Extrusion‐based three‐dimensional (3D) printing has emerged as a powerful fabrication strategy in tissue engineering. However, achieving reliable printability and structural stability in hydrogel‐based systems remains a persistent challenge. Alginate‐based hydrogels are among the most widely investigated biomaterial inks for this purpose, due to their biocompatibility, biodegradability, and capacity for ionic crosslinking. This preliminary study investigated the influence of calcium chloride (CaCl
2
) concentration on the rheological behavior, extrudability, and scaffold geometric fidelity of alginate hydrogel inks for extrusion‐based 3D printing. Formulations were prepared at three CaCl
2
concentrations (2.73, 3.33, and 3.91 mg/mL) and characterized by oscillatory rheology to determine storage modulus (
G
′), loss modulus (
G
″), yield stress, and complex viscosity. Gelation behavior was evaluated through inversion assays, and printability was assessed via extrusion tests, filament spreadability analysis, and scaffold geometric fidelity evaluation across multiple printed geometries. Among the formulations evaluated, the intermediate CaCl
2
concentration (3.33 mg/mL) yielded the most favorable rheological profile, exhibiting
G
′ >
G
″ in the small‐amplitude oscillatory shear region and a yield stress compatible with continuous filament extrusion. Scaffold fidelity assessment revealed persistent structural limitations: including rounded pores, pore‐size variation, and partial layer collapse indicating that printability was improved relative to the other formulations but not fully resolved at this crosslinking level. These findings establish a rheological‐to‐printability framework for CaCl
2
‐crosslinked alginate inks, identifying yield stress and
G
′ dominance in the SAOS regime as predictive criteria for extrusion‐based printability, and provide a reproducible technical foundation for systematic formula optimization prior to biological validation and tissue engineering application.
Three-dimensional (3D) printing enables the fabrication of hydrogel constructs with precise architecture, yet developing photocurable hydrogel biomaterial ink that combine printability, structural stability, and biofunctionality remains a challenge. Here, we present a gallol-functionalized gellan gum methacrylate (GGMA-GA) hydrogel as a robust photocrosslinkable biomaterial ink for extrusion-based 3D bioprinting. A dual-crosslinking strategy was employed in which mild ionic pre-crosslinking enhances shear-thinning and print fidelity, followed by photocrosslinking of methacrylate groups to reinforce mechanical stability post-printing. Incorporation of gallol moieties provides antioxidant activity and tissue adhesion, mitigating oxidative stress and promoting construct integration. We systematically evaluated rheological and swelling properties, printability, and cytocompatibility, demonstrating that GGMA-GA hydrogels maintain structural fidelity while supporting cell viability. The combination of low swelling degree, enhanced functionality, and precise printability positions GGMA-GA as a versatile photocurable hydrogel platform for extrusion-based 3D fabrication, with potential for long-term and in situ biomedical applications.
S. Annurakshita, Hatai Jongprasitkul, Marianne Niemelä et al.· International Journal of Bio...· 0 citations
This study reports the fabrication of curcuminoid-loaded nanofibrillated cellulose (NFC)–alginate scaffolds via extrusion-based 3D printing, integrating supercritical CO2 extraction with biofabrication. NFC–alginate inks were pre-crosslinked with CaCl2 (1 to 10 mM) to tune structure and properties. Rheological analysis confirmed shear-thinning behavior suitable for extrusion printing. Mechanical testing revealed a non-linear dependence on crosslinking: optimal performance was achieved by Ink 2 (1 mM CaCl2 with curcuminoid extract), with tensile strength increasing from ~0.60 to ~0.80 MPa and Young’s modulus from ~1.5 to ~3.0 MPa relative (Ink 1, 10 mM CaCl2, without extract), reflecting the combined effect of extract incorporation and ionic pre-crosslinking rather than crosslinker concentration alone; higher crosslinking reduced stiffness (~1.15 MPa). SEM revealed porous architectures (Ink 1: 542 ± 63 μm; Ink 4: 398 ± 71 μm) with increasing structural heterogeneity upon curcuminoid incorporation. In vitro release exhibited biphasic, diffusion-dominated behavior, reaching ~50 to 60% in ethanol-containing media; PBS inclusion as a physiological reference confirmed minimal release (<5%), consistent with the known hydrophobicity and pH-dependent instability of curcuminoids and defining the physicochemical delivery boundaries of the system. The highest release (~372 ng/mL) was achieved at intermediate loading (10×). Kinetic modeling confirmed Higuchi-type diffusion as the dominant mechanism (R2 ≈ 0.90 to 0.99). These results establish a clear structure–property–release relationship and position the scaffolds as a tunable, diffusion-controlled delivery platform for hydrophobic bioactives in topical or formulation-assisted applications employing co-solvents or solubilizing excipients.
Gal Slaček, P. Kotnik, Ž. Knez et al.· Polysaccharides· 0 citations
A careful balance between extrusion flowability and rapid viscoelastic recovery is essential for direct ink writing (DIW). The ink must flow easily under shear during extrusion and quickly recover a solid‐like structure after extrusion to maintain the printed architecture. Conventional ionic crosslinking methods to tune the rheological features often lead to inhomogeneity, nozzle clogging, and printing failure. To overcome these challenges, we introduce a two‐step ionic crosslinking strategy for weakly structured graphene oxide (GO)/sodium alginate (SA) inks. First, to stabilize each printed layer of weak hydrogels while preventing nozzle clogging, each extruded layer is immediately sprayed with an ionic solution upon deposition to induce partial crosslinking. Second, the fully printed partially crosslinked scaffold is submerged in an ionic bath to complete the crosslinking. Using this method, flowing hydrogels are turned into tough or brittle 3D‐printed structures by methodically fine‐tuning materials’ qualities, affected by GO content, SA concentration, and crosslinker valency. Moreover, the effect of salt type on the hydrogels’ shape retention and printing quality, as well as on the morphological features of the resulting cryogels, is investigated. All in all, this study introduces a two‐step ionic crosslinking technique that separates printability from high rheological requirements to overcome complications in the DIW process.
Asal Jaberansari, R. Bakhtiari, S. Samsami et al.· Chemistry–Methods· 0 citations
This study provides a practical framework for creating intrafilamentary porosity into 3D-printed PCL scaffolds with improved surface-mediated biological performance.
Mikaela Kutrolli, Noah S Pereira, Delaram Ghanbariamin et al.· ACS Biomaterials Science & E...· 0 citations
Three-dimensional, interconnected hydrogel networks are central to tissue engineering and disease modeling, where tailored pore architecture and mechanical robustness are essential for supporting cellular functions. However, the limited ability to engineer microstructural features in vat polymerization 3D-printed natural hydrogels often compromises scaffold performance, as oversized pores reduce cell attachment and cell-cell interactions while smooth pore walls lack essential topographical cues. Here, we report an emulsion-based ink for vat polymerization 3D printing that enables the fabrication of hydrogels with finely tunable and highly interconnected porous architectures. An oil-in-water resin formulated using gelatin methacrylate (GelMA) contains stable solvent nanodroplets that act as sacrificial templates during photopolymerization. Removal of the dispersed phase yields additive-free porous hydrogels with pore sizes ranging from 0.66 to 46.15 µm and a 2.5-fold enhancement in compressive toughness. This strategy is compatible with digital light processing (DLP) and broadly applicable to multiple photocurable biopolymers, including alginate methacrylate (ALMA) and hyaluronic acid methacrylate (HAMA). The resulting porous scaffolds promote enhanced cell attachment, proliferation, and cell-cell interactions, highlighting the potential of this vat polymerization-compatible platform for advanced biofabrication.
Liwei Liu, Liwen Zhang, Xumin Huang et al.· Small Methods· 0 citations
A microgel-based biphasic bioink that leverages microgels' advantages while maintaining porosity to enhance cellular performance is developed, enabling the high-fidelity fabrication of complex, spatially controlled heterogeneous 3D structures with tunable mechanical properties.
S. Sadeghzade, Min Wang, Ajinkya Nene et al.· International Journal of Bio...· 0 citations