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静电纺丝DegraPol管将干细胞/肌腱细胞共培养衍生的分泌组输送至切断的兔跟腱——体外和体内评估

Electrospun DegraPol Tube Delivering Stem Cell/Tenocyte Co-Culture-Derived Secretome to Transected Rabbit Achilles Tendon-In Vitro and In Vivo Evaluation.

作者信息

Rieber Julia, Miescher Iris, Wolint Petra, Meier Bürgisser Gabriella, Grigioni Jeroen, Snedeker Jess G, Vogel Viola, Giovanoli Pietro, Calcagni Maurizio, Buschmann Johanna

机构信息

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.

Institute for Biomechanics, ETH Zurich, 8092 Zurich, Switzerland.

出版信息

Int J Mol Sci. 2025 Jun 6;26(12):5457. doi: 10.3390/ijms26125457.

Abstract

Tendon ruptures have recently reached incidences of 18-35 cases/100,000 and often lead to adhesion formation during healing. Furthermore, scar formation may result in inferior biomechanics and often leads to re-ruptures. To address these problems, we cultivated rabbit adipose-derived stem cells in a co-culture with rabbit Achilles tenocytes and harvested their secretome. Following a cell-free approach, we incorporated such secretome into an electrospun tube via emulsion electrospinning. These novel implants were characterized by SEM, the WCA, and FTIR. Then, they were implanted in the rabbit Achilles tendon full transection model with an additional injection of secretome, and the adhesion extent as well as the biomechanics of extracted tendons were assessed three weeks postoperatively. The fiber thickness was around 3-5 μm, the pore size 11-13 μm, and the tube wall thickness approximately 265 μm. The WCA indicated slightly hydrophilic surfaces in the secretome-containing layer, with values of 80-90°. In vivo experiments revealed a significant reduction in adhesion formation (-22%) when secretome-treated tendons were compared to DegraPol (DP) tube-treated tendons (no secretome). Furthermore, the cross-sectional area was significantly smaller in secretome-treated tendons compared to DP tube-treated ones (-32%). The peak load and stiffness of secretome-treated tendons were not significantly different from native tendons, while tendons treated with pure DP tubes exhibited significantly lower values. We concluded that secretome treatment supports tendon healing, with anti-adhesion effects and improved biomechanics at 3 weeks, making this approach interesting for clinical application.

摘要

肌腱断裂近来的发病率达到了18 - 35例/10万,并且在愈合过程中常常导致粘连形成。此外,瘢痕形成可能导致生物力学性能较差,并常常导致再次断裂。为了解决这些问题,我们将兔脂肪来源干细胞与兔跟腱细胞共培养,并收集它们的分泌产物。采用无细胞方法,我们通过乳液静电纺丝将这种分泌产物掺入静电纺丝管中。这些新型植入物通过扫描电子显微镜(SEM)、水接触角(WCA)和傅里叶变换红外光谱(FTIR)进行表征。然后,将它们植入兔跟腱完全横断模型中,并额外注射分泌产物,术后三周评估提取肌腱的粘连程度以及生物力学性能。纤维厚度约为3 - 5μm,孔径为11 - 13μm,管壁厚度约为265μm。水接触角表明含分泌产物层的表面具有轻微亲水性,角度值为80 - 90°。体内实验显示,与DegraPol(DP)管处理的肌腱(无分泌产物)相比,经分泌产物处理的肌腱粘连形成显著减少(-22%)。此外,与DP管处理的肌腱相比,经分泌产物处理的肌腱横截面积显著更小(-32%)。经分泌产物处理的肌腱的峰值负荷和刚度与天然肌腱无显著差异,而用纯DP管处理的肌腱则表现出显著更低的值。我们得出结论,分泌产物处理有助于肌腱愈合,在3周时具有抗粘连作用并改善生物力学性能,使得这种方法在临床应用中具有吸引力。

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