Development of a Cell-Derived Human Skin Substitute for Acute and Chronic Wounds

开发细胞衍生的人类皮肤替代品来治疗急性和慢性伤口

基本信息

批准号：
7993001
负责人：
Allen R. Comer
金额：
$ 49.98万
依托单位：
STRATATECH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-03-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7993001
关键词：
Acute Address Adoption Affect Age Allogenic Amendment American Amputation Animals Automation Benchmarking Biological Models Burn Trauma Burn injury Caring Cell Line Cells Chronic Clinical Trials Collagen Complex Culture Media Data Defect Dehydration Dermal Development Drug Formulations Engineering Engraftment Extracellular Matrix Fibroblasts Frequencies Gel Goals Histology Human Immunosuppression In Vitro Individual Infection Injury Investigational New Drug Application Lead Left Life Manuals Medical Metabolic Methods Modeling National Institute of Arthritis and Musculoskeletal and Skin Diseases Necrotizing fasciitis Patient Care Phase Poison Population Process Production Property Proteins Research Safety Skin Skin Substitutes Skin Tissue Small Business Innovation Research Grant Source System Testing Therapeutic Thick Time Tissue Engineering Tissues Translations United States Vendor Work Wound Healing Wound Infection base commercialization cost density effective therapy improved in vivo innovation keratinocyte manufacturing process meetings next generation novel pathogen public health relevance scaffold scale up standard care standard of care success tumorigenic wound

项目摘要

DESCRIPTION (provided by applicant): Burns and trauma to the skin affect an estimated 1.25 million Americans each year. Extensive damage to the skin has serious repercussions, leading to dehydration, increased metabolic load, entry of toxic substances, immunosuppression, and wound infection. Currently, there are no full-thickness skin substitutes approved for use in treating these debilitating and life-threatening injuries. In addition to these forms of acute skin damage, chronic non-healing wounds are a significant medical problem and are expected to increase in frequency as the US population ages. The care of patients with severe skin wounds represents an enormous cost that can be reduced significantly by altering the current wound care paradigm through the cost-effective manufacture of innovative and efficacious wound care products. The proposed work will improve upon Stratatech's established production processes for StrataGraft(R) tissue, an innovative, clinically-tested skin substitute for the treatment of traumatic and chronic skin wounds. StrataGraft(R) skin tissue is produced using human dermal fibroblasts and the proprietary NIKS(R) human keratinocyte cell line, a consistent source of genetically-uniform, non-tumorigenic, pathogen-free human keratinocytes. Stratatech recently completed a Phase I/II clinical trial of StrataGraft(R) skin tissue for the temporary management of traumatic skin wounds, the results of which indicated that StrataGraft(R) tissue is well-tolerated and comparable to the standard of care for these wounds. The goal of this SBIR Phase II Competing Renewal application is to develop improved manufacturing processes for Stratatech's line of innovative, cell-based tissues. We propose to develop and optimize completely cell-derived, closed-system manufacturing conditions for production of the clinically-tested StrataGraft(R) living human skin substitute tissue. The objective of this SBIR Phase II Competing Renewal proposal represents an important step in the refinement of our manufacturing process, increasing the safety and consistency of the product, while also reducing costs and facilitating the transition to the closed and automated manufacturing systems that will be necessary to meet the growing demand for these novel wound care products. The improvements proposed in this application would be applicable to Stratatech's entire product line, including not only StrataGraft(R) tissue, but also our line of next generation, genetically-enhanced ExpressGraft" tissues, and our in vitro skin model system. PUBLIC HEALTH RELEVANCE: More than 40,000 people are hospitalized each year in the United States for burns and millions more are affected by nonhealing chronic wounds that, if left untreated, can lead to infection or even amputation. Standard treatments are unable to adequately address these problems. The goal of this SBIR Phase II Competing Renewal proposal is to develop closed-system manufacturing processes for production of Stratatech's clinically-tested StrataGraft(R) skin substitute for the treatment of acute and chronic wounds. The proposed research will refine the current manufacturing process for StrataGraft(R) skin tissue, improving product safety and consistency, reducing costs, and facilitating process scale-up. The proposed process improvements will benefit Stratatech's entire line of therapeutic products and will facilitate the commercialization of these therapies for the treatment of traumatic and chronic wounds.

描述（由申请人提供）：皮肤的烧伤和创伤每年影响125万美国人。对皮肤的广泛损害具有严重的影响，导致脱水，代谢负荷增加，有毒物质的进入，免疫抑制和伤口感染。目前，尚无批准用于治疗这些令人衰弱和威胁生命的伤害的全厚皮肤替代品。除了这些形式的急性皮肤损害外，慢性非愈合伤口是一个重大的医疗问题，随着美国人口年龄的增长，频率将增加。严重皮肤伤口的患者的护理代表了巨大的成本，可以通过通过成本效益的创新和有效的伤口护理产品来改变当前的伤口护理范式来大大降低。拟议的工作将改善Stratatech既定的Stratagraft（R）组织的生产过程，这是一种创新的，临床测试的皮肤替代品，用于治疗创伤性和慢性皮肤伤口。使用人类皮肤成纤维细胞和专有的NIKS（R）人角质形成细胞系生产Stratagraft（R）皮肤组织，这是遗传均匀，非肿瘤，无病原体的人角质形成细胞的一致来源。 Stratatech最近完成了一项临时治疗外伤皮肤伤口的Stratagraft（R）皮肤组织的I/II期临床试验，其结果表明Stratagraft（R）组织具有良好的耐受性且与这些伤口的护理标准相当。 SBIR II期竞争性更新应用的目的是为Stratatech的创新，基于细胞的组织开发改进的制造过程。我们建议开发和优化完全衍生细胞的封闭系统制造条件，以生产经过临床测试的Stratagraft（R）活人皮肤替代组织。该SBIR II期竞争续约提案的目的是改进我们制造过程的重要一步，提高了产品的安全性和一致性，同时还降低了成本并促进过渡到封闭和自动化的制造系统，这是满足对这些新型伤口护理产品不断增长的需求所必需的。本应用中提出的改进将适用于Stratatech的整个产品线，不仅包括Stratagraft（R）组织，还适用于我们的下一代，遗传增强的Expressgraft“ Tissure”组织和我们的体外皮肤模型系统。公共卫生相关性：美国每年有40,000多人因烧伤而住院，数以百万计的慢性伤口受到影响，如果不及时治疗，这些伤口可能会导致感染甚至截肢。标准治疗无法充分解决这些问题。 SBIR II期竞争的续签建议的目的是开发封闭系统制造过程，用于生产Stratatech临床测试的Stratagraft（R）皮肤替代急性和慢性伤口的皮肤替代品。拟议的研究将完善当前Stratagraft（R）皮肤组织的制造过程，提高产品安全性和一致性，降低成本并促进过程规模。拟议的过程改进将使Stratatech的整个治疗产品系列有益于这些疗法的商业化，以治疗创伤性和慢性伤口。