Cell-laden microfluidic microgels for tissue regeneration

Abstract

Regenerating the diseased tissue is one of the foremost concerns for the millions of patients who suffer from tissue damage each year. Local delivery of cell-laden hydrogels offers an attractive approach for tissue repair. However, due to the typical macroscopic size of these cell constructs, the encapsulated cells often suffer from poor nutrient exchange. These issues can be mitigated by incorporating cells into microscopic hydrogels, or microgels, whose large surface-to-volume ratio promotes efficient mass transport and enhanced cell-matrix interactions. Using microfluidic technology, monodisperse cell-laden microgels with tunable sizes can be generated in a high-throughput manner, making them useful building blocks that can be assembled into tissue constructs with spatially controlled physicochemical properties. In this review, we examine microfluidics-generated cell-laden microgels for tissue regeneration applications. We provide a brief overview of the common biomaterials, gelation mechanisms, and microfluidic device designs that are used to generate these microgels, and summarize the most recent works on how they are applied to tissue regeneration. Finally, we discuss future applications of microfluidic cell-laden microgels as well as existing challenges that should be resolved to stimulate their clinical application.

Jammed Microgel Inks for 3D Printing Applications

“…To fabricate microgel inks, we first used microfluidic devices (e.g., fluid focusing, T‐junctions) to form microgels, where controlled emulsions (continuous oil phase) were used to form droplets from hydrogel precursor components that were then stabilized during cross‐linking (Figure S1, Supporting Information). There is much versatility to this approach, allowing the fabrication of microgels from numerous materials, across a wide range of sizes, and incorporating biological components (e.g., cells, therapeutics) . To illustrate this versatility, we fabricated microgels from norbornene‐modified hyaluronic acid (NorHA), poly(ethylene glycol) diacrylate (PEGDA), and agarose, where cross‐linking was performed in either the presence of a photoinitiator and light (NorHA and PEGDA) or with cooling (agarose) ( Figure a).…”

Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

“…[1,2] A large surface area-to-volume ratio of MPs allows an efficient loading of cargos as well as improves nutrient and water transfer and cell-matrix interactions. [2,3] Recently, biopolymers, biomacromolecules derived from living organisms including plants, animals, and bacteria, are increasingly being utilized for the design of biomedical-grade MPs due to their excellent biocompatibility and biodegradability. [4,5] Several biopolymers have structures that are similar to the extracellular matrix (ECM) and thus can be recognized by and metabolized in a physiological environment.…”

Cell Encapsulation in Soft, Anisometric Poly(ethylene) Glycol Microgels Using a Novel Radical‐Free Microfluidic System

“…In general, efficient diffusion of nutrients is limited by the overall size of the hydrogel, its mesh size, and the cell density. Therefore, large hydrogels can potentially cause cell death toward their center when dense tissue is being formed . Encapsulation of a defined number of cells in micron‐scale hydrogels overcomes diffusion limitations due to the high surface area‐to‐volume ratio of the microgels .…”

“…Therefore, large hydrogels can potentially cause cell death toward their center when dense tissue is being formed . Encapsulation of a defined number of cells in micron‐scale hydrogels overcomes diffusion limitations due to the high surface area‐to‐volume ratio of the microgels . Additionally, cell‐laden microgels offer the possibility to generate minimal‐invasive, injectable cell/material therapies by local delivery to damaged tissues in the body .…”