SBIR Phase I: Improving cell loading efficiency for suture mediated cell therapy

这个小企业创新（SBIR）第一阶段项目将在理解间充质干细胞和新型纤维蛋白微线缝合结构之间的相互作用方面取得关键进展，以克服细胞治疗领域的显著低效。这项工作将开发一种新的播种容器和相关方案，用于高效的间充质干细胞加载，以应用于纤维蛋白微线缝合。一旦开发出这样的方案，将所得装置肌内植入大鼠模型中，以探索细胞递送效率和宿主对细胞负载的纤维蛋白微丝装置的反应。所得的细胞接种数据将提供对体外细胞接种效率可通过对常见接种条件（包括容器几何形状、细胞浓度和总细胞负载）进行简单修改来操纵的程度的了解。体内工作将提供关键信息，分别描述纤维蛋白微线的生物相容性，与纤维蛋白微线介导的干预相比，生物素介导的细胞递送效率，以及这些干预的炎症/纤维化潜力。反过来，该项目中开发的系统将有望为进一步研究细胞治疗提供平台，这些细胞治疗使用谨慎递送、高活性和准确剂量的细胞群进行。该项目更广泛的影响/商业潜力不仅涉及特定的靶向适应症，跟腱，而且更广泛地涉及其他结缔组织修复，其他增强愈合适应症，和其它细胞递送应用。一旦完全实现，仅跟腱修复增强市场预计在美国每年价值5亿美元。虽然缝合线样形状因子可能不是所有应用的理想选择，但在愈合不良或未愈合的器官系统上进行的几种类型的开放手术可以容易地受益于通过该技术进行的细胞递送。这将包括诸如心肌梗死修复、中风病例中的神经组织再生和耳蜗组织再生等适应症。我们项目的成功商业化代表着组织工程和下一代细胞药物向前迈出了重要一步，有望改善无数人的寿命和生活质量。

This Small Business Innovation (SBIR) Phase I project will provide critical advances in the understanding of interactions between mesenchymal stem cells and a novel fibrin microthread suture construct in an effort to overcome significant inefficiencies in the field of cell therapy delivery. This work will develop a novel seeding vessel and associated regimen for highly efficient mesenchymal stem cell loading to be applied to fibrin microthread sutures. Once such a regimen has been developed, resultant devices will be implanted intramuscularly in a rat model to explore cell delivery efficiency and host response to the cell-loaded fibrin microthread device. The resultant cell seeding data will provide insight into the extent to which cell seeding efficiency in vitro may be manipulated by simplistic modifications to common seeding conditions including vessel geometry, cell concentration, and total cell load. The in vivo work will provide critical information describing the biocompatibility of fibrin microthreads, cell delivery efficiency of syringe-mediated compared to fibrin microthread-mediated interventions, and inflammatory/fibrotic potential of these interventions respectively. In turn, the systems developed in this project will be expected to provide a platform for further research of cell therapy performed with discreetly delivered, highly viable, and accurately dosed cell populations.The broader impact/commercial potential of this project relates not only to the specific indication targeted, Achilles tendon, but more broadly to other connective tissue repairs, other enhanced healing indications, and other cell delivery applications. Once fully realized, the Achilles tendon repair augmentation market alone is projected to be worth $500M annually in the United States. While the suture-like form factor may not be ideal for all applications, several types of open surgeries performed upon poorly healing or non-healing organ systems could readily benefit from cell delivery by this technology. This would include indications such as myocardial infarct repair, neural tissue regeneration in cases of stroke, and cochlear tissue regeneration. The successful commercialization of our project represents a significant step forward in tissue engineering and next generation cell-based medicines, promising to improve both longevity and quality of life for countless people.