*6.3. Compartmentalization*

The more naïve bio-inspired setups summarized in Table 2 and some of the approaches in Table 3 contain several models that represent compartmentalization as a key factor in inducing mimicry. Diverse methods are used to create di fferent functional zones, e.g., including structured compartments [21], di fferential matrix regions such as suspension vs. solid compartment [69,73], co-culture of di fferent cells [70] or generation of biochemically di fferent areas by gradients [72]. However, the combinatorial approaches are the most commonly used [74–76]. When moving forward towards the reviewed cell engineered approaches [65,77,78] it appears that in vivo-mediated vascularization, native ECM remodeling or including di fferent cell types in the engineered models will indirectly lead to better functional compartmentalization than the initial design. Therefore, compartmentalization seems necessary to mimic functional BMN di fferentiation either by directly including it in the model or by indirect cell-mediated remodeling (Box 5). This has led the authors to consider the possible future role of bottom-up tissue engineering strategies in functional artificial BMN modeling, as this field aims to engineer complex tissues by the modular assembly of di fferent living building blocks into customized architectures [122].
