Department of Mining and Materials Engineering, McGill University, Montreal, Quebec, Canada H3A 2B2.
Innovhub - Stazioni Sperimentali per l'Industria, Div. Stazione Sperimentale per la Seta, Milan, Italy.
Biomaterials. 2014 Aug;35(24):6236-47. doi: 10.1016/j.biomaterials.2014.04.040. Epub 2014 May 10.
Airway tracts serve as a conduit of transport in the respiratory system. Architecturally, these are composed of cartilage rings that offer flexibility and prevent collapse during normal breathing. To this end, the successful regeneration of an airway tract requires the presence of differentiated chondrocytes and airway smooth muscle cells. This study investigated the role of physiological dynamic mechanical stimulation, in vitro, on the differentiation of mesenchymal stem cells (MSCs), three-dimensionally seeded within a tubular dense collagen matrix construct-reinforced with rings of electrospun silk fibroin mat (TDC-SFC). In particular, the role of either shear stress supplied by laminar fluid flow or cyclic shear stress in combination with circumferential strain, provided by pulsatile flow, on the chondrogenic differentiation, and contractile lineage of MSCs, and their effects on TDC-SFC morphology and mechanical properties were analysed. Chondrogenic differentiation of MSCs was observed in the presence of chondrogenic supplements under both static and laminar flow cultures. In contrast, physiological pulsatile flow resulted in preferential cellular orientation within TDC-SFC, as dictated by dynamic circumferential strain, and induced MSC contractile phenotype expression. In addition, pulsatile flow decreased MSC-mediated collagen matrix remodelling and increased construct circumferential strength. Therefore, TDC-SFC demonstrated the central role of a matrix in the delivery of mechanical stimuli over chemical factors, by providing an in vitro niche to control MSC differentiation, alignment and its capacity to remodel the matrix.
气道作为呼吸系统的传输通道。在结构上，这些通道由软骨环组成，在正常呼吸时提供灵活性并防止塌陷。为此，气道的成功再生需要分化的软骨细胞和气道平滑肌细胞的存在。本研究调查了生理动态机械刺激在体外对三维接种在管状密集胶原基质构建体中的间充质干细胞 (MSCs) 分化的作用，该构建体由纺丝丝素纤维基质环增强（TDC-SFC）。特别是，层流提供的剪切应力或结合脉动流提供的循环剪切应力和周向应变对 MSCs 的软骨分化和收缩谱系的作用，以及它们对 TDC-SFC 形态和力学性能的影响进行了分析。在静态和层流培养中，在软骨生成补充剂存在的情况下观察到 MSCs 的软骨分化。相比之下，生理脉动流导致 TDC-SFC 内的细胞优先定向，这是由动态周向应变决定的，并诱导 MSC 收缩表型表达。此外，脉动流减少了 MSC 介导的胶原基质重塑，并增加了构建体的周向强度。因此，TDC-SFC 证明了基质在传递机械刺激而不是化学因素方面的核心作用，通过提供体外小生境来控制 MSC 分化、排列及其重塑基质的能力。
