Bisulfite-initiated crosslinking of gelatin methacryloyl hydrogels for embedded 3D bioprinting

Abstract

Recent studies on three-dimensional (3D) bioprinting of cell-laden gelatin methacryloyl (GelMA) hydrogels have provided promising outcomes for tissue engineering applications. However, the reliance on the use of photo-induced gelation processes for the bioprinting of GelMA and the lack of an alternative crosslinking process remain major challenges for the fabrication of cell-laden structures. Here, we present a novel crosslinking approach to form cell-laden GelMA hydrogel constructs through 3D embedded bioprinting without using any external irradiation that could drastically affect cell viability and functionality. This approach consists of a one-step type of crosslinking via bisulfite-initiated radical polymerization, which is combined with embedded bioprinting technology to improve the structural complexity of printed structures. By this means, complex-shaped hydrogel bio-structures with cell viability higher than 90 % were successfully printed within a support bath including sodium bisulfite. This study offers an important alternative to other photo-induced gelation processes to improve the bio-fabrication of GelMA hydrogel with high cell viability.

Regulable Supporting Baths for Embedded Printing of Soft Biomaterials with Variable Stiffness

“…Since the results of the first 3 days are crucial to verify the injury from residual chemicals to cells coming from embedded printing and washing procedure, 34 this study confirmed the great biocompatibility of the HP supporting bath, the embedded printing, and the removal strategy. Although the applied α-CD has a small molecular weight, it is a type of highly safe material for animals and humans and is approved by FDA.…”

“…While encapsulated in the low-concentration PF-127 (<10%), cells could successfully survive and proliferate. , Though Laponite was added to the PF-127 solution to modify its performance, the addition of CaCl 2 or NaHSO 3 is indispensable, improving the complexity of the material system. Besides, the presence of Laponite makes the bath difficult to be removed. , …”

“…Besides, the presence of Laponite makes the bath difficult to be removed. 9,34 Herein, an easily regulable assembled supporting bath for embedded 3D bioprinting was designed. The bath is comprised of PF-127 and a type of commercial hydrophobically modified hydroxypropylmethyl cellulose (H-HPMC), termed the HP supporting bath.…”

Three-Dimensional Printing in Stimuli-Responsive Yield-Stress Fluid with an Interactive Dual Microstructure

“…In this nanoclay concentration range, nanoclay platelets present an exfoliated morphology to maintain sufficient yield-stress behavior during printing and the interactions between nanoclay and Pluronic F127 are inhibited with negligible effects. Thus, the dense “house-of-cards” microstructure of nanoclay enables the reported nanocomposites to have a stably high viscosity at any temperatures, − making it difficult for adding and/or removing support bath materials by controlling the temperature. Because nanoclay platelets may actively interact with polymer chains in a less-dense intercalated morphology − at lower concentrations, in this study, we aim to explore nanoclay-Pluronic F127 with the nanoclay concentration below the threshold value so that an interactive dual microstructure can form for enabling the nanocomposite to present a highly regulable rheology at different temperatures.…”

“…Thus, both applied shear stress and temperature change can trigger the reversible phase transition of the nanocomposite. It is noted that the material system consisting of nanoclay and Pluronic F127 has been investigated and used as a matrix bath for 3D bioprinting, 34,35 in which the nanoclay concentration is equivalent to or higher than a threshold concentration (e.g., 3−4% (w/v)). 36 In this nanoclay concentration range, nanoclay platelets present an exfoliated morphology to maintain sufficient yield-stress behavior during printing and the interactions between nanoclay and Pluronic F127 are inhibited with negligible effects.…”