@article{HaiderAhmadYangetal.2021,
  author    = {Haider, Malik Salman and Ahmad, Taufiq and Yang, Mengshi and Hu, Chen and Hahn, Lukas and Stahlhut, Philipp and Groll, J{\"u}rgen and Luxenhofer, Robert},
  title     = {Tuning the thermogelation and rheology of poly(2-oxazoline)/poly(2-oxazine)s based thermosensitive hydrogels for 3D bioprinting},
  series = {Gels},
  volume    = {7},
  journal   = {Gels},
  number    = {3},
  issn      = {2310-2861},
  doi       = {10.3390/gels7030078},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241781},
  year      = {2021},
  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.},
  language  = {en}
}
@phdthesis{Hahn2022,
  author    = {Hahn, Lukas},
  title     = {Novel Thermoresponsive Hydrogels Based on Poly(2-oxazoline)s and Poly(2-oxazine)s and their Application in Biofabrication},
  doi       = {10.25972/OPUS-27129},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271299},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In this work, the influence of aromatic structures on drug encapsulation, self-assembly and hydrogel formation was investigated. The physically crosslinked gelling systems were characterized and optimized for the use in biofabrication and applied in initial (bio)printing experiments. Chapter I: The cytocompatible (first in vitro and in vivo studies) amphiphile PMeOx-b-PBzOx-b- PMeOx (A-PBzOx-A) was used for the solubilization of PTX, schizandrin A (SchA), curcumin (CUR), niraparib and HS-173. Chapter II: Compared to the polymers A-PPheOx-A, A-PBzOx-A and A-PBzOzi-A, only the polymer A-PPheOzi-A showed a reversible temperature- and concentration-dependent inverse thermogelation, which is accompanied by a morphology change from long wormlike micelles in the gel to small spherical micelles in solution. The worm formation results from novel interactions between the hydrophilic and hydrophobic aromatic polymer blocks. Changes in the hydrophilic block significantly alter the gel system. Rheological properties can be optimized by concentration and temperature, which is why the hydrogel was used to significantly improve the printability and stability of Alg in a blend system. Chapter III: By extending the side chain of the aromatic hydrophobic block, the inverse thermogelling polymer A-poly(2-phenethyl-2-oxazoline)-A (A-PPhenEtOx-A) is obtained. Rapid gelation upon cooling is achieved by inter-correlating spherical micelles. Based on ideal rheological properties, first cytocompatible bioprinting experiments were performed in combination with Alg. The polymers A- poly(2-benzhydryl-2-oxazoline)-A (A-PBhOx-A) and A-poly(2-benzhydryl-2-oxazine) (A-PBhOzi-A) are characterized by two aromatic benzyl units per hydrophobic repeating unit. Only the polymer A- PBhOzi-A exhibited inverse thermogelling behavior. Merging micelles could be observed by electron microscopy. The system was rheologically characterized and discussed with respect to an application in 3D printing. Chapter IV: The thermogelling POx/POzi system, in particular the block copolymer PMeOx-b- PnPrOzi, was used in different applications in the field of biofabrication. The introduction of maleimide and furan units along the hydrophilic polymer part ensured additional stabilization by Diels-Alder crosslinking after the printing process.},
  subject      = {Polymer Science},
  language  = {en}
}
@article{HahnLuxenhoferHeltenetal.2021,
  author    = {Hahn, Lukas and Luxenhofer, Robert and Helten, Holger and Forster, Stefan and Fritze, Lars and Polzin, Lando and Keßler, Larissa},
  title     = {ABA Type Amphiphiles with Poly(2-benzhydryl-2-oxazine) Moieties: Synthesis, Characterization and Inverse Thermogelation},
  series = {Macromolecular Chemistry and Physics},
  volume    = {222},
  journal   = {Macromolecular Chemistry and Physics},
  number    = {17},
  doi       = {10.1002/macp.202100114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265124},
  year      = {2021},
  abstract  = {Thermoresponsive polymers are frequently involved in the development of materials for various applications. Here, polymers containing poly(2- benzhydryl-2-oxazine) (pBhOzi) repeating units are described for the first time. The homopolymer pBhOzi and an ABA type amphiphile comprising two flanking hydrophilic A blocks of poly(2-methyl-2-oxazoline) (pMeOx) and the hydrophobic aromatic pBhOzi central B block (pMeOx-b-pBhOzi-b-pMeOx) are synthesized and the latter is shown to exhibit inverse thermogelling properties at concentrations of 20 wt.\% in water. This behavior stands in contrast to a homologue ABA amphiphile consisting of a central poly(2-benzhydryl-2-oxazoline) block (pMeOx-b-pBhOx-b-pMeOx). No inverse thermogelling is observed with this polymer even at 25 wt.\%. For 25 wt.\% pMeOx-b-pBhOzi-b-pMeOx, a surprisingly high storage modulus of ≈22 kPa and high values for the yield and flow points of 480 Pa and 1.3 kPa are obtained. Exceeding the yield point, pronounced shear thinning is observed. Interestingly, only little difference between self-assemblies of pMeOx-b-pBhOzi-b-pMeOx and pMeOx-b-pBhOx-b-pMeOx is observed by dynamic light scattering while transmission electron microscopy images suggest that the micelles of pMeOx-b-pBhOzi-b-pMeOx interact through their hydrophilic coronas, which is probably decisive for the gel formation. Overall, this study introduces new building blocks for poly(2-oxazoline) and poly(2-oxazine)-based self-assemblies, but additional studies will be needed to unravel the exact mechanism.},
  language  = {en}
}
@article{HahnBeudertGutmannetal.2021,
  author    = {Hahn, Lukas and Beudert, Matthias and Gutmann, Marcus and Keßler, Larissa and Stahlhut, Philipp and Fischer, Lena and Karakaya, Emine and Lorson, Thomas and Thievessen, Ingo and Detsch, Rainer and L{\"u}hmann, Tessa and Luxenhofer, Robert},
  title     = {From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking},
  series = {Macromolecular Bioscience},
  volume    = {21},
  journal   = {Macromolecular Bioscience},
  number    = {10},
  doi       = {10.1002/mabi.202100122},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257542},
  year      = {2021},
  abstract  = {Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.},
  language  = {en}
}
@article{HuHahnYangetal.2021,
  author    = {Hu, Chen and Hahn, Lukas and Yang, Mengshi and Altmann, Alexander and Stahlhut, Philipp and Groll, J{\"u}rgen and Luxenhofer, Robert},
  title     = {Improving printability of a thermoresponsive hydrogel biomaterial ink by nanoclay addition},
  series = {Journal of Materials Science},
  volume    = {56},
  journal   = {Journal of Materials Science},
  issn      = {0022-2461},
  doi       = {10.1007/s10853-020-05190-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234894},
  pages     = {691-705},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}