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In Situ-Forming Fibrin Gel Encapsulation of MSC-Exosomes for Partial-Thickness Rotator Cuff Tears in a Rabbit Model: Effectiveness Shown in Preventing Tear Progression and Promoting Healing
The Journal of Bone & Joint Surgery ( IF 4.4 ) Pub Date : 2022-08-17 , DOI: 10.2106/jbjs.21.01157
Chongyang Wang 1 , Jiaqi Tan 1 , Yao Zhang 2 , Daoyun Chen 1 , Yaohua He 1, 3
Affiliation  

Background: 

Current nonoperative treatments for partial-thickness rotator cuff tears (PTRCTs) have limited effectiveness in preventing tear progression or promoting tendon healing. This study aimed to establish a rabbit model using in situ-forming fibrin gel containing adipose stem cell-derived exosomes (ASC-Exos/fibrin) to treat PTRCTs.

Methods: 

Fifty-six rabbits (112 shoulders) were included in this study and assigned to 4 groups: the control group (32 shoulders; PTRCTs without treatment), the fibrin group (32 shoulders; PTRCTs treated with fibrin gel), the ASC-Exo/fibrin group (32 shoulders; PTRCTs treated with ASC-Exos/fibrin), and the sham group (16 shoulders; sham surgery). Bilateral, 50%-thickness, bursal-side PTRCTs of 1 mm (depth) × 3 mm (width) × 5 mm (length) on the supraspinatus tendon were established by a number-11 scalpel blade, with accuracy of the measurement ensured by a digital vernier caliper. At 6 and 12 weeks postoperatively, gross observation, measurement of the thickness of residual supraspinatus tendons, and histological and biomechanical analyses were performed to analyze tendon repair.

Results: 

At 12 weeks postoperatively, the tendon thickness in the ASC-Exos/fibrin group (mean and standard deviation, 1.63 ± 0.19 mm) was significantly greater than in the control group (0.85 ± 0.09 mm) (p < 0.0001) and fibrin group (1.16 ± 0.17 mm) (p < 0.0001). The histological score in the ASC-Exos/fibrin group (6.25 ± 0.53) was significantly better than in the control group (11.38 ± 0.72) (p < 0.0001) and fibrin group (9.00 ± 0.54) (p < 0.0001). Overall, immunohistochemical staining of types-I and III collagen and biomechanical testing also showed ASC-Exos/fibrin to be more effective in repairing PTRCTs than fibrin alone and no treatment.

Conclusions: 

Local administration of in situ-forming ASC-Exos/fibrin effectively facilitated the healing of bursal-side PTRCTs in rabbits. This approach may be a candidate for the nonoperative management of PTRCTs.

Clinical Relevance: 

Ultrasound-guided injection of ASC-Exos/fibrin may be a novel nonoperative strategy to treat PTRCTs.



中文翻译:

MSC-外泌体的原位形成纤维蛋白凝胶包封用于兔模型中的部分厚度肩袖撕裂:在防止撕裂进展和促进愈合方面显示的有效性

背景: 

目前对部分厚度肩袖撕裂 (PTRCTs) 的非手术治疗在预防撕裂进展或促进肌腱愈合方面效果有限。本研究旨在建立使用含有脂肪干细胞衍生的外泌体 (ASC-Exos/fibrin) 的原位形成纤维蛋白凝胶治疗 PTRCT 的兔模型。

方法: 

56 只兔子(112 只肩部)被纳入本研究并分为 4 组:对照组(32 只肩部;未治疗的 PTRCTs)、纤维蛋白组(32 只肩部;用纤维蛋白凝胶治疗的 PTRCTs)、ASC-Exo/纤维蛋白组(32 肩;用 ASC-Exos/纤维蛋白治疗的 PTRCT)和假手术组(16 肩;假手术)。用 11 号手术刀刀片在冈上肌腱上建立 1 mm(深度)×3 mm(宽度)×5 mm(长度)的双侧、50% 厚度、法氏囊侧 PTRCT,测量的准确性通过以下方式确保数字游标卡尺。在术后 6 周和 12 周,进行大体观察,测量残余冈上肌肌腱的厚度,并进行组织学和生物力学分析以分析肌腱修复情况。

结果: 

术后 12 周,ASC-Exos/纤维蛋白组的肌腱厚度(平均值和标准差,1.63 ± 0.19 mm)显着大于对照组(0.85 ± 0.09 mm)(p < 0.0001)和纤维蛋白组( 1.16 ± 0.17 毫米)(p < 0.0001)。ASC-Exos/纤维蛋白组 (6.25 ± 0.53) 的组织学评分显着优于对照组 (11.38 ± 0.72) (p < 0.0001) 和纤维蛋白组 (9.00 ± 0.54) (p < 0.0001)。总体而言,I 型和 III 型胶原蛋白的免疫组织化学染色和生物力学测试也表明 ASC-Exos/纤维蛋白在修复 PTRCT 方面比单独使用纤维蛋白和不治疗更有效。

结论: 

局部施用原位形成的 ASC-Exos/纤维蛋白有效地促进了兔法氏囊侧 PTRCT 的愈合。这种方法可能是 PTRCT 非手术治疗的候选方法。

临床相关性: 

超声引导下注射 ASC-Exos/纤维蛋白可能是治疗 PTRCT 的一种新型非手术策略。

更新日期:2022-08-17
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