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

描述（由申请人提供）：每年约有125万美国人受到皮肤烧伤和创伤的影响。皮肤大面积损伤会产生严重后果，导致脱水、代谢负荷增加、有毒物质进入、免疫抑制和伤口感染。目前，还没有被批准用于治疗这些使人衰弱和危及生命的损伤的全层皮肤替代品。除了这些形式的急性皮肤损伤外，慢性无法愈合的伤口也是一个重要的医疗问题，随着美国人口的老龄化，预计这种情况会增加。严重皮肤伤口患者的护理是一项巨大的成本，通过成本效益高的创新和有效的伤口护理产品的制造，可以改变当前的伤口护理模式，从而显著降低成本。拟议的工作将改进Stratatech现有的StrataGraft(R)组织的生产工艺，这是一种创新的、经过临床测试的皮肤替代品，用于治疗创伤性和慢性皮肤伤口。StrataGraft(R)皮肤组织是使用人类真皮成纤维细胞和专有的NIKS(R)人类角质细胞系生产的，NIKS(R)人类角质细胞系是遗传均匀，非致瘤性，无病原体的人类角质细胞的一致来源。Stratatech最近完成了StrataGraft(R)皮肤组织暂时治疗创伤性皮肤伤口的I/II期临床试验，结果表明StrataGraft(R)组织耐受性良好，可与这些伤口的标准护理相媲美。这项SBIR II期竞争更新申请的目标是为Stratatech的创新细胞组织产品线开发改进的制造工艺。我们建议开发和优化完全细胞衍生的封闭系统制造条件，用于生产经临床测试的StrataGraft(R)活体人体皮肤替代组织。SBIR第二阶段竞争更新提案的目标是改进我们的制造工艺，提高产品的安全性和一致性，同时降低成本并促进向封闭和自动化制造系统的过渡，这将是满足这些新型伤口护理产品不断增长的需求所必需的。本申请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，还包括我们的下一代基因增强ExpressGraft组织，以及我们的体外皮肤模型系统。

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.