3D Printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/β-TCP composite scaffold by 3D printing method, using a computer-assisted design (CAD) model. Rheological characterization of various gelatin/alginate/β-TCP formulations led to an optimized paste as a printable bioink, at room temperature. VEGF-loaded PLGA microspheres were then incorporated into the paste, prior to printing, to ensure sustained release of the growth factor. The in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs), seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98 ± 11 MPa, was found to be in the range of cancellous bone, suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds, after 2 weeks of culture. In conclusion, the 3D printed gelatin/alginate/β-TCP scaffold, with slow releasing of VEGF, can be considered as a potential candidate for regeneration of craniofacial defects.

Keywords:

3D printing , β-tricalcium phosphate , PLGA microsphere , VEGF , Scaffold , Tissue engineering.