4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture

Abstract

Granular synthetic hydrogels are useful bioinks for their compatibility with a variety of chemistries, affording printable, stimuli‐responsive scaffolds with programmable structure and function. Additive manufacturing of microscale hydrogels, or microgels, allows for the fabrication of large cellularized constructs with percolating interstitial space, providing a platform for tissue engineering at length scales that are inaccessible by bulk encapsulation where transport of media and other biological factors are limited by scaffold density. Herein, synthetic microgels with varying degrees of degradability are prepared with diameters on the order of hundreds of microns by submerged electrospray and UV photopolymerization. Porous microgel scaffolds are assembled by particle jamming and extrusion printing, and semi‐orthogonal chemical cues are utilized to tune the void fraction in printed scaffolds in a logic‐gated manner. Scaffolds with different void fractions are easily cellularized post printing and microgels can be directly annealed into cell‐laden structures. Finally, high‐throughput direct encapsulation of cells within printable microgels is demonstrated, enabling large‐scale 3D culture in a macroporous biomaterial. This approach provides unprecedented spatiotemporal control over the properties of printed microporous annealed particle scaffolds for 2.5D and 3D tissue culture.

Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

“…A similar strategy was used to print MSCs-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, in gelatin methacrylamide-gellan gum bioinks [ 103 ]. Bioprinting of microgels was also widely used to fabricate large viable constructs with percolating interstitial space following in silico designs [ 104 , 105 , 106 ]. Synthetic microgels with varying degrees of degradability were assembled with or without encapsulated cells, by particle jamming and extrusion printing, and semi-orthogonal chemical cues were employed to tune the void fraction in printed scaffolds [ 104 ].…”

“…Bioprinting of microgels was also widely used to fabricate large viable constructs with percolating interstitial space following in silico designs [ 104 , 105 , 106 ]. Synthetic microgels with varying degrees of degradability were assembled with or without encapsulated cells, by particle jamming and extrusion printing, and semi-orthogonal chemical cues were employed to tune the void fraction in printed scaffolds [ 104 ]. The high-throughput direct encapsulation of cells within printable microgels scaffolds with different void fractions provided unprecedented spatiotemporal control over the mechanical, topographical, and geometric cues necessary for the proper maturation of printed constructs [ 104 ].…”

“…Synthetic microgels with varying degrees of degradability were assembled with or without encapsulated cells, by particle jamming and extrusion printing, and semi-orthogonal chemical cues were employed to tune the void fraction in printed scaffolds [ 104 ]. The high-throughput direct encapsulation of cells within printable microgels scaffolds with different void fractions provided unprecedented spatiotemporal control over the mechanical, topographical, and geometric cues necessary for the proper maturation of printed constructs [ 104 ]. Cell-laden microgels can be directly assembled into well-defined 3D shapes and structures under low-level ultraviolet light [ 105 ].…”

Nanogel Degradation at Soft Interfaces and in Bulk: Tracking Shape Changes and Interfacial Spreading

“…Nanogels and microgels find their uses in a broad range of applications including drug and biomolecule delivery and controlled release, , catalyst carriers, interfacial catalysis, stimulus-responsive emulsion stabilizers, and fabrication of scaffolds for cell and tissue culture . These polymeric particles can be fabricated of various shapes, sizes, and softness , and with tailored stimulus-responsive functionalities.…”

“…This balance can be externally controlled for a broad range of stimulus-responsive hydrogel networks that can respond to environmental changes such as changes in pH, temperature, , and external light . As an example, thermoresponsive poly­( N -isopropylacrylamide)-based gels undergo a temperature-induced volume phase transition resulting in a fraction of water being expelled from the network, ultimately causing a particle collapse and respective reduction in microgel size. ,, Photodegradation of nanogels and microgels can be used to remotely control drug delivery or to control properties of scaffolds for multidimensional cell culture …”