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

提案标题：PECASE：一个系统的方法，在确定材料的表面性能，促进干细胞分化机构：基金会@ NJIT，新泽西理工学院这一建议详细介绍了一个综合的研究和教育计划的发展为中心的组织工程和生物材料计划在生物医学工程系在新泽西理工学院。该研究部分调查了一种系统的方法，评估生物材料作为基于细胞的疗法的潜在支架，并将这些概念分别整合到生物材料和生物相容性以及组织工程原理的新本科和研究生课程中。其目标还在于制定一项计划，通过向来自代表性不足的少数群体的高中生介绍概念，并培训所有女子学校的高中教师采用互动方法向学生教授工程学，从而对增加工程和科学领域代表性不足的群体的数量产生影响。许多受损或患病的组织和器官的再生。该方法是使用细胞而不是药物来治疗各种疾病或病症。研究的最前沿是使用干细胞，因为它们能够分化成各种细胞类型，从而促进受损或患病组织的再生。间充质干细胞（Mesenchymal stem cells，MSCs）是一种具有沿着多种分化途径的多潜能细胞。从成人骨髓中获得并在培养中扩增的MSC被认为是组织工程领域中容易获得且丰富的细胞来源。然而，为了治疗受损或患病的结缔组织，例如大骨折、骨关节炎、肌腱和韧带损伤以及脊髓损伤，MSC必须与促进附着和分化的适当支架材料组合。为了使该技术进入临床应用，需要开发改进的支架材料。该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。主要研究者和其他人已经证明，当与生物活性陶瓷支架结合时，MSC在大的长骨缺损中诱导骨形成。然而，由于陶瓷材料的脆性和/或不良重塑，长骨的完全修复和机械功能的恢复受到限制。其他具有改善的机械和降解性能的合成和天然生物材料已在体外实验中作为MSC的潜在支架进行了研究，但一旦植入，MSC不能诱导骨修复。因此，拟议研究的目标是双重的。首先，本研究旨在通过检查表面特性（例如化学和形貌）和离子溶解/反应在影响干细胞如何粘附、它们呈现的形态和随后的分化中的作用，更清楚地了解磷酸钙陶瓷促进MSC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改进。第二，作为这项工作的延伸，一种新的研究检查聚合物材料，具有明确的表面性质和/或结构，调节干细胞形态将进行调查。作为细胞形状的函数，将检查干细胞分化成骨、软骨和脂肪组织的细胞表型。该项目最初作为CAREER奖资助，并于2004年9月转换为工程师和科学家总统早期职业奖（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.