Enhanced Tendon Healing through Growth Factor and Cell Therapies

描述（由申请人提供）：美国每年约有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败和肌腱与其周围滑膜鞘之间形成粘连。我们的目标是开发治疗方案，以防止修复部位失败，并减少滑膜内肌腱修复后粘连形成。屈肌腱的早期愈合依赖于肌腱表面细胞的迁移和/或外源性细胞从滑膜鞘延伸到修复部位。修复的机械性能不会改善，直到迁移细胞填充该部位并合成细胞外基质。然而，肌腱表面细胞的增殖和外源性血管的向内生长可导致肌腱与其鞘之间的粘连形成，并伴随手指功能的丧失。先前的研究表明，致密结缔组织的愈合可以通过基于生长因子和细胞的疗法来增强。我们以前的研究表明，持续输送生长因子PDGF-BB可以改善屈肌腱修复后的活动范围。其他研究表明，成体干细胞可以促进滑膜外肌腱、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/生长因子联合治疗可以改善修复后滑膜内屈肌腱的滑动和强度。为了验证这一假设，我们将研究自体脂肪来源的间充质干细胞治疗的影响，有和没有生长因子管理，对滑膜内屈肌腱愈合。将使用一种能够控制细胞和生长因子递送的新型生物相容性支架。为了在愈合过程中促进干细胞分化，一种生腱生长因子将与干细胞结合并输送到修复部位。为了在愈合过程中增加运动范围，抗粘连生长因子将 与生腱生长因子和干细胞结合，并输送到修复部位。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的共同治疗的影响。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。

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.