Figure 1.

Microvasculature fabrication within multifunctional hydrogel biomaterials. A) Hydrogels are generated by cytocompatible strain-promoted azide-alkyne cycloaddition (SPAAC) between a poly(ethylene gycol) tetrabicyclononyne (PEG-tetraBCN, where BCN is shown in red) and a diazide-modified synthetic peptide (azides shown in blue). The peptide contains a photodegradable ortho-nitrobenzyl linker (oNB, orange), a matrix metalloproteinase (MMP)-cleavable sequence (GPQGIWGQ, purple), and a cell-adhesive region (RGDS, green). B) User-programmed multiphoton excitation induces localized degradation of the hydrogel through oNB photocleavage, resulting in the microchannel (pink) generation in the presence of encapsulated stromal cells (green). C) Photodegraded networks are then seeded with endothelial cells (pink) to created cell-laden hydrogels with perfusable, endothelialized vasculature. D) oNB photocleavage yields nitroso- and acid-terminated byproducts. E) RGDS moieties included within the peptide crosslinker promote cell attachment and proliferation. F) The GPQGIWGQ peptide sequence is cleaved enzymatically by secreted MMPs, enable cell-mediated matrix remodeling of the hydrogel network.