Engineering a GelMA-dECM-based 3D bioprinted liver fibrosis model: methotrexate-induced functional and molecular...

Area of Science:

• Bioprinting and Tissue Engineering
• Regenerative Medicine
• Biomaterials Science

Background:

• Three-dimensional (3D) bioprinting enables precise fabrication of in vitro tissue models.
• Developing physiologically relevant models is crucial for understanding liver diseases and drug development.

Purpose of the Study:

• To fabricate a 3D bioprinted hepatic construct using a composite bioink.
• To establish and validate a 3D in vitro model of methotrexate-induced liver fibrosis.

Main Methods:

• A composite bioink was synthesized using gelatin methacryloyl (GelMA), liver-derived decellularized extracellular matrix (dECM), and HepG2 cells.
• Constructs were crosslinked for structural integrity and characterized for cytocompatibility, metabolic activity, and liver-specific enzyme function.
• Methotrexate (MTX) was used to induce liver fibrosis, and the fibrotic phenotype was validated through gene expression analysis.

Main Results:

• The fabricated hepatic constructs exhibited good cytocompatibility and maintained hepatic function, indicated by albumin and urea secretion.
• The 3D bioprinted model successfully recapitulated methotrexate-induced liver fibrosis, showing functional decline and upregulation of fibrosis-associated genes.
• The combination of GelMA and dECM enhanced cellular functionality and supported accurate fibrosis modeling.

Conclusions:

• A robust and physiologically relevant 3D bioprinted in vitro platform for modeling liver fibrosis was successfully developed.
• This platform offers a promising tool for preclinical drug screening and translational research in hepatic diseases.
• The study highlights the potential of advanced bioprinting techniques in creating complex disease models.