Closed, Aseptic Production Process for Engineered Living Human Skin Tissue

工程化活人皮肤组织的封闭式无菌生产工艺

• 批准号: 7054179
• 负责人: Allen R. Comer
• 金额: $ 19.61万
• 依托单位: STRATATECH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054179
• 关键词: antiseptic sterilization; artificial skin; bioengineering /biomedical engineering; cryopreservation; keratinocyte; patient safety /medical error; skin derivative; skin transplantation; therapy design /development; tissue /cell culture; tissue engineering; tissue support frame; xenotransplantation

DESCRIPTION (provided by applicant): Tissue engineering (TE) is poised to make an enormous impact on the range of therapeutic options for treatment of life-threatening conditions that afflict millions of Americans. To date, however, no marketed TE product has proven to be commercially successful. One of the primary factors contributing to this lack of profitability is the need for aseptic processing at all steps. Unlike traditional pharmaceutical and biotechnology products, engineered tissues and cell-based therapies must be processed aseptically throughout their manufacture. For this reason, these therapies come with extremely high facility and production costs. New, innovative approaches for aseptic processing and scale-up are required before cell- based therapies can become accessible to patients in the US health care system. Stratatech Corporation has approval from the FDA to begin Phase I/I I clinical trials with StrataGraft(tm), a human skin substitute tissue based on Stratatech's patented NIKS(tm) human keratinocyte cell line. In addition, Stratatech is developing a pipeline of genetically enhanced living skin products (ExpressGraft(tm)) for use in the chronic, non-healing diabetic, venous stasis, and decubitus skin wound markets. This Fast Track proposal is designed to develop a closed, aseptic manufacturing process for these innovative products which will greatly reduce production costs and increase patient safety. In Phase I we will address the issue of closed, aseptic keratinocyte culture and scale-up as well as the PHS and FDA concerns regarding xenotransplantation. We will determine parameters for cryopreservation of NIKS(tm) keratinocytes in sterile bag format. We will then thaw and propagate these preserved NIKS(tm) cells in closed cell factories without the aid of murine feeder cells. Finally, we will scale-up methods for NIKS(tm) culture to enable harvest and passage at a sufficient scale for full scale commercial manufacture. In Phase II we will extend these results by developing methods for production of StrataGraft(tm) skin tissue in closed tissue growth chambers. We will construct prototype chambers and test their ability to produce skin tissue in batch and perfusion modes with on-line process monitoring. Then, we will design an optimized second-generation tissue growth chamber which would also function as the final storage container. RELEVANCE: This proposal will develop innovative closed, aseptic processing methods for the manufacture of engineered living human skin substitute products, StrataGraft(tm) and ExpressGraft(tm) skin tissue, in development at Stratatech Corporation. By manufacturing these products in a closed, aseptic fashion without the need for mouse feeder cells, we will bring these breakthrough therapies to millions of Americans afflicted with chronic, non-healing diabetic, venous stasis, and pressure ulcers.

描述（由申请人提供）：组织工程 (TE) 有望对治疗困扰数百万美国人的危及生命的疾病的一系列治疗方案产生巨大影响。然而，迄今为止，还没有任何上市的 TE 产品被证明在商业上取得了成功。导致盈利能力不足的主要因素之一是所有步骤都需要无菌处理。与传统的制药和生物技术产品不同，工程组织和细胞疗法必须在整个制造过程中进行无菌处理。因此，这些疗法的设施和生产成本极高。在美国医疗保健系统的患者能够获得基于细胞的疗法之前，需要新的、创新的无菌加工和放大方法。 Stratatech Corporation 已获得 FDA 批准开始使用 StrataGraft(tm) 进行 I/I I 期临床试验，StrataGraft(tm) 是一种基于 Stratatech 获得专利的 NIKS(tm) 人类角质形成细胞系的人类皮肤替代组织。此外，Stratatech 正在开发一系列基因增强活性皮肤产品 (ExpressGraft(tm))，用于慢性、不可愈合的糖尿病、静脉淤滞和褥疮皮肤伤口市场。该快速通道提案旨在为这些创新产品开发封闭的无菌制造工艺，这将大大降低生产成本并提高患者安全。在第一阶段，我们将解决封闭、无菌角质形成细胞培养和扩大规模的问题，以及 PHS 和 FDA 对异种移植的担忧。我们将确定以无菌袋形式冷冻保存 NIKS(tm) 角质形成细胞的参数。然后，我们将在封闭的细胞工厂中解冻并繁殖这些保存的 NIKS(tm) 细胞，而无需鼠饲养细胞的帮助。最后，我们将扩大 NIKS(tm) 培养方法的规模，以实现足够规模的收获和传代，以实现全面的商业生产。在第二阶段，我们将通过开发在封闭的组织生长室中生产 StrataGraft(tm) 皮肤组织的方法来扩展这些结果。我们将建造原型室并通过在线过程监控测试其以批量和灌注模式生产皮肤组织的能力。然后，我们将设计一个优化的第二代组织生长室，它也可作为最终的储存容器。相关性：该提案将开发创新的封闭式无菌加工方法，用于制造由 Stratatech Corporation 开发的工程活体人类皮肤替代产品 StrataGraft(tm) 和 ExpressGraft(tm) 皮肤组织。通过以封闭、无菌的方式生产这些产品，无需小鼠饲养细胞，我们将为数百万患有慢性、不可治愈的糖尿病、静脉淤滞和压疮的美国人带来这些突破性的疗法。