Cell Encapsulation Systems Toward Modular Tissue Regeneration: From Immunoisolation to Multifunctional Devices

In the primordial cell encapsulation systems, the main goal is to treat endocrine diseases avoiding the action of the immune system. Although lessons afforded by such systems are of outmost importance for the demands of tissue engineering and regenerative medicine, the paradigm has recently completely changed. If before the most important feature was to mask the encapsulated cells from the immune system, now it is known that the synergetic interplay between immune cells and the engineered niche is responsible for an adequate regenerative process. Combined with such immuno-awareness, novel or nonconventional emerging techniques are being proposed to develop the new generation of cell encapsulation systems, namely layer-by-layer, microfluidics, superhydrophobic surfaces, and bioprinting technologies. Alongside the desire to create more realistic cell encapsulation systems, cell-laden hydrogels are being explored as building blocks for bottom-up strategies, within the concept of modular tissue engineering. The idea is to use the well-established cell-friendly environment provided by hydrogels and create more close-to-native systems that possess high heterogeneity, while providing multifunctional and adaptive inputs.