Microfluidic Fabrication of Fully-Resorbable Stereocomplex Crosslinked Hydrogel Microparticles with Tunable Material Properties

Abstract

Hydrogel microparticles (HMPs) have demonstrated significant advantages over bulk hydrogels in terms of injectability and the flexibility to incorporate diverse chemistries, physical properties, and bioactive payloads. The state-of-the-art HMP fabrication employs photo-initiated “click” reactions to form hydrogel networks with advanced control over network properties; however, these covalently crosslinked networks limit the material’s degradation. Stereocomplexation (SC), a stereospecific form of physical crosslinking, provides a robust yet degradable alternative for creating translationally relevant HMPs. Herein, we show the first SC crosslinked HMPs fabricated via microfluidics that require no toxic photoinitiators or UV light during fabrication. HMPs were composed of 4-arm poly(ethylene glycol) (PEG) stars with oligomeric poly(L-lactic acid) (PLLA) chain ends and complementary, propargyl-containing ABA crosslinkers with enantiomeric poly(D-lactic acid) (PDLA) chain ends. Droplets of these precursors were formed using a microfluidic chip where they self-assembled into a network via SC after exposure to water. In this system, well-defined SC HMPs with diameters from ~30 to 100 µm were fabricated. We also demonstrate that varying the PEG and PLA arm lengths of gel precursors directly affects network properties such as thermal stability, mechanical stability, and network defect formation. Variation also has a large impact on the concentration of crosslinker need for fabrication, which further influences the hydrogel’s final characteristics such as swelling and drug release. Overall, this system provides a tunable, hydrolytically degradable alternative to the current state-of-the-art HMP systems.