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

Abstract

In the primordial cell encapsulation systems, the main goal was to treat endocrine diseases avoiding the action of the immune system. Although lessons afforded by such systems were 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 by an adequate regenerative process. Combined with such immuno-awareness, novel or non-conventional emerging techniques are being proposed developed the new generation of cell encapsulation systems, namely layer-by-layer, microfluidics, superhydrophobic surfaces, and bioprinting technologies.Alongside with 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 owning high heterogeneity, while providing multifunctional and adaptive inputs.

Design of Protein‐Based Liquefied Cell‐Laden Capsules with Bioinspired Adhesion for Tissue Engineering

“…[1] Upholding superior multifunctionality, liquid environments can be fabricated under mild conditions providing cell containment and protection while offering higher nutrient diffusion. [2] The increased knowledge behind the cellular microenvironment complexity and the possibility of better mimic the native physical and biochemical cues make the choice of the biomaterials critical in the design of high-class platforms. [3] Up to date, a wide variety of polymers DOI: 10.1002/adhm.202100782 (synthetic and natural), biofabrication technologies (e.g., electrospray, microfluidic, among others) and approaches (e.g., layer-by-layer, aqueous biphasic systems) are underneath the design of a shell confinement (i.e., a barrier able to confine cells in a controlled environment).…”

Geometrically Controlled Liquefied Capsules for Modular Tissue Engineering Strategies

“…[ 8 ] While spherical systems are the most widely used, the generation of multi‐shaped complex 3D structures are being increasingly explored to mimic the complexity of native tissues. [ 9 ] For example, cylinder‐shaped microgels can be projected to resemble structures of the human body, such as muscle fibers [ 10 ] or blood vessels. [ 11 ]…”

“…While spherical systems are the most widely used, the generation of multi-shaped complex 3D structures are being increasingly explored to mimic the complexity of native tissues. [9] For example, cylinder-shaped microgels can be projected to resemble structures of the human body, such as muscle fibers [10] or blood vessels. [11] Despite the favorable properties of hydrogels as 3D cell encapsulation systems, macroscopic hydrogels, as those arose from the assemble of modular units, still present key issues, namely, limited cell-cell contact and signaling, as well as poor mass transportation of essential molecules.…”

Minimalist Tissue Engineering Approaches Using Low Material‐Based Bioengineered Systems

“…While at the beginning of the TERM field it was believed that engineered structures should replicate the architecture of the tissue microenvironment from the microscopic to macroscopic dimension levels, nowadays it is well-established that there are other and more relevant key criteria that should be integrated during the design of biomaterials. [1][2][3] This paradigm shift in the TERM field was boosted by a deepened knowledge about the complex endogenous tissue repair process, which contributed to the identification of the key players involved, including cells and signaling molecules, and how the orchestration of spatial and temporal cues occurs in vivo. [4,5] Since then, a wide range of bioengineered strategies with tunable biophysical and biochemical characteristics have been proposed.…”