The assembly of cell-encapsulating microscale hydrogels using acoustic waves

Abstract

Microscale hydrogels find widespread applications in medicine and biology, e.g., as building blocks for tissue engineering and regenerative medicine. In these applications, these microgels are assembled to fabricate large complex 3D constructs. The success of this approach requires non-destructive and high throughput assembly of the microgels. Although various assembly methods have been developed based on modifying interfaces, and using microfluidics, so far, none of the available assembly technologies have shown the ability to assembly microgels using non-invasive fields rapidly within seconds in an efficient way. Acoustics has been widely used in biomedical area to manipulatedroplets, cells and biomolecules. In this study, we developed a simple, non-invasiveacoustic assembler for cell-encapsulating microgels with maintained cell viability (>93%). We assessed the assembler for both microbeads (with diameter of 50 µm and 100 µm) and microgels of different sizes and shapes (e.g., cubes, lock-and-key shapes, tetris, saw) in microdroplets (with volume of 10 µL, 20 µL, 40 µL, 80 µL). The microgels were assembled in second sin a non-invasive manner. These results indicate that the developed acoustic approach could become an enabling biotechnology tool for tissue engineering, regenerative medicine, pharmacology studies and high throughput screening applications.

Stokes trap for multiplexed particle manipulation and assembly using fluidics

“…From this perspective, it might be possible to access new levels of spatial ordering and hierarchical assembly by coupling external fields during the assembly process in a nonperturbative fashion. In the past, directed assembly of colloidal particles has been achieved by using external electrical fields (33,34), acoustic fields (35), or optical fields (36). Nevertheless, not all techniques are well suited for directed assembly.…”

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

“…72 Recently, the bottom-up approach has emerged as an assembly process for microscale building blocks (eg, cell-encapsulating microgels) which holds great potential to fabricate complex tissue constructs, with control over the shape and compositional features of the individual building blocks. 24,25,73,74 Another advantage of the bottom-up method is the superior diffusion properties of microgels due to their controllable volume, which can obtain a high cell density after encapsulating cells. A variety of methods have been developed to fabricate microgels, including molding, 75 folding, photolithography, 21 molecular synthesis, 76 and generation of microdroplets.…”

“…These microscale building blocks can be successfully assembled into complex tissue constructs, with control over features such as the shape and composition of individual blocks. 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.…”

Fabrication of 3D Cellular Tissue Utilizing MEMS Technologies

“…Among various strategies of self-assembly methods based on molecular interactions [6,63,[66][67][68][69][70][71][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90], only few strategies can be utilized for tissue engineering; aqueous condition, salt and pH concentration as well as cell culture condition in temperature and gas concentration need to be maintained, external fields and forces cannot interfere with life functions of cells. Due to the strict requirements, biocompatible self-assembly methods strongly rely on hydrogel technologies [5,6,58,63,[90][91][92][93].…”