3D Printed Nanofiber Reinforced Tissue Engineering Scaffolds with Controlled Release of Growth Factor

Abstract

3D printing has greatly improved our ability to create complex tissue engineering scaffolds with high precision. Biomaterials, growth factors or even living cells are accurately deposited layer-by-layer in 3D printing to construct the scaffolds. Hydrogels have been commonly used biomaterials in 3D printing of scaffolds owing to their various advantages. However, most hydrogels, particularly natural hydrogels, have poor mechanical properties, which severely limit their tissue engineering applications. It has been shown that adding polymer nanofibers into hydrogels can lead to improved mechanical properties that can be comparable to the body tissues. Growth factors (GFs) in the body can promote wound healing, cell growth, proliferation and differentiation. Incorporating GFs into scaffolds may accelerate tissue regeneration. Fibroblast growth factor (FGF) is generally used in the regeneration of tissues such as cornea and skin. In this study, nanofiber reinforced scaffolds with the controlled release of GF were investigated with 3D printing of PLGA nanofiber (PLGAf) reinforced alginate hydrogel containing FGF. To control the FGF release, two strategies were adopted: (1) FGF was directly included in the biomaterial (PLGAf and alginate hydrogel mixture) for 3D printing, (2) FGF was firstly encapsulated in PLGA nanofibers via emulsion electrospinning and the nanofibers were then dispersed in alginate hydrogel for 3D printing. Thus two types of inks were made for 3D printing: FGF/alginate/PLGAf ink, and alginate/PLGAf-FGF ink. They were used in an extrusion-based 3D bioprinter to fabricate reinforced scaffolds according to the CAD design. The experiments showed that the addition of PLGAf into alginate hydrogel greatly improved its viscosity and mechanical strength. In vitro release studies were conducted for scaffolds 3D printed from the two type of inks. Release results showed that both types of scaffolds exhibited two-stage release profiles: an initial fast release period in the first 2 days, and the subsequent slower and sustained release period. In addition, alginate/PLGAf-FGF scaffolds displayed a slower release than FGF/alginate/PLGAf scaffolds, which was mainly due to the different incorporation site of FGF within the scaffolds. It can be concluded that the GF release behaviour from 3D printed scaffolds can be controlled through choosing the loading site in scaffolds for GFs, which enables designing personalized GF delivery specific for the targeted tissue engineering application.