## 5 Perspectives  
Continuum modeling and simulation in BTE has been proved to be a useful tool at several stages of the methodology according to the revised literature. On one hand, the design of the scaffold in terms of its desired characteristics, such as porosity, pore connectivity, permeability, or overall mechanical behavior, according to a specific application, has been a niche of research using numerical  
Figure 4: Validation of the simulation of magnesium screw degradation obtained by the mathematical modeling presented by [PERSON] et al. [118] (**bottom**), compared with the experimental setup by [PERSON] et al. [119] (**top**). Reprinted with permission from [118]. methods. The literature is nowadays vast regarding computer-aided scaffold design, and, traditionally, researchers involved in this part have not always been connected with the fabrication process, which has been performed in collaboration with biomaterial scientists. Currently, 3D printing has brought both fields together, and now computer design of scaffolds is usually complemented by 3D printing of prototypes and mechanical testing of the specimens in the lab [122]. In addition, bioprinting techniques, i.e., 3D printing technology using biological materials, are being explored as an alternative to traditional BTE [123; 124; 125; 126; 127]. Numerical methods can be particularly useful in this context for the design of the printing strategy and simulation of the biofabrication technique [128; 129; 130; 131; 132; 133]. Other physical phenomena that are relevant to analyze in the design phase of a BTE product have not been treated and investigated in detail by computer simulation. These phenomena include biomaterial dissolution and biodegradation since a limited number of mathematical models have been presented in the literature, despite the clear advantages that introduce simulation-based design of degradable materials as concluded in the referred examples. This is a clear line for future research in the modeling of BTE. On the other hand, the evolution of the scaffold in terms of tissue growth, tissue differentiation, and tissue-scaffold interaction has been extensively modeled and simulated in BTE applications in the last decades. Some elaborated models including multiscale, multiphasic, and multiphysics elements have been presented in several examples of interest, showing a great potential. First, the models predict in silico the performance of a certain in vivo applications by means of a virtual assay conducted in the computer. The simulation can be patient-specific accounting for the specific characteristics in hands. Second, in silico simulations reduce time and cost of the assays, as well as reducing animal experimentation with its subsequent ethical implications. However, the main drawback of the computer simulation of clinical BTE applications is the fact that the models are based on empirical laws of tissue growth and evolution. These theories have not been sufficiently validated although some of them were proposed several decades ago. It is therefore necessary to advance the validation of the models in connection with a multidisciplinary team of clinicians, veterinarians and biologists, by no means a trivial task. Model validation is then identified as another research line in BTE collateral to in silico BTE. Moreover, multiscale and multiphasic analyses have been limited by the computational cost of this kind of modeling. In particular, multiphasic models traditionally consider both the solid and fluid domains of the scaffold in a simplified way, either using diffusive or poroelastic approaches. A coupled CFD (fluid phase) and mechanical (solid phase) approach, including solid-fluid interaction, can be useful to account in a detailed fashion both the mechanobiological stimulus, as well as degradation phenomena that take place in the biomaterial. Finally, even a model available for BTE simulation that has been validated at some conditions, may not be predictive in a different scenario.