NSF/FDA Scholar In Residence: 3D Printed Biomaterials for MSC Attachment and Targeted Differentiation

PI: Fisher, John p .提案：1445700标题：NSF/FDA驻场学者：用于MSC附着和靶向分化的3D打印生物材料意义组织工程和再生医学的临床前景可能取决于分离，培养和输送干细胞的可行策略。因此，美国食品和药物管理局（FDA）必须站在干细胞生物学的最前沿。虽然存在各种各样的干细胞群体，但自体和异体间充质干细胞是研究最广泛的群体之一，因为它们能够很容易地分化成任何中胚层组织，包括骨、软骨、脂肪、肌腱和韧带。目前，通过差速离心和/或塑料粘附获得丰富的MSCs群体。虽然这两种方法都能产生丰富的MSC群体，但都不能一步分离并随后培养MSC。最关键的是，这些方法只适用于MSCs的体外培养。PI建议开发一种改良的生物材料，可以捕获、培养和分化富集的MSC群体，从而产生表型稳定的软骨细胞。拟议的工作将使FDA保持在干细胞技术的前沿，无论是用于再生医学的生物材料开发的技术，还是干细胞与新型生物材料的相互作用。最后，这项工作将促进FDA？通过发展内部专业知识来评估基于干细胞的技术，从而发挥美国监管作用。技术描述间充质干细胞（MSCs）是一种多能干细胞系，具有巨大的治疗潜力，因为它们能够分化成各种谱系，如骨、脂肪和软骨。然而，骨髓间充质干细胞只占骨髓和脂肪组织中细胞的一小部分，并且缺乏独特的识别标记，这增加了分离的难度。这项工作的目标是开发一种组织工程策略，以表征基于粘附的MSC分离，并模拟可生物降解生物材料表面的特定粘附相互作用，以捕获，培养和分化MSCs用于工程软骨组织应用。为此，PI建议开发一种设备，允许MSCs在体内招募和富集，并提供一种简单的体外捕获MSCs的方法。

PI: Fisher, John P.Proposal: 1445700Title: NSF/FDA Scholar In Residence: 3D Printed Biomaterials for MSC Attachment and Targeted DifferentiationSignificanceThe clinical promise of tissue engineering and regenerative medicine will likely depend upon a viable strategy for the isolation, culture, and delivery of stem cells. Therefore, the U.S. Food and Drug Administration (FDA) must be on the forefront of stem cell biology. Although a variety of stem cell populations exist, autogenic and allogeneic mesenchymal stem cells are among the most widely investigated population owing to their ability to be readily differentiated into any of the mesodermal tissues, including bone, cartilage, fat, tendon, and ligament. Currently an enriched population of MSCs is obtained by differential centrifugation and/or plastic adherence. While both of these methods yield an enriched MSC population, neither offers a means to isolate and subsequently culture MSCs in one step. Most critically, these methods are only useful for in vitro culture of MSCs. The PI proposes the development of a modified biomaterial that can capture, culture, and differentiate an enriched MSC population, resulting in phenotypically stable chondrocytes. The proposed work will allow the FDA to remain on the forefront of stem cell technologies, both in the techniques utilized in the development of biomaterials for regenerative medicine and the interaction of stem cells with novel biomaterials. Finally, this work will promote FDA?s regulatory role by developing the in-house expertise to evaluate stem cell based technologies.Technical DescriptionMesenchymal stem cells (MSCs), a multipotent stem cell line, have tremendous therapeutic potential, as they are capable of differentiating into various lineages such as bone, adipose, and cartilage. However, MSCs represent only a fraction of the cells that are found in the bone marrow and adipose tissue and lack unique identifying markers, which increases the difficulty of isolation. The goal of this proposed work is to develop a tissue engineering strategy to characterize MSC isolation based on adhesion, and to mimic the specific adhesive interactions on the surface of a biodegradable biomaterial to capture, culture, and differentiate MSCs for engineered cartilage tissue applications. To this end, the PI proposes to develop a device that will allow for in vivo recruitment and enrichment of MSCs, as well as provide a simple method for in vitro capture of MSCs.