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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要拟议的工作解决了对一种新型治疗工具的需求，该工具可改善高危手术切口的恢复。美国每年进行 4830 万例外科手术，其中 1/3 在年龄超过 65 岁的人。在这一人群中，相当多的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性缺血（CLTI），因此需要下肢尽管最近经皮和血管内介入治疗的数量激增，但开放手术仍在继续。由于长期耐用、较低的发生率，仍然是大量 CLTI 病例的首选血运重建方法考虑到与术后相关的再入院成本较高，某些解剖结构中的再狭窄和更好的血流动力学效率。由于手术愈合并发症，迫切需要开发先进技术来解决高风险问题硫化氢 (H2S) 是一种内源性 VOC，最近被认为是一种有害物质。气体递质，已被证明可以通过激活内皮细胞促进血管生成相关行为途径包括一氧化氮信号传导以及典型的 HIF-1α 和 VEGF-A 介导的血管生成级联。也是内源性 H2S 缺乏与内皮功能障碍相关的重要证据，因此（外源性）H2S 供体的全身给药已被证明会导致微血管紊乱和灌注不良。显着提高缺血组织的再生率，然而，全身和广泛的 H2S 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。在拟议的 SBIR I 期研究中，通过有针对性的精确输送 H2S 来实现个性化患者护理的机会。我们打算展示一种独特的治疗系统，可以局部提供精确控制的外源性剂量需要通过透皮检测将 H2S 浓度维持在治疗窗口内的目标位置 Exhalix 和纽大学的合作研究了当地的内源性和外源性 H2S 水平。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实现我们的目标将导致原型开发的第二阶段努力大型动物的示范。