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

描述（由申请人提供）：烧伤和皮肤创伤每年影响大约125万美国人。对皮肤的广泛损伤具有严重的影响，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，还没有全层皮肤替代品被批准用于治疗这些使人衰弱和危及生命的损伤。除了这些形式的急性皮肤损伤之外，慢性不愈合伤口是一个重要的医学问题，并且随着美国人口的老龄化，预计其发生频率会增加。严重皮肤伤口患者的护理代表了巨大的成本，通过创新和有效伤口护理产品的成本效益制造来改变当前伤口护理模式，可以显著降低该成本。 拟议的工作将改善Stratatech的StrataGraft（R）组织的既定生产工艺，StrataGraft（R）组织是一种创新的，经过临床测试的皮肤替代品，用于治疗创伤和慢性皮肤伤口。StrataGraft（R）皮肤组织是使用人真皮成纤维细胞和专有的NIKS（R）人角质形成细胞系生产的，NIKS（R）人角质形成细胞系是遗传均匀、非致瘤性、无病原体的人角质形成细胞的一致来源。Stratatech最近完成了StrataGraft（R）皮肤组织用于创伤性皮肤伤口临时管理的I/II期临床试验，结果表明StrataGraft（R）组织耐受性良好，与这些伤口的护理标准相当。 SBIR第二阶段竞争更新申请的目标是为Stratatech的创新细胞基组织系列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生产条件，用于生产经过临床测试的StrataGraft（R）活体人类皮肤替代组织。此次SBIR第二阶段竞争性更新提案的目标代表了我们在改进制造工艺方面迈出的重要一步，提高了产品的安全性和一致性，同时还降低了成本并促进了向封闭和自动化制造系统的过渡，这对于满足这些新型伤口护理产品不断增长的需求是必要的。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、基因增强的“皮肤移植”组织和我们的体外皮肤模型系统。 公共卫生相关性：在美国，每年有4万多人因烧伤住院，还有数百万人受到不愈合的慢性伤口的影响，如果不加以治疗，可能导致感染甚至截肢。标准治疗无法充分解决这些问题。这项SBIR第二阶段竞争性更新提案的目标是开发封闭系统制造工艺，用于生产Stratatech经过临床测试的StrataGraft（R）皮肤替代品，用于治疗急性和慢性伤口。拟议的研究将完善StrataGraft（R）皮肤组织的当前制造工艺，提高产品安全性和一致性，降低成本，并促进工艺放大。拟议的工艺改进将使Stratatech的整个治疗产品线受益，并将促进这些治疗创伤和慢性伤口的商业化。

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.