Therapeutic cells encapsulation and delivery for improved healing of chronic diabetic wounds

治疗细胞封装和递送以改善慢性糖尿病伤口的愈合

基本信息

批准号：
9409430
负责人：
Manav Mehta
金额：
$ 29.85万
依托单位：
GEL4MED, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9409430
关键词：
Address Admission activity Adult Amputation Antibiotic Resistance Area Beds Biological Cell Count Cell Survival Cell Transplants Cell-Matrix Junction Cells Cessation of life Charge Chronic Clinic Clinical Complex Data Debridement Delaware Diabetes Mellitus Diabetic Foot Ulcer Diabetic mouse Diabetic ulcer Diabetic wound Encapsulated Environment Exhibits Family suidae Formulation Future Gel Goals Granulation Tissue Health Care Costs Health Professional Histopathology Hospitals Hydrogels In Vitro Infection Injectable Lead Legal patent Lower Extremity Mammalian Cell Materials Testing Mesenchymal Modeling Mus Natural regeneration Pathogenicity Patients Peptide Hydrolases Peptides Phase Physiological Pre-Clinical Model Predisposition Preparation Prevalence Procedures Property Public Health Quality Control Resistance Rights Risk Saline Small Business Innovation Research Grant Staining method Stains Stromal Cells Subcutaneous Injections Supporting Cell Surgical wound Technology Therapeutic Therapeutic Uses Thick Thinness TimeLine Tissues Transplantation United States Universities Work Wound Healing animal tissue antimicrobial base biomaterial compatibility chronic wound density design diabetic diabetic wound healing extracellular healing improved in vivo limb amputation mouse model pathogen point of care pre-clinical prevent protein aminoacid sequence scaffold self assembly stem tissue regeneration wound wound closure

项目摘要

The goal of this Phase I SBIR proposal is to demonstrate feasibility of a flowable, antimicrobial cell delivery vehicle for improving tissue regeneration in clean and pathogen-contaminated diabetic wounds. Diabetic ulcers are a major burden on public health and the economy, as they represent least 33 % of the annual $116 billion in direct diabetic health care cost in the United States. This burden is projected to increase in the near future, since it is estimated that the prevalence of diabetes in the US, which is currently at 9.3%, could reach up to 1 in 3 adults by 2050. Delayed diabetic wound healing complicated by infection is the primary cause of non-traumatic lower-limb amputations, representing ~100,000 cases annually. The proposed product will deliver therapeutic cells into diabetic wounds that are at risk for infection by (i) allowing simple, point-of-care cell encapsulation and application to wound beds (ii) providing an extracellular cell scaffolding matrix that promotes retention and viability of transplanted cells (iii) preventing pathogenic contamination through intrinsic, broad-spectrum antimicrobial activity. The proposed product is intended for use by healthcare professionals following surgical wound debridement procedures. To establish feasibility for this product, we propose the following two specific aims: Specific Aim 1: Evaluate gel formulations for their ability to effectively encapsulate therapeutic cells and support cell viability in vivo. Milestones: Show high viability of therapeutic cells following encapsulation in gels both in vitro and in vivo. Specific Aim 2: Demonstrate in vivo efficacy of gels delivering therapeutic cells for promoting improved healing of full-thickness clean and pathogen-contaminated wounds in diabetic mice. Milestones: Show accelerated wound healing and improved quality of regenerated tissue at days 14 and 28. In Phase II SBIR studies, we will validate the product in a diabetic swine model of wound healing, establish GMP manufacturing, and execute GLP studies in preparation for an FDA pre-submission discussion.

该阶段I SBIR提案的目的是证明可行性的抗菌细胞用于改善清洁和病原体污染糖尿病的组织再生的输送车辆伤口。糖尿病性溃疡是公共卫生和经济的重大负担，因为它们占33％在美国，每年1,160亿美元的直接糖尿病医疗保健费用中。这个负担预计在不久的将来增加，因为据估计，美国目前处于美国的糖尿病患病率到2050年，9.3％的人最多可以达到三分之一的成年人。延迟的糖尿病伤口愈合因感染而复杂的是非创伤性下limb截肢的主要原因，每年约为100,000例。拟议的产品将将治疗细胞输送到糖尿病伤口中，该糖尿病伤口受到（i）的感染风险允许简单的护理单元封装并应用于伤口床（ii），提供细胞外促进移植细胞（III）的保留和生存能力的细胞脚手架基质（III）防止致病性通过内在的，广谱的抗菌活性来污染。拟议的产品旨在遵循手术伤口清创程序的医疗保健专业人员使用。为了确定该产品的可行性，我们提出以下两个具体目标：特定目标1：评估凝胶配方的有效封装治疗细胞的能力和在体内支持细胞活力。里程碑：在体外和体内封装后，在凝胶封装后显示出高的治疗细胞活力。特定目的2：证明凝胶的体内功效可促进治疗细胞以改进糖尿病小鼠中全厚度清洁和被病原体污染的伤口的愈合。里程碑：在第14天和第28天显示出加速的伤口愈合和改善再生组织的质量。在II期SBIR研究中，我们将在伤口愈合的糖尿病猪模型中验证产物，建立 GMP制造和执行GLP研究，以准备FDA预审讨论。