SBIR Phase I: Novel Polymer Brush-like Architecture for Temperature Dependent Cell Release and Attachment

SBIR 第一阶段：新型聚合物刷状结构，用于温度依赖性细胞释放和附着

• 批准号: 1248865
• 负责人: Tahmina Naqvi
• 金额: $ 14.9万
• 依托单位: Innovative Surface Technologies, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1248865&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; Polymer; Brush

This Small Business Innovation Research (SBIR) Phase I project is designed to offer two uniquely tailored thermoresponsive surfaces for the attachment and release of weakly and strongly adherent cells. The commercially available surfaces are highly crosslinked hydrogels that do not work well with either strongly or weakly adherent cells. The goal is to transform the current thermoresponsive cell culture technology by providing novel polymer brush-like architectures to the culture surface to reduce protein adsorption, and allow efficient hydration to release the strongly adherent cells. Moreover, addition of functionalities to polymer brush-like architectures will increase the adhesive strength of the surfaces for weakly adherent cells. Major research objectives of this proposal include: 1) Synthesis of photoreactive thermoresponsive brush architectures for strongly adherent cells 2) Synthesis of functionalized brush architectures for weakly adherent cells and 3) Develop coatings in a variety of different cultureware not presently available in market due to the method used. The goal is 90% release of strongly adherent cells within 30 minutes at room temperature and 80% attachment of weakly adherent cells. The broader impact /commercial potential of this project will be the generation of functional cells or cell sheets. The generation of physiologically active functional cells is often the roadblock in technology development. For example, cells recovered from conventional growth surfaces are released using digestive enzymes and chemicals such as Trypsin and EDTA, which alter signal transduction pathways and affect overall cell viability. Thermoresponsive cell cultureware involving the use of Poly N-isopropylacrylamide (PNIPAAm) obviates the use of digestive enzymes; however, major roadblocks with the use of thermoresponsive cultureware remain. The commercially available thermoresponsive plates work well with several cell lines, but do not work well with strongly adherent or weakly adherent cell types, and are available only in multiwell formats. This Phase I grant will develop a new generation of thermoresponsive cell cultureware that could gain wide market acceptance, and become an enabling technology. The process uses simple equipment, is manufacture-friendly, cost-effective, and is available in formats needed for tissue engineering and high-throughput applications. Thus, clinical applications of cell types that were previously considered impossible may be realized, and cell therapy, drug discovery, and tissue engineering applications may proceed at an accelerated pace.

该小型企业创新研究（SBIR）第一阶段项目旨在提供两种独特定制的温敏表面，用于弱粘附和强粘附细胞的附着和释放。可商购的表面是高度交联的水凝胶，其不能很好地与强或弱粘附的细胞一起工作。目标是通过向培养表面提供新型聚合物刷状结构以减少蛋白质吸附，并允许有效水合以释放强粘附细胞来改变当前的温敏细胞培养技术。此外，向聚合物刷状结构中添加官能团将增加弱粘附细胞的表面的粘附强度。该提案的主要研究目标包括：1）用于强粘附细胞的光反应性温度响应刷结构的合成2）用于弱粘附细胞的功能化刷结构的合成和3）在由于所使用的方法而目前在市场上不可用的各种不同培养皿中开发涂层。目标是在室温下30分钟内90%的强粘附细胞释放和80%的弱粘附细胞附着。该项目更广泛的影响/商业潜力将是功能细胞或细胞片的产生。生理活性功能细胞的产生往往是技术发展的障碍。例如，从常规生长表面回收的细胞使用消化酶和化学品如胰蛋白酶和EDTA释放，这改变了信号转导途径并影响整体细胞活力。涉及使用聚N-异丙基丙烯酰胺（PNIPAAm）的温敏细胞培养皿避免了消化酶的使用;然而，使用温敏培养皿的主要障碍仍然存在。 市售的温敏板与几种细胞系配合良好，但与强粘附或弱粘附细胞类型配合不好，并且仅以多孔形式提供。第一阶段的资助将开发新一代的温敏细胞培养器，该培养器将获得广泛的市场认可，并成为一项使能技术。该过程使用简单的设备，是无菌的，具有成本效益，并在组织工程和高通量应用所需的格式。因此，可以实现以前认为不可能的细胞类型的临床应用，并且细胞治疗、药物发现和组织工程应用可以加速进行。