3D printing of PLGA nanofiber reinforced alginate scaffolds for skin tissue engineering

Abstract

3D printing has significantly improved our ability to fabricate complex tissue engineering scaffolds. Alginate (Alg) hydrogels are widely used for 3D printing in tissue engineering owing to its good thixotropic property. However, 3D printed Alg structures have poor mechanical strength. PLGA is a widely used synthetic polymer in tissue engineering. The addition of electrospun PLGA nanofiber (PLGAf) into Alg hydrogel should improve its mechanical property. Epidermal growth factor (EGF) is often used in the regeneration of tissues such as skin. It may be incorporated in 3D printed scaffolds for enhancing tissue regeneration. In this study, new inks were developed for 3D printing by mixing an Alg solution (and EGF solution) with PLGAf (or EGF-encapsulated PLGAf). Aqueous PLGAf suspensions with different fiber concentrations were prepared. Alg was then added into PLGAf suspensions and stirred to obtain PLGAf/Alg inks. The distribution of PLGAf in 3D printed PLGAf/Alg structures was investigated using confocal microscopy and the results showed a good dispersion of PLGAf in Alg scaffolds. The influence of PLGAf on rheological property, mechanical property and degradation behaviour of Alg was studied. The results revealed that PLGAf/Alg structures exhibited increased shear viscosity and mechanical strength with the increase of PLGAf amount. For EGF incorporation, EGF loaded PLGAf (EGF-PLGAf) was prepared via emulsion electrospinning, followed by mixing EGF-PLGAf and Alg to form EGF-PLGAf/Alg ink. EGF was also directly added in the PLGAf/Alg ink to obtain EGF/PLGAf/Alg ink. Both EGF-PLGAf/Alg ink and EGF/PLGAf/Alg ink were used to fabricate square-patterned scaffolds via 3D printing. The in vitro release behaviors of EGF in 3D printed EGF-PLGAf/Alg scaffolds and EGF/PLGAf/Alg scaffolds were compared. The higher retention and slower release of EGF from EGF-PLGAf/Alg scaffolds would provide longer and more sustained stimulation for fibroblast proliferation.