BRIGE: Peptide-Based Cues for Mesenchymal Stem Cell Differentiation in Cartilage Graft Applications

BRIGE：软骨移植应用中间充质干细胞分化的基于肽的线索

• 批准号: 0927100
• 负责人: Julie Liu
• 金额: $ 17.5万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0927100&HistoricalAwards=false
• 关键词: BRIGE; Peptide; Based; Cues; Mesenchymal

0927100LiuThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."Designing materials with cues to induce or enhance adult stem cell differentiation into cartilage cells would improve treatment options for patients suffering from osteoarthritis, a degenerative disease that affects articular cartilage. Healthy cartilage protects load-bearing bones and serves as a lubricant for moving joint surfaces but once damaged, cartilage has a limited regenerative potential. There is increasing interest in developing tissue engineered cartilage replacements using adult stem cells seeded on a scaffold. These cells are often differentiated in vitro using soluble growth factors and chemical compounds. Some of the drawbacks of this method include the extensive cell culture time, the use of super-physiological concentrations of growth factors, and the difficulty in maintaining the articular cartilage phenotype and preventing cartilage hypertrophy. Development of materials that incorporate cues for targeted cell differentiation could circumvent these issues and have the added benefit of facilitating the design and construction of a complex three-dimensional tissue.Intellectual MeritThe proposed work will investigate peptide sequences that are derived from chondrogenic growth factors and have been shown to elicit activity in other biological systems. The objectives of this work are to 1) evaluate soluble peptides for their ability to induce or promote mesenchymal stem cell differentiation into cartilage cells, 2) investigate synergistic effects and maintenance of the cartilage phenotype using experimental design techniques, and 3) develop a novel protein-based scaffold and demonstrate the activity of these peptides within the context of a three-dimensional scaffold. The results from this proposal will demonstrate proof of principle and serve as preliminary data for a future NSF proposal that establishes the peptides as a general design rule by systematically examining them in the context of different scaffolds. The future proposal will also explore the interactions of biochemical and biomechanical properties in controlling cell differentiation. In addition, the work proposed here will demonstrate the utility of a new resilin-based protein scaffold containing chemical and photocrosslinking sites. These results will serve as the preliminary data for a separate proposal that investigates the biocompatibility, mechanical properties, and in vivo use for cartilage engineering applications.Broader ImpactThe proposed work will improve technologies for treating cartilage damaged from disease or injury. In addition, the methodology developed here can be extended for use in other applications such as bone or soft tissue grafts and for the design of multicellular tissues such the liver or vascularized organs. The PI is committed to the recruitment and retention of underrepresented groups in engineering and will engage in individual and group mentoring of female students (high school, undergraduate, and graduate). As part of the Women in Engineering Program, she is actively involved with the graduate mentoring program and is developing a laboratory module to introduce high school students to a high-throughput technique used to evaluate tissue engineering scaffolds. Undergraduate students from underrepresented groups will be recruited through the Louis Stokes Alliance for Minority Participation (LSAMP) Indiana to participate in research during the summer and academic year. The work will also train a female graduate student and mentor her through the process of obtaining a faculty position where she will serve as a role model and mentor to future students. The research will be integrated into the development of undergraduate and graduate level courses on tissue engineering and protein engineering. These courses will emphasize criticalanalysis and introduce students to cutting edge technologies through the use of primary literature papers.

0927100Liu该奖项根据 2009 年美国复苏和再投资法案（公法 111-5）提供资金。“设计具有诱导或增强成体干细胞分化为软骨细胞的线索的材料将改善骨关节炎患者的治疗选择，骨关节炎是一种影响关节软骨的退行性疾病。健康的软骨可以保护承重骨，并充当移动关节表面的润滑剂，但 一旦受损，软骨的再生潜力就有限。人们对使用种植在支架上的成体干细胞开发组织工程软骨替代物越来越感兴趣。这些细胞通常使用可溶性生长因子和化学化合物在体外分化。该方法的一些缺点包括细胞培养时间长、使用超生理浓度的生长因子以及难以维持关节软骨表型和预防 软骨肥大。开发包含靶向细胞分化线索的材料可以规避这些问题，并具有促进复杂三维组织的设计和构建的额外好处。 智力价值拟议的工作将研究源自软骨生长因子的肽序列，并已被证明可以在其他生物系统中引发活性。这项工作的目标是 1) 评估可溶性肽的能力 诱导或促进间充质干细胞分化为软骨细胞，2) 使用实验设计技术研究软骨表型的协同效应和维持，以及 3) 开发一种新型的基于蛋白质的支架，并在三维支架的背景下证明这些肽的活性。该提案的结果将证明原理证明，并作为未来 NSF 建立肽的提案的初步数据 作为一般设计规则，通过在不同支架的背景下系统地检查它们。未来的提案还将探索生化和生物力学特性在控制细胞分化方面的相互作用。此外，这里提出的工作将证明含有化学和光交联位点的新型基于节肢动物蛋白的蛋白质支架的实用性。这些结果将作为研究生物相容性的单独提案的初步数据， 机械性能，以及软骨工程应用的体内使用。更广泛的影响拟议的工作将改进治疗因疾病或损伤而受损的软骨的技术。此外，这里开发的方法可以扩展到其他应用，例如骨或软组织移植，以及多细胞组织的设计，例如肝脏或血管器官。 PI 致力于招募和保留 工程领域代表性不足的群体，并将参与对女学生（高中、本科生和研究生）的个人和团体指导。作为女性工程项目的一部分，她积极参与研究生指导项目，并正在开发一个实验室模块，向高中生介绍用于评估组织工程支架的高通量技术。来自代表性不足群体的本科生将通过路易斯大学招募 印第安纳州斯托克斯少数民族参与联盟 (LSAMP) 在夏季和学年期间参与研究。 这项工作还将培训一名女研究生，并在她获得教职的过程中为她提供指导，她将成为未来学生的榜样和导师。 该研究将被纳入组织工程和蛋白质工程本科和研究生课程的开发中。这些课程将强调批判性分析并向学生介绍 通过使用原始文献论文来实现尖端技术。