Geometrically Controlled Liquefied Capsules for Modular Tissue Engineering Strategies

Abstract

tissues. Living tissues are characterized by repetitive functional units, which include combinations of heterogenous cell populations and extracellular matrix (ECM), structured across multiple length scales. In an attempt to mimic such hierarchical, adaptive and complex functionality and spatial organization, the assemble of 3D functional units with defined microarchitectural features was envisaged, in a concept termed modular TE. [1,2] In modular TE approaches, cell-laden hydrogels are being considerably explored as building blocks to create modular tissues with specific geometries and mechanical properties. [3,4] Hydrogels are attractive 3D cell supportive platforms due to their highly hydrated nature, resembling the tissuelike compliance of the native ECM. [5] Cellladen modular units enable the spatial and temporal manipulation of the biomaterials microenvironment, while avoid the invasive procedures inherent to scaffolds implantation into a defect site. Once created, the modular units can be assembled into larger multifunctional tissues, structured in a scale-range manner. Each modular unit can carry distinct cargo, including multiphenotypic cells and biomolecules of interest. The assembly of 3D modular units was already proposed for the fabrication of different tissues, such as cartilage, [6] hepatic, [7] and heart tissues. [8]

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

“…[24,25] After forming the coordinated shell, Gel-HOPO beads were incubated at 37°C, where the non-coordinated proteins were dissolved, yielding liquefied capsules (Figure 1B3). Differing from the systems that use alginate as sacrificial core, [26] gelatin liquefaction at physiological temperatures enables this step to be performed in vivo after implantation. This easily madeup methodology allows control over the bead size by changing the volume dropped on top of the SH surface, with size ranges be-tween 1 to 3 mm easily achieved without losing the overall spherical shape.…”

An Immunomodulatory Miniaturized 3D Screening Platform Using Liquefied Capsules

“…The liquefied capsules were already tested as a cell encapsulation system for tissue engineering applications in an alternative to avoid the use of conventional scaffolds with fixed geometries and open surgery implantations, while also be injectable by minimally invasive procedures. [12,[22][23][24][25][26] The system was already tested in vivo, however, due to the use of immunocompromised mice models, the interaction with the immune system remains uncertain. [24] Herein, we envisioned the use of liquefied capsules as an immunomodulatory in vitro screening platform able to provide a more predictive environment of the bioperformance of biomedical devices following implantation.…”

Multiparametric Material Functionality of Microtissue‐Based In Vitro Models as Alternatives to Animal Testing

“…[157] The change of the total surface charge restricts its swelling behavior and promotes the mechanical polymer strength. [164,165] Pasqua et al for example have synthesized cell-laden alginate-PLL-based microbeads for extracorporeal liver supply. Herein, PLL reinforced the mechanical stability of pure alginate microbeads, whereby the elastic module increased from ≈1 to 5 kPa with PLL modification.…”