PECASE: A Systematic Approach in Determining Material Surface Properties that Promote Stem Cell Differentiation

提案标题：PECASE：确定促进干细胞分化的材料表面特性的系统方法机构：基金会@ NJIT，新泽西理工学院该提案详细介绍了新泽西理工学院生物医学工程系组织工程和生物材料项目发展的综合研究和教育计划。研究部分研究了一种系统的方法来评估生物材料作为细胞基础疗法的潜在支架，并将这些概念分别整合到生物材料、生物相容性和组织工程原理的本科和研究生课程中。目标还在于制定一个项目，通过向高中学生介绍来自代表性不足的少数群体的概念，并培训所有女校的高中教师以互动方式向学生教授工程，从而增加工程和科学领域代表性不足的群体的数量。组织工程的新兴技术有可能成为许多受损或患病组织和器官再生的治疗选择。这种方法是用细胞代替药物来治疗各种疾病或失调。研究的前沿是干细胞的使用，因为它们能够分化成各种细胞类型，从而促进受损或病变组织的再生。间充质干细胞（MSCs）是一种多能细胞，能够沿着几种谱系途径分化。从成人骨髓中获得并在培养中扩增的间充质干细胞被认为是组织工程领域一种容易获得和丰富的细胞来源。然而，为了治疗受损或病变的结缔组织，如大骨折、骨关节炎、肌腱和韧带损伤以及脊髓损伤，间充质干细胞必须与适当的支架材料结合，以促进附着和分化。为了使该技术进入临床应用，需要改进支架材料的开发。本研究计划的目标是以系统的方式研究促进干细胞分化的材料的最佳表面特性和特征。首席研究员和其他人已经证明，当MSCs与生物活性陶瓷支架结合时，可以诱导大型长骨缺损的骨形成。然而，由于陶瓷材料的脆性和/或重塑不良，长骨的完全修复和机械功能的恢复受到限制。在体外实验中已经研究了其他具有改进力学和降解性能的合成和天然生物材料作为MSCs的潜在支架，但是一旦植入MSCs，就不能诱导骨修复。因此，提出的研究目标是双重的。首先，本研究旨在通过考察表面性质（如化学和形貌）和离子溶解/反应对干细胞粘附方式、形态和随后分化的影响，更清楚地了解磷酸钙陶瓷促进间充质干细胞分化和新骨组织合成的机制。这些基础研究将进一步推动干细胞诱导骨再生材料的发展。其次，作为这项工作的延伸，将研究一项新的研究，研究具有明确定义的表面特性和/或结构的聚合物材料，以调节干细胞形态。作为细胞形状的功能，干细胞分化为骨、软骨和脂肪组织的细胞表型将被检查。该项目最初是作为职业奖资助的，并于2004年9月转换为工程师和科学家的总统早期职业奖（PECASE）奖。

Proposal Title: PECASE: A Systematic Approach in Determining Material SurfaceProperties that Promote Stem Cell DifferentiationInstitution: Foundation @ NJIT, New Jersey Institute of TechnologyThis proposal details an integrated research and educational plan centered on the development of a tissue engineering and biomaterials program in the department of Biomedical Engineering at New Jersey Institute of Technology. The research component investigates a systematic approach in evaluating biomaterials as potential scaffolds for cell based therapies and integrating these concepts in new undergraduate and graduate courses in biomaterials and biocompatibility and principles of tissue engineering, respectively. The goal is to also develop a program that will have an impact on increasing the number of underrepresented groups in the field of engineering and science by introducing concepts to high school students from underrepresented minority groups and training high school teachers of all girl schools interactive approaches to teaching engineering to their students.The emerging technology of tissue engineering has the potential of becoming the therapy of choice for the regeneration of a number of damaged or diseased tissues and organs. The approach is to use cells, instead of drugs, to treat various diseases or disorders. At the forefront of investigation is the use of stem cells because of their ability to differentiate into various cell types and thus, promote the regeneration of the damaged or diseased tissue of interest. Mesenchymal stem cells (MSCs) are multipotential cells that are capable of differentiating along several lineage pathways. MSCs, which are obtained from adult bone marrow and expanded in culture, are believed to be valuable as a readily available and abundant source of cells in the tissue engineering field. However, for treating damaged or diseased connective tissues, such as large bone fracture, osteoarthritis, tendon and ligament injuries, and spinal cord injury, MSCs must be combined with an appropriate scaffold material that promotes attachment and differentiation. For this technology to advance into clinical application, the development of improved scaffold materials is needed. The goal of this research program is to investigate in a systematic fashion the optimal surface properties and characteristics of materials that promote stem cell differentiation. The principal investigator and others have demonstrated that MSCs, when combined with bioactive ceramic scaffolds induce bone formation in large, long bone defects. However, complete repair and return of mechanical function of the long bone is limited due to the brittle nature and/or poor remodeling of the ceramic material. Other synthetic and natural biomaterials with improved mechanical and degradation properties have been investigated in in vitro experiments as potential scaffolds for the MSCs, but once implanted, MSCs fail to induce bone repair. Therefore, the objectives of the proposed research are two-fold. First, this study is designed to gain a clearer understanding of the mechanism by which calcium phosphate ceramics promote MSC differentiation and synthesis of new bone tissue by examining the effect of surface properties (e.g. chemistry and topography) and ion dissolution/reactions in influencing how stem cells adhere, the morphology they assume, and subsequent differentiation. These fundamental studies will further advance the development of improved materials for stem cell induced bone regeneration. Second, as an extension of this work, a novel study examining polymeric materials that have well defined surface properties and/or architectures that modulate stem cell morphology will be investigated. As a function of cell shape, stem cell differentiation into cell phenotypes of bone, cartilage, and adipose tissue will be examined.This project was originally funded as a CAREER award, and was converted to a Presidential Early Career Award for Engineers and Scientists (PECASE) award in September 2004.