I-Corps: Cell Culture Platform Using Engineered Micropatterns to Control Differentiation

这个i-Corps项目的更广泛的影响/商业潜力是开发一种用于骨关节炎(OA)的体外关节软骨模型。该模型旨在增加成功地将有关骨性关节炎病因的研究转化为可能的治疗方法的可能性。骨性关节炎通常随年龄或受伤而发生，影响超过3250万美国成年人。目前还没有已知的疾病修正疗法来阻止或逆转骨性关节炎的进展--所有目前的治疗方法都局限于各种疼痛管理方法或外科组织置换。这项拟议的技术将通过使用传统和最先进的基因组、蛋白质组和成像技术促进对软骨细胞的研究，从而促进对骨关节炎研究的翻译。软骨细胞是引起骨关节炎的主要细胞。预计拟议中的技术将弥合2D和3D细胞培养市场之间的差距，美国的年市场规模约为10亿美元。由于骨关节炎的流行和残废性质，关节置换在美国每年代表着190亿美元的行业。除了在骨关节炎治疗中的作用外，该模型可能在改善自体软骨细胞移植的结果方面具有临床意义，增加其商业影响。这个I-Corps项目基于一个细胞培养平台的开发，该平台改善了对软骨细胞分化的控制。这种控制是通过纳米技术、微图案化和机械可调薄膜复合材料的新颖组合来调节细胞形状来实现的。在标准的2D培养体系中，软骨细胞迅速转化为非生理性细胞类型。更先进的3D培养系统避免了这个问题，但在与分析技术的兼容性方面带来了困难。这项拟议的技术可以充当单个细胞的蛋箱，将每个细胞嵌套在一个环境中，使其能够保持其生理性质，而不限制它们被研究的能力。这项技术可以将软骨细胞的生理细胞形状保持至少28天，是竞争对手微图案化技术的四倍。这项技术在药物开发、基因治疗、干细胞医学、组织工程、阐明分子发病机制和其他生物医学应用方面具有潜在的应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of an in vitro, articular cartilage model for osteoarthritis (OA). This model is designed to increase the likelihood of successful clinical translation of research on the causes of OA into potential treatments. OA often occurs with age or injury and affects over 32.5 million US adults. There are currently no known disease-modifying treatments to stop or reverse the progression of OA – all current treatments are limited to either various methods of pain management or surgical tissue replacement. The proposed technology will advance the translation of OA research by facilitating studies of chondrocytes, the primary cells that cause OA, using traditional and state-of-the-art genomic, proteomic, and imaging techniques. It is expected that the proposed technology will bridge the gap between the 2D and 3D cell culture markets, represented by an annual market of ~$1 billion in the US. Due to the prevalence and crippling nature of OA, joint replacements represent a $19 billion industry annually in the US. In addition to its role in OA treatments, the model may clinical implications in improving outcomes for autologous chondrocyte transplantation, increasing its commercial impact.This I-Corps project is based on the development of a cell culture platform that improves control over the differentiation of chondrocytes. This control is enabled through the regulation of cell shape via a novel combination of nanotechnology, micropatterning, and mechanically-tunable, thin-film composite materials. Chondrocytes rapidly transform into non-physiological cell types in standard 2D culture systems. More advanced 3D culture systems prevent this problem but introduce difficulties in compatibility with analytical techniques. The proposed technology may act as an egg crate for individual cells, nesting each one in an environment that allows it to maintain its physiological nature without restricting their ability to be studied. The technology may maintain the physiological cell shape of chondrocytes for at least 28 days, four times as long as competing micropatterned technologies. The technology has potential applications in drug development, gene therapy, stem cell medicine, tissue engineering, the elucidation of molecular pathogeneses, and other biomedical applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.