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磁性 SPIO-BMSCs 接种到双相支架中可促进肩袖修复后腱骨愈合。

Magnetic Seeding of SPIO-BMSCs Into a Biphasic Scaffold Can Promote Tendon-Bone Healing After Rotator Cuff Repair.

机构信息

Department of Orthopedic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Am J Sports Med. 2024 Jun;52(7):1707-1718. doi: 10.1177/03635465241247288. Epub 2024 May 4.

DOI:10.1177/03635465241247288
PMID:38702986
Abstract

BACKGROUND

The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration.

HYPOTHESIS

Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR.

STUDY DESIGN

Controlled laboratory study.

METHODS

BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation.

RESULTS

BMSCs labeled with 100 μg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model.

CONCLUSION

Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model.

CLINICAL RELEVANCE

This study provides an alternative strategy for improving TBI healing after RCR.

摘要

背景

肩袖肌腱骨界面(TBI)的自我愈合能力较差,这增加了肩袖修复(RCR)后再撕裂的风险。然而,促进 TBI 的再生仍然是一个巨大的临床挑战。在此,作者建立了一种基于磁播种的新策略,以增强 TBI 的再生。

假设

将超顺磁性氧化铁(SPIO)标记的骨髓间充质干细胞(BMSCs)播种到双相支架中,可以促进 RCR 后的肌腱骨愈合。

研究设计

对照实验室研究。

方法

BMSCs 用 SPIOs 标记。普鲁士蓝染色、CCK-8 试验、Western blot 和定量逆转录聚合酶链反应(PCR)用于确定 SPIOs 对细胞生物活性和能力的最佳作用浓度。然后,将 SPIO-BMSCs 在磁场下播种到双相支架中。通过扫描电子显微镜评估播种效果,并通过 Western blot 和 PCR 评估播种 SPIO-BMSCs 后在支架中向软骨分化的潜在机制。此外,使用大鼠模型检查 SPIO-BMSC/双相支架对 RCR 后肌腱骨愈合的影响,使用组织学分析、酶联免疫吸附测定和生物力学评估。

结果

100μg/mL SPIO 标记的 BMSCs 对细胞生物活性和软骨分化能力没有影响。SPIO-BMSCs 被磁播种到双相支架中,通过 CDR1as/miR-7/FGF2 通路提供了高的播种效率,从而增强了 SPIO-BMSCs 的软骨分化,形成了体外 TBI。此外,体内应用双相支架与磁播种 SPIO-BMSCs 显示出其再生潜力,表明它们可以在大鼠旋转袖撕裂模型中显著加速和促进 RCR 后的 TBI 愈合,并具有优异的生物力学性能。

结论

将 SPIO-BMSCs 磁播种到双相支架中提高了播种效率,促进了细胞的分布和凝聚。该构建物通过 CDR1as/miR-7/FGF2 通路增强了软骨形成过程,并进一步促进了大鼠旋转袖撕裂模型中 RCR 后的肌腱骨愈合。

临床相关性

这项研究为改善 RCR 后 TBI 愈合提供了一种替代策略。

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