A structure-supporting, self-healing, and high permeating hydrogel bioink for establishment of diverse homogeneous tissue-like constructs

Abstract

The ready-to-use, structure-supporting hydrogel bioink can shorten the time for ink preparation, ensure cell dispersion, and maintain the preset shape/microstructure without additional assistance during printing. Meanwhile, ink with high permeability might facilitate uniform cell growth in biological constructs, which is beneficial to homogeneous tissue repair. Unfortunately, current bioinks are hard to meet these requirements simultaneously in a simple way. Here, based on the fast dynamic crosslinking of aldehyde hyaluronic acid (AHA)/N-carboxymethyl chitosan (CMC) and the slow stable crosslinking of gelatin (GEL)/4-arm poly(ethylene glycol) succinimidyl glutarate (PEG-SG), we present a time-sharing structure-supporting (TSHSP) hydrogel bioink with high permeability, containing 1% AHA, 0.75% CMC, 1% GEL and 0.5% PEG-SG. The TSHSP hydrogel can facilitate printing with proper viscoelastic property and self-healing behavior. By crosslinking with 4% PEG-SG for only 3 min, the integrity of the cell-laden construct can last for 21 days due to the stable internal and external GEL/PEG-SG networks, and cells manifested long-term viability and spreading morphology. Nerve-like, muscle-like, and cartilage-like in vitro constructs exhibited homogeneous cell growth and remarkable biological specificities. This work provides not only a convenient and practical bioink for tissue engineering, targeted cell therapy, but also a new direction for hydrogel bioink development.

Finding the sweet spot: a library of hydrogels with tunable degradation for tissue model development

“…24,54 Chemical crosslinking can also be toxic to cells, but the SG approach has been used extensively and show low toxicity. [55][56][57] In this work, we created a library of gels and looked at cell survival. The gels that showed maximum longterm survival, adhesion, migration, and capillary-like network formation (4 : 1 and 8 : 1-75% PLL gels) have a low concentration of PAA in the hydrogel and the lowest number of free amines in the system (Fig.…”

Advances of Hydrogel-Based Bioprinting for Cartilage Tissue Engineering

“…Moreover, in vitro and in vivo experiments showed the favorable cell viability, attachment and proliferation, and obvious chondrogenic expression to verify the cartilage regeneration ( He et al, 2020 ). Chen et al synthesized a structure-supporting, self-healing, and high permeating hydrogel bio-ink, which was composed of aldehyde HA (AHA)/N-carboxymethyl chitosan (CMC) and gelatin (Gel)/4-arm poly (ethylene glycol) succinimidyl glutarate (PEG-SG) ( Chen et al, 2021 ). The obtained hydrogel bio-inks possessed good printability, self-healing capacity, and high permeability, thus achieving long-term cell viability, attachment, and growth for biological application ( Figure 6 ).…”

“…(E) Proliferation pattern of cells in low permeating constructs. Reproduced from Chen et al, (2021 ) with permission from Copyright 2021 Elsevier.…”

Translational Application of 3D Bioprinting for Cartilage Tissue Engineering

“…These materials are also widely used in drug delivery applications for the controlled release of hydrophobic drugs. Chen et al developed a structure for supporting hydrogel bioink, containing aldehyde hyaluronic acid, N-carboxymethyl chitosan, gelatin, and PEG succinimidyl glurate [101]. They demonstrated that this bioink enabled the printing of constructs with viscoelastic properties and self-healing behaviour with the potential for use in cartilage tissue engineering applications.…”