Amphiphilic block copolymers that undergo (reversible) physical gelation in aqueous media are of great interest in different areas including drug delivery, tissue engineering, regenerative medicine and biofabrication. We investigated a small library of ABA-type triblock copolymers comprising poly(2-methyl-2-oxazoline) as the hydrophilic shell A and different aromatic poly(2-oxazoline)s and poly(2-oxazine)s cores B in aqueous solution at different concentrations and temperatures. Interestingly, aqueous solutions of poly(2-methyl-2-oxazoline)-block-undergo inverse thermogelation below a critical temperature by forming a reversible nanoscale worm-like network. The viscoelastic properties of the resulting gel can be conveniently tailored by the concentration and the polymer composition. Storage moduli of up to 110 kPa could be obtained while the material remains shear-thinning and retains rapid self-healing properties. We demonstrate 3D-printing of excellently defined and shape persistent 24-layered scaffolds at different aqueous concentrations to highlight its application potential e.g. in the research area of biofabrication. A mesoporous microstructure, which is stable throughout the printing process, could be confirmed via cryo-SEM analysis. The absence of cytotoxicity even at very high concentrations opens wide range of different applications for this first-in-class material in the field of biomaterials.

The synthesis and characterization of an ABA triblock copolymer based on hydrophilic poly(2-methyl-2-oxazoline) (pMeOx) blocks A and a modestly hydrophobic poly(2-iso-butyl-2-oxazoline) (piBuOx) block B is described. Aqueous polymer solutions were prepared at different concentrations (1–20 wt %) and their thermogelling capability using visual observation was investigated at different temperatures ranging from 5 to 80 °C. As only a 20 wt % solution was found to undergo thermogelation, this concentration was investigated in more detail regarding its temperature-dependent viscoelastic profile utilizing various modes (strain or temperature sweep). The prepared hydrogels from this particular ABA triblock copolymer have interesting rheological and viscoelastic properties, such as reversible thermogelling and shear thinning, and may be used as bioink, which was supported by its very low cytotoxicity and initial printing experiments using the hydrogels. However, the soft character and low yield stress of the gels do not allow real 3D printing at this point.

As a promising biofabrication technology, extrusion-based bioprinting has gained significant attention in the last decade and major advances have been made in the development of bioinks. However, suitable synthetic and stimuli-responsive bioinks are underrepresented in this context. In this work, we described a hybrid system of nanoclay Laponite XLG and thermoresponsive block copolymer poly(2-methyl-2-oxazoline)-b-poly(2-n-propyl-2-oxazine) (PMeOx-b-PnPrOzi) as a novel biomaterial ink and discussed its critical properties relevant for extrusion-based bioprinting, including viscoelastic properties and printability. The hybrid hydrogel retains the thermogelling properties but is strengthened by the added clay (over 5 kPa of storage modulus and 240 Pa of yield stress). Importantly, the shear-thinning character is further enhanced, which, in combination with very rapid viscosity recovery (~ 1 s) and structure recovery (~ 10 s), is highly beneficial for extrusion-based 3D printing. Accordingly, various 3D patterns could be printed with markedly enhanced resolution and shape fidelity compared to the biomaterial ink without added clay. Graphic abstract

Amphiphilic block copolymers that undergo (reversible) physical gelation in aqueous media are of great interest in different areas including drug delivery, tissue engineering, regenerative medicine and biofabrication. We investigated a small library of ABA-type triblock copolymers comprising poly(2-methyl-2-oxazoline) as the hydrophilic shell A and different aromatic poly(2-oxazoline)s and poly(2-oxazine)s cores B in aqueous solution at different concentrations and temperatures. Interestingly, aqueous solutions of poly(2-methyl-2-oxazoline)-block-poly(2-phenyl-2-oxazine)-block-poly(2-methyl-2-oxazoline) (PMeOx-b-PPheOzi-b-PMeOx) undergo inverse thermogelation below a critical temperature. The viscoelastic properties of the resulting gel can be conveniently tailored by the concentration and the polymer composition. Storage moduli of up to 110 kPa could be obtained while the material remains shear-thinning and retains rapid self-healing properties. We demonstrate 3D-printing of excellently defined and shape persistent 24-layered scaffolds at different aqueous concentrations to highlight its application potential e.g. in the research area of biofabrication. A mesoporous microstructure, which is stable throughout the printing process, could be confirmed via cryo-SEM analysis. The absence of cytotoxicity even at very high concentrations opens wide range of different applications for this first-in-class material in the field of biomaterials.<br>