The long-term success of surgical repair of rotator cuff tears is largely dependent on restoration of a functional tendon-to-bone interface. We implemented micro-precise spatiotemporal delivery of growth factors in three-dimensional printed scaffolds for integrative regeneration of a fibrocartilaginous tendon-to-bone interface. Sustained and spatially controlled release of tenogenic, chondrogenic and osteogenic growth factors was achieved using microsphere-based delivery carriers embedded in thin membrane-like scaffolds. In vitro, the scaffolds embedded with spatiotemporal delivery of growth factors successfully guided regional differentiation of mesenchymal progenitor cells, forming multiphase tissues with tendon-like, cartilage-like and bone-like regions. In vivo, when implanted at the interface between the supraspinatus tendon and the humeral head in a rat rotator cuff repair model, these scaffolds promoted recruitment of endogenous tendon progenitor cells followed by integrative healing of tendon and bone via re-formation of strong fibrocartilaginous interfaces. Our findings demonstrate the potential of in situ tissue engineering of tendon-to-bone interfaces by endogenous progenitor cells. The in situ tissue engineering approach shows translational potential for improving outcomes after rotator cuff repair.

中文翻译：

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内源性干/祖细胞对肌腱到骨的界面进行原位组织工程。

肩袖撕裂手术修复的长期成功在很大程度上取决于功能性腱-骨界面的恢复。我们在三维印刷支架中实现了生长因子的超精确时空传递，以实现纤维软骨art腱与骨骼界面的整合再生。使用嵌入在薄膜状支架中的基于微球的递送载体，实现了成腱，成软骨和成骨生长因子的持续和空间控制释放。在体外，嵌入生长因子时空传递的支架成功地指导了间充质祖细胞的区域分化，形成了具有肌腱样，软骨样和骨样区域的多相组织。体内，当在大鼠肩袖修复模型中的棘上肌腱和肱骨头之间的界面上植入这些支架时，这些支架可促进内源性肌腱祖细胞的募集，然后通过重新形成牢固的纤维软骨结合界面来促进肌腱和骨骼的整体愈合。我们的发现证明了内源性祖细胞对肌腱-骨界面进行原位组织工程的潜力。原位组织工程方法显示了修复肩袖修复后改善预后的潜力。我们的发现证明了内源性祖细胞对肌腱-骨界面进行原位组织工程的潜力。原位组织工程方法显示了修复肩袖修复后改善预后的潜力。我们的发现证明了内源性祖细胞对肌腱-骨界面进行原位组织工程的潜力。原位组织工程方法显示了修复肩袖修复后改善预后的潜力。