4.5 Modeling flow through scaffolds
One of the preeminent challenges in tissue engineering is developing a suitable support material to facilitate the attachment and subsequent development of anchorage-dependent cells into full tissue [43]. This material, called a scaffold, must at least partially mimic the in vivo properties of the extracellular matrix of the tissue of interest [43], and should offer i) sufficient mechanical strength, ii) a network of interconnected pores, iii) adequate transport of oxygen and nutrients and iv) easy removal of waste products [44]. Scaffold dynamics and functionality have been well-studied in tissue engineering applications [43], but novel scaffold systems are required in cultivated meat research and development. Additionally, cultivated meat scaffolds will need to be considerably larger than those currently in use in tissue engineering if this nascent technology has a chance to off-set conventional meat demand. Optimization and scaling of scaffolding design is another area where computer modeling will be an invaluable tool in cultivated meat research and development.
Computational modeling has been broadly utilized in tissue engineering scaffold characterization and design [44,45]; however, we will focus on three specific examples that should also be applicable in cultivated meat research. One foundational way that modeling techniques can be useful is in developing scaffold geometries. Here, it is particularly important that the physical scaffold architecture provides adequate porosity, and three-dimensional computer-aided design models have been used to examine 119 polyhedrons as base units for scaffold construction and to assess the performance of these designs [46]. Beyond the physical architecture of the scaffold, it will be fundamentally important to understand cell-scaffold material interactions to achieve a controlled and reproducible cultivated meat growth system. In this regard, computer modeling should be useful, as numerous mathematical and computational models have focused on, for example, modeling the active mechanosensing behavior in cell-matrix interactions [47].
In general, computational analysis of scaffold properties should consider two phases: a solid bulk scaffold and a fluid medium inside the pores [44]. Indeed, computational fluid dynamics are an important part of computer modeling of scaffolds. Application of these techniques may be used to determine optimal pore size, branching and flow rates within the scaffold and how these may change as a scaffold becomes cell-laden, and the influence of these parameters on the overall cultivated meat bioreactor design [48].