A Hybrid Model of Cartilage Regeneration Capturing the Interactions Between Cellular Dynamics and Porosity

Abstract

To accelerate the development of strategies for cartilage tissue engineering, models are necessary to investigate the interactions between cellular dynamics and scaffold porosity. In experiments, cells are seeded in a porous scaffold or hydrogel where over the time course of a month, the scaffold slowly degrades while cells divide and synthesize extracellular matrix constituents. We use an off-lattice cellular automaton framework to model the individual behavior of cells within the scaffold. The movement of cells and the ability to reproduce is determined by the nutrient profile in the construct and/or 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., 1994). We investigate the total cell count and location of different cell populations within the construct for different initial scaffold porosities. Similar to experiments, we observe cell counts that level off around day 15 with higher cell counts in scaffolds of higher initial solid volume fraction (lower porosity). Cell clustering is observed and characterized 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 a sensitivity to porosity allows cells to move in a smarter or more optimal arrangement. We investigate the spatiotemporal 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 scaffold porosities, observing higher average cell speed over the course of 30 days for the lowest initial scaffold porosity. This model provides a framework to further investigate how changes in biological parameters such as cell division and movement can change the cellular count and distribution in scaffolds of different initial porosity.

Stem Cells Promote the Regeneration of Knee Joint Degenerative Bone and Articular Cartilage

“…It often manifests as pain when going up and down stairs, walking, unstable and bumpy, and poor flexion and extension. In severe cases, loss of joint function may occur, leading to loss of labor and living ability [ 9 , 10 ]. There are about 250 million patients with knee pain around the world, and the elderly account for 30% of those with knee pain.…”