Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells.
Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells.
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DOI：
10.1016/j.biomaterials.2018.09.013
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发表时间：
2018-09
期刊：
影响因子：
14
通讯作者：
Linxiao Wu;Adrián Magaz;Tao Wang;Chaozong Liu;A. Darbyshire;M. Loizidou;M. Emberton;M. Birchall-M.-Birchal
中科院分区：
文献类型：
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作者：
Linxiao Wu;Adrián Magaz;Tao Wang;Chaozong Liu;A. Darbyshire;M. Loizidou;M. Emberton;M. Birchall-M.-Birchal
细胞微环境是动态的，终身重塑组织。细胞外基质的生物力学性质影响干细胞的功能和分化。虽然用于组织工程的常规人工基质或支架主要是呈现明确定义的刚度的静态模型，但它们缺乏动态生理设置中所需的响应性变化。具有不同弹性模量的工程支架是可能的，但通常导致分子结构的硬化和化学交联，对支架结构的控制有限。最近开发了一系列间接3D打印的弹性体纳米混合支架，其具有在体温下通过反向自组装软化的热响应机械性能。通过免疫组织化学、组织学、ELISA和qPCR测量，支架的初始刚度和随后的刚度松弛在4周内调节人骨髓源性间充质干细胞（hBM-MSC）向软骨形成和成骨谱系的增殖和分化。hBM-MSCs在较软的支架上表现出更强的成软骨分化，在较硬的支架上表现出更强的成骨分化，其相对表达与人股骨头组织相似。总体而言，刚度松弛有利于体外成骨活性超过软骨生成。
The cellular microenvironment is dynamic, remodeling tissues lifelong. The biomechanical properties of the extracellular matrix (ECM) influence the function and differentiation of stem cells. While conventional artificial matrices or scaffolds for tissue engineering are primarily static models presenting well-defined stiffness, they lack the responsive changes required in dynamic physiological settings. Engineering scaffolds with varying elastic moduli is possible, but often lead to stiffening and chemical crosslinking of the molecular structure with limited control over the scaffold architecture. A family of indirectly 3D printed elastomeric nanohybrid scaffolds with thermoresponsive mechanical properties that soften by reverse self-assembling at body temperature have been developed recently. The initial stiffness and subsequent stiffness relaxation of the scaffolds regulated proliferation and differentiation of human bone-marrow derived mesenchymal stem cells (hBM-MSCs) towards the chondrogenic and osteogenic lineages over 4 weeks, as measured by immunohistochemistry, histology, ELISA and qPCR. hBM-MSCs showed enhanced chondrogenic differentiation on softer scaffolds and osteogenic differentiation on stiffer ones, with similar relative expression to that of human femoral head tissue. Overall, stiffness relaxation favored osteogenic activity over chondrogenesisin vitro.