Enhanced Tendon Healing through Growth Factor and Cell Therapies

通过生长因子和细胞疗法增强肌腱愈合

基本信息

批准号：
8720698
负责人：
RICHARD H GELBERMAN
金额：
$ 52.15万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-15 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8720698
关键词：
Address Adhesions Adhesives Adipose tissue Affect Anatomic Sites Apoptosis Articular Range of Motion Autologous BMP-12 Biomechanics Canis familiaris Cell Proliferation Cell Therapy Cell surface Cells Characteristics Clinical Coculture Techniques Connective Tissue Dense Connective Tissue Environment Extracellular Matrix Failure Fibrin Fibroblast Growth Factor Fibroblast Growth Factor 2 Fibroblasts Flexor Goals Growth Factor Hand Healed Health Care Costs Heparin In Vitro Inflammation Inflammatory Injury Interleukin-1 Knee Lead Ligaments Location Mechanics Mesenchymal Stem Cells Methods Modeling Natural regeneration Operative Surgical Procedures Outcome Pilot Projects Polymers Process Production Property Rehabilitation therapy Rotator Cuff Rupture Site Solutions Staging Stem cells Study Section Surface Surgical sutures Synovial Cell System Tendon Injuries Tendon structure Testing Therapeutic Time Tissues Transplantation United States Up-Regulation Upper Extremity adult stem cell articular cartilage base cell growth cell motility clinical care clinically relevant cost cytokine digital disability healing improved in vivo injured ligament injury migration musculoskeletal injury nanofiber novel platelet-derived growth factor BB prevent reconstruction repaired research study scaffold soft tissue stem cell therapy success translational study

项目摘要

DESCRIPTION (provided by applicant): Approximately 30 billion dollars are spent on musculoskeletal injuries in the United States each year. Tendon and ligament injuries represent almost half of these injuries. In the upper extremity, flexor tendon wounds to the hand often require surgical reconstruction and lead to prolonged disability. Poor clinical outcomes typically result from early repair-site failure and the formation of adhesions between the tendon and its surrounding synovial sheath. Our goal is to develop therapeutic solutions to prevent repair-site failure and to reduce adhesion formation following intrasynovial tendon repair. Early healing of flexor tendons relies on the migration of tendon surface cells and/or the extension of extrinsic cells from the synovial sheath to the repair site. The mechanical properties of the repair do not improve until migrating cells populate the site and synthesize extracellular matrix. The proliferation of cells on the tendon surface and the ingrowth of extrinsic vessels, however, can lead to adhesion formation between the tendon and its sheath, with associated loss of digital function. Prior studies have shown that the healing of dense connective tissues can be enhanced via growth factor- and cell-based therapies. Our previous studies demonstrated that sustained delivery of the growth factor PDGF-BB can improve range of motion after flexor tendon repair. Others have shown that adult stem cells can enhance healing in extrasynovial tendons, articular cartilage, and other tissues. However, few have applied this approach to repair pauci-cellular intrasynovial flexor tendons. The central hypothesis of this study is that a combined cell/growth factor therapy can improve gliding and strength of intrasynovial flexor tendons following repair. To test this hypothesis, we will examine the effects of autologous adipose derived mesenchymal stem cell therapy, with and without growth factor administration, on intrasynovial flexor tendon healing. A novel nanofiber scaffold capable of controlling the delivery of cells and growth factors will be used. In an effort to promote stem cell differentiatio during healing, a tenogenic growth factor will be combined with stem cells and delivered to the repair. In an effort to enhance range of motion during healing, an anti-adhesive growth factor will be combined with a tenogenic growth factor and stem cells and delivered to the repair. The effects of mesenchymal stem cell application will be determined and the impact of co-treatment using both mesenchymal stem cells and growth factors will be evaluated. Results will be directly translatable to clinical repair of flexor tendons and broadly applicable to tendon and ligament repair at other anatomic sites.

描述（由申请人提供）：美国每年大约花费 300 亿美元用于肌肉骨骼损伤。肌腱和韧带损伤几乎占这些损伤的一半。在上肢，手部屈肌腱伤口通常需要手术重建，并导致长期残疾。不良的临床结果通常是由于早期修复部位失效以及肌腱与其周围滑膜鞘之间形成粘连所致。我们的目标是开发治疗解决方案，以防止修复部位失效并减少滑膜内肌腱修复后粘连的形成。屈肌腱的早期愈合依赖于肌腱表面细胞的迁移和/或外在细胞从滑膜鞘到修复部位的延伸。直到迁移细胞填充该部位并合成细胞外基质后，修复的机械性能才会得到改善。然而，肌腱表面细胞的增殖和外在血管的向内生长可能导致肌腱与其鞘之间形成粘连，从而导致手指功能丧失。先前的研究表明，通过生长因子和细胞疗法可以增强致密结缔组织的愈合。我们之前的研究表明，持续输送生长因子 PDGF-BB 可以改善屈肌腱修复后的运动范围。其他研究表明，成体干细胞可以增强滑膜外肌腱、关节软骨和其他组织的愈合。然而，很少有人应用这种方法来修复少细胞滑膜内屈肌腱。这项研究的中心假设是细胞/生长因子联合疗法可以改善修复后滑膜内屈肌腱的滑动和强度。为了检验这一假设，我们将检查自体脂肪来源的间充质干细胞疗法（有或没有施用生长因子）对滑膜内屈肌腱愈合的影响。将使用一种能够控制细胞和生长因子输送的新型纳米纤维支架。为了在愈合过程中促进干细胞分化，肌腱生长因子将与干细胞结合并输送至修复部位。为了增强愈合过程中的运动范围，抗粘连生长因子将与肌腱生长因子和干细胞结合并进行修复。将确定间充质干细胞应用的效果，并评估使用间充质干细胞和生长因子共同治疗的影响。结果将直接转化为屈肌腱的临床修复，并广泛适用于其他解剖部位的肌腱和韧带修复。