3D bioprinting of novel biocompatible scaffolds for endothelial cell repair

Abstract

The aim of this study was to develop and evaluate an optimized 3D bioprinting technology in order to fabricate novel scaffolds for the application of endothelial cell repair. Various biocompatible and biodegradable macroporous scaffolds (D = 10 mm) with interconnected pores (D = ~500 μm) were fabricated using a commercially available 3D bioprinter (r3bEL mini, SE3D, USA). The resolution of the printing layers was set at ~100 μm for all scaffolds. Various compositions of polylactic acid (PLA), polyethylene glycol (PEG) and pluronic F127 (F127) formulations were prepared and optimized to develop semi-solid viscous bioinks. Either dimethyloxalylglycine (DMOG) or erythroprotein (EPO) was used as a model drug and loaded in the viscous biocompatible ink formulations with a final concentration of 30% (w/w). The surface analysis of the bioinks via a spectroscopic analysis revealed a homogenous distribution of the forming materials throughout the surface, whereas SEM imaging of the scaffolds showed a smooth surface with homogenous macro-porous texture and precise pore size. The rheological and mechanical analyses showed optimum rheological and mechanical properties of each scaffold. As the drug, DMOG, is a HIF-1 inducer, its release from the scaffolds into PBS solution was measured indirectly using a bioassay for HIF-1α. This showed that the release of DMOG was sustained over 48 h. The release of DMOG was enough to cause a significant increase in HIF-1α levels in the bioassay, and when incubated with rat aortic endothelial cells (RAECs) for 2 h resulted in transcriptional activation of a HIF-1α target gene (VEGF). The optimum time for the increased expression of VEGF gene was approximately 30 min and was a 3-4-fold increase above baseline. This study provides a proof of concept, that a novel bioprinting platform can be exploited to develop biodegradable composite scaffolds for potential clinical applications in endothelial cell repair in cardiovascular disease (CVD), or in other conditions in which endothelial damage occurs.