Repair by Local Infusion of Sulfides (ReLIS™) for Treatment of Disadvantaged Surgical Incisions

硫化物局部灌注修复 (ReLIS™) 用于治疗不良手术切口

• 批准号: 10474641
• 负责人: Reza Shekarriz
• 金额: $ 30.04万
• 依托单位: EXHALIX, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10474641
• 关键词: Address; Advanced Development; Anatomy; Animal Model; Animals; Apoptosis; Atherosclerosis; Behavior; Blood Vessels; Blood flow; Cardiovascular Physiology; Caring; Cell Death; Chronic; Clinical; Coma; Competence; Coughing; Cytoprotection; Data; Development; Devices; Diabetes Mellitus; Diagnosis; Disadvantaged; Disease; Elderly; Endothelial Cells; Endothelium; Ensure; Environment; Enzymes; Evaluation; Failure; Family suidae; Feasibility Studies; Government; Granulation Tissue; Health Care Costs; Hemorrhage; Hepatotoxicity; High Prevalence; Histology; Human; Hydrogen Sulfide; Hypotension; Impairment; Individual; Inflammation; Infusion procedures; Intervention; Ischemia; Knowledge; Laboratories; Lead; Light; Limb structure; Link; Location; Lower Extremity; Lung; Lyase; Malignant - descriptor; Measurement; Mediating; Methods; Microfluidics; Modality; Molecular Analysis; Monitor; Morbidity - disease rate; Natural regeneration; Neoplasm Metastasis; New Mexico; Nitric Oxide; Operative Surgical Procedures; Paralysed; Pathway interactions; Patients; Perfusion; Peripheral arterial disease; Phase; Physiological; Population; Populations at Risk; Postoperative Period; Rattus; Recovery; Regulation; Research; Research Personnel; Resources; Risk; Role; Safety; Seizures; Shortness of Breath; Signal Transduction; Signaling Molecule; Small Business Innovation Research Grant; Sprague-Dawley Rats; Sterile coverings; Study Subject; Sulfides; Surgical Flaps; Surgical incisions; System; Systems Development; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Tissues; Toxic effect; United States; Universities; VEGFA gene; Validation; Vascular Endothelial Growth Factors; Vascular Endothelium; Vascularization; Vasodilation; Wound models; aging population; angiogenesis; base; biodegradable scaffold; commercialization; comorbidity; cost; diabetic; diabetic rat; dosage; endothelial dysfunction; healing; hemodynamics; hospital readmission; human subject; hypoxia inducible factor 1; improved; improved outcome; innovation; interest; medical schools; meetings; necrotic tissue; novel; novel therapeutics; personalized care; phase 1 study; phase 2 study; pre-clinical; professor; prototype; regenerative agent; repaired; restenosis; restoration; scaffold; sensor; side effect; subcutaneous; success; surgical risk; tissue regeneration; tissue repair; tool; tumor growth; validation studies; wound; wound care

Project Summary/Abstract The proposed effort addresses the need for a novel therapeutic tool that improves the recovery of at-risk surgical incisions. There are 48.3 million surgical procedures performed in the United States each year, 1/3 of which are performed on individuals older than 65. Among this population, a significant number suffer from endothelial dysfunction and impaired blood flow leading to peripheral artery disease and chronic limb threatening ischemia (CLTI), thus requiring lower limb revascularization. Despite a recent surge in the number of percutaneous and endovascular interventions, open surgery is still a preferred method of revascularization for a large number of CLTI cases due to long term durability, lower rate of restenosis and better hemodynamic efficiency in certain anatomies. Given the high cost of readmission related to post- operative healing complications, there is a critical need for development of advanced techniques to address the at-risk and disadvantaged incision healing failure. Hydrogen sulfide (H2S), an endogenous VOC and recently recognized as a gasotransmitter, has been shown to promote angiogenesis-related behavior in endothelial cells through activation of pathways that include nitric oxide signaling and the canonical HIF-1 and VEGF-A-mediated angiogenesis cascade. There is also significant evidence linking deficiency in endogenous H2S to endothelial dysfunction and consequently microvascular disorder and poor perfusion. Systemic administration of (exogenous) H2S donors have been shown to markedly improve the rate of regeneration in ischemic tissue. However, systemic and widespread delivery of H2S can lead to unintended consequences including hypotension, hepatotoxicity, and malignant angiogenesis. This leaves a significant opportunity for individualizing patient care through targeted, precision delivery of H2S. In the proposed SBIR Phase I study, we intend to demonstrate a unique therapeutic system that locally delivers a precisely controlled exogenous amount needed to sustain the concentration of H2S at the target location within a therapeutic window by transdermally detecting the local endogenous and exogenous H2S levels. In this collaborative effort between Exhalix and the University of New Mexico School of Medicine, we will show the feasibility and merits of this sustained ReLIS™ therapeutic approach for treatment of surgical incisions on small animal models. We anticipate that the proposed feasibility study will last 12 months and success in reaching our objectives will lead to a Phase II effort for development of prototypes and demonstration on larger animals.

项目摘要/摘要 拟议的努力解决了对一种新的治疗工具的需求，该工具可以改善有风险的外科伤口的恢复。 美国每年有4830万例外科手术，其中三分之一是在 65岁以上的个人。在这一人群中，相当一部分人患有内皮功能障碍和受损。 血流导致外周动脉疾病和慢性肢体威胁缺血(CLTI)，因此需要下肢 血运重建。尽管最近经皮和血管内介入治疗的数量激增，但开放手术 由于长期的耐用性，仍然是大量CLTI患者的首选血管重建方法，较低的 在某些解剖结构中，再狭窄和更好的血流动力学效率。鉴于重新入院的费用较高，与后 手术愈合并发症，迫切需要开发先进的技术来解决高危 和不利的伤口愈合失败。硫化氢(H2S)是一种内源性VOC，最近被认为是一种 气体递质，已被证明通过激活血管内皮细胞促进血管生成相关的行为 包括一氧化氮信号和典型的缺氧诱导因子-1、和血管内皮生长因子-A介导的血管生成级联反应的通路。那里 也是内源性硫化氢缺乏与内皮功能障碍有关的重要证据，因此 微血管紊乱，血流灌注不良。系统地给予(外源性)硫化氢捐赠者已被证明 显著提高缺血组织的再生率。然而，系统和广泛的硫化氢输送可能会导致 导致意想不到的后果，包括低血压、肝毒性和恶性血管生成。这就留下了一个重要的 通过有针对性、精准地提供硫化氢，为患者提供个性化护理的机会。在拟议的SBIR第一阶段研究中， 我们打算展示一种独特的治疗系统，该系统在局部提供精确控制的外源性数量。 需要通过经皮检测来维持治疗窗口内目标位置的硫化氢浓度 局部内源和外源H_2S水平。在Exhalix和纽约大学之间的合作努力中 我们将展示这种持续的REIS™治疗方法的可行性和优点 小动物模型手术伤口的处理。我们预计拟议的可行性研究将持续12年。 几个月的时间和成功地实现我们的目标将导致第二阶段的原型开发工作和 在更大的动物身上进行演示。