Bioengineering vascularised composite skin equivalents via Living Assembly through Templated Tissue Integration and Construct Engineering (LATTICE)

Engineering vascularised skin substitutes capable of supporting both macro- and microvascular perfusion remains a critical unmet challenge in reconstructive surgery. Here, we describe VascuDerm, a hierarchically vascularised dermal construct assembled using LATTICE (Living Assembly through Templated Tissue Integration and Construct Engineering) a modular biofabrication strategy combining coaxial bioprinting, sacrificial tungsten-wire templating and fibroblast-laden hydrogel layering. VascuDerm integrates a central perfusable vein-like macrochannel with spatially distributed capillary-mimicking microvessels (CMMs), all embedded within a human dermal fibroblast-rich matrix and cellularised with adipose-derived stem cell (ADSC)-derived endothelial and smooth muscle cells. Rheologically optimised VascuBiomatrix supported robust print fidelity and sustained cell viability across all compartments. Dynamic perfusion culture significantly enhanced endothelial organisation, extracellular matrix deposition, barrier function and mechanical integrity compared with static controls. Gene expression analysis confirmed progressive upregulation of lineage-specific vascular and stromal markers under flow conditioning. The chick chorioallantoic membrane assay demonstrated active angiogenic recruitment and early host-construct integration. Collectively, LATTICE provides a scalable, clinically adaptable platform for generating perfusion-competent hierarchical vascular constructs with direct applications in disease modelling, drug screening and translational reconstructive surgery.