Alginate Self-Crosslinking Ink for 3D Extrusion-Based Cryoprinting and Application for Epirubicin-HCl Delivery on MCF-7 Cells

Abstract

3D-printed hydrogels are particularly advantageous as drug-delivery platforms but their loading with water-soluble active compounds remains a challenge requiring the development of innovative inks. Here, we propose a new 3D extrusion-based approach that, by exploiting the internal gelation of the alginate, avoids the post-printing crosslinking process and allows the loading of epirubicin-HCl (EPI). The critical combinations of alginate, calcium carbonate and d-glucono-δ-lactone (GDL) combined with the scaffold production parameters (extrusion time, temperature, and curing time) were evaluated and discussed. The internal gelation in tandem with 3D extrusion allowed the preparation of alginate hydrogels with a complex shape and good handling properties. The dispersion of epirubicin-HCl in the hydrogel matrix confirmed the potential of this self-crosslinking alginate-based ink for the preparation of 3D-printed drug-delivery platforms. Drug release from 3D-printed hydrogels was monitored, and the cytotoxic activity was tested against MCF-7 cells. Finally, the change in the expression pattern of anti-apoptotic, pro-apoptotic, and autophagy protein markers was monitored by liquid-chromatography tandem-mass-spectrometry after exposure of MCF-7 to the EPI-loaded hydrogels.

Aloe vera‐based biomaterial ink for 3D bioprinting of wound dressing constructs

“…The AC ink (extruded directly at ambient conditions) achieved a maximum swelling rate of 1270% of its initial weight, consistent with the authors' past study 50 . Lastly, a combination of alginate and hydrolyzed glucono‐delta‐lactone (GDL) for the development of an alginate‐based self‐crosslinking bioink, reached a rehydration percentage of about 900% in 1 min for both alkaline and acidic conditions 54 …”

“…50 Lastly, a combination of alginate and hydrolyzed gluconodelta-lactone (GDL) for the development of an alginate-based selfcrosslinking bioink, reached a rehydration percentage of about 900% in 1 min for both alkaline and acidic conditions. 54 3.9 | Mesenchymal stem cell culture and biocompatibility study…”

Optimizing Gel Formulations Using Carbopol 940 and Sodium Alginate Containing Andrographis paniculata Extract for Burn-Wound Healing

“…The main property of sodium alginate is its ability to form gels in the presence of divalent cations (Cardenas et al, 2003). If a lot of Ca2+ ions are released into the gel-making process, more cross-links that can be formed between alginate molecules are obtained from the increasing concentration of CaCO3 (Remaggi et al, 2022). Sodium alginate also influences the adhesion parameter, namely 87.351%.…”

Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting

“…Such an approach infers requirements on the biomaterial with regard to both injectability and shape stability in vivo, with these potentially achieved through in situ crosslinking, for example through exposure to physiological concentrations of Ca 2+ . Previous studies demonstrate that gradual ALG crosslinking can be achieved using ionization of calcium carbonate (CaCO 3 ) via hydrolysis of glucono-δ-lactone (gluconolactone; GDL) [18][19][20][21]. GDL hydrolyses in water, lowers the pH and increases the solubility of CaCO 3 particles, resulting in release of calcium and bicarbonate ions that induce crosslinking and pH neutralization, respectively.…”