Islam Anowarul, Mbimba Thomas, Younesi Mousa, Akkus Ozan
Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States.
Acta Biomater. 2017 Aug;58:244-253. doi: 10.1016/j.actbio.2017.05.058. Epub 2017 Jun 5.
Extracellular matrix modulus plays an important role in regulating cell morphology, proliferation and differentiation during regular and diseased states. Although the effects of substrate topography and modulus on MSC differentiation are well known with respect to osteogenesis and adipogenesis, there has been relatively little investigation on the effects of this phenomenon on tenogenesis. Furthermore, relative roles of topographical factors (matrix alignment vs. matrix modulus) in inducing tenogenic differentiation is not well understood. In this study we investigated the effects of modulus and topographical alignment of type I collagen substrate on tendon differentiation. Type I collagen sheet substrates with random topographical alignment were fabricated with their moduli tuned in the range of 0.1, 1, 10 and 100MPa by using electrocompaction and controlled crosslinking. In one of the groups, topographical alignment was introduced at 10MPa stiffness, by controlled unidirectional stretching of the sheet. RT-PCR, immunohistochemistry and immunofluorescence results showed that mimicking the tendon topography, i.e. increasing the substrate modulus as well as alignment increased the tenogenic differentiation. Higher substrate modulus increased the expression of COLI, COLIII, COMP and TSP-4 about 2-3-fold and increased the production of COLI, COLIII and TSP-4 about 2-4-fold. Substrate alignment up regulated COLIII and COMP expression by 2-fold. Therefore, the tenoinductive collagen material model developed in this study can be used in the research and development of tissue engineering tendon repair constructs in future.
Although the effects of substrate topography and modulus on MSC differentiation are well known with respect to osteogenesis and adipogenesis, there has been relatively little investigation on the effects of this phenomenon on tenogenesis. Furthermore, a relative role of topographical factors (matrix alignment vs. matrix modulus) in inducing tenogenic differentiation is not well understood. We investigated the effects of modulus and topographical alignment of type I collagen substrate on tendon differentiation. This study showed mimicking the tendon topography, i.e. increasing the substrate modulus as well as alignment increased the tenogenic differentiation. Therefore, the tenoinductive collagen material model developed in this study can be used in the research and development of tissue engineering tendon repair constructs in future.
细胞外基质模量在正常和疾病状态下调节细胞形态、增殖和分化方面起着重要作用。尽管底物拓扑结构和模量对间充质干细胞（MSC）分化在成骨和脂肪生成方面的影响已广为人知，但关于这种现象对肌腱生成的影响的研究相对较少。此外，地形因素（基质排列与基质模量）在诱导肌腱分化中的相对作用尚不清楚。在本研究中，我们研究了I型胶原底物的模量和拓扑排列对肌腱分化的影响。通过电压实和可控交联制备了具有随机拓扑排列的I型胶原片底物，其模量在0.1、1、10和100MPa范围内调节。在其中一组中，通过对片材进行可控的单向拉伸，在10MPa刚度下引入拓扑排列。逆转录聚合酶链反应（RT-PCR）、免疫组织化学和免疫荧光结果表明，模拟肌腱拓扑结构，即增加底物模量以及排列增加了肌腱分化。较高的底物模量使I型胶原（COLI）、III型胶原（COLIII）、富含亮氨酸的小分子蛋白聚糖（COMP）和血小板反应蛋白4（TSP-4）的表达增加约2-3倍，并使COLI、COLIII和TSP-4的产量增加约2-4倍。底物排列使COLIII和COMP表达上调2倍。因此，本研究中开发的肌腱诱导性胶原材料模型可用于未来组织工程肌腱修复构建体的研发。
尽管底物拓扑结构和模量对MSC分化在成骨和脂肪生成方面的影响已广为人知，但关于这种现象对肌腱生成的影响的研究相对较少。此外，地形因素（基质排列与基质模量）在诱导肌腱分化中的相对作用尚不清楚。我们研究了I型胶原底物的模量和拓扑排列对肌腱分化的影响。本研究表明，模拟肌腱拓扑结构，即增加底物模量以及排列增加了肌腱分化。因此，本研究中开发的肌腱诱导性胶原材料模型可用于未来组织工程肌腱修复构建体的研发。
