Rapid and Facile Light‐Based Approach to Fabricate Protease‐Degradable Poly(ethylene glycol)−norbornene Microgels for Cell Encapsulation

Abstract Thiol‐norbornene photoclickable poly (ethylene glycol) (PEG)‐based (PEG‐NB) hydrogels are attractive biomaterials for cell encapsulation, drug delivery, and regenerative medicine applications. Although many crosslinking strategies and chemistries have been developed for PEG‐NB bulk hydrogels, fabrication approaches of PEG‐NB microgels have not been extensively explored. Here, a fabrication strategy for 4‐arm amide‐linked PEG‐NB (PEG‐4aNB) microgels using flow‐focusing microfluidics for human mesenchymal stem/stromal cell (hMSCs) encapsulation is presented. PEG‐4aNB photochemistry allows high‐throughput, ultrafast generation, and cost‐effective synthesis of monodispersed microgels (diameter 340 ± 18, 380 ± 24, and 420 ± 15 µm, for 6, 8, and 10 wt% of PEG‐4aNB, respectively) using an in situ crosslinking methodology in a microfluidic device. PEG‐4aNB microgels show in vitro degradability due to the incorporation of a protease‐degradable peptide during photocrosslinking and encapsulated cells show excellent viability and metabolic activity for at least 13 days of culture. Furthermore, the secretory profile (i.e., MMP‐13, ICAM‐1, PD‐L1, CXCL9, CCL3/MIP‐1, IL‐6, IL‐12, IL‐17E, TNF‐ α , CCL2/MCP‐1) of encapsulated hMSCs shows increased expression in response to IFN‐ γ stimulation. Collectively, this work shows a versatile and facile approach for the fabrication of protease‐degradable PEG‐4aNB microgels for cell encapsulation.