Enhanced tendon to bone healing

增强肌腱到骨骼的愈合

• 批准号: 7576879
• 负责人: Stavros Thomopoulos
• 金额: $ 12.94万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7576879
• 关键词: Adult; Animal Model; Autologous; BMP-12; Biomechanics; Biomedical Engineering; Bone Density; Bone Regeneration; Bone Resorption; Canis familiaris; Cells; Clinical; Clinical Sciences; Collagen; Defect; Development; Doctor of Philosophy; Elderly; Environment; Equilibrium; Failure; Fetal Development; Fibrocartilages; Flexor; Goals; Healed; Immune; Implant; Inferior; Injury; Joints; Lead; Ligaments; Maintenance; Mechanics; Mentors; Mesenchymal Stem Cells; Modeling; Molecular Biology; Motivation; Nature; Osteoblasts; Osteogenesis; Pain; Population; Property; Rattus; Recurrence; Relaxation; Reporting; Research; Research Personnel; Role; Rotator Cuff; Site; Solutions; Stress; Structure; Techniques; Tendon structure; Testing; Therapeutic; Time; Tissue Engineering; Tissues; Wound Healing; aggrecan; bone; bone healing; bone loss; bone morphogenetic protein 2; bone stress; disability; healing; improved; interest; programs; regenerative; repaired; response; supraspinatus muscle

Tendon to bone insertion site injuries are a leading cause of pain and disability in elderly as well as young populations. At the rotator cuff, where there are no repair techniques that are immune from recurrent tears, short to mid term failure rates have been reported to be as high as 94%. Similarly, flexor tendon insertion site repairs do not heal well. The two key features of the failed healing response are loss of bone mineral density and lack of fibrocartilage formation at the interface. Therefore,the overall objective of this study is to use bioengineering approaches to promote bone and fibrocartilage formation in order to improve the tendon to bone repair. Our tissue engineering approach will use the fetal development of tendon to bone insertions as motivation for promoting a regenerative healing response in our two well established animal models. Specifically, the expression of bone morphogenetic protein 2 (BMP-2) and bone morphogenetic protein 12 (BMP-12) will be upregulated to promote the formation of bone and fibrocartilage, respectively. BMP-2 has been implicated in bone fetal development and has successfully been used to promote bone formation in adult tissues. BMP-12 has been implicated in joint fetal development and has been demonstrated to induce neo-tendon/fibrocartilage formation when implanted subcutaneously. In this study, autologous mesenchymal stem cells will be transformed to produce the factors of interest and delivered using a collagen matrix. The mechanical loading environment has also been implicated in the development and maintenance of bone. Fetal development and adult healing studies have demonstrated that increased loading results in the formation of bone, while decreased loading results in the resorption of bone. The role of mechanical loading during healing will be explored by removing the loading across the repair site in one group and enhancing the loading across the repair site in a second group. In specific aim 1 we will stimulate osteoblasts to produce bone at the healing canine flexor tendon- bone insertion site through biologic (i.e., BMP-2) and mechanical (i.e., increased loading) means. In specific aim 2 we will develop biomechanical models to predict the stresses at the tendon to bone interface. In specific aim 3 we will stimulate repair site cells to produce fibrocartilage at the healing rat supraspinatu tendon-bone insertion through biologic (i.e., BMP-12) means. The long term goal of our research program is to provide therapeutic solutions to the clinical problem of tendon to bone healing. The candidate's expertise in bioengineering will be combined with the mentors strengths in clinical science and molecular biology to form a unique and well balanced interdisciplinary team.

肌腱骨插入部位损伤是老年人疼痛和残疾的主要原因 年轻的人口。在肩袖，没有修复技术可以避免复发 据报道，撕裂、短期至中期失败率高达94%。同样，屈肌腱 插入部位修复不能很好地愈合。失败的愈合反应的两个关键特征是骨丢失 矿物质密度和界面处纤维软骨形成的缺乏。因此，这一总体目标 研究是利用生物工程方法促进骨和纤维软骨的形成， 改善肌腱到骨的修复。 我们的组织工程方法将利用胎儿发育的肌腱到骨的插入， 在我们的两个良好建立的动物模型中促进再生愈合反应的动机。 具体地，骨形态发生蛋白2（BMP-2）和骨形态发生蛋白12（BMP-12）的表达在骨形成过程中起重要作用。 BMP-12将被上调以分别促进骨和纤维软骨的形成。BMP-2具有 与骨胎儿发育有关，并已成功用于促进骨形成， 成人组织BMP-12与胎儿的关节发育有关，并已证实可诱导 皮下植入时形成新肌腱/纤维软骨。在这项研究中， 干细胞将被转化以产生感兴趣的因子并使用胶原基质递送。的 机械负荷环境也与骨的发育和维持有关。 胎儿发育和成人愈合研究表明，增加负荷导致 骨的形成，而减少的负荷导致骨的吸收。机械载荷的作用 在愈合期间，将通过在一组中移除修复部位的负荷并增强 在第二组中的修复部位上的载荷。 在具体目标1中，我们将刺激成骨细胞在愈合的犬屈肌腱处产生骨- 骨插入部位通过生物（即，BMP-2）和机械（即，增加负载）的方法。在特定 目的2我们将建立生物力学模型来预测肌腱-骨界面的应力。在 具体目标3我们将刺激修复部位细胞在愈合的大鼠冈上产生纤维软骨 通过生物学的腱-骨插入（即，BMP-12）的意思。 我们研究项目的长期目标是为临床问题提供治疗解决方案 肌腱到骨头的愈合候选人在生物工程方面的专业知识将与导师相结合 在临床科学和分子生物学的优势，形成一个独特的和平衡的跨学科团队。