On-demand delivery of therapeutic extracellular vesicles by encapsulating in monodispersed photodegradable hydrogel microparticles using a droplet microfluidic device

Abstract

Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been studied for therapeutic applications due to easier endocytosis and fewer adverse effects than MSCs. However, EVs injected medicinally are diluted by body fluids and inefficiently delivered to the therapeutic target, limiting original therapeutic effects. Therefore, biocompatible carriers such as hydrogels are needed in EVs delivery systems to enhance EVs retention and release EVs sustainably at therapeutic targets. In addition to the advantages of delivering EVs using hydrogels, photodegradable hydrogels provide a controllable degradation process via ultraviolet (UV) irradiation. However, long-term UV irradiation to degrade the photodegradable hydrogel may potentially damage EVs and targets; therefore, a carrier that can be degraded with shorter UV irradiation is required. Herein, we generate photodegradable hydrogel microparticles (PHMPs) that can release encapsulated EVs sustainably within 2 min of UV irradiation by droplet-based microfluidics. By regulating the fluidic resistance of the channels, monodisperse PHMPs, which can avoid undesired variations in EVs release kinetics, were generated. EVs were successfully retained in PHMPs in the absence of external stimuli, and EVs were released from PHMPs and enhanced cell proliferation following UV irradiation. Therefore, PHMPs can overcome the limitations of conventional EVs delivery, including their inability to deliver EVs sustainably and on-demand, and low EVs retention. © 2023 Elsevier B.V.