Cell-Friendly Indirect 3D Printing Strategy for Scaffold Fabrication

This study aims to evaluate the use of polyvinyl alcohol (PVA) moulds for the fabrication of cell-containing hydrogel scaffolds exploiting a bottom-up tissue engineering (TE) approach. To this end, different gelatin derivatives are functionalized and their physical gelation behaviour are investigated. The modified recombinant collagen peptide (RCPhC1) materials exhibit lower viscosity than the animal-derived gelatin, rendering them unsuitable to be exploited in extrusion-based 3D printing. Hence, indirect printing using water-soluble PVA moulds is explored, and the moulds demonstrate excellent water solubility, biocompatibility and photo-transmittance. The obtained scaffolds show a computer-aided design/computer-aided manufacturing (CAD/CAM) mimicry of ∼110% and mass swelling ratios (4-24) suitable for soft TE applications. Moreover, mechanical properties in line with those of native fatty tissue (Young's moduli 0.8-2 kPa) were obtained. The cell viability remains high (>80%) throughout the 14-day assessment period, indicating the biocompatibility of the encapsulated adipose tissue-derived stem cells (ASCs) within the scaffolds, irrespective of the applied hydrogel materials, being gelatin-methacryloyl (Gel-MA), gelatin norbornene/thiolated gelatin (Gel-NB/SH), RCPhC1-MA and RCPhC1-NB/SH. In conclusion, PVA moulds can be exploited to shape gelatin derivatives while ensuring cell compatibility. As a result, viscosity challenges can be overcome enabling the application of low viscous (<30 mPa.s) photo-crosslinkable hydrogels in extrusion-based 3D-printing serving TE applications, offering control over the scaffold architecture and cell behaviour.