3D-Printed Gelatin Methacrylate Scaffolds with Controlled Architecture and Stiffness Modulate the Fibroblast Phenotype towards Dermal Regeneration

• Published in: Polymers Vol. 13; no. 15; p. 2510
• Main Authors: R. Ibañez, Rita I., do Amaral, Ronaldo J. F. C., Reis, Rui L., Marques, Alexandra P., Murphy, Ciara M., O’Brien, Fergal J.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30.07.2021; MDPI
• Subjects: 3-D printers; 3D printing; Biocompatibility; biomaterial stiffness; Biomedical materials; Collagen; Design; fibroblast; Fibroblasts; Fibronectin; Fibrosis; Gelatin; GelMA; Gene expression; Glucose; Growth factors; Hydrogels; Mechanical properties; Morphology; Muscles; Pore size; Porosity; Proteins; Regeneration; Scaffolds; Scars; Skin; Stiffness; Three dimensional printing; Tissue engineering; Wound healing; United Kingdom > UK; United States > US; Ireland; Germany
• ISSN: 2073-4360; 2073-4360
• DOI: 10.3390/polym13152510

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.