Biofabrication of nanoenhanced hydrogel fibers for muscle tissue engineering using surface chaotic flows: Chaotic 2D-printing

Abstract

Multiple human tissues exhibit a fibrous nature. Therefore, the fabrication of hydrogel filaments for biomedical engineering applications is a trending topic. Current tissue models are made of materials that often require further enhancement for appropriate cell attachment, proliferation and differentiation. Here we present a simple strategy, based on the use of mathematically modelable surface chaotic flows, to fabricate continuous, long and thin filaments of gelatin methacryloyl (GelMA) added with Turnip mosaic virus (TuMV) for enhanced muscle tissue engineering. The fabrication of these filaments was achieved by chaotic advection in a finely controlled and miniaturized version of the journal bearing (JB) system. A drop of a pre-gel solution of GelMA was injected on a higher-density viscous fluid (glycerin) and a chaotic flow was applied through an iterative process. The hydrogel drop exponentially deformed and elongated to generate a fiber, which was then photocrosslinked under exposure to UV light. Computational fluid dynamics (CFD) simulations were conducted for the design and prediction of our results. GelMA fibers were then used as scaffolds for C2C12 myoblast cells, and the effect of adding plant-based viral nanoparticles (VNP) to the hydrogel fibers as nano-scaffolds for cellular growth was evaluated. Chaotic 2D-printing was proven to be a viable method for the fabrication of hydrogel fibers. CFD simulations accurately predicted the lengths of the printed fibers, and a correlation coefficient of R2=0.9289 was determined from the experimental and simulated data of the first two cycles. The hydrogel fibers were effective scaffolds for muscle cells and show potential to be used as cost-effective models for muscle tissue engineering purposes. TuMV significantly increased the metabolic activity of the cell-seeded fibers (p<0.05), strengthened cell attachment throughout the first 28 days, improved cell alignment to ~50%, and promoted the generation of structures that resemble natural mammal muscle tissue.