Designing Gelatin Methacryloyl (GelMA)‐Based Bioinks for Visible Light Stereolithographic 3D Biofabrication

Abstract

Bioinks play a key role in determining the capability of the biofabricatoin processes and the resolution of the printed constructs. Excellent biocompatibility, tunable physical properties, and ease of chemical or biological modifications of gelatin methacryloyl (GelMA) have made it an attractive choice as bioinks for biomanufacturing of various tissues or organs. However, the current preparation methods for GelMA‐based bioinks lack the ability to tailor their physical properties for desired bioprinting methods. Inherently, GelMA prepolymer solution exhibits a fast sol–gel transition at room temperature, which is a hurdle for its use in stereolithography (SLA) bioprinting. Here, synthesis parameters are optimized such as solvents, pH, and reaction time to develop GelMA bioinks which have a slow sol–gel transition at room temperature and visible light crosslinkable functions. A total of eight GelMA combinations are identified as suitable for digital light processing (DLP)‐based SLA (DLP‐SLA) bioprinting through systematic characterizations of their physical and rheological properties. Out of various types of GelMA, those synthesized in reverse osmosis (RO) purified water (referred to as RO‐GelMA) are regarded as most suitable to achieve high DLP‐SLA printing resolution. RO‐GelMA‐based bioinks are also found to be biocompatible showing high survival rates of encapsulated cells in the photocrosslinked gels. Additionally, the astrocytes and fibroblasts are observed to grow and integrate well within the bioprinted constructs. The bioink's superior physical and photocrosslinking properties offer pathways of tuning the scaffold microenvironment and highlight the applicability of developed GelMA bioinks in various tissue engineering and regenerative medicine applications.

High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins

“…The possibility to perfuse these structures was proven via the infusion of a colored dye solution, and the smallest tubular feature within the complex Willis vessel network was measured to be 183 ​± ​25 ​μm. Overall, the possibility to generate such high resolution, convoluted structures via vat polymerization printing has not been achieved with other gels with low compressive properties, not even when utilizing other types of low viscosity gelatins obtained from the partial degradation of the polymer backbone [ 65 ]. It should be noted that, in the proof-of-concept prints reported in our study, perfusion was demonstrated via manual injection, recent reports in the literature highlight elegant strategies for enabling the connection of hydrogel-based constructs to fluidic tubing and circuits, which could be applied to automate fluid flow [ 66 ].…”

Biofabrication of natural hydrogels for cardiac, neural, and bone Tissue engineering Applications

“…Hydrogels are high water content materials and one of the few biomaterials that can be used to fabricate extracellular matrix (ECM) mimicking scaffolds [ 11 , 12 ]. Moreover, in addition to being highly biocompatible, hydrogels possess an advantageous physical and biological tunability, and desirable robustness in biofabrication [ [13] , [14] , [15] ]. Although some synthetic materials have been shown to be less prone to evoke an immune response [ 16 ], naturally-derived crosslinked polymeric networks are preferred to avoid the potential risk of inflammatory and immunological responses induced by synthetic polymeric materials [ [17] , [18] , [19] , [20] , [21] , [22] ].…”

The Rheology and Printability of Cartilage Matrix-Only Biomaterials

“…Consequently, the 20 ME MeSDVC may not be suitable for implanting into a cartilage defect (i.e., can leak out before crosslinking). However, it is worthwhile to note that such low-viscosity precursors may be suitable for other types of bioprinting (e.g., digital light processing, inkjet) [ 40 , 41 ].…”