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.

Highlights

  • Three-dimensional bioprinting (3DP), which has emerged as an innovative additive manufacturing technology [1,2,3], is revolutionizing the field of tissue engineering and the future of medicine and Polymers 2019, 11, 1924; doi:10.3390/polym11121924 www.mdpi.com/journal/polymersPolymers 2019, 11, 1924 medical implants

  • There is an opportunity for technological innovation in the fabrication of novel scaffolds or biomaterials using 3DP that requires a convergence of expertise in biomaterial, pharmaceutical, and vascular biological fields

  • Polylactic acid (PLA) MW 60,000, polyethylene glycol (PEG) MW 400 were purchased from Sigma

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Summary

Introduction

Three-dimensional bioprinting (3DP), which has emerged as an innovative additive manufacturing technology [1,2,3], is revolutionizing the field of tissue engineering and the future of medicine and Polymers 2019, 11, 1924; doi:10.3390/polym11121924 www.mdpi.com/journal/polymersPolymers 2019, 11, 1924 medical implants. Studies have revealed that the critical characteristic of a biomaterial, as well as the control of the inner micro- and macro-scale features of the engineered-tissue, is considered a key quality parameter to fabricate complex anatomical, patient-specific structures with high shape fidelity in tissue engineering applications [4,5]. In response to this currently unmet need, advances in additive manufacturing and 3DP have inspired scientists to employ this innovative technology for biomaterial and tissue engineering strategies [6,7].

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