Development of novel iron(III) crosslinked bioinks comprising carboxymethyl cellulose, xanthan gum, and hyaluronic acid for soft tissue engineering applications.

The advent of three-dimensional (3D) bioprinting offers a feasible approach to construct complex structures for soft tissue regeneration. Carboxymethyl cellulose (CMC) has been emerging as a very promising biomaterial for 3D bioprinting. However, due to the inability to maintain the post-printed stability, CMC needs to be physically blended and/or chemically crosslinked with other polymers. In this context, this study presents the combination of CMC with xanthan gum (XG) and hyaluronic acid (HA) to formulate a multicomponent bioink, leveraging the printability of CMC and XG, as well as the cellular support properties of HA. The ionic crosslinking of printed constructs with iron(III) via the metal-ion coordination between ferric cations and carboxylate groups of the three polymers was introduced to induce improved mechanical strength and long-term stability. Moreover, immortalized human epidermal keratinocytes (HaCaT) and human foreskin fibroblasts (HFF) encapsulated within iron-crosslinked printed hydrogels exhibited excellent cell viability (more than 95%) and preserved morphology. Overall, the presented study highlights that the combination of these three biopolymers and the ionic crosslinking with ferric ions is a valuable strategy to be considered for the development of new and advanced hydrogel-based bioinks for soft tissue engineering applications.

Oxidized Xanthan Gum Crosslinked NOCC: Hydrogel System and Their Biological Stability from Oxidation Levels of the Polymer.

Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications.