Synthesis and Characterization of Dual Stimuli-Sensitive Biodegradable Polyurethane Soft Hydrogels for 3D Cell-Laden Bioprinting

Abstract

Three-dimensional bioprinting serves as an attractive platform to fabricate customized tissue-engineered substitutes from biomaterials and cells for the repair or replacement of injured tissues and organs. A common challenge for 3D bioprinting materials is that the structures printed from the biodegradable polymer hydrogels tend to collapse because of the poor mechanical stability. In this study, dual stimuli-responsive biodegradable polyurethane (PU) dispersions (PUA2 and PUA3) were synthesized from an eco-friendly waterborne process. Acrylate group was introduced in the PU chain end to serve as a photosensitive moiety for UV-induced cross-linking and improvement of the printability, while mixed oligodiols in the soft segment remained to be the thermosensitive moiety. The photo/thermal-induced morphological changes of PU nanoparticles were verified by dynamic light scattering, small-angle X-ray scattering, and rheological measurement of the dispersions. It was observed that these PU nanoparticles became more rod-like in shape after UV treatment and formed compact packing structures upon further heating. With the thermosensitive properties, these UV-cured PU dispersions underwent rapid thermal gelation with gel moduli in the range 0.5-2 kPa near body temperature. The rheological properties of the PU hydrogels including dynamic viscoelasticity, creep recovery, and shear thinning behavior at 37 °C were favorable for processing by microextrusion-based 3D printing and could be easily mixed with cells before printing to produce cell-laden constructs. The dual-responsive hydrogel constructs demonstrated higher resolution and shape fidelity as well as better cell viability and proliferation than the thermoresponsive control. Moreover, the softer hydrogel (PUA3) with a low modulus (<1 kPa) could offer neural stem cells a tofu-like, stable, and inductive 3D microenvironment to proliferate and differentiate. We expect that the photo/thermoresponsive biodegradable polyurethane ink may offer unique rheological properties to contribute toward the custom-made bioprinting of soft tissues.

Hydrogels for Bioprinting: A Systematic Review of Hydrogels Synthesis, Bioprinting Parameters, and Bioprinted Structures Behavior

“…Finally, the last three papers use polycaprolactone (PCL) (Lin et al, 2016 ), a blend of polyurethane (PU), PCL, poly(L-lactic acid) (PLLA) and poly[D,L-lactic acid] (PDLLA) (Hsiao and Hsu, 2018 ), and Thixotropic Magnesium Phosphate-based gel (TMP-BG) (Chen et al, 2018 ). This last hydrogel is prepared mildly (gelling method) with inorganic compound and thixotropic features that obtains promising results.…”

Recent progress in extrusion 3D bioprinting of hydrogel biomaterials for tissue regeneration: a comprehensive review with focus on advanced fabrication techniques

“…The Schwann cell-, rodent neuronal cell-, and human glioma cell encapsulated bioink was subjected to form neural constructs. In another work on designing suitable bioink that possesses proper mechanical properties while promoting cell proliferation and tissue formation, Hsiao et al [249], synthesized dual stimuli-responsive biodegradable polyurethane hydrogel. The advantage of the developed hydrogels bioink was its relatively low viscosity that could avoid excessive fluid shear stress and potential for jamming during extrusion.…”

Synthetic Polymers for Organ 3D Printing

“…For example, waterborne PU is often synthesized by introducing ionic hydrophilic groups that transform PU to an ionomer and make it disperse in water. The thermosensitivity of PU hydrogels is strongly dependent on the soft segment oligodiol compositions [120]. Acrylate groups serve as an ultraviolet (UV) curing site, and can be incorporated into thermosensitive PUs for cell and tissue 3D printing.…”