Negative printing for the reinforcement of in situ tissue engineered cartilage

• Published in: Tissue engineering. Part A 2024-04 (ja)
• Main Authors: Doyle, Stephanie, Snow, Finn, Onofrillo, Carmine, Di Bella, Claudia, O'Connell, Cathal D., Pirogova, Elena, Duchi, Serena
• Format: Article
• Language: English
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.TEA.2023.0358

In the realm of in situ cartilage engineering, the targeted delivery of both cells and hydrogel materials to the site of a defect serves to directly stimulate chondral repair. While the in situ application of stem cell-laden soft hydrogels to tissue defects holds great promise for cartilage regeneration, a significant challenge lies in overcoming the inherent limitation of these soft hydrogels, which must attain mechanical properties akin to the native tissue to withstand physiological loading. We therefore developed a system where a gelatin methacryloyl hydrogel laden with human adipose derived mesenchymal stem cells is combined with a secondary structure to provide bulk mechanical reinforcement. In this study we used the negative embodied sacrificial template 3D printing technique to generate 8 different lattice-based reinforcement structures made of polycaprolactone, which ranged in porosity from 80-90% with stiffnesses from 28 ± 5 kPa to 2853 ± 236 kPa. The most promising of these designs, the hex prism edge, was combined with the cellular hydrogel and retained a stable stiffness over 41 days of chondrogenic differentiation. There was no significant difference between the hydrogel only and hydrogel scaffold group in the sulphated glycosaminoglycan production (340.46 ± 13.32 µg and 338.92 ± 47.33 µg respectively) or collagen type II gene expression. As such, the use of negative printing represents a promising solution for the integration of bulk reinforcement without losing the ability to produce new chondrogenic matrix.