Impaired skin wound healing due to severe injury often leads to dysfunctional
scar tissue formation as a result of excessive and persistent myofibroblast activation, characterised by the increased expression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM)
proteins. Yet, despite extensive research on impaired wound healing and the advancement in tissue-engineered
skin substitutes,
scar formation remains a significant clinical challenge. This study aimed to first investigate the effect of
methacrylate gelatin (GelMA)
biomaterial stiffness on human dermal fibroblast behaviour in order to then design a range of 3D-printed GelMA scaffolds with tuneable structural and mechanical properties and understand whether the introduction of pores and porosity would support fibroblast activity, while inhibiting myofibroblast-related gene and
protein expression. Results demonstrated that increasing GelMA stiffness promotes myofibroblast activation through increased
fibrosis-related gene and
protein expression. However, the introduction of a porous architecture by 3D printing facilitated healthy fibroblast activity, while inhibiting myofibroblast activation. A significant reduction was observed in the gene and
protein production of αSMA and the expression of ECM-related
proteins, including
fibronectin I and
collagen III, across the range of porous 3D-printed GelMA scaffolds. These results show that the 3D-printed GelMA scaffolds have the potential to improve dermal skin healing, whilst inhibiting
fibrosis and
scar formation, therefore potentially offering a new treatment for skin repair.