To accelerate the development of strategies for cartilage tissue engineering, models are necessary to investigate the interactions between cellular dynamics and the local microenvironment. We use a discrete framework to capture the individual behavior of cells, modeling experiments where cells are seeded in a porous scaffold or hydrogel and over the time course of a month, the scaffold slowly degrades while cells divide and synthesize extracellular matrix constituents. The movement of cells and the ability to proliferate is a function of the local porosity, defined as the volume fraction of fluid in the surrounding region. A phenomenological approach is used to capture a continuous profile for the degrading scaffold and accumulating matrix, which will then change the local porosity throughout the construct. We parameterize the model by first matching total cell counts in the construct to chondrocytes seeded in a polyglycolic acid scaffold (Freed et al. in Biotechnol Bioeng 43:597–604, 1994). We investigate the influence of initial scaffold porosity on the total cell count and spatial profiles of cell and ECM in the construct. Cell counts were higher at day 30 in scaffolds of lower initial porosity, and similar cell counts were obtained using different models of scaffold degradation and matrix accumulation (either uniform or cell-specific). Using this modeling framework, we study the interplay between a phenomenological representation of scaffold architecture and porosity as well as the potential continuous application of growth factors. We determine parameter regimes where large cellular aggregates occur, which can hinder matrix accumulation and cellular proliferation. The developed modeling framework can easily be extended and can be used to identify optimal scaffolds and culture conditions that lead to a desired distribution of extracellular matrix and cell counts throughout the construct.

中文翻译：

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捕捉细胞动力学和孔隙度之间相互作用的软骨再生混合模型

为了加快软骨组织工程策略的发展，需要模型来研究细胞动力学与局部微环境之间的相互作用。我们使用离散框架来捕捉细胞的个体行为，模拟将细胞接种在多孔支架或水凝胶中的实验，在一个月的时间过程中，支架缓慢降解，而细胞分裂并合成细胞外基质成分。细胞的运动和增殖能力是局部孔隙度的函数，定义为周围区域中流体的体积分数。现象学方法用于捕获降解支架和累积基质的连续轮廓，然后将改变整个构造的局部孔隙率。我们通过首先将构建体中的总细胞计数与接种在聚乙醇酸支架中的软骨细胞进行匹配来参数化模型（Freed 等，在 Biotechnol Bioeng 43:597–604, 1994）。我们研究了初始支架孔隙率对构建体中细胞和 ECM 的总细胞计数和空间分布的影响。在初始孔隙率较低的支架中，第 30 天的细胞计数较高，并且使用不同的支架降解和基质积累模型（均匀或细胞特异性）获得了相似的细胞计数。使用此建模框架，我们研究了脚手架结构的现象学表示与孔隙率以及生长因子的潜在连续应用之间的相互作用。我们确定出现大细胞聚集体的参数机制，它可以阻碍基质积累和细胞增殖。开发的建模框架可以轻松扩展，并可用于确定最佳支架和培养条件，从而在整个构建体中实现所需的细胞外基质和细胞计数分布。