Novel bioprinting technique successfully replicates mature human fat tissue

A research team has developed a support-bath bioprinting method that enables fragile, mature human adipocytes to be incorporated into geometrically defined three-dimensional (3D) constructs while retaining their viability, characteristic lipid-filled morphology, and metabolic activity. By combining an agarose support bath with a low-concentration gellan gum bioink, the researchers achieved substantially greater structural stability and printing accuracy than conventional free extrusion. The accessible workflow could support the development of more physiologically relevant adipose tissue models for studying obesity and metabolic disorders, conducting preliminary drug and cosmetic testing, and advancing soft-tissue engineering.

Adipose tissue is a metabolically active organ involved in energy storage, endocrine signaling, and whole-body metabolic regulation. Dysfunction of adipocytes contributes to obesity, insulin resistance, type 2 diabetes, and other diseases, creating strong demand for human-relevant laboratory models. Two-dimensional cultures cannot adequately reproduce the soft mechanical environment, spatial organization, or buoyancy effects found in native adipose tissue, while animal models are affected by species differences and ethical and financial constraints.

Although 3D adipose models have advanced, most rely on adipose-derived stem cells rather than mature adipocytes. Fully differentiated adipocytes offer greater physiological relevance but are difficult to bioprint because their large size, buoyancy, hydrophobicity, and sensitivity to shear forces make them vulnerable to mechanical damage. Consequently, a reproducible method is needed to print mature adipocytes without compromising their structure or function.

A study (DOI: 10.48130/els-0026-0006) published in Engineering in Life Sciences on 10 August 2026 by Petra J. Kluger's team, University of Stuttgart, demonstrates that an agarose-supported extrusion process can accurately print mature adipocytes while preserving their viability, unilocular morphology, and metabolic responsiveness.

The researchers first isolated mature adipocytes from human adipose tissue obtained during elective surgery and incorporated them into a gellan gum bioink with a final polymer concentration of 0.3%. They evaluated gellan gum formulations containing different phosphate-buffered saline concentrations and characterized the viscosity of both the bioink and 0.5% agarose support baths across a range of shear rates. These measurements identified a formulation that remained sufficiently fluid for gentle extrusion but could be stabilized after deposition. The selected cell-laden bioink was extruded through a 600-µm nozzle into a chilled agarose bath at a pressure of 4–6 kPa and a speed of 14–16 mm/s.

Calcium chloride was subsequently added to crosslink the printed structures before their recovery and culture. Printing performance was assessed using 20 × 20 × 1 mm grid structures, while 10 × 10 × 6 mm dome-shaped constructs were produced for biological evaluation. Without a support bath, the soft bioink spread after extrusion and could not be reliably layered. By contrast, support-bath printing produced stable grids with uniform pores and well-aligned filaments. Construct length deviated from the computer-aided design by only 2.66%, while pore width and filament width differed by 2.87% and 3.35%, respectively. Live/dead staining showed that most adipocytes remained viable through three days, with viable cells also observed on day eight in an exploratory assessment.

Lactate dehydrogenase release decreased significantly from 29.09% on day one to 9.66% on day three, suggesting recovery from transient printing-related membrane stress. Lipid staining revealed uniformly distributed, lipid-filled cells, while perilipin A expression confirmed the preservation of lipid-vacuole integrity. The cells also retained functional lipolytic responses: isoproterenol stimulation increased glycerol release from 40.60 to 137.88 ng/mL on day one and from 65.86 to 200.54 ng/mL on day three.

Overall, the study establishes a gentle and reproducible strategy for fabricating 3D constructs containing mature human adipocytes. The support bath counteracts bioink spreading and cell buoyancy, enabling accurate deposition without sacrificing key structural and functional characteristics. Although future work is needed to extend culture duration, introduce vascularization, and incorporate endothelial, immune, or stromal cells, the method provides a practical foundation for modeling adipose tissue physiology and metabolic dysfunction. It may ultimately facilitate controlled preclinical testing and the development of more complex constructs for regenerative and reconstructive applications.