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

描述(申请人提供)：据估计，每年有125万美国人受到烧伤和皮肤创伤的影响。对皮肤的广泛损害会产生严重的后果，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，还没有全层皮肤替代品被批准用于治疗这些虚弱和危及生命的损伤。除了这些形式的急性皮肤损伤外，慢性无法愈合的伤口是一个重大的医疗问题，预计随着美国人口的老龄化，这种伤口的频率将会增加。护理严重皮肤创伤的患者是一项巨大的成本，可以通过具有成本效益的创新和有效的伤口护理产品的生产来改变目前的伤口护理模式，从而显著降低成本。这项拟议的工作将改进Stratech公司现有的StrataGraft(R)组织的生产工艺，StrataGraft(R)组织是一种用于治疗创伤性和慢性皮肤创伤的创新的、经过临床测试的皮肤替代品。StrataGraft(R)皮肤组织是使用人类皮肤成纤维细胞和专利的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统一、无肿瘤、无病原体的人类角质形成细胞的始终如一的来源。Stratech公司最近完成了用于临时治疗创伤性皮肤创伤的StrataGraft(R)皮肤组织的I/II期临床试验，结果表明，StrataGraft(R)组织耐受性良好，可与这些伤口的护理标准相媲美。这一SBIR第二阶段竞争性更新应用的目标是为Stratech的创新细胞组织系列开发改进的制造工艺。我们建议为生产经过临床测试的StrataGraft(R)活体人类皮肤替代组织开发和优化完全由细胞衍生的封闭系统制造条件。SBIR第二阶段竞争性更新建议的目标是在改进我们的制造工艺方面迈出重要的一步，提高产品的安全性和一致性，同时降低成本并促进向封闭式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日益增长的需求所必需的。本申请中提出的改进建议将适用于Stratech的整个产品线，不仅包括StrataGraft(R)组织，还包括我们的下一代、基因增强型ExpressGraft“组织和我们的体外皮肤模型系统。 与公共卫生相关：在美国，每年有超过4万人因烧伤而住院，还有数百万人受到无法愈合的慢性伤口的影响，如果不治疗，这些伤口可能会导致感染甚至截肢。标准的治疗方法无法充分解决这些问题。这项SBIR第二阶段竞争性更新建议的目标是开发用于生产Stratech经过临床测试的用于治疗急慢性伤口的StrataGraft(R)皮肤替代品的闭合系统制造工艺。拟议中的研究将改进目前StrataGraft(R)皮肤组织的制造工艺，提高产品的安全性和一致性，降低成本，并促进工艺的扩大。拟议的工艺改进将使Stratech的整个治疗产品系列受益，并将促进这些用于治疗创伤和慢性伤口的治疗方法的商业化。

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.