@article{ShanBoeckKelleretal.2021,
  author    = {Shan, Junwen and B{\"o}ck, Thomas and Keller, Thorsten and Forster, Leonard and Blunk, Torsten and Groll, J{\"u}rgen and Teßmar, J{\"o}rg},
  title     = {TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid},
  series = {Molecules},
  volume    = {26},
  journal   = {Molecules},
  number    = {19},
  issn      = {1420-3049},
  doi       = {10.3390/molecules26195963},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248362},
  year      = {2021},
  abstract  = {Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer's backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker.},
  language  = {en}
}
@article{KarakayaBiderFranketal.2022,
  author    = {Karakaya, Emine and Bider, Faina and Frank, Andreas and Teßmar, J{\"o}rg and Sch{\"o}bel, Lisa and Forster, Leonard and Schr{\"u}fer, Stefan and Schmidt, Hans-Werner and Schubert, Dirk Wolfram and Blaeser, Andreas and Boccaccini, Aldo R. and Detsch, Rainer},
  title     = {Targeted printing of cells: evaluation of ADA-PEG bioinks for drop on demand approaches},
  series = {Gels},
  volume    = {8},
  journal   = {Gels},
  number    = {4},
  issn      = {2310-2861},
  doi       = {10.3390/gels8040206},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267317},
  year      = {2022},
  abstract  = {A novel approach, in the context of bioprinting, is the targeted printing of a defined number of cells at desired positions in predefined locations, which thereby opens up new perspectives for life science engineering. One major challenge in this application is to realize the targeted printing of cells onto a gel substrate with high cell survival rates in advanced bioinks. For this purpose, different alginate-dialdehyde—polyethylene glycol (ADA-PEG) inks with different PEG modifications and chain lengths (1-8 kDa) were characterized to evaluate their application as bioinks for drop on demand (DoD) printing. The biochemical properties of the inks, printing process, NIH/3T3 fibroblast cell distribution within a droplet and shear forces during printing were analyzed. Finally, different hydrogels were evaluated as a printing substrate. By analysing different PEG chain lengths with covalently crosslinked and non-crosslinked ADA-PEG inks, it was shown that the influence of Schiff's bases on the viscosity of the corresponding materials is very low. Furthermore, it was shown that longer polymer chains resulted in less stable hydrogels, leading to fast degradation rates. Several bioinks highly exhibit biocompatibility, while the calculated nozzle shear stress increased from approx. 1.3 and 2.3 kPa. Moreover, we determined the number of cells for printed droplets depending on the initial cell concentration, which is crucially needed for targeted cell printing approaches.},
  language  = {en}
}
@article{JanzenBakirciFaberetal.2022,
  author    = {Janzen, Dieter and Bakirci, Ezgi and Faber, Jessica and Andrade Mier, Mateo and Hauptstein, Julia and Pal, Arindam and Forster, Leonard and Hazur, Jonas and Boccaccini, Aldo R. and Detsch, Rainer and Teßmar, J{\"o}rg and Budday, Silvia and Blunk, Torsten and Dalton, Paul D. and Villmann, Carmen},
  title     = {Reinforced Hyaluronic Acid-Based Matrices Promote 3D Neuronal Network Formation},
  series = {Advanced Healthcare Materials},
  volume    = {11},
  journal   = {Advanced Healthcare Materials},
  number    = {21},
  doi       = {10.1002/adhm.202201826},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318682},
  year      = {2022},
  abstract  = {3D neuronal cultures attempt to better replicate the in vivo environment to study neurological/neurodegenerative diseases compared to 2D models. A challenge to establish 3D neuron culture models is the low elastic modulus (30-500 Pa) of the native brain. Here, an ultra-soft matrix based on thiolated hyaluronic acid (HA-SH) reinforced with a microfiber frame is formulated and used. Hyaluronic acid represents an essential component of the brain extracellular matrix (ECM). Box-shaped frames with a microfiber spacing of 200 µm composed of 10-layers of poly(ɛ-caprolactone) (PCL) microfibers (9.7 ± 0.2 µm) made via melt electrowriting (MEW) are used to reinforce the HA-SH matrix which has an elastic modulus of 95 Pa. The neuronal viability is low in pure HA-SH matrix, however, when astrocytes are pre-seeded below this reinforced construct, they significantly support neuronal survival, network formation quantified by neurite length, and neuronal firing shown by Ca\(^{2+}\) imaging. The astrocyte-seeded HA-SH matrix is able to match the neuronal viability to the level of Matrigel, a gold standard matrix for neuronal culture for over two decades. Thus, this 3D MEW frame reinforced HA-SH composite with neurons and astrocytes constitutes a reliable and reproducible system to further study brain diseases.},
  language  = {en}
}
@article{HauptsteinForsterNadernezhadetal.2022,
  author    = {Hauptstein, Julia and Forster, Leonard and Nadernezhad, Ali and Horder, Hannes and Stahlhut, Philipp and Groll, J{\"u}rgen and Blunk, Torsten and Teßmar, J{\"o}rg},
  title     = {Bioink Platform Utilizing Dual-Stage Crosslinking of Hyaluronic Acid Tailored for Chondrogenic Differentiation of Mesenchymal Stromal Cells},
  series = {Macromolecular Bioscience},
  volume    = {22},
  journal   = {Macromolecular Bioscience},
  number    = {2},
  doi       = {10.1002/mabi.202100331},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257556},
  pages     = {2100331},
  year      = {2022},
  abstract  = {3D bioprinting often involves application of highly concentrated polymeric bioinks to enable fabrication of stable cell-hydrogel constructs, although poor cell survival, compromised stem cell differentiation, and an inhomogeneous distribution of newly produced extracellular matrix (ECM) are frequently observed. Therefore, this study presents a bioink platform using a new versatile dual-stage crosslinking approach based on thiolated hyaluronic acid (HA-SH), which not only provides stand-alone 3D printability but also facilitates effective chondrogenic differentiation of mesenchymal stromal cells. A range of HA-SH with different molecular weights is synthesized and crosslinked with acrylated (PEG-diacryl) and allylated (PEG-diallyl) polyethylene glycol in a two-step reaction scheme. The initial Michael addition is used to achieve ink printability, followed by UV-mediated thiol-ene reaction to stabilize the printed bioink for long-term cell culture. Bioinks with high molecular weight HA-SH (>200 kDa) require comparably low polymer content to facilitate bioprinting. This leads to superior quality of cartilaginous constructs which possess a coherent ECM and a strongly increased stiffness of long-term cultured constructs. The dual-stage system may serve as an example to design platforms using two independent crosslinking reactions at one functional group, which allows adjusting printability as well as material and biological properties of bioinks.},
  language  = {en}
}
@article{HauptsteinForsterNadernezhadetal.2022,
  author    = {Hauptstein, Julia and Forster, Leonard and Nadernezhad, Ali and Groll, J{\"u}rgen and Teßmar, J{\"o}rg and Blunk, Torsten},
  title     = {Tethered TGF-β1 in a hyaluronic acid-based bioink for bioprinting cartilaginous tissues},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23020924},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284239},
  year      = {2022},
  abstract  = {In 3D bioprinting for cartilage regeneration, bioinks that support chondrogenic development are of key importance. Growth factors covalently bound in non-printable hydrogels have been shown to effectively promote chondrogenesis. However, studies that investigate the functionality of tethered growth factors within 3D printable bioinks are still lacking. Therefore, in this study, we established a dual-stage crosslinked hyaluronic acid-based bioink that enabled covalent tethering of transforming growth factor-beta 1 (TGF-β1). Bone marrow-derived mesenchymal stromal cells (MSCs) were cultured over three weeks in vitro, and chondrogenic differentiation of MSCs within bioink constructs with tethered TGF-β1 was markedly enhanced, as compared to constructs with non-covalently incorporated TGF-β1. This was substantiated with regard to early TGF-β1 signaling, chondrogenic gene expression, qualitative and quantitative ECM deposition and distribution, and resulting construct stiffness. Furthermore, it was successfully demonstrated, in a comparative analysis of cast and printed bioinks, that covalently tethered TGF-β1 maintained its functionality after 3D printing. Taken together, the presented ink composition enabled the generation of high-quality cartilaginous tissues without the need for continuous exogenous growth factor supply and, thus, bears great potential for future investigation towards cartilage regeneration. Furthermore, growth factor tethering within bioinks, potentially leading to superior tissue development, may also be explored for other biofabrication applications.},
  language  = {en}
}
@phdthesis{Forster2023,
  author    = {Forster, Leonard},
  title     = {Hyaluronic acid based Bioinks for Biofabrication of Mesenchymal Stem Cells},
  doi       = {10.25972/OPUS-29860},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298603},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {As a major component of the articular cartilage extracellular matrix, hyaluronic acid is a widely used biomaterial in regenerative medicine and tissue engineering. According to its well-known interaction with multiple chondrocyte surface receptors which positively affects many cellular pathways, some approaches by combining mesenchymal stem cells and hyaluronic acid-based hydrogels are already driven in the field of cartilage regeneration and fat tissue. Nevertheless, a still remaining major problem is the development of the ideal matrix for this purpose. To generate a hydrogel for the use as a matrix, hyaluronic acid must be chemically modified, either derivatized or crosslinked and the resulting hydrogel is mostly shaped by the mold it is casted in whereas the stem cells are embedded during or after the gelation procedure which does not allow for the generation of zonal hierarchies, cell density or material gradients. This thesis focuses on the synthesis of different hyaluronic acid derivatives and poly(ethylene glycol) crosslinkers and the development of different hydrogel and bioink compositions that allow for adjustment of the printability, integration of growth factors, but also for the material and biological hydrogel, respectively bioink properties.},
  language  = {en}
}
@article{BrandForsterBoecketal.2022,
  author    = {Brand, Jessica S. and Forster, Leonard and B{\"o}ck, Thomas and Stahlhut, Philipp and Teßmar, J{\"o}rg and Groll, J{\"u}rgen and Albrecht, Krystyna},
  title     = {Covalently Cross-Linked Pig Gastric Mucin Hydrogels Prepared by Radical-Based Chain-Growth and Thiol-ene Mechanisms},
  series = {Macromolecular Bioscience},
  volume    = {22},
  journal   = {Macromolecular Bioscience},
  number    = {4},
  doi       = {10.1002/mabi.202100274},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318453},
  year      = {2022},
  abstract  = {Mucin, a high molecular mass hydrophilic glycoprotein, is the main component of mucus that coats every wet epithelium in animals. It is thus intrinsically biocompatible, and with its protein backbone and the o-glycosidic bound oligosaccharides, it contains a plethora of functional groups which can be used for further chemical modifications. Here, chain-growth and step-growth (thiol-ene) free-radical cross-linked hydrogels prepared from commercially available pig gastric mucin (PGM) are introduced and compared as cost-efficient and easily accessible alternative to the more broadly applied bovine submaxillary gland mucin. For this, PGM is functionalized with photoreactive acrylate groups or allyl ether moieties, respectively. Whereas homopolymerization of acrylate-functionalized polymers is performed, for thiol-ene cross-linking, the allyl-ether-functionalized PGM is cross-linked with thiol-functionalized hyaluronic acid. Morphology, mechanical properties, and cell compatibility of both kinds of PGM hydrogels are characterized and compared. Furthermore, the biocompatibility of these hydrogels can be evaluated in cell culture experiments.},
  language  = {en}
}