Printing the keloid scar: Tunable GelMA-based bioinks for 3D modeling of skin fibrosis

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The development of mechanically tunable and cytocompatible hydrogels is critical for advancing 3D bioprinting in tissue engineering. Here, we report a composite bioink composed of gelatin methacrylate (GelMA), methylcellulose (MC), sodium alginate, and Laponite-RDS. This formulation supports extrusion-based printing without ionic crosslinkers, mimics the extracellular matrix (ECM), and maintains stable viscoelasticity under physiological conditions (37 °C, pH 7.4). Electrostatic and hydrogen bonding interactions among the charged polymers enhance pre-gel viscosity, shear-thinning behavior, and print fidelity. To evaluate its potential in disease modeling, patient-derived keloid fibroblasts were encapsulated in 3D-bioprinted constructs using two GelMA-based formulations with different stiffness levels, such as soft (G4A1M1R1, 2.1 kPa) and stiff (G5A1M1R1, 7.9 kPa), chosen to replicate the mechanical properties of normal dermis and keloid tissue, respectively. Both constructs exhibited excellent cell viability after three days, confirming cytocompatibility. Furthermore, matrix stiffness significantly regulated fibrotic gene expression. The stiffer hydrogel induced higher expression of COL1, MMP2, and IL6, suggesting enhanced myofibroblast activation and ECM remodeling. Immunofluorescence staining further confirmed elevated protein levels of α-SMA, FSP1, and actin stress fibers (F-actin) in the stiff construct, consistent with keloid pathology. Taken together, these results demonstrate that the GelMA-based bioink enables stiffness-dependent modulation of fibrotic responses, offering a simplified yet relevant 3D model of fibrotic skin. This platform may provide a useful basis for future studies on keloid progression and preliminary antifibrotic drug screening.

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