Antimicrobial, Angiogenic Skin Substitutes for Diabetic*

抗菌、血管生成的糖尿病皮肤替代品*

基本信息

批准号：
7478590
负责人：
Allen R. Comer
金额：
$ 87.24万
依托单位：
STRATATECH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7478590
关键词：
Address Adherent Culture Admission activity American Amputation Animal Model Animals Ankle Antibiotic Resistance Antibiotic Therapy Antibiotics Antimicrobial Cationic Peptides Bacteria Bacterial Infections Beds Biocompatible Materials Biological Blood flow CAP18 lipopolysaccharide-binding protein Cell Line Cells Centers for Disease Control and Prevention (U.S.)Chronic Chronic Care Classification Clinical Closure Collagen Complication Complications of Diabetes Mellitus Contralateral Coupled Cytostatics Data Dermal Development Diabetes Mellitus Diabetic Foot Ulcer Diabetic wound Drug resistance Engineering Environment Epidermis Epithelial Evaluation Research Exhibits Fibroblasts Gangrene Gel Generations Genetic Genetic Engineering Genus staphylococcus Goals Healed Heel Hospitals Host Defense Mechanism Human Human Cell Line Human Engineering Impaired wound healing In Vitro Individual Infection Insulin-Dependent Diabetes Mellitus International Invaded Label Legal patent Life Limb structure Localized Lower Extremity Marketing Materials Testing Minor Morbidity - disease rate Morphology Neuropathy North America Numbers Patients Peripheral Vascular Diseases Phase Positioning Attribute Production Property Range Reporting Research Personnel Resistance Site Skin Skin Substitutes Skin Ulcer Small Business Funding Mechanisms Small Business Innovation Research Grant Societies Source Standards of Weights and Measures Staphylococcus aureus Sterile coverings Survival Rate Terminology Testing Therapeutic Tissues Today Toxic effect Transgenes Trauma Ulcer United States United States Food and Drug Administration Vancomycin Vancomycin-resistant S. aureus Vascularization Viral Work Wound Healing Wound Infection analog antimicrobial antimicrobial peptide base cathelicidin cathelicidin antimicrobial peptide cell motility cell type design design and construction diabetic diabetic wound healing experience expression vector foot healing improved in vivo innovation keratinocyte killings microbial microorganism mortality neovascularization novel novel therapeutics outcome forecast pathogen prevent programs research clinical testing tissue regeneration transgene expression tumorigenic type I diabetic wound

项目摘要

DESCRIPTION (provided by applicant): The goal of this application is to develop a genetically engineered therapeutic human skin substitute with enhanced antimicrobial and angiogenenic properties for use in the treatment of type 1 diabetic skin ulcers. Chronic diabetic skin ulcers exhibit poor blood flow and typically become infected resulting in impaired wound healing and amputation, a life threatening complication of diabetes. The standard of care for chronic, infected, nonhealing diabetic wounds is antibiotic treatment and synthetic dressings. Because bacterial strains typically encountered often become antibiotic resistant, especially in the chronic wound, the clinician is limited to more potent antibiotics with undesirable effects on viability and migration of cells in the diabetic skin ulcer. This, coupled with the growing concern over emerging new multi-resistant strains of bacteria, underscores the need for innovative approaches to supplement antibiotic treatment regimes used in open wound therapy. Stratatech Corporation's strategy to promote wound healing in infected diabetic skin ulcers is to develop a novel human skin substitute possessing a range of enhanced antimicrobial, re-epithelialization, and vascularization properties. Our FastTrack SBIR proposal outlines proven strategies for the generation of human skin substitutes genetically engineered to secrete biologically active antimicrobial peptides (AMPs) capable of stimulating vascularization and cell migration. Animal models of type 1 diabetes and chronic wound healing will be used to test the hypothesis that a human skin substitute tissue containing human AMPexpressing cells will prevent chronic wound infection, facilitate re epithelialization, and vascularization, and thus provide an optimal environment for the healing of diabetic wounds. Advances in ex vivo genetic engineering of a patented human keratinocyte cell line at Stratatech Corporation has made our young company uniquely positioned to generate genetically enhanced human skin substitutes for use in the treatment of type 1 diabetic skin ulcers.

描述（由申请人提供）：该申请的目标是开发一种基因工程治疗性人类皮肤替代品，具有增强的抗菌和血管生成特性，用于治疗 1 型糖尿病皮肤溃疡。慢性糖尿病皮肤溃疡表现出血流不良，通常会受到感染，导致伤口愈合受损和截肢，这是一种危及生命的糖尿病并发症。慢性、感染、不愈合的糖尿病伤口的标准治疗是抗生素治疗和合成敷料。由于通常遇到的细菌菌株通常会对抗生素产生耐药性，尤其是在慢性伤口中，因此临床医生只能使用更有效的抗生素，而这些抗生素会对糖尿病皮肤溃疡中细胞的活力和迁移产生不良影响。再加上人们对新出现的多重耐药细菌菌株的日益关注，强调需要创新方法来补充开放性伤口治疗中使用的抗生素治疗方案。 Stratatech Corporation 促进感染糖尿病皮肤溃疡伤口愈合的战略是开发一种新型人类皮肤替代品，该替代品具有一系列增强的抗菌、上皮再生和血管化特性。我们的 FastTrack SBIR 提案概述了经过验证的策略，用于生成经过基因工程改造的人类皮肤替代品，以分泌能够刺激血管形成和细胞迁移的生物活性抗菌肽 (AMP)。 1型糖尿病和慢性伤口愈合的动物模型将用于检验这样的假设：含有人类AMP表达细胞的人类皮肤替代组织将预防慢性伤口感染，促进上皮化和血管化，从而为伤口愈合提供最佳环境。糖尿病伤口。 Stratatech Corporation 在获得专利的人类角质形成细胞系的离体基因工程方面取得的进展，使我们这家年轻的公司在生产用于治疗 1 型糖尿病皮肤溃疡的基因增强型人类皮肤替代品方面处于独特的地位。