Cross-scale biomimicry of resilin and resilin-like proteins: From phase separation and dityrosine photocrosslinking to tissue repair and soft robotic devices

Resilin and resilin-like proteins (RLPs) provide a programmable platform for bioinspired soft materials that spans molecular design, condensate microstructures, and device-level function. This review advances a cross-scale "write-then-lock" framework: reversible microstructures are first encoded through upper critical solution temperature (UCST)-type liquid-liquid phase separation (LLPS), and then stabilized on demand through visible-light-mediated dityrosine (DiY) and trityrosine (TriY) photocrosslinking. We summarize how stickers-spacers sequence grammar, solvent/ionic cues, and aging processes regulate UCST-type LLPS, and we organize the currently available quantitative and semi-quantitative evidence linking microstructural descriptors to viscoelastic readouts, and we further dissect the reaction mechanisms and processing boundaries of photocuring. Particular emphasis is placed on the coupled effects of dose, sample thickness, oxygen transport, and redox conditions, as well as reactive oxygen species (ROS)-mediated side reactions and the control of catalyst residues. To enhance reproducibility and translational readiness, we propose standard operating procedure (SOP)-oriented minimal reporting standards and connect critical quality attributes to process characterization within a workflow aligned with Quality by Design (QbD) and Chemistry, Manufacturing, and Controls (CMC) principles. Finally, we discuss prospects for RLP-based hydrogels in tissue repair and for soft robotic actuators. STATEMENT OF SIGNIFICANCE: Resilin-like proteins (RLPs) are programmable biomaterials for hydrated elastic networks, tissue repair, and soft devices. This review introduces a cross-scale "write-then-lock" framework in which upper critical solution temperature (UCST)-type liquid-liquid phase separation (LLPS) first generates mesoscale morphology, followed by dityrosine/trityrosine (DiY/TriY) photocrosslinking to stabilize the structure. We synthesize how sequence features, phase behavior, curing chemistry, microstructure, and dynamic mechanics are connected, while distinguishing direct RLP evidence from principles inferred from related elastomeric protein systems. We further discuss photocuring safety, reproducibility, and Chemistry, Manufacturing, and Controls (CMC)-oriented reporting standards for translational development.