Pro-chondrogenic and immunomodulatory melatonin-loaded electrospun membranes for tendon-to-bone healing.
Pro-chondrogenic and immunomodulatory melatonin-loaded electrospun membranes for tendon-to-bone healing.
复制标题
用于肌腱到骨愈合的促软骨形成和免疫调节的负载褪黑激素的电纺膜
DOI：
10.1039/c9tb01516g
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发表时间：
2019
影响因子：
7
通讯作者：
He Yaohua
中科院分区：
文献类型：
--
作者：
Song Wei;Ma Zhijie;Wang Chongyang;Li Haiyan;He Yaohua
肩袖修复术中重建肌腱-骨附着点(末端)的天然结构一直是骨科医生面临的巨大挑战。困难的主要原因是有限的再生力和严重的炎性细胞浸润，导致纤维血管瘢痕的形成，而不是天然的软骨样吻合术。因此，具有促软骨和免疫调节功能的组织工程支架可能为牙本质再生提供一种新的策略。本研究制备了褪黑素定向聚己内酯(PCL)电纺纤维膜。在长期软骨颗粒模型中，褪黑素的持续释放显著促进了人骨髓间充质干细胞(HBMSCs)向软骨方向的分化。在大鼠急性肩袖撕裂模型中植入膜后，在愈合早期，褪黑素负载的PCL膜抑制了肌腱-骨界面的巨噬细胞的渗透，增加了软骨带的形成，促进了胶原的成熟，减少了纤维血管组织的形成，最终提高了再生的末端的生物力学强度。综上所述，负载褪黑素的PCL膜在肌腱到骨的愈合方面具有巨大的临床应用潜力。
Reconstructing the native structure of the tendon-to-bone insertion site (enthesis) in rotator cuff repair has always been a great challenge for orthopedic surgeons. Difficulty arises mainly due to the limited enthesis regenerative capability and severe inflammatory cell infiltration, which result in fibrovascular scar formation instead of native cartilage-like enthesis. Therefore, tissue engineering scaffolds with pro-chondrogenic and immunomodulatory capabilities may offer a new strategy for native enthesis regeneration. In this study, melatonin-loaded aligned polycaprolactone (PCL) electrospun fibrous membranes were fabricated. The sustained release of melatonin from this membrane significantly promoted the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in a long-term chondroid pellet model. After the membranes were implanted in a rat acute rotator cuff tear model, melatonin-loaded PCL membranes inhibited macrophage infiltration in the tendon-to-bone interface at the early healing phase, increasing chondroid zone formation, promoting collagen maturation, decreasing fibrovascular tissue formation and eventually improving the biomechanical strength of the regenerated enthesis. Taken together, melatonin-loaded PCL membranes possess great clinical application potential for tendon-to-bone healing.