Methods for Generating Hydrogel Particles for Protein Delivery

Abstract

Proteins represent a major class of therapeutic molecules with vast potential for the treatment of acute and chronic diseases and regenerative medicine applications. Hydrogels have long been investigated for their potential in carrying and delivering proteins. As compared to bulk hydrogels, hydrogel microparticles (microgels) hold promise in improving aspects of delivery owing to their less traumatic route of entry into the body and improved versatility. This review discusses common methods of fabricating microgels, including emulsion polymerization, microfluidic techniques, and lithographic techniques. Microgels synthesized from both natural and synthetic polymers are discussed, as are a series of microgels fashioned from environment-responsive materials.

Protease-degradable microgels for protein delivery for vascularization

“…Of various synthesis routes available to generate synthetic microgels, microfluidics-based polymerization is particularly well-suited for preparing microgels containing proteins and cells because of the aqueous, cytocompatible nature and precise control over particle size of this continuous process [7]. Microgels for protein delivery rely on passive diffusion of the protein through a non-degradable microgel network, and therefore the release kinetics are solely dictated by protein size and microgel mesh size [16].…”

Injectable Supramolecular Hydrogel/Microgel Composites for Therapeutic Delivery

“…Norbornenes react to form covalent bonds via thiol‐ene reactions with thiols in the presence of UV light and a photoinitiator (Figure D), which can be used to form microgels (Figure E). There are numerous techniques that can be used to fabricate covalently cross‐linked microgels, primarily through water‐in‐oil emulsions . Here, microgels were fabricated using a recently developed microfluidic device to generate particles that were cross‐linked with UV light as they flowed out of the device and into a collection vial ( Figure 2 A–C).…”

“…There are numerous techniques that can be used to fabricate covalently cross-linked microgels, primarily through water-in-oil emulsions. [52,53] Here, microgels were fabricated using a recently developed microfluidic device [40] to generate particles that were cross-linked with UV light as they flowed out of the device and into a collection vial (Figure 2A-C). Microgels were spherical and generally uniform in size with a diameter of 59 ± 7 µm ( Figure 2D,E).…”

Parallel droplet microfluidics for high throughput cell encapsulation and synthetic microgel generation

“…Delivery of encapsulated proteins and cells in hydrogel microspheres, or microgels, has emerged as a promising therapeutic strategy for the treatment of various diseases 1 . Synthetic polymers provide tuneable release rates of encapsulated proteins that can be tailored based on diffusion through the hydrogel network or hydrolytic/enzymatic degradation of microgels [2][3][4] .…”