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

提案标题：PECASE：确定材料表面的系统方法促进干细胞分化的特性机构：Foundation@NJIT，新泽西理工学院本提案详细说明了一项以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为中心的综合研究和教育计划。研究部分研究一种系统的方法，评估生物材料作为基于细胞的治疗的潜在支架，并将这些概念分别纳入生物材料、生物兼容性和组织工程原理的新本科生和研究生课程。我们的目标也是开发一个项目，通过向来自代表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向他们的学生传授工程学的互动方法，从而对增加工程和科学领域中代表不足的群体的数量产生影响。新兴的组织工程技术有可能成为许多受损或患病组织和器官再生的首选疗法。方法是使用细胞，而不是药物，来治疗各种疾病或紊乱。研究的前沿是干细胞的使用，因为它们能够分化为各种类型的细胞，从而促进受损或患病组织的再生。间充质干细胞(MSCs)是一种具有多向分化潜能的细胞，具有多种分化途径。骨髓间充质干细胞是从成人骨髓中获得并在培养中扩增的干细胞，在组织工程领域被认为是一种容易获得和丰富的细胞来源。然而，为了治疗受损或疾病的结缔组织，如大骨骨折、骨关节炎、肌腱和韧带损伤以及脊髓损伤，MSCs必须与促进附着和分化的适当支架材料结合。为了将这项技术推进到临床应用，需要开发改进的支架材料。这项研究计划的目标是系统地研究促进干细胞分化的材料的最佳表面属性和特征。主要研究人员和其他人已经证明，当MSCs与生物活性陶瓷支架结合时，可以在大而长的骨缺损中诱导骨形成。然而，由于陶瓷材料的脆性和/或改建不良，长骨的完全修复和机械功能的恢复是有限的。其他具有改善力学性能和降解性能的合成和天然生物材料已在体外实验中作为MSCs的潜在支架进行了研究，但一旦植入，MSCs无法诱导骨修复。因此，拟议研究的目标是双重的。首先，本研究旨在通过检测表面性质(如化学和形貌)和离子溶解/反应对干细胞的黏附方式、形态和随后的分化的影响，更清楚地了解钙磷陶瓷促进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发展。其次，作为这项工作的延伸，将研究一项新的研究，考察具有明确表面属性和/或结构的聚合物材料，这些材料可以调节干细胞的形态。作为细胞形状的一项功能，干细胞分化为骨、软骨和脂肪组织的细胞表型将被研究。该项目最初是作为职业奖资助的，并于2004年9月转变为总统工程师和科学家早期职业奖(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.