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A hybrid cellular automaton model of cartilage regeneration capturing the interactions between cellular dynamics and scaffold porosity

To accelerate the development of strategies for cartilage tissue engineering, models are necessary to study the interactions between cellular dynamics and scaffold (SC) porosity. In experiments, cells are seeded in a porous SC where over a month, the SC slowly degrades while cells divide and synthesize extracellular matrix (ECM) constituents. We use an off-lattice cellular automaton framework to model the individual behavior of cells within the SC. The movement of cells and the ability to reproduce is determined by the nutrient profile and local porosity. A phenomenological approach is used to capture a continuous profile for SC and ECM evolution, which will then change the local porosity. We parameterize the model by matching total cell counts to chondrocytes seeded in a polyglycolic acid SC. We investigate the total cell count and location of various cell populations for different initial SC porosities. Similar to experiments, we observe cell counts that level off around day 15 with higher values in SCs of lower initial porosity. Cell clustering is observed in regions at the edge of the construct that are close to the nutrient-rich medium in the fluid bath. Model results show that a bias in motion due to sensitivity to porosity allows cells to move in a more optimal arrangement. We investigate the distribution of cells as the cell reproduction rate, cell movement distance, and sensitivity to porosity is varied. We observe non monotonic changes in total cell counts within different regions of the construct due to the interplay between porosity and cellular movement. We also analyze the emergent average cell speed for different initial SC porosities, observing an higher average for the lowest initial SC porosity. This model provides a framework to further investigate how changes in biological parameters can change the cellular count and distribution in SCs of different initial porosity

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