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

PI：Fisher，John P.Proposal：1445700题目：NSF/FDA常驻学者：3D打印生物材料用于MSC附着和定向分化意义组织工程和再生医学的临床前景可能取决于干细胞分离、培养和输送的可行策略。因此，美国食品和药物管理局(FDA)必须站在干细胞生物学的前沿。尽管存在多种干细胞群体，但自体和同种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为任何中胚层组织，包括骨、软骨、脂肪、肌腱和韧带。目前，通过差速离心法和/或塑料贴壁法获得丰富的骨髓间充质干细胞。虽然这两种方法都能产生丰富的骨髓间充质干细胞种群，但都不能提供一种分离和随后一步培养骨髓间充质干细胞的方法。最关键的是，这些方法只对MSCs的体外培养有用。PI建议开发一种改进的生物材料，可以捕获、培养和分化丰富的MSC群体，从而产生表型稳定的软骨细胞。拟议中的工作将使FDA在干细胞技术方面保持领先地位，无论是在用于再生医学的生物材料开发技术方面，还是在干细胞与新生物材料的相互作用方面。最后，这项工作将通过发展内部专业知识来评估基于干细胞的技术，从而促进FDA？S的调节作用。技术描述间充质干细胞(MSCs)是一种多潜能干细胞系，具有巨大的治疗潜力，因为它们能够分化为各种谱系，如骨、脂肪和软骨。然而，MSCs只代表了骨髓和脂肪组织中发现的细胞的一小部分，并且缺乏唯一的识别标记，这增加了分离的难度。这项拟议工作的目标是开发一种组织工程策略来表征基于黏附的MSC分离，并模拟可生物降解生物材料表面的特定黏附相互作用，以捕获、培养和分化MSCs，用于工程化软骨组织应用。为此，PI建议开发一种设备，允许在体内招募和浓缩MSCs，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.