Grooved poly(lactide-co-trimethylene carbonate) substrates in tenogenic media maintain human tendon derived cell phenotype in culture – A preliminary report✰

Sofia Ribeiro , Eugenia Pugliese , Stefanie H. Korntner , Emanuel M. Fernandes , Manuela E. Gomes , Rui L. Reis , Alan O'Riordan , Stephen Kearns , Jack L. Kelly , Manus Biggs , Yves Bayon , Dimitrios I. Zeugolis
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Abstract

Tissue engineering strategies for tendon repair and regeneration rely heavily on the use of tendon derived cells. However, these cells frequently undergo phenotypic drift in vitro, which compromises their therapeutic potential. In order to maintain the phenotype of tendon derived cells in vitro, microenvironmental cues (biophysical, biochemical and/or biological in origin) have been used to better imitate the complex tendon microenvironment. Herein, the influence of planar and grooved (groove width of ∼1.0 µm, groove depth of ∼1.4 µm and distance between groves of ∼1.7 µm) poly(glycolide-co-ε-caprolactone) substrates with elastic modulus of 7 kPa and poly(lactide-co-trimethylene carbonate) substrates with elastic modulus of 12 kPa on human tendon derived cell response was assessed, using planar tissue culture plastic substrates of 3 GPa elastic modulus as control, in both basal and tenogenic media. At day 17, the grooved 12 kPa poly(lactide-co-trimethylene carbonate) substrate induced the highest deposition and alignment of collagen type I in tenogenic media. At day 17, the grooved 12 kPa poly(lactide-co-trimethylene carbonate) substrate and the tissue culture plastic induced the highest deposition and the tissue culture plastic and the planar 7 kPa poly(glycolide-co-ε-caprolactone) induced the lowest alignment of tenascin C in tenogenic media. Also at day 17 in tenogenic media, the grooved 12 kPa poly(lactide-co-trimethylene carbonate) substrate induced the upregulation of most tenogenic genes (COL1A1, COL3A1, MKX, TNMD). Our data further support the notion of multifactorial tissue engineering for effective control over cell fate in vitro setting.

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肌腱形成培养基中的凹槽聚(丙交酯-碳酸三甲酯)基质在培养中保持人肌腱衍生细胞表型——初步报告✰
肌腱修复和再生的组织工程策略在很大程度上依赖于肌腱衍生细胞的使用。然而,这些细胞在体外经常发生表型漂移,这损害了它们的治疗潜力。为了在体外维持肌腱衍生细胞的表型,微环境线索(生物物理、生物化学和/或生物学起源)已被用于更好地模拟复杂的肌腱微环境。在此,评估了弹性模量为7kPa的平面和凹槽(凹槽宽度~1.0µm,凹槽深度~1.4µm,槽间距离~1.7µm)聚(乙交酯-ε-己内酯)基质和弹性模量为12kPa的聚(丙交酯-碳酸三甲酯)基质对人腱衍生细胞反应的影响,使用3GPa弹性模量的平面组织培养塑料基质作为对照。在第17天,开槽的12kPa聚(丙交酯-碳酸三甲烯酯)基质在肌腱形成介质中诱导了I型胶原的最高沉积和排列。在第17天,开槽的12kPa聚(丙交酯-碳酸三甲烯酯)基质和组织培养塑料诱导了最高的沉积,而组织培养塑料和平面7kPa聚(乙交酯-ε-己内酯)在肌腱形成介质中诱导了最低的tenascin C排列。同样在肌腱形成培养基中的第17天,具有凹槽的12kPa聚(丙交酯-碳酸三甲烯酯)底物诱导大多数肌腱形成基因(COL1A1、COL3A1、MKX、TNMD)的上调。我们的数据进一步支持了多因素组织工程在体外环境中有效控制细胞命运的概念。
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Biomedical engineering advances
Biomedical engineering advances Bioengineering, Biomedical Engineering
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