Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable gelatin methacryloyl microenvironments

Abstract

Bioinks with shear-thinning/rapid solidification properties and strong mechanics are usually needed for the bioprinting of three-dimensional (3D) cell-laden constructs. As such, it remains challenging to generate soft constructs from bioinks at low concentrations that are favorable for cellular activities. Herein, we report a strategy to fabricate cell-laden constructs with tunable 3D microenvironments achieved by bioprinting of gelatin methacryloyl (GelMA)/alginate core/sheath microfibers, where the alginate sheath serves as a template to support and confine the GelMA pre-hydrogel in the core during the extrusion process, allowing for subsequent UV crosslinking. This novel strategy minimizes the bioprinting requirements for the core bioink, and facilitates the fabrication of cell-laden GelMA constructs at low concentrations. We first showed the capability of generating various alginate hollow microfibrous constructs using a coaxial nozzle setup, and verified the diffusibility and perfusability of the bioprinted hollow structures that are important for the tissue engineering applications. More importantly, the hollow alginate microfibers were then used as templates for generating cell-laden GelMA constructs with soft microenvironments, by using GelMA pre-hydrogel as the bioink for the core phase during bioprinting. As such, GelMA constructs at extremely low concentrations (<2.0%) could be extruded to effectively support cellular activities including proliferation and spreading for various cell types. We believe that our strategy is likely to provide broad opportunities in bioprinting of 3D constructs with cell-favorable microenvironments for applications in tissue engineering and pharmaceutical screening.

A Facile Strategy for Fabricating Tissue Engineering Scaffolds with Sophisticated Prevascularized Networks for Bulk Tissue Regeneration

“…The gelation has good biocompatibility and was used to fabricated issue scaffold repeatedly due to it is the denatured product of collagen . In addition, it showed comparable biological properties with collagen to support endothelial cells spreading and growth whether in vitro or in vivo studies . Enzymatically crosslinked gelatin has also been widely used in tissue engineering as a facile approach .…”

Bioprinting of Multiscaled Hepatic Lobules within a Highly Vascularized Construct

“…[ 21 ] Thus, to avoid ischemic conditions, many researchers have utilized sacrificial materials to create microchannels [ 21,22,7,23,11 ] or coaxial nozzles for in situ creation of blood vessels. [ 24–26 ] Further, since capillaries are too small to be printed, a predefined experimental design is essential for interconnection of the microchannels during angiogenesis. [ 27 ] As a result, to create large tissue constructs, both microchannels and a predefined design for angiogenesis are needed.…”

Beyond the Modification Degree: Impact of Raw Material on Physicochemical Properties of Gelatin Type A and Type B Methacryloyls

“…Additional modification of gelatin with inert acetyl functions (GMA) has been introduced by our group to tune viscosity and gelation of aqueous GM solutions independently from its cross‐linking potential . Formulations of GM(A) with adjusted properties are also increasingly used for sophisticated fabrication techniques such as inkjet‐printing, robotic dispensing, fused deposition modeling, or two‐photon polymerization . Differences in mechanical properties of resulting GM hydrogels and tissue‐specific additives are utilized to emulate most diverse tissues such as bone, cartilage, adipose tissue, cardiac tissue, and as matrix for formation of capillary structures .…”