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 拟议的努力解决了需要一种新型的治疗工具，以改善高危手术切口的恢复。 每年在美国进行4830万手术程序，其中1/3进行 年龄在65岁以上的个人。在这个人群中，大量遭受内皮功能障碍并受损 血流导致周围动脉疾病和慢性肢体威胁性缺血（CLTI），因此需要下肢 血运重建。尽管最近的经皮和血管内干预数量激增，但开放手术是 由于长期耐用性，较低的速率仍然是大量CLTI案例的血运重建方法 再狭窄和某些解剖学的血液动力学效率更好。考虑到与后有关 操作愈合并发症，需要开发高级技术来解决高危技术 和处境不利的切口治愈失败。硫化氢（H2S），一种内源性VOC，最近被公认为 气递质已被证明可以通过激活来促进内皮细胞中与血管生成相关的行为 包括一氧化氮信号传导以及规范HIF-1和VEGF-A介导的血管生成级联的途径。那里 也是将内源性H2缺乏与内皮功能障碍联系起来的大量证据，因此 微血管疾病和灌注不良。已显示（外源）H2S供体的系统性给药已显示为 明显提高了缺血组织的再生速率。但是，H2S的全身和宽度交付可以领导 意想不到的后果，包括低血压，肝毒性和恶性血管生成。这留下了重要的 通过针对性的，精确交付H2S来个性化患者护理的机会。在拟议的SBIR I期研究中， 我们打算展示一个独特的治疗系统，该系统本地提供精确控制的外源量 需要通过透射检测来维持治疗窗口内目标位置的H2s浓度 局部内源性和外源H2S水平。在exhalix与新大学之间的合作努力中 墨西哥医学院，我们将展示这种持续Relis™治疗方法的可行性和优点 在小动物模型上处理手术切口。我们预计拟议的可行性研究将持续12 几个月和达到我们目标的成功将导致第二阶段的原型发展和 大型动物的示范。