"In Vitro Mechanical Stimulation to Enhance Tendon Repair"

描述（由申请人提供）：拟议的研究将优化应用于间充质干细胞（MSC）构建的机械刺激，以测试提供体内应变模拟既加强修复又缩短愈合时间的全球假设。本研究解决了3个重要的临床问题：用生物结构体填充肌腱缺损以减轻疼痛和僵硬，并为翻修手术提供移植物；大肌腱套撕裂修复及韧带重建；修复慢性退行性肌腱损伤。使用功能组织工程或FTE路线图与体外和体内研究相关联，我们将在兔髌骨肌腱模型（PT）中建立4种日常生活活动的体内力和位移（目的1）。使用一种新颖的设计策略，6个机械治疗因素将在培养中变化，以在手术前优化结构的切线刚度（目的2）。将具有显著不同切线刚度值的结构体植入兔PT缺陷，以检查修复刚度的显着改善（目的3）。因此，我们将测试一系列相关假设：兔PT在所有活动中保持非零组织应变和力。忧郁2。增加步态表面的坡度或倾斜度会增加体内力和应变参数。忧郁3。暴露于体内应变形状的兔和小鼠构建体比暴露于梯形或正弦剖面的构建体具有更高的切线刚度。忧郁4。在生理限度内增加应变幅度，可增加培养物的切线刚度。忧郁。5。与体内信号相似的上升和下降时间和相似周期的应变模式在培养中表现出最大的刚度值。忧郁6。具有最大切线刚度的小鼠构建物在培养中表现出最大的col I基因表达增加。忧郁7。在培养中增加结构刚度可以增加手术后的修复刚度，并更好地对齐修复部位的细胞和细胞外基质。我们新颖的，相互作用的体外/体内研究应该有助于开发手术后体内修复结果的体外预测因子，也适用于其他组织系统。

DESCRIPTION (provided by applicant): The proposed studies will optimize mechanical stimuli applied to mesenchymal stem cell (MSC) constructs to test the global hypothesis that delivering in vivo strain simulations boths stiffens repairs and shortens healing time. This research addresses 3 important clinical problems: filling tendon defects with biological constructs to reduce pain and stiffness and to provide grafts for revision surgery; repairing large rotator cuff tears and augmenting ligament reconstructions; and repairing chronic degenerative tendon injuries. Using a functional tissue engineering or FTE roadmap with linked in vitro and in vivo studies, we will establish in vivo forces and displacements for 4 activities of daily living in the rabbit patellar tendon model (PT) (Aim 1). Using a novel design strategy, 6 mechanical treatment factors will then be varied in culture to optimize the construct's tangent stiffness before surgery (Aim 2). Constructs with significantly different tangent stiffness values will be implanted in rabbit PT defects to examine significant improvements in repair stiffness (Aim 3). We will thus test a series of related hypotheses: Hyp 1. The rabbit PT maintains non-zero tissue strain and force for all activities. Hyp 2. Increasing the grade or inclination of the gait surface increases in vivo force and strain parameters. Hyp 3. Rabbit and mouse constructs exposed to in vivo strain shapes develop higher tangent stiffness than constructs exposed to trapezoidal or sinusoidal profiles. Hyp 4. Increasing strain amplitude, within physiological limits, increases tangent stiffness in culture. Hyp. 5. Strain patterns with similar times to rise and fall and similar periods as in vivo signals exhibit the largest stiffness values in culture. Hyp 6. Mouse constructs having the largest tangent stiffness in culture exhibit the greatest increases in col I gene expression. Hyp 7. Increasing construct stiffness in culture increases repair stiffness after surgery and better aligns cells and extracellular matrix in the repair site. Our novel, interactive in vitro / in vivo study should help to develop in vitro predictors of in vivo repair outcome after surgery that also apply to other tissue systems.