Emerging Technologies for Assembly of Microscale Hydrogels

Abstract

Assembly of cell encapsulating building blocks (i.e., microscale hydrogels) has significant applications in areas including regenerative medicine, tissue engineering, and cell-based in vitro assays for pharmaceutical research and drug discovery. Inspired by the repeating functional units observed in native tissues and biological systems (e.g., the lobule in liver, the nephron in kidney), assembly technologies aim to generate complex tissue structures by organizing microscale building blocks. Novel assembly technologies enable fabrication of engineered tissue constructs with controlled properties including tunable microarchitectural and predefined compositional features. Recent advances in micro- and nano-scale technologies have enabled engineering of microgel based three dimensional (3D) constructs. There is a need for high-throughput and scalable methods to assemble microscale units with a complex 3D micro-architecture. Emerging assembly methods include novel technologies based on microfluidics, acoustic and magnetic fields, nanotextured surfaces, and surface tension. In this review, we survey emerging microscale hydrogel assembly methods offering rapid, scalable microgel assembly in 3D, and provide future perspectives and discuss potential applications.

Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface

“…[14], [82], [118] Various assembling approaches have been used including microfluidics, nanotextured surfaces, and surface tension. [119], [120], [121] These techniques allow microtissues scale-up into larger tissues and permit the creation of complex and well-defined 3D-architectures.…”

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.…”

“…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.…”

Noncontact orientation of objects in three-dimensional space using magnetic levitation

“…Components in assembly lines often have random orientations, and they must be oriented properly before assembly (2)(3)(4). Advanced and "next-generation" approaches based on biomimetic (5)(6)(7)(8) and soft robotic (9) strategies, and hierarchically organized, self-assembled, and stimulus-responsive materials (10)(11)(12)(13)(14)(15) particularly require methods capable of orienting and assembling soft, sticky, and easily damaged materials. Few methods exist to manipulate these types of materials without damaging them.…”