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. 2011 Nov;32(31):7847-55.
doi: 10.1016/j.biomaterials.2011.07.010. Epub 2011 Aug 6.

The Assembly of Cell-Encapsulating Microscale Hydrogels Using Acoustic Waves

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Free PMC article

The Assembly of Cell-Encapsulating Microscale Hydrogels Using Acoustic Waves

Feng Xu et al. Biomaterials. .
Free PMC article

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 assemble microgels using non-invasive fields rapidly within seconds in an efficient way. Acoustics has been widely used in biomedical arena to manipulate droplets, cells and biomolecules. In this study, we developed a simple, non-invasive acoustic 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 seconds in 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.

Figures

Figure 1
Figure 1. Acoustic microgel assembly process
(a) Fabrication of microgels using photolithography. (b) Assembly of the microgels within a liquid droplet using an acoustic assembler. Distributed microgels were assembled at the center area of the transducer during the acoustic excitation.
Figure 2
Figure 2. Acoustic assembly of microbeads
Images of (a) distributed 50 µm microbeads before acoustic excitation, and (b) after acoustic excitation. Bead concentration was 50 mg/mL. Images of (c) distributed 100 µm microbeads before acoustic excitation, and (d) after acoustic excitation. Bead concentration was 50 mg/mL. Assembly time versus frequency for different drop sizes for (e) 50 µm beads and (f) 100µm beads. (g) Assembly time versus amplitude of excitation for a 20µL droplet. (h) Assembly time versus bead concentration within a 20µL droplet.
Figure 2
Figure 2. Acoustic assembly of microbeads
Images of (a) distributed 50 µm microbeads before acoustic excitation, and (b) after acoustic excitation. Bead concentration was 50 mg/mL. Images of (c) distributed 100 µm microbeads before acoustic excitation, and (d) after acoustic excitation. Bead concentration was 50 mg/mL. Assembly time versus frequency for different drop sizes for (e) 50 µm beads and (f) 100µm beads. (g) Assembly time versus amplitude of excitation for a 20µL droplet. (h) Assembly time versus bead concentration within a 20µL droplet.
Figure 3
Figure 3. Single-layer assembly of microgels via acoustic excitation
(a) Images of 200µm square microgels before and after acoustic excitation. (b) Change of normalized area with duration of the acoustic excitation. (c)–(d) Images of lock-and-key microgels before and after acoustic excitation. Circlar microgels (200 µm in diameter) were connected by a star-shaped microgel, while 200 µm circular microgels were enclosed in 1 mm square microgels. (e) Images of Z-shaped tetris blocks before and after acoustic excitation. (f) Images of 1 mm saw-shaped microgels before and after acoustic excitation.
Figure 3
Figure 3. Single-layer assembly of microgels via acoustic excitation
(a) Images of 200µm square microgels before and after acoustic excitation. (b) Change of normalized area with duration of the acoustic excitation. (c)–(d) Images of lock-and-key microgels before and after acoustic excitation. Circlar microgels (200 µm in diameter) were connected by a star-shaped microgel, while 200 µm circular microgels were enclosed in 1 mm square microgels. (e) Images of Z-shaped tetris blocks before and after acoustic excitation. (f) Images of 1 mm saw-shaped microgels before and after acoustic excitation.
Figure 4
Figure 4. Multi-layer assembly of microgels via acoustics
(a) Distributed microgels were first assembled into (b) single layer using acoustic excitation. (c) The single-layer assembly was stabilized by second crosslinking. (d) New microgels were then introduced on the surface of the assembled single layer to form assembled second layer. (e) Enlarged image of single-layer assembly. (f) Enlarged image of double-layer assembly. (g) Image of fabricated multi-layer hydrogel construct.
Figure 5
Figure 5. Viability of cells encapsulated in microgels during the acoustic assembly process
(a) Fabricated cell-encapsulating microgels and (b) corresponding fluorescent images of live/dead staining after crosslinking. Cell viability in individual microgels after (c) crosslinking and (d) after acoustic excitation for 5 seconds. (e) Quantification of cell viability in medium, in PEG, after crosslinking and after acoustic excitation (5 seconds and 30 seconds).

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