Interface‐Directed Self‐Assembly of Cell‐Laden Microgels

Abstract

Cell-laden hydrogels show great promise for creating engineered tissues. However, a major shortcoming with these systems has been the inability to fabricate structures with controlled microscale features on a biologically relevant length scale. Here we demonstrate a rapid method for creating centimeter-scale, cell-laden hydrogels through the assembly of shape-controlled microgels. This was achieved by using an approach that uses the liquid-air interface of a hydrophobic solution to drive the assembly of microgels. Cell-laden microgels of specific shapes were randomly placed on the surface of a high density, hydrophobic solution and induced to aggregate and were subsequently crosslinked into macroscale tissue-like structures. The resultant assemblies were cell-laden hydrogel sheets consisting of tightly-packed ordered microgel units. In addition, a hierarchical approach created complex multi-gel building blocks which were then assembled into tissues with precise spatial control over the cell distribution. These data demonstrate that forces at an air-liquid interface can be used to self-assemble spatially controllable, co-cultured tissue-like structures.

Synthesis and Characterization of Tunable Poly(Ethylene Glycol): Gelatin Methacrylate Composite Hydrogels

“…24,31 NIH3T3 fibroblasts were encapsulated in composite hydrogels and the percent viability was analyzed at 6 and 48 h post-encapsulation. For cell viability in composite hydrogels there was a significant effect of GelMA concentration ( p < 0.05), PEG concentration ( p < 0.05), an interactive effect of time and GelMA ( p < 0.05), an interactive effect of PEG and GelMA ( p < 0.05), and an interactive effect of time, GelMA, and PEG ( p < 0.05) (Fig.…”

Micropatterned Cell–Cell Interactions Enable Functional Encapsulation of Primary Hepatocytes in Hydrogel Microtissues

“…30 While these earlier studies have focused on modeling the diseased state of tumor biology, here we seek to apply microtissues to primary mammalian cells and the area of hepatic tissue engineering. There has also been considerable interest in using microtissues as building blocks for bottom-up assembly of patterned tissues 28,31,32 and packed-reactor-like devices. [33][34][35] However, these studies have yet to be extended to primary hepatocytes, thus far incorporating only the more easily cultured but phenotypically distorted hepatic cell lines.…”

Techniques for fabrication and construction of three-dimensional scaffolds for tissue engineering

“…The high hydrophobicity of the solvent resulted in enhanced surface tension and closely packed microgels at the liquid-air interface. 26,74 The assembly process could also be controlled by changing the stirring speed and duration. Comparing with the railed microfluidic assembly approach, emerging surface tension assembly strategies hold great potential for fabrication of organized complex three-dimensional tissue constructs with spatial control in vitro.…”

“…21,22 Various assembly methods have been investigated, including those based on microfluidics, 23 acoustic fields, 24 magnetic fields, 25 and surface tension. 26 In this review, we firstly describe state-of-the-art methods for fabricating nanofibrous biomimetic scaffolds, including electrospinning, phase-separation, freeze-drying, and self-assembly. A brief overview of their applications for tissue engineering is also presented.…”