Microfluidic Spinning of Cell‐Responsive Grooved Microfibers

Abstract

Engineering living tissues that simulate their natural counterparts is a dynamic area of research. Among the various models of biological tissues being developed, fiber‐shaped cellular architectures, which can be used as artificial blood vessels or muscle fibers, have drawn particular attention. However, the fabrication of continuous microfiber substrates for culturing cells is still limited to a restricted number of polymers (e.g., alginate) having easy processability but poor cell–material interaction properties. Moreover, the typical smooth surface of a synthetic fiber does not replicate the micro‐ and nanofeatures observed in vivo, which guide and regulate cell behavior. In this study, a method to fabricate photocrosslinkable cell‐responsive methacrylamide‐modified gelatin (GelMA) fibers with exquisite microstructured surfaces by using a microfluidic device is developed. These hydrogel fibers with microgrooved surfaces efficiently promote cell encapsulation and adhesion. GelMA fibers significantly promote the viability of cells encapsulated in/or grown on the fibers compared with similar grooved alginate fibers used as controls. Importantly, the grooves engraved on the GelMA fibers induce cell alignment. Furthermore, the GelMA fibers exhibit excellent processability and could be wound into various shapes. These microstructured GelMA fibers have great potential as templates for the creation of fiber‐shaped tissues or tissue microstructures.

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

“…generated GelMA fibers by injecting the pre-polymer solution into a cold solution to solidify the fibers first and then chemically crosslinked them using UV illumination [69]. However, the rapid dispersion of GelMA into the cold solution significantly affected the controllability of the process.…”

Spatially and temporally controlled hydrogels for tissue engineering

“…In one example, GelMA hydrogel prepolymer solution was injected into a low-temperature solution to induce rapid thermally induced gelation, after which the solidified fibers were photocrosslinked to form stable constructs (Fig. 4b) [99, 103]. However, this method suffered from significant dispersion of the hydrogel stream into the cold aqueous solution, resulting in poor controllability of the composition of the final fibers.…”

“…To challenge this, sacrificial polymeric templates were introduced to assist in generating fibers (Fig. 4c) [103]. In this method, the target polymer was mixed with alginate and then injected into a CaCl 2 crosslinking solution.…”

“…(iii) Micrograph showing a typical braided construct from composite fibers. Reproduced with permission from: (a) [99], (b) [103], (c) [104], (d–e) [107], (f) [109]. …”

Hydrogel Templates for Rapid Manufacturing of Bioactive Fibers and 3D Constructs

“…Although the mentioned techniques are capable of fabricating complex fibers and constructs, they cannot be easily applied to hydrogels with slow crosslinking process. As a result, limited successful studies are available in the literature for the fabrication of fibers from photocrosslinkable, temperature sensitive, and chemically crosslinkable materials [1, 8, 16, 17] . In a recent study, GelMA fibers were fabricated by direct injection of the solution into a cold solution, which resulted in rapid solidifacation of gelatin forming a fiber.…”