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

• 批准号: 8457419
• 负责人: RICHARD H GELBERMAN
• 金额: $ 54.52万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 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/8457419
• 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; 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

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. PUBLIC HEALTH RELEVANCE: Treatment of musculoskeletal injuries results in 30 billion dollars in healthcare costs in the United States each year. Approximately half of these injuries involve tendons and ligaments. Growth factor- and cell- based therapy has the potential to improve healing for a broad range of connective tissue injuries. Our long-term goal is to apply growth factor and cell therapy solutions in order to positively affect the clinical outcomes of tendon repair.

描述（由申请人提供）：每年在美国，大约300亿美元用于肌肉骨骼损伤。肌腱和韧带损伤几乎占这些伤害的一半。在上肢，手上的屈肌伤口通常需要手术重建并导致长时间的残疾。临床结果不佳通常是由于早期修复位点的失败以及肌腱及其周围滑膜鞘之间的粘附形成而导致的。我们的目标是开发治疗溶液，以防止修复位点失效并减少沟内膜肌腱修复后的粘附形成。屈肌的早期愈合取决于肌腱表面细胞的迁移和/或外部细胞从滑膜鞘向修复位点延伸。维修的机械性能直到迁移细胞占地并合成细胞外基质后才能改善。然而，细胞在肌腱表面的增殖和外部血管的向内生长会导致肌腱与其鞘之间的粘附形成，并与数字功能的相关损失。先前的研究表明，可以通过基于生长因子和基于细胞的疗法来增强致密结缔组织的愈合。我们以前的研究表明，持续的生长因子PDGF-BB可以改善屈肌肌腱修复后的运动范围。其他人则表明，成年干细胞可以增强外膜肌腱，关节软骨和其他组织中的愈合。但是，很少有这种方法应用这种方法来修复细胞细胞内电屈肌腱。这项研究的中心假设是，修复后，组合的细胞/生长因子治疗可以改善助理内屈肌肌腱的滑行和强度。为了检验这一假设，我们将研究自体脂肪衍生的间充质干细胞疗法的影响，具有或不具有生长因子的给药，对内膜内屈肌肌腱愈合的影响。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，将与干细胞结合使用，并递送进行修复。为了增强愈合过程中的运动范围，抗粘附生长因子将 将其与延伸性生长因子和干细胞结合使用，并递送到修复中。将确定间质干细胞施用的影响，并将评估使用间充质干细胞和生长因子共同处理的影响。结果将直接转化为屈肌肌腱的临床修复，并广泛适用于其他解剖部位的肌腱和韧带修复。 公共卫生相关性：每年美国对肌肉骨骼损伤的治疗导致300亿美元的医疗费用。这些伤害中约有一半涉及肌腱和韧带。生长因子和细胞基疗法有可能改善各种结缔组织损伤的愈合。我们的长期目标是应用生长因子和细胞疗法溶液，以积极影响肌腱修复的临床结果。