Tuning the Thermogelation and Rheology of Poly(2-Oxazoline)/Poly(2-Oxazine)s Based Thermosensitive Hydrogels for 3D Bioprinting

Gels. 2021 Jun 24;7(3):78. doi: 10.3390/gels7030078.

Abstract

As one kind of "smart" material, thermogelling polymers find applications in biofabrication, drug delivery and regenerative medicine. In this work, we report a thermosensitive poly(2-oxazoline)/poly(2-oxazine) based diblock copolymer comprising thermosensitive/moderately hydrophobic poly(2-N-propyl-2-oxazine) (pPrOzi) and thermosensitive/moderately hydrophilic poly(2-ethyl-2-oxazoline) (pEtOx). Hydrogels were only formed when block length exceeded certain length (≈100 repeat units). The tube inversion and rheological tests showed that the material has then a reversible sol-gel transition above 25 wt.% concentration. Rheological tests further revealed a gel strength around 3 kPa, high shear thinning property and rapid shear recovery after stress, which are highly desirable properties for extrusion based three-dimensional (3D) (bio) printing. Attributed to the rheology profile, well resolved printability and high stackability (with added laponite) was also possible. (Cryo) scanning electron microscopy exhibited a highly porous, interconnected, 3D network. The sol-state at lower temperatures (in ice bath) facilitated the homogeneous distribution of (fluorescently labelled) human adipose derived stem cells (hADSCs) in the hydrogel matrix. Post-printing live/dead assays revealed that the hADSCs encapsulated within the hydrogel remained viable (≈97%). This thermoreversible and (bio) printable hydrogel demonstrated promising properties for use in tissue engineering applications.

Keywords: bio-printability; cyto-compatibility; poly(2-ethyl-2-oxazoline); shape fidelity; shear thinning.