Facile Micromolding-Based Fabrication of Biopolymeric–Synthetic Hydrogel Microspheres with Controlled Structures for Improved Protein Conjugation

Hydrogel microparticles with controlled structures have drawn attention in various biomedical applications, yet it remains challenging to fabricate such microparticles in a simple manner. We demonstrate facile fabrication of chemically functional and monodisperse hydrogel microspheres with controlled macroporous structures. Specifically, highly uniform poly(ethylene glycol)-based microspheres containing an aminopolysaccharide chitosan are fabricated in a simple micromolding technique utilizing surface tension-induced droplet formation followed by photoinduced polymerization. The as-prepared microspheres show macroporous and/or intriguing core–shell structures by polymerization-induced phase separation. Fluorescent labeling studies indicate stable incorporation of chitosan with retained chemical reactivity. The utility of the controlled macroporous structures in programmable biomacromolecular assembly is thoroughly examined with conjugation of model biomolecules via click chemistries.