A multiscale approach in the computational modeling of the biophysical environment in artificial cartilage tissue regeneration.

Tissue Engineering is a strongly interdisciplinary scientific area aimed at understanding the principles of tissue growth to produce biologically functional replacements for clinical use. To achieve such an ambitious goal, complex biophysical phenomena must be understood in order to provide the appropriate environment to cells (nutrient delivery, fluid-mechanical loading and structural support) in the bioengineered device. Such a problem has an inherent multiphysics/multiscale nature, as it is characterized by material heterogeneities and interplaying processes occurring within a wide range of temporal and spatial scales. In this context, computational models are useful to gain a quantitative and comprehensive understanding of phenomena often difficult to be accessed experimentally. In this paper, we propose a mathematical and computational model that represents, to our knowledge, the first example of a self-consistent multiscale description of coupled nutrient mass transport, fluid-dynamics and biomass production in bioengineered constructs. We specifically focus on articular cartilage regeneration based on dynamically perfused bioreactors, and we investigate by numerical simulations three issues critical in this application. First, we study oxygen distribution in the construct, since achieving an optimal level throughout the construct is a main control variable to improve tissue quality. Second, we provide a quantitative evaluation of how interstitial perfusion can enhance nutrient delivery and, ultimately, biomass production, compared with static culture. Third, we perform a sensitivity analysis with respect to biophysical parameters related to matrix production, assessing their role in tissue regeneration.