Schemes of droplet microfluidics-assisted production of hyaluronic acid-based microgels by means of Passerini three-component reaction and Ugi four-component reaction. (A) A water-in-oil emulsion of an aqueous solution of hyaluronic acid as microgel backbone and PEG-dialdehyde crosslinker is formed within a continuous phase made of fluorinated oil, tert-butyl isocyanide, and a home-made triblock copolymer surfactant to prevent coalescence of the as-formed droplets. The isocyanide component diffuses into the aqueous droplets through the surfactant layer to initiate the Passerini-3CR. After gelation, the microgels are purified by transferring them into an aqueous medium assisted by PFO that induces emulsion coalescence. The chemical structure of the crosslinking site is depicted within the yellow box. (B) Production of microgels by Ugi-4CR analogous to (A), but with formaldehyde instead of PEG-dialdehyde and a homobifunctional amine component, PEG-diamine, serving as crosslinker.