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流体静压增强基于丝素蛋白的3D生物打印水凝胶中间充质干细胞的软骨分化。

Hydrostatic Pressure Enhances Chondrogenic Differentiation of Mesenchymal Stem Cells in Silk Fibroin-Based 3D Bioprinted Hydrogels.

作者信息

Fritz Jennifer, Moser Anna-Christina, Otahal Alexander, Kramer Karina, Casurovic Salih, Teuschl-Woller Andreas H, Nehrer Stefan

机构信息

Center for Regenerative Medicine, University for Continuing Education Krems, Dr.-Karl-Dorrek-Straße 30, Krems 3500, Austria.

Austrian Cluster for Tissue Regeneration, Donaueschingenstrasse 13, Vienna 1200, Austria.

出版信息

Biomacromolecules. 2025 Jun 9;26(6):3432-3445. doi: 10.1021/acs.biomac.5c00048. Epub 2025 May 20.

Abstract

The human meniscus experiences mechanical forces and converts axial loads into hoop stresses. Meniscus injuries and meniscectomies can compromise this function, and therefore, meniscus implants are required. To assess their performance , it is crucial to recreate a physiological environment. Therefore, we investigated the effect of TGFβ-3-supplemented and TGFβ-free cyclic hydrostatic pressure (HP) up to 10 MPa on 3D bioprinted silk fibroin (SF) polymer-based hydrogels. The bioink was seeded with human infrapatellar fat pad-derived MSCs and supplemented with an extracellular matrix and gelatin. We found that HP stimulation did not alter cell-free biomaterial maturation, while it partially stimulated metabolic activity and cell proliferation. Remarkably, TGFβ-3-supplemented HP led to the highest expression levels of chondrogenic markers, followed by TGFβ-3-supplemented unloaded incubation and then TGFβ-free HP. Despite the low cell density, the combined exposure to TGFβ-3 and HP also facilitated localized glycosaminoglycan and collagen deposition, demonstrating promising prospects for future meniscus regeneration.

摘要

人类半月板承受机械力并将轴向载荷转化为环向应力。半月板损伤和半月板切除术会损害这种功能,因此需要半月板植入物。为了评估它们的性能,重建生理环境至关重要。因此,我们研究了补充TGFβ-3和不含TGFβ的循环静水压力(HP)高达10 MPa对基于3D生物打印丝素蛋白(SF)聚合物的水凝胶的影响。生物墨水接种了源自人髌下脂肪垫的间充质干细胞,并补充了细胞外基质和明胶。我们发现HP刺激并未改变无细胞生物材料的成熟过程,而它部分刺激了代谢活性和细胞增殖。值得注意的是,补充TGFβ-3的HP导致软骨生成标志物的表达水平最高,其次是补充TGFβ-3的无负荷孵育,然后是不含TGFβ的HP。尽管细胞密度较低,但联合暴露于TGFβ-3和HP也促进了局部糖胺聚糖和胶原蛋白的沉积,为未来半月板再生展示了广阔的前景。

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