和小鼠模型进行初步的动物研究，证明水凝胶有助于加速伤口闭合。这些具体目标的成功完成应该会证明这种新的伤口敷料技术的充分可行性，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收缩水凝胶敷料技术平台，包括水凝胶相变引发的生长因子、抗菌药物和基质金属蛋白酶抑制剂的缓慢释放。这种新型创面敷料技术的最终商业应用可能会对患有慢性创面类型的患者的生活质量产生高度积极的影响。 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保持高度积极的影响，并专门为我们的收缩水凝胶敷料技术的可行性提供概念证明。这项研究如果成功，还将在医用伤口敷料市场上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。对大约2700万患有DFU的公民来说，潜在的好处是很多的，包括减轻疼痛，更快的伤口愈合时间，从生理和美容的角度来看更好的愈合结果，以及降低治疗成本。

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.