Biomimetic hydrogel design strategies for vascular grafts and vascularized tissue constructs

Biomimetic design strategies offer rational approaches for reconstructing functional vascular structures within hydrogel platforms. Hydrogels provide unique advantages through tissue-like hydration, tunable architectures, and biochemical functionalization capacity. These properties enable implementation of design principles derived from native vasculature. This review proposes an integrated analytical framework extracting design principles from native vascular architecture and demonstrating their application across two conventionally separate research directions, namely, vascular graft engineering and tissue vascularization. The framework encompasses four fundamental design dimensions. These are hierarchical organization spanning from arteries to capillaries, multi-layered wall architectures enabling functional stratification, biochemical microenvironments supporting vascular morphogenesis, and mechanical compliance matching physiological demands. These principles guide engineering of vascular grafts for vessel replacement and vascularized tissue constructs requiring internal perfusion. Applications include small-diameter arterial grafts, endovascular repair materials, bone tissue engineering with coupled osteogenesis and angiogenesis, chronic wound healing, and cardiac tissue regeneration. The relative weight of each design dimension varies across application contexts. Biomimetic principles function most effectively as selective design tools rather than prescriptive templates demanding maximum anatomical fidelity. Persistent challenges include temporal misalignment between scaffold degradation and vessel maturation, unpredictable anastomotic integration with host circulation, and manufacturing scalability limitations. Emerging technologies incorporating spatially controlled fabrication and stimuli-responsive behaviors offer pathways toward functional regulation beyond passive structural mimicry. This framework provides rational guidance for developing vascularized hydrogel platforms across specific therapeutic contexts.