Abstract
Digital micromirror device (DMD)–based bioprinting enables high-resolution fabrication of hydrogel-based tissue constructs, but print fidelity and hydrogel mechanics are typically coupled through polymer concentration, light exposure, and crosslinking density. This creates a materials constraint for vascular bioprinting, where constructs must preserve microscale architecture during fabrication while supporting multicellular remodeling, lumen formation, and long-term tissue organization. To meet these requirements, we developed a 4D GelMA–Cad/gelatin hydrogel with time-dependent mechanics that maintains print fidelity while providing a soft, cell-permissive matrix. GelMA–Cad provides a covalently photocrosslinked, bioactive network containing an N-cadherin-mimetic peptide, while uncrosslinked gelatin serves as a transient matrix-modifying component that diffuses from the hydrogel after fabrication, producing further softening without bulk degradation of the GelMA–Cad network. We characterized hydrogel chemistry with NMR, quantified time-dependent changes in stiffness, visualized pore morphology with cryo–SEM, and evaluated the platform in retinal and pulmonary constructs. The 4D hydrogel supports 3D–patterned accuracy, cell viability, inner blood–retinal barrier vasculature, and vascularized lung–alveolar tissue models. Single–cell RNA–sequencing of the pulmonary vascular–alveolar model demonstrated compartment-specific transcriptional responses, including enrichment of lung capillary–associated endothelial features and AT1–like epithelial states. Overall, this platform decouples DMD print fidelity from post-print matrix mechanics for vascularized soft tissue bioprinting and tissue modeling.