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

• 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
• 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

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.

项目概要： 此生物工程研究合作伙伴 (BRP) 申请，来自生物医学系的 PI 辛辛那提大学工程系和辛辛那提儿童医院发育生物学系 医院医疗中心，是根据 NIH PAR-07-352 和 NIAMS NOT-AR-002 编写的。大学 辛辛那提大学是牵头机构。拟议研究的目的是使用多 功能组织工程策略刺激整个肌腱中质和插入的修复 利用正常发育的遗传模式。该程序的目标是正常识别基因 在发育中的肌腱中表达，该肌腱将用作组织工程构建体的诊断工具 (TEC) 在培养物中的成熟，以及控制细胞活性以指导肌腱 TEC 的信号通路 文化上的成熟。在每种情况下，我们都会将 TEC 的成熟程度与其生物力学联系起来 特性及其影响肌腱修复的能力。这将产生更多的功能性组织工程 加速肌肉骨骼修复的策略和设计标准。我们的中短期目标是：1) 识别 FGF 和 BMP 信号配体、受体和靶标表达的空间和时间模式 正常小鼠髌腱发育过程中的下游。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TECs的体外机械刺激对FGF的影响程度 和 BMP 信号传导以及由此产生的构建生物力学。将这些模式与期间表达的模式进行比较 正常的肌腱发育和成人自然愈合期间。 3) 确定是否调节表达 培养中的鼠、兔和羊 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。我们已经拥有关于骨髓源性细胞结构修复能力的大型数据集 兔子的肌腱受损。我们将关联物种之间的 TEC 行为，以便快速识别 提出进行兔肌腱手术的理想候选人。到 5 年底，我们将产生 正常肌腱发育过程中基因表达的时空图，涉及的信号通路 肌腱发育中的变化，以及这些信息可用于改善 TEC 成熟度的程度 培养和肌腱修复以扩展到绵羊模型。三个关键咨询小组（研究指导 委员会、行业合作伙伴和临床科学家）将定期参与监测进展和 确定研究的转化方面。