Department of Orthopedic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Am J Sports Med. 2024 Jun;52(7):1707-1718. doi: 10.1177/03635465241247288. Epub 2024 May 4.
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.
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。
Am J Sports Med. 2018-4-5
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