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基于拓扑-tenoinductive 胶原生物纺织品的间充质干细胞递送可增强节段性肌腱缺损的再生。

Mesenchymal Stem Cell Delivery via Topographically Tenoinductive Collagen Biotextile Enhances Regeneration of Segmental Tendon Defects.

机构信息

Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio, USA.

Department of Orthopaedic Surgery, University Hospitals Cleveland Medical Center, Ohio, USA.

出版信息

Am J Sports Med. 2022 Jul;50(8):2281-2291. doi: 10.1177/03635465221097939. Epub 2022 Jun 1.

Abstract

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 ( = .014). ELAC + MSCs possessed comparable biomechanical strength (178 ± 50 N) to intact control shoulders (199 ± 35 N) ( = .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; = .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.

摘要

背景

由于天然肌腱的内在愈合能力有限,以及修复失败的风险,巨大肩袖(RC)肌腱撕裂的成功管理是一项治疗挑战。利用支架增强巨大 RC 撕裂,这些支架能够再生大量腱组织,实现机械功能修复,代表了临床日益关注的一个领域。

目的

使用一种新型生物支架,该支架由编织的电化学定向胶原(ELAC)线制成,用作缝线固定、完全承重、缺陷桥接支架,在新西兰白兔模型中,与直接修复相比,评估其在治疗临界大小 RC 缺损中的组织学和生物力学结果,该支架有无间充质干细胞(MSCs)。

研究设计

对照实验室研究。

方法

共有 34 只新西兰白兔,单侧肩的冈下肌腱发生医源性临界大小(6mm)缺损,对侧肩作为完整对照。标本分为 4 组:(1)无修复的间隙阴性对照;(2)冈下肌腱的直接修复——手术对照;(3)ELAC 肌腱修复;(4)ELAC+MSCs 肌腱修复。使用微计算机断层扫描、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,ELAC 处理的标本肌腱回缩明显减少(P =.014)。ELAC+MSCs 的生物力学强度(178±50N)与完整对照肩相似(199±35N)(P=.554)。组织学分析显示,ELAC 线周围有大量排列整齐的新生胶原,ELAC 和 ELAC+MSC 肩均有大量排列整齐的新生胶原,ELAC+MSC 标本的 ELAC 吸收增加(分别为 7%和 37%;P=.002)。在 ELAC 和 ELAC+MSC 组均观察到细胞外基质成分、I 型胶原和腱调蛋白,表明形成腱样组织。

结论

与直接修复相比,MSCs 应用于 ELAC 支架可改善生物力学和组织学结果,用于治疗兔模型中的 RC 临界大小缺损。

临床相关性

这项研究在动物模型中证明了用承重胶原生物纺织品修复节段性肌腱缺损的可行性,表明使用同种异体干细胞补充 RC 修复具有潜在的适用性。

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