Hypoxia Promotes Cartilage Regeneration in Cell-Seeded 3D-Printed Bioscaffolds Cultured with a Bespoke 3D Culture Device

In this study, we investigated the effect of oxygen tension on the expansion of ADMSCs and on their differentiation toward their chondrocytic phenotype, regenerating a lab-based cartilaginous tissue with superior characteristics. Controversial results with reference to MSCs that were cultured under different hypoxic levels, mainly in 2D culturing settings combined with or without other biochemical stimulus factors, prompted our team to study the role of hypoxia on MSCs chondrogenic differentiation within an absolute 3D environment. Specifically, we used 3D-printed honeycomb-like PCL matrices seeded with ADMSCs in the presence or absence of TGF and cultured with a prototype 3D cell culture device, which was previously shown to favor nutrient/oxygen supply, cell adhesion, and infiltration within scaffolds. These conditions resulted in high-quality hyaline cartilage that was distributed uniformly within scaffolds. The presence of the TGF medium was necessary to successfully produce cartilaginous tissues with superior molecular and increased biomechanical properties. Despite hypoxia's beneficial effect, it was overall not enough to fully differentiate ADMSCs or even promote cell expansion within 3D scaffolds alone.

Automated summary

This study examined the effects of oxygen tension on ADMSCs expansion and their differentiation into a chondrocytic phenotype, with the aim of regenerating high-quality cartilaginous tissue. Previous studies on MSCs cultured under different hypoxic levels prompted our team to investigate the role of hypoxia on MSCs chondrogenic differentiation within a 3D environment. The use of 3D-printed honeycomb-like PCL matrices seeded with ADMSCs, along with the presence of TGF and a prototype 3D cell culture device, resulted in uniformly distributed hyaline cartilage with superior molecular and biomechanical properties. However, hypoxia alone was not enough to fully differentiate ADMSCs or promote cell expansion within the 3D scaffolds.