Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
The Second Xiangya Hospital, Central South University, Changsha, P.R. China.
J Tissue Eng Regen Med. 2018 Jul;12(7):1690-1701. doi: 10.1002/term.2696. Epub 2018 Jun 3.
Surgical repair of rotator cuff tears presents a significant clinical challenge with high failure rates and inferior functional outcomes. Graft augmentation improves repair outcomes; however, currently available grafting materials have limitations. Although cell-seeded decellularized tendon slices may facilitate cell infiltration, promote tendon incorporation, and preserve original mechanical strength, the unique fibrocartilage zone is yet to be successfully reestablished. In this study, we investigated the biological and mechanical properties of an engineered tendon-fibrocartilage-bone composite (TFBC) with cyclic tension (3% strain; 0.2 Hz). Decellularized TFBCs seeded with bone marrow-derived mesenchymal stem cell (BMSCs) sheets and subjected to mechanical stimulation for up to 7 days were characterised by histology, immunohistochemistry, scanning electron microscopy, mechanical testing, and transcriptional regulation. The decellularized TFBC maintained native enthesis structure and properties. Mechanically stimulated TFBC-BMSC constructs displayed increased cell migration after 7 days of culture compared with static groups. The seeded cell sheet not only integrated well with tendon scaffold but also distributed homogeneously and aligned to the direction of stretch under dynamic culture. Developmental genes were regulated including scleraxis, which was significantly upregulated with mechanical stimulation. The Young's modulus of the cell-seeded constructs was significantly higher compared with the noncell-seeded controls. In conclusion, the results of this study reveal that the TFBC-BMSC composite provides an ideal multilayer construct for cell seeding and growth, with mechanical preconditioning further enhances cell penetration and differentiation. The BMSC cell sheet revitalised TFBC in conjunction with mechanical stimulation could serve as a novel and primed biological patch to improve rotator cuff repair.
肩袖撕裂的外科修复是一项具有重大临床挑战的手术,其修复失败率高,功能恢复效果差。移植物增强可以改善修复效果;然而,目前可用的移植物材料存在局限性。虽然细胞接种去细胞肌腱片可以促进细胞浸润、促进肌腱结合和保持原有的机械强度,但独特的纤维软骨区尚未成功重建。在这项研究中,我们研究了具有循环张力(3%应变;0.2 Hz)的工程化肌腱-纤维软骨-骨复合(TFBC)的生物学和机械性能。用骨髓间充质干细胞(BMSCs)片接种并进行机械刺激长达 7 天的去细胞 TFBC 通过组织学、免疫组织化学、扫描电子显微镜、机械测试和转录调控进行了表征。去细胞 TFBC 保持了天然的附着结构和特性。与静态组相比,机械刺激后的 TFBC-BMSC 构建体在培养 7 天后显示出细胞迁移增加。接种的细胞片不仅与肌腱支架很好地整合,而且在动态培养下均匀分布并沿拉伸方向排列。发育基因受到调节,包括机械刺激下显著上调的 Scleraxis。与非细胞接种对照相比,细胞接种构建体的杨氏模量明显更高。总之,这项研究的结果表明,TFBC-BMSC 复合材料为细胞接种和生长提供了理想的多层结构,机械预处理进一步增强了细胞渗透和分化。与机械刺激相结合的 BMSC 细胞片使 TFBC 恢复活力,可作为一种新颖的、有活力的生物补片,以改善肩袖修复。