Combining Adipose‐Derived Stromal Cell Spheroids and Melt Electrowritten Scaffolds for a 3D Adipose Model Mimicking Structure and Function of Fat Tissue

Adipose tissue represents an active metabolic and endocrine organ that influences (patho‐)physiological processes in metabolism, immune response, or cancer progression. Given the close relationship between morphology and functionality, adipose models that recapitulate the phenotype of mature adipocytes embedded in a tissue‐specific matrix are essential for studies on adipose tissue biology. In order to mimic the high cell density and 3D architecture of the native tissue, scaffolds made of ultrathin fibers produced with melt electrowriting (MEW) technology are combined with adipose‐derived stromal cell (ASC) spheroids. Fabricated constructs develop an adipose phenotype, demonstrated by storage of triglycerides, expression of adipogenic marker genes, and the development of a tissue‐specific extracellular matrix. Upon oleic acid supplementation, differentiated adipocytes significantly increase lipid storage. Tissue functionality is demonstrated by analysis of secreted adipokines and β‐adrenergic stimulation of lipolysis. Long‐term culture (10 weeks) favors adipocyte maturation to lipid droplet sizes close to those in native tissue, while tissue stability and functionality are unaffected. This hybrid tissue engineering approach, using spheroids as building blocks in tailored MEW scaffolds, provides an adipose model that closely mimics structural and functional characteristics of fat tissue and is therefore an excellent tool for studies on the function and (patho‐)physiology of adipose tissue.