In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair
In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair
复制标题
DOI：
10.1089/ten.tea.2015.0101
复制
发表时间：
2015-11-01
影响因子：
4.1
通讯作者：
Thomopoulos, Stavros
中科院分区：
文献类型：
--
作者：
Lipner, Justin;Shen, Hua;Thomopoulos, Stavros
肩袖撕裂很常见，会导致大量生产力损失、疼痛和残疾。通常通过将肌腱缝合回其骨附着处来修复撕裂。不幸的是，在健康组织中产生牢固附着的结构（例如，排列的胶原蛋白）和成分（例如，矿物质的梯度）元素在愈合过程中不会再生，并且修复很容易失败。愈合反应失败的两个特征是排列不良的疤痕组织沉积和修复部位骨质流失。因此，当前研究的目的是通过使用接种多能细胞的仿生支架促进排列的胶原蛋白沉积和增加骨形成来改善肌腱到骨骼的愈合。将脂肪源性基质细胞（ASC）接种到具有矿物质含量梯度的对齐纳米纤维聚（乳酸-乙醇酸）支架上，并将其植入大鼠肩袖模型的修复部位。在一组中，细胞用成骨因子骨形态发生蛋白 2 (BMP2) 转导。使用 14、28 和 56 天的组织学、骨形态和生物力学结果检查四组（仅缝线、脱细胞支架、细胞支架和细胞 BMP2 支架）的愈合反应。组织学上，所有组中的愈合界面均以纤维血管疤痕反应为主。与其他组相比，无细胞支架组显示出延迟的愈合反应。在检查骨形态参数时，28 天时，与其他组相比，细胞 BMP2 组的骨丢失明显。当检查修复部位的机械性能时，与其他组相比，细胞 BMP2 组的强度和模量在 28 天和 56 天时有所下降。这些结果表明，该动物模型中的肌腱到骨骼的愈合主要是疤痕形成，从而阻碍了植入的仿生支架的任何积极作用。此外，用成骨因子 BMP2 转导的细胞会导致愈合受损，这表明这种生长因子不应用于肌腱到骨的修复。
Rotator cuff tears are common and cause a great deal of lost productivity, pain, and disability. Tears are typically repaired by suturing the tendon back to its bony attachment. Unfortunately, the structural (e.g., aligned collagen) and compositional (e.g., a gradient in mineral) elements that produce a robust attachment in the healthy tissue are not regenerated during healing, and the repair is prone to failure. Two features of the failed healing response are deposition of poorly aligned scar tissue and loss of bone at the repair site. Therefore, the objective of the current study was to improve tendon-to-bone healing by promoting aligned collagen deposition and increased bone formation using a biomimetic scaffold seeded with pluripotent cells. An aligned nanofibrous poly(lactic-co-glycolic acid) scaffold with a gradient in mineral content was seeded with adipose-derived stromal cells (ASCs) and implanted at the repair site of a rat rotator cuff model. In one group, cells were transduced with the osteogenic factor bone morphogenetic protein 2 (BMP2). The healing response was examined in four groups (suture only, acellular scaffold, cellular scaffold, and cellular BMP2 scaffold) using histologic, bone morphology, and biomechanical outcomes at 14, 28, and 56 days. Histologically, the healing interface was dominated by a fibrovascular scar response in all groups. The acellular scaffold group showed a delayed healing response compared to the other groups. When examining bone morphology parameters, bone loss was evident in the cellular BMP2 group compared to other groups at 28 days. When examining repair-site mechanical properties, strength and modulus were decreased in the cellular BMP2 groups compared to other groups at 28 and 56 days. These results indicated that tendon-to-bone healing in this animal model was dominated by scar formation, preventing any positive effects of the implanted biomimetic scaffold. Furthermore, cells transduced with the osteogenic factor BMP2 led to impaired healing, suggesting that this growth factor should not be used in the tendon-to-bone repair setting.