3D Bioprinting-Assisted Tissue Assembly of Endocrine Adipose Units for Enhanced Skin Regeneration

Despite the growing recognition of adipose tissue as an endocrine organ, engineering it remains a challenge owing to difficulties in replicating its native structure and densely packed lipid droplets. Furthermore, integrating adipose tissue with other tissues, though critical for its endocrine function, remains underexplored, limiting the understanding of its roles in metabolic homeostasis and tissue repair. This study introduces a rapid tissue printing method that constructs adipose units by extruding preadipocyte-laden bioink within 0.3 s using a modular polycaprolactone framework optimized through rheological and computational analyses. In standard, cell-friendly environments, preadipocytes typically proliferate and migrate, inhibiting the formation of dense lipid droplets. To address this issue, a hybrid bioink that limits cell migration and promotes adipocyte maturation is developed. The optimal adipose unit diameter (<= 600 mu m) is calculated, with adipogenic markers evaluated in various spatial configurations. Tissue assembly integrates the adipose module and dermis module, validating its functionality as endocrine tissue. In vivo studies show that the endocrine activity of the adipose units significantly enhances wound closure, vascularization, and re-epithelialization. These findings highlight the regenerative capabilities of the proposed tissue assembly strategy for fabricating large-scale, multicellular, 3D composite tissues.