Department of Mining and Materials Engineering, McGill University, Montreal, Quebec, Canada.
Acta Biomater. 2010 Oct;6(10):3978-87. doi: 10.1016/j.actbio.2010.04.028. Epub 2010 May 6.
Optimal scaffold characteristics are essential for the therapeutic application of engineered tissues. Hydraulic permeability (k) affects many properties of collagen gels, such as mechanical properties, cell-scaffold interactions within three dimensions (3D), oxygen flow and nutrient diffusion. However, the cellular response to 3D gel scaffolds of defined k values has not been investigated. In this study, unconfined plastic compression under increasing load was used to produce collagen gels with increasing solid volume fractions. The Happel model was used to calculate the resulting permeability values in order to study the interaction of k with gel mechanical properties and mesenchymal stem cell (MSC)-induced gel contraction, metabolism and differentiation in both non-osteogenic (basal medium) and osteogenic medium for up to 3 weeks. Collagen gels of fibrillar densities ranging from 0.3 to >4.1 wt.% gave corresponding k values that ranged from 1.00 to 0.03 microm(2). Mechanical testing under compression showed that the collagen scaffold modulus increased with collagen fibrillar density and a decrease in k value. MSC-induced gel contraction decreased as a direct function of decreasing k value. Relative to osteogenic conditions, non-osteogenic MSC cultures exhibited a more than 2-fold increase in gel contraction. MSC metabolic activity increased similarly under both osteogenic and non-osteogenic culture conditions for all levels of plastic compression. Under osteogenic conditions MSC differentiation and mineralization, as indicated by alkaline phosphatase activity and von Kossa staining, respectively, increased in response to an elevation in collagen fibrillar density and decreased gel permeability. In this study, gel scaffolds with higher collagen fibrillar densities and corresponding lower k values provided a greater potential for MSC differentiation and appear most promising for bone grafting purposes. Thus, cell-scaffold interactions can be optimized by defining the 3D properties of collagen scaffolds through k adjustment.
优化的支架特性对于工程组织的治疗应用至关重要。水力传导率（k）会影响胶原凝胶的许多性质，如机械性能、三维（3D）内的细胞-支架相互作用、氧气流动和营养扩散。然而，尚未研究细胞对具有特定 k 值的 3D 凝胶支架的反应。在这项研究中，使用逐渐增加负载的无约束塑性压缩来制备胶原凝胶，从而增加固体体积分数。使用 Happel 模型计算所得渗透率值，以研究 k 值与凝胶机械性能以及间充质干细胞（MSC）在非成骨（基础培养基）和成骨培养基中诱导凝胶收缩、代谢和分化之间的相互作用，为期长达 3 周。纤维密度范围从 0.3 到 >4.1wt.%的胶原凝胶产生的相应 k 值范围从 1.00 到 0.03 微米 2。压缩下的机械测试表明，胶原支架的模量随胶原纤维密度的增加和 k 值的降低而增加。MSC 诱导的凝胶收缩随着 k 值的降低呈直接函数降低。与成骨条件相比，非成骨 MSC 培养物的凝胶收缩增加了两倍以上。在所有塑性压缩水平下，非成骨 MSC 培养条件下的 MSC 代谢活性与成骨培养条件下相似。在成骨条件下，碱性磷酸酶活性和 von Kossa 染色分别表示 MSC 分化和矿化，随着胶原纤维密度的增加和凝胶渗透性的降低而增加。在这项研究中，具有较高胶原纤维密度和相应较低 k 值的凝胶支架为 MSC 分化提供了更大的潜力，并且在骨移植方面似乎最有前景。因此，可以通过通过 k 值调整来定义胶原支架的 3D 特性来优化细胞-支架相互作用。
