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Mesenchymal Stem Cell Delivery via Topographically Tenoinductive Collagen Biotextile Enhances Regeneration of Segmental Tendon Defects
The American Journal of Sports Medicine ( IF 4.2 ) Pub Date : 2022-06-01 , DOI: 10.1177/03635465221097939
Phillip McClellan 1 , Jason G Ina 2 , Derrick M Knapik 2 , Ilaha Isali 3 , Greg Learn 4 , Alexis Valente 1 , Yujing Wen 1 , Ruiqi Wen 4 , James M Anderson 4, 5, 6 , Robert J Gillespie 2 , Ozan Akkus 1, 2, 4
Affiliation  

Background:

Successful management of massive rotator cuff (RC) tendon tears represents a treatment challenge because of the limited intrinsic healing capacity of native tendons and the risk of repair failure. Biologic augmentation of massive RC tears utilizing scaffolds—capable of regenerating bulk tendon tissue to achieve a mechanically functional repair—represents an area of increasing clinical interest.

Purpose:

To investigate the histological and biomechanical outcomes after the use of a novel biologic scaffold fabricated from woven electrochemically aligned collagen (ELAC) threads as a suture-holding, fully load-bearing, defect-bridging scaffold with or without mesenchymal stem cells (MSCs) compared with direct repair in the treatment of critically sized RC defects using a rabbit model.

Study Design:

Controlled laboratory study.

Methods:

A total of 34 New Zealand White rabbits underwent iatrogenic creation of a critically sized defect (6 mm) in the infraspinatus tendon of 1 shoulder, with the contralateral shoulder utilized as an intact control. Specimens were divided into 4 groups: (1) gap—negative control without repair; (2) direct repair of the infraspinatus tendon—operative control; (3) tendon repair using ELAC; and (4) tendon repair using ELAC + MSCs. Repair outcomes were assessed at 6 months using micro–computed tomography, biomechanical testing, histology, and immunohistochemistry.

Results:

Specimens treated with ELAC demonstrated significantly less tendon retraction when compared with the direct repair group specimens (P = .014). ELAC + MSCs possessed comparable biomechanical strength (178 ± 50 N) to intact control shoulders (199 ± 35 N) (P = .554). Histological analyses demonstrated abundant, well-aligned de novo collagen around ELAC threads in both the ELAC and the ELAC + MSC shoulders, with ELAC + MSC specimens demonstrating increased ELAC resorption (7% vs 37%, respectively; P = .002). The presence of extracellular matrix components, collagen type I, and tenomodulin, indicating tendon-like tissue formation, was appreciated in both the ELAC and the ELAC + MSC groups.

Conclusion:

The application of MSCs to ELAC scaffolds improved biomechanical and histological outcomes when compared with direct repair for the treatment of critically sized defects of the RC in a rabbit model.

Clinical Relevance:

This study demonstrates the feasibility of repairing segmental tendon defects with a load-bearing, collagen biotextile in an animal model, showing the potential applicability of RC repair supplementation using allogeneic stem cells.



中文翻译:

通过地形肌腱诱导胶原生物纺织品进行间充质干细胞递送可增强节段肌腱缺损的再生

背景:

由于天然肌腱的内在愈合能力有限且存在修复失败的风险,成功治疗大量肩袖(RC)肌腱撕裂是一项治疗挑战。利用支架对大量 RC 撕裂进行生物增强——能够再生大量肌腱组织以实现机械功能修复——代表了一个日益受到临床关注的领域。

目的:

为了研究使用由电化学排列胶原 (ELAC) 线编织而成的新型生物支架作为缝合、完全承重、缺损桥接支架(有或没有间充质干细胞 (MSC))后的组织学和生物力学结果,与使用兔子模型直接修复治疗临界大小的 RC 缺陷。

学习规划:

受控实验室研究。

方法:

总共 34 只新西兰白兔在 1 只肩部的冈下肌腱中接受了医源性的严重缺损(6 毫米),并以对侧肩部作为完整对照。标本分为4组:(1)间隙——未修复的阴性对照;(2)直接修复冈下肌腱——手术控制;(3)使用ELAC修复肌腱;(4) 使用 ELAC ​​+ MSC 进行肌腱修复。使用显微计算机断层扫描、生物力学测试、组织学和免疫组织化学在 6 个月时评估修复结果。

结果:

与直接修复组标本相比,经过 ELAC ​​处理的标本表现出明显较少的肌腱回缩 ( P = .014)。ELAC ​​+ MSC 具有与完整对照肩部 (199 ± 35 N) 相当的生物力学强度 (178 ± 50 N) ( P = .554)。组织学分析表明,ELAC ​​和 ELAC ​​+ MSC 肩部的 ELAC ​​线周围都有丰富、排列良好的从头胶原蛋白,ELAC ​​+ MSC 标本显示 ELAC ​​吸收增加(分别为 7% 和 37%;P = .002 。细胞外基质成分、I 型胶原蛋白和肌腱调节蛋白的存在表明肌腱样组织的形成,在 ELAC ​​和 ELAC ​​+ MSC 组中均得到认可。

结论:

与直接修复兔模型中严重大小的 RC 缺损相比,将 MSC 应用于 ELAC ​​支架可改善生物力学和组织学结果。

临床相关性:

这项研究证明了在动物模型中使用承重胶原生物织物修复节段肌腱缺损的可行性,显示了使用同种异体干细胞补充 RC 修复的潜在适用性。

更新日期:2022-06-05
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