A Developmentally-Based Tissue Engineering Approach to Improve Tendon Repair

一种基于发育的组织工程方法来改善肌腱修复

基本信息

批准号：
8293428
负责人：
DAVID L BUTLER
金额：
$ 62.94万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-10 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8293428
关键词：
Accounting Activities of Daily Living Acute Adult Affect Affinity Allografting Animal Model Attenuated Autologous Autologous Transplantation BMP2 gene Behavior Binding Biological Biology Biomechanics Biomedical Engineering Bone Marrow Candidate Disease Gene Cell Density Cells Chemical Stimulation Chemicals Chronic Clinical Complex Cues Data Data Set Defect Development Developmental Biology Diagnostic Environment Evaluation Face Failure Fatigue Fibroblast Growth Factor Fibroblast Growth Factor Receptors Gene Expression Gene Expression Profile Generations Genes Genetic Genetic Models Genomics Goals Grant Growth and Development function Healed Homologous Gene Implant In Vitro Individual Industry Infection Inferior Injury Institution Joints Knowledge Lead Left Length Ligaments Ligands Limb Development Limb structure Maps Measures Mechanical Stimulation Mechanics Medical center Mesenchymal Stem Cells Methodology Modeling Monitor Morbidity - disease rate Mus Musculoskeletal National Institute of Arthritis and Musculoskeletal and Skin Diseases Operative Surgical Procedures Oryctolagus cuniculus Outcome Pathway interactions Patients Pattern Pediatric Hospitals Postoperative Pain Process Property Protein Isoforms Proteins Quality of life Rattus Recovery Regulation Research Research Personnel Risk Rotator Cuff Rupture Scientist Secondary pain Sheep Signal Pathway Signal Transduction Site Source Specificity Speed Stimulus Surface Tenascin Tendon Injuries Tendon structure Testing Text Time Tissue Engineering Tissues Transgenes Transgenic Mice Transgenic Organisms Translating United States National Institutes of Health Universities Workplace Writing aggrecan base bone bone morphogenetic protein 2 bone morphogenetic protein 4 candidate marker design design and construction experience fibroblast growth factor receptor 2c gene discovery healing improved improved functioning in vitro testing in vivo industry partner injured innovation ligament injury mRNA Expression meetings musculoskeletal injury programs protein expression receptor repaired research study response scaffold scleraxis soft tissue spatiotemporal stem cell differentiation success thrombospondin 4 tissue repair tool transcription factor wound

项目摘要

Project Summary: This Bioengineering Research Partnership (BRP) application, from PI's in the Department of Biomedical Engineering at the University of Cincinnati and the Division of Developmental Biology at Cincinnati Children's Hospital Medical Center, is written in response to NIH PAR-07-352 and NIAMS NOT-AR-002. The University of Cincinnati is serving as the lead institution. The purpose of the proposed research is use a Multi- Functional Tissue Engineering Strategy to stimulate repair of the entire tendon midsubstance and insertion using genetic patterns of normal development. The goal of the program is to identify genes normally expressed in a developing tendon, which will be used as a diagnostic tool for tissue engineered construct (TEC) maturation in culture, and the signaling pathways that control cellular activity so as to direct tendon TEC maturation in culture. In each case, we will correlate the degree of TEC maturation with its biomechanical properties, and its ability to effect tendon repair. This will generate more functional tissue engineering strategies and design criteria to speed musculoskeletal repair. Our short- to intermediate-term goals are: 1) Identify spatial and temporal patterns of expression of FGF and BMP signaling ligands, receptors, and targets downstream during normal murine patellar tendon development. Contrast these patterns with those expressed during adult PT healing. 2) Determine the extent to which in vitro mechanical stimulation of TECs affects FGF and BMP signaling and resulting construct biomechanics. Compare these patterns to those expressed during normal tendon development and during natural adult healing. 3) Determine if modulating expression of candidate markers within murine, rabbit and sheep TECs in culture can control in vitro biomechanics and biology and, furthermore, whether implanting corresponding rabbit TECs improves tendon repair in the rabbit model. We already have a large dataset on the ability of bone marrow-derived cellular constructs to repair damaged tendons in the rabbit. We will correlate TEC behavior between species in order to rapidly identify desirable candidates to bring forward for rabbit tendon surgery. By the end of 5 years, we will have generated a spatiotemporal map of gene expression during normal tendon development, the signaling pathways involved in tendon development, and the degree to which this information can be used to improve TEC maturation in culture and tendon repair for extension to the sheep model. Three key advisory groups (Research Steering Committee, Industry Partners and Clinician-Scientists) will regularly participate in monitoring progress and identifying translational aspects of the research.

项目摘要：该生物工程研究合作伙伴（BRP）应用程序，来自生物医学系的PI 辛辛那提大学的工程和辛辛那提儿童的发展生物学系医院医疗中心是根据NIH PAR-07-352和NIAMS NOT-AR-002编写的。大学辛辛那提（Cincinnati）担任主要机构。拟议研究的目的是使用多种多样功能性组织工程策略，以刺激整个肌腱中部和插入的修复使用正常发育的遗传模式。该程序的目的是正常识别基因在发育中的肌腱中表达，该肌腱将用作组织工程结构的诊断工具（TEC）培养的成熟以及控制细胞活性的信号传导途径，以指导肌腱TEC 文化成熟。在每种情况下，我们都将TEC成熟程度与其生物力学相关特性及其实施肌腱修复的能力。这将产生更多功能的组织工程策略和设计标准，以加快肌肉骨骼修复。我们的短期至中期目标是：1）确定FGF和BMP信号配体，受体和靶标的空间和时间模式正常鼠tellar肌腱发育中的下游。将这些模式与表达的模式进行对比在成人PT愈合期间。 2）确定TEC的体外机械刺激在多大程度上影响FGF 以及BMP信号传导和由此产生的构建生物力学。将这些模式与在正常的肌腱发育和天然成人愈合期。 3）确定是否调制表达文化中鼠，兔子和绵羊TEC中的候选标记可以控制体外生物力学和生物学，此外，植入相应的兔子TEC是否可以改善兔子的肌腱修复模型。我们已经有一个关于骨髓衍生的细胞构建体能力的大数据集兔子中受损的肌腱。我们将将物种之间的TEC行为相关联，以迅速识别理想的候选人提出兔肌腱手术。到5年结束时，我们将产生正常肌腱发育过程中基因表达的时空图，涉及信号通路在肌腱发育中，以及该信息可用于改善TEC成熟的程度培养和肌腱修复，以扩展到绵羊模型。三个关键咨询小组（研究转向委员会，行业伙伴和临床医生 - 科学家）将定期参加监视进度和确定研究的翻译方面。