Hydrogel Ink for 3D Printing with High and Widely Tunable Mechanical Properties via the Salting‐Out Effect

Background

Hydrogels are candidates for synthetic organs for surgical training, implants and organoids, but these uses require both 3D printability and mechanical properties close to those of tissues. DIW-printable hydrogels are generally soft with a narrow modulus range, because the precursor ink must hold its printed shape and composition changes that raise stiffness also alter chain entanglement, crosslinking and flow behavior. Double-network, dual-crosslinking, nanocomposite and hierarchical-network strategies raise hydrogel modulus, but they often make the required rheology difficult to achieve or need a separate step after extrusion.

Design and approach

The ink combines PF127DMA, synthesized by methacrylation of Pluronic F-127, with acrylamide (AM), the crosslinker N,N'-methylenebis(acrylamide) and NaCl. PF127DMA is a triblock copolymer that forms micelles in water, which gives the ink shear-thinning and shear-recovery behavior. AM is needed for stiffness but hinders micelle formation and raises the gelation temperature, whereas NaCl promotes micelle formation and reduces micelle size, which the authors attribute to enhanced hydrophobicity of the polypropylene oxide blocks and dehydration of the polyethylene oxide blocks. After printing, UV curing for 60 s copolymerizes the PF127DMA micelles with polyacrylamide, and the AM content sets the final stiffness; NaCl was chosen because it does not precipitate at high molar concentration and is inexpensive.

How it was evaluated

Micelle behavior was examined by dynamic light scattering (DLS), cryo-transmission electron microscopy and small-angle X-ray scattering (SAXS), and the gelation temperature was taken from temperature sweeps of the storage and loss moduli. Rheology covered shear rates of 0.1 to 100 s−1 and alternating strains of 0.1% and 100%, and extrusion width was measured for each ink (n = 150) as a function of printing speed and pneumatic pressure. Cured hydrogels were tested in tension and compression, with digital image correlation, and printed patterns were compared with molded samples. Printed vessels were subjected to an internal pressure test up to 150 mmHg, electrocautery (cutting mode, 70 W) and end-to-end anastomosis with sutures, and NIH-3T3 fibroblasts were cultured with the hydrogel for a live/dead assay.

Key results

In DLS, adding AM reduced the micelle peak and increased the unimer peak, whereas adding 0.5 or 1 M NaCl removed the unimer peak and reduced the average micelle size. SAXS of NaCl-containing gels showed three diffraction peaks consistent with a body-centered cubic micelle arrangement, and the distance between nearest micelles increased from 16.631 nm at 1 M to 17.296 nm at 2 M NaCl. Raising the AM content from 0 to 30 wt% increased the gelation temperature from 7.2 to 55.3 °C, and raising NaCl from 0 to 3.5 M in the 30 wt% AM ink lowered it from 55.3 to 23.5 °C. After printing, inks without NaCl returned to a solution within minutes and lost their structure, while NaCl-containing inks kept their shape.

The salt-modified inks showed shear-thinning between 0.1 and 100 s−1, became sol-like at 100% strain and returned to the gel state at 0.1% strain. Extrusion width decreased with printing speed and increased with pneumatic pressure (n = 150 per ink) without die swell, so that different inks could be printed with the same line width for multi-material structures.

The modulus of the cured hydrogels increased with AM content, spanning 0.193–1.072 MPa, with ultimate tensile strengths of 0.092–0.415 MPa; the Introduction gives this range as 0.210–1.098 MPa. Digital image correlation gave a Poisson's ratio of 0.41, and all samples were compressed to 90% without breaking and recovered. At 50% infill, parallel and perpendicular patterns gave moduli of about 0.904 and 0.901 MPa, and the alternating rectilinear pattern gave 0.931 MPa, 84.8% of the molded hydrogel; the rectilinear-printed hydrogel lifted a 1 kg weight, about 1230 times its own weight.

Hollow vessels with outer diameters of 2.16, 9, 20 and 32 mm and a three-layer vessel were printed, and ink formulations were matched to vessel moduli reported for different ages. A 32 mm vessel with a 2 mm wall, tested up to 150 mmHg, reached a maximum hoop stress of 249 kPa, and the modulus derived from it, about 900 kPa, followed the trend of the tensile tests. The salt in the hydrogel allowed electrocautery in both cutting and coagulation modes, sutured vessels were joined without tearing or leakage, and NIH-3T3 fibroblast viability was approximately 94% on day 7, similar to the control.

How it connects to other research

Sun and colleagues obtained tough, highly stretchable hydrogels by combining ionically and covalently crosslinked networks, whereas this study keeps inks of different stiffness printable by using salt to control micelle-driven gelation and sets the modulus through the acrylamide content.