Multi-compartment scafold fabricated via 3D-printing as in vitro co-culture osteogenic model
Elvira De Giglio1, MariaA. Bonifacio1, Ana M. Ferreira 2, StefaniaCometa3, ZhiYuanTi2, Antonella Stanzione1, Kenny Dalgarno2 & PiergiorgioGentile 2
The development of in vitro 3D models to get insights into the mechanisms of bone regeneration could accelerate the translation of experimental fndings to the clinic, reducing costs and duration of experiments. This work explores the design and manufacturing of multi-compartments structures in poly(ε-caprolactone) (PCL) 3D-printed by Fused Filament Fabrication technique. The construct was designed with interconnected stalls to host stem cells and endothelial cells. Cells were encapsulated within an optimised gellan gum (GG)-based hydrogel matrix, crosslinked using strontium (Sr2+) ions to exploit its bioactivity and fnally, assembled within compartments with diferent sizes. Calcium (Ca2+)- crosslinked gels were also used as control for comparison of Sr2+ osteogenic efect. The results obtained demonstrated that Sr2+ ions were successfully difused within the hydrogel matrix and increased the hydrogel matrix strength properties under compressive load. The in vitro co-culture of humanTERT mesenchymal stem cells (TERT- hMSCs) and human umbilical vein endothelial cells (HUVECs), encapsulated within Sr2+ ions containing GG-hydrogels and inter-connected by compartmentalised scafolds under osteogenic conditions, enhanced cell viability and supported osteogenesis, with a signifcant increase of alkaline phosphatase activity, osteopontin and osteocalcin respect with the Ca2+-crosslinked GG-PCL scafolds. These outcomes demonstrate that the design and manufacturing of compartmentalised co-culture of TERT-hMSCs and HUVEC populations enables an effective system to study and promote osteogenesis.
SCIENTIFIC REPORTS | (2018) 8:15130 | DOI:10.1038/s41598-018-33472-1