DLP 3D cell bioprinting of gelatin methacryloyl-tannic acid hydrogels as a tunable platform for bioactive skin tissue engineering scaffolds.

Abstract

Although 3D cell bioprinting has emerged as a powerful strategy for engineering biomimetic skin substitutes and wound-related materials, the development of bioinks that simultaneously provide structural integrity, cytocompatibility, and bioactivity remains challenging. In this work, gelatin methacryloyl (GelMA)-based hydrogels incorporating tannic acid (TA) were developed and processed via digital light processing to fabricate 3D scaffolds as prototype platforms for skin-related applications. The incorporation of TA significantly enhanced hydrogel stability, mechanical stiffness, and antibacterial activity, while maintaining high water content and improving print fidelity. Structural characterization by SEM and micro-CT revealed that TA promoted the formation of a more compact and homogeneous porous network, consistent with increased storage modulus, improved compressive strength and delayed degradation under physiological conditions. Rheological analysis confirmed that GelMA+TA systems exhibit enhanced viscoelastic stability and resistance to deformation. Sustained TA release over 25 days endowed the scaffolds with antibacterial activity against E. coli and S. aureus. Importantly, 3D bioprinting and encapsulation studies demonstrated cell-type-dependent biological responses. Human skin fibroblasts exhibited robust long-term viability and proliferation within pure GelMA scaffolds, while TA-containing hydrogels promoted early cell-material interactions and fibronectin deposition but were associated with reduced long-term fibroblast proliferation, suggesting a dose- and exposure-dependent effect of TA. In contrast, Vero cells, used as a model epithelial cell line, showed improved viability and morphology under encapsulation conditions in GelMA+TA scaffolds. These results highlight the critical interplay between macromolecular composition, 3D microenvironment, and cell response, demonstrating that GelMA+TA systems represent a promising preliminary platform for the development of tunable bioactive scaffolds for wound-related applications.