@article{GeffersGrollGbureck2015,
  author    = {Geffers, Martha and Groll, J{\"u}rgen and Gbureck, Uwe},
  title     = {Reinforcement strategies for load-bearing calcium phosphate biocements},
  series = {Materials},
  volume    = {8},
  journal   = {Materials},
  doi       = {10.3390/ma8052700},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148636},
  pages     = {2700-2717},
  year      = {2015},
  abstract  = {Calcium phosphate biocements based on calcium phosphate chemistry are well-established biomaterials for the repair of non-load bearing bone defects due to the brittle nature and low flexural strength of such cements. This article features reinforcement strategies of biocements based on various intrinsic or extrinsic material modifications to improve their strength and toughness. Altering particle size distribution in conjunction with using liquefiers reduces the amount of cement liquid necessary for cement paste preparation. This in turn decreases cement porosity and increases the mechanical performance, but does not change the brittle nature of the cements. The use of fibers may lead to a reinforcement of the matrix with a toughness increase of up to two orders of magnitude, but restricts at the same time cement injection for minimal invasive application techniques. A novel promising approach is the concept of dual-setting cements, in which a second hydrogel phase is simultaneously formed during setting, leading to more ductile cement-hydrogel composites with largely unaffected application properties.},
  language  = {en}
}
@article{JakobEbertRudertetal.2012,
  author    = {Jakob, Franz and Ebert, Regina and Rudert, Maximilian and N{\"o}th, Ulrich and Walles, Heike and Docheva, Denitsa and Schieker, Matthias and Meinel, Lorenz and Groll, J{\"u}rgen},
  title     = {In situ guided tissue regeneration in musculoskeletal diseases and aging},
  series = {Cell and Tissue Research},
  volume    = {347},
  journal   = {Cell and Tissue Research},
  number    = {3},
  doi       = {10.1007/s00441-011-1237-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124738},
  pages     = {725-735},
  year      = {2012},
  abstract  = {In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide "minimal invasive" applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future.},
  language  = {en}
}
@article{HuettenDhanasinghHessleretal.2014,
  author    = {H{\"u}tten, Mareike and Dhanasingh, Anandhan and Hessler, Roland and St{\"o}ver, Timo and Esser, Karl-Heinz and M{\"o}ller, Martin and Lenarz, Thomas and Jolly, Claude and Groll, J{\"u}rgen and Scheper, Verena},
  title     = {In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0104564},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119375},
  pages     = {e104564},
  year      = {2014},
  abstract  = {Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.},
  language  = {en}
}
@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{ProjahnSimsekyilmazSinghetal.2014,
  author    = {Projahn, Delia and Simsekyilmaz, Sakine and Singh, Smriti and Kanzler, Isabella and Kramp, Birgit K. and Langer, Marcella and Burlacu, Alexandrina and Bernhagen, J{\"u}rgen and Klee, Doris and Zernecke, Alma and Hackeng, Tilman M. and Groll, J{\"u}rgen and Weber, Christian and Liehn, Elisa A. and Koenen, Roy R.},
  title     = {Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction},
  series = {Journal of Cellular and Molecular Medicine},
  volume    = {18},
  journal   = {Journal of Cellular and Molecular Medicine},
  number    = {5},
  issn      = {1582-4934},
  doi       = {10.1111/jcmm.12225},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116597},
  pages     = {790-800},
  year      = {2014},
  abstract  = {Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.},
  language  = {en}
}
@article{KastenNaserBruellhoffetal.2014,
  author    = {Kasten, Annika and Naser, Tamara and Br{\"u}llhoff, Kristina and Fiedler, J{\"o}rg and M{\"u}ller, Petra and M{\"o}ller, Martin and Rychly, Joachim and Groll, J{\"u}rgen and Brenner, Rolf E.},
  title     = {Guidance of Mesenchymal Stem Cells on Fibronectin Structured Hydrogel Films},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0109411},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114897},
  pages     = {e109411},
  year      = {2014},
  abstract  = {Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 mu m and 80 mu m and spacings between 5 mu m and 20 mu m that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.},
  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{TylekBlumHrynevichetal.2020,
  author    = {Tylek, Tina and Blum, Carina and Hrynevich, Andrei and Schlegelmilch, Katrin and Schilling, Tatjana and Dalton, Paul D and Groll, J{\"u}rgen},
  title     = {Precisely defined fiber scaffolds with 40 μm porosity induce elongation driven M2-like polarization of human macrophages},
  series = {Biofabrication},
  volume    = {12},
  journal   = {Biofabrication},
  number    = {2},
  doi       = {10.1088/1758-5090/ab5f4e},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254012},
  year      = {2020},
  abstract  = {Macrophages are key players of the innate immune system that can roughly be divided into the pro-inflammatory M1 type and the anti-inflammatory, pro-healing M2 type. While a transient initial pro-inflammatory state is helpful, a prolonged inflammation deteriorates a proper healing and subsequent regeneration. One promising strategy to drive macrophage polarization by biomaterials is precise control over biomaterial geometry. For regenerative approaches, it is of particular interest to identify geometrical parameters that direct human macrophage polarization. For this purpose, we advanced melt electrowriting (MEW) towards the fabrication of fibrous scaffolds with box-shaped pores and precise inter-fiber spacing from 100 μm down to only 40 μm. These scaffolds facilitate primary human macrophage elongation accompanied by differentiation towards the M2 type, which was most pronounced for the smallest pore size of 40 μm. These new findings can be important in helping to design new biomaterials with an enhanced positive impact on tissue regeneration.},
  language  = {en}
}
@article{SunStarlyDalyetal.2020,
  author    = {Sun, Wei and Starly, Binil and Daly, Andrew C and Burdick, Jason A and Groll, J{\"u}rgen and Skeldon, Gregor and Shu, Wenmiao and Sakai, Yasuyuki and Shinohara, Marie and Nishikawa, Masaki and Jang, Jinah and Cho, Dong-Woo and Nie, Minghao and Takeuchi, Shoji and Ostrovidov, Serge and Khademhosseini, Ali and Kamm, Roger D and Mironov, Vladimir and Moroni, Lorenzo and Ozbolat, Ibrahim T},
  title     = {The bioprinting roadmap},
  series = {Biofabrication},
  volume    = {12},
  journal   = {Biofabrication},
  number    = {2},
  doi       = {10.1088/1758-5090/ab5158},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254027},
  year      = {2020},
  abstract  = {This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field.},
  language  = {en}
}
@article{HochleitnerJuengstBrownetal.2015,
  author    = {Hochleitner, Gernot and J{\"u}ngst, Tomasz and Brown, Toby D and Hahn, Kathrin and Moseke, Claus and Jakob, Franz and Dalton, Paul D and Groll, J{\"u}rgen},
  title     = {Additive manufacturing of scaffolds with sub-micron filaments via melt electrospinning writing},
  series = {Biofabrication},
  volume    = {7},
  journal   = {Biofabrication},
  number    = {3},
  doi       = {10.1088/1758-5090/7/3/035002},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254053},
  year      = {2015},
  abstract  = {The aim of this study was to explore the lower resolution limits of an electrohydrodynamic process combined with direct writing technology of polymer melts. Termed melt electrospinning writing, filaments are deposited layer-by-layer to produce discrete three-dimensional scaffolds for in vitro research. Through optimization of the parameters (flow rate, spinneret diameter, voltage, collector distance) for poly-ϵ-caprolactone, we could direct-write coherent scaffolds with ultrafine filaments, the smallest being 817 ± 165 nm. These low diameter filaments were deposited to form box-structures with a periodicity of 100.6 ± 5.1 μm and a height of 80 μm (50 stacked filaments; 100 overlap at intersections). We also observed oriented crystalline regions within such ultrafine filaments after annealing at 55 °C. The scaffolds were printed upon NCO-sP(EO-stat-PO)-coated glass slide surfaces and withstood frequent liquid exchanges with negligible scaffold detachment for at least 10 days in vitro.},
  language  = {en}
}
@article{PaxtonSmolanBoecketal.2017,
  author    = {Paxton, Naomi and Smolan, Willi and B{\"o}ck, Thomas and Melchels, Ferry and Groll, J{\"u}rgen and Jungst, Tomasz},
  title     = {Proposal to assess printability of bioinks for extrusion-based bioprinting and evaluation of rheological properties governing bioprintability},
  series = {Biofabrication},
  volume    = {9},
  journal   = {Biofabrication},
  number    = {4},
  doi       = {10.1088/1758-5090/aa8dd8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254061},
  year      = {2017},
  abstract  = {The development and formulation of printable inks for extrusion-based 3D bioprinting has been a major challenge in the field of biofabrication. Inks, often polymer solutions with the addition of crosslinking to form hydrogels, must not only display adequate mechanical properties for the chosen application but also show high biocompatibility as well as printability. Here we describe a reproducible two-step method for the assessment of the printability of inks for bioprinting, focussing firstly on screening ink formulations to assess fibre formation and the ability to form 3D constructs before presenting a method for the rheological evaluation of inks to characterise the yield point, shear thinning and recovery behaviour. In conjunction, a mathematical model was formulated to provide a theoretical understanding of the pressure-driven, shear thinning extrusion of inks through needles in a bioprinter. The assessment methods were trialled with a commercially available cr{\`e}me, poloxamer 407, alginate-based inks and an alginate-gelatine composite material. Yield stress was investigated by applying a stress ramp to a number of inks, which demonstrated the necessity of high yield for printable materials. The shear thinning behaviour of the inks was then characterised by quantifying the degree of shear thinning and using the mathematical model to predict the window of printer operating parameters in which the materials could be printed. Furthermore, the model predicted high shear conditions and high residence times for cells at the walls of the needle and effects on cytocompatibility at different printing conditions. Finally, the ability of the materials to recover to their original viscosity after extrusion was examined using rotational recovery rheological measurements. Taken together, these assessment techniques revealed significant insights into the requirements for printable inks and shear conditions present during the extrusion process and allow the rapid and reproducible characterisation of a wide variety of inks for bioprinting.},
  language  = {en}
}
@article{RoedelTessmarGrolletal.2019,
  author    = {R{\"o}del, Michaela and Teßmar, J{\"o}rg and Groll, J{\"u}rgen and Gbureck, Uwe},
  title     = {Tough and Elastic alpha-Tricalcium Phosphate Cement Composites with Degradable PEG-Based Cross-Linker},
  series = {Materials},
  volume    = {12},
  journal   = {Materials},
  number    = {53},
  doi       = {10.3390/ma12010053},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226437},
  pages     = {1-20},
  year      = {2019},
  abstract  = {Dual setting cements composed of an in situ forming hydrogel and a reactive mineral phase combine high compressive strength of the cement with sufficient ductility and bending strength of the polymeric network. Previous studies were focused on the modification with non-degradable hydrogels based on 2-hydroxyethyl methacrylate (HEMA). Here, we describe the synthesis of suitable triblock degradable poly(ethylene glycol)-poly(lactide) (PEG-PLLA) cross-linker to improve the resorption capacity of such composites. A study with four different formulations was established. As reference, pure hydroxyapatite (HA) cements and composites with 40 wt\% HEMA in the liquid cement phase were produced. Furthermore, HEMA was modified with 10 wt\% of PEG-PLLA cross-linker or a test series containing only 25\% cross-linker was chosen for composites with a fully degradable polymeric phase. Hence, we developed suitable systems with increased elasticity and 5-6 times higher toughn ess values in comparison to pure inorganic cement matrix. Furthermore, conversion rate from alpha-tricalcium phosphate (alpha-TCP) to HA was still about 90\% for all composite formulations, whereas crystal size decreased. Based on this material development and advancement for a dual setting system, we managed to overcome the drawback of brittleness for pure calcium phosphate cements.},
  language  = {en}
}
@article{HorvatVogelKampfetal.2020,
  author    = {Horvat, Sonja and Vogel, Patrick and Kampf, Thomas and Brandl, Andreas and Alshamsan, Aws and Alhadlaq, Hisham A. and Ahamed, Maqusood and Albrecht, Krystyna and Behr, Volker C. and Beilhack, Andreas and Groll, J{\"u}rgen},
  title     = {Crosslinked Coating Improves the Signal-to-Noise Ratio of Iron Oxide Nanoparticles in Magnetic Particle Imaging (MPI)},
  series = {ChemNanoMat},
  volume    = {6},
  journal   = {ChemNanoMat},
  number    = {5},
  doi       = {10.1002/cnma.202000009},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214718},
  pages     = {755 -- 758},
  year      = {2020},
  abstract  = {Magnetic particle imaging is an emerging tomographic method used for evaluation of the spatial distribution of iron-oxide nanoparticles. In this work, the effect of the polymer coating on the response of particles was studied. Particles with covalently crosslinked coating showed improved signal and image resolution.},
  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}
}
@article{HorderGuazaLasherasGrummeletal.2021,
  author    = {Horder, Hannes and Guaza Lasheras, Mar and Grummel, Nadine and Nadernezhad, Ali and Herbig, Johannes and Erg{\"u}n, S{\"u}leyman and Teßmar, J{\"o}rg and Groll, J{\"u}rgen and Fabry, Ben and Bauer-Kreisel, Petra and Blunk, Torsten},
  title     = {Bioprinting and differentiation of adipose-derived stromal cell spheroids for a 3D breast cancer-adipose tissue model},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {4},
  doi       = {10.3390/cells10040803},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236496},
  year      = {2021},
  abstract  = {Biofabrication, including printing technologies, has emerged as a powerful approach to the design of disease models, such as in cancer research. In breast cancer, adipose tissue has been acknowledged as an important part of the tumor microenvironment favoring tumor progression. Therefore, in this study, a 3D-printed breast cancer model for facilitating investigations into cancer cell-adipocyte interaction was developed. First, we focused on the printability of human adipose-derived stromal cell (ASC) spheroids in an extrusion-based bioprinting setup and the adipogenic differentiation within printed spheroids into adipose microtissues. The printing process was optimized in terms of spheroid viability and homogeneous spheroid distribution in a hyaluronic acid-based bioink. Adipogenic differentiation after printing was demonstrated by lipid accumulation, expression of adipogenic marker genes, and an adipogenic ECM profile. Subsequently, a breast cancer cell (MDA-MB-231) compartment was printed onto the adipose tissue constructs. After nine days of co-culture, we observed a cancer cell-induced reduction of the lipid content and a remodeling of the ECM within the adipose tissues, with increased fibronectin, collagen I and collagen VI expression. Together, our data demonstrate that 3D-printed breast cancer-adipose tissue models can recapitulate important aspects of the complex cell-cell and cell-matrix interplay within the tumor-stroma microenvironment},
  language  = {en}
}
@article{RoedelBaumannGrolletal.2018,
  author    = {R{\"o}del, Michaela and Baumann, Katrin and Groll, J{\"u}rgen and Gbureck, Uwe},
  title     = {Simultaneous structuring and mineralization of silk fibroin scaffolds},
  series = {Journal of Tissue Engineering},
  volume    = {9},
  journal   = {Journal of Tissue Engineering},
  doi       = {10.1177/2041731418788509},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226427},
  pages     = {1-16},
  year      = {2018},
  abstract  = {Silk fibroin is commonly used as scaffold material for tissue engineering applications. In combination with a mineralization with different calcium phosphate phases, it can also be applied as material for bone regeneration. Here, we present a study which was performed to produce mineralized silk fibroin scaffolds with controlled macroporosity. In contrast to former studies, our approach focused on a simultaneous gelation and mineralization of silk fibroin by immersion of frozen silk fibroin monoliths in acidic calcium phosphate solutions. This was achieved by thawing frozen silk fibroin monoliths in acidic calcium phosphate solution, leading to the precipitation of monocalcium phosphate within the silk fibroin matrix. In the second approach, a conversion of incorporated -tricalcium phosphate particles into brushite was successfully achieved. Furthermore, a controlled cryostructuring process of silk fibroin scaffolds was carried out leading to the formation of parallel-oriented pores with diameters of 30-50 mu m.},
  language  = {en}
}
@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}
}
@article{SeifertGruberGburecketal.2021,
  author    = {Seifert, Annika and Gruber, Julia and Gbureck, Uwe and Groll, J{\"u}rgen},
  title     = {Morphological control of freeze-structured scaffolds by selective temperature and material control in the ice-templating process},
  series = {Advanced Engineering Materials},
  volume    = {24},
  journal   = {Advanced Engineering Materials},
  number    = {3},
  doi       = {10.1002/adem.202100860},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256330},
  year      = {2021},
  abstract  = {Herein, it is aimed to highlight the importance of the process parameter choice during directional solidification of polymer solutions, as they have a significant influence on the pore structure and orientation. Biopolymer solutions (alginate and chitosan) are directionally frozen, while systematically varying parameters such as the external temperature gradient, the temperature of the overall system, and the temperatures of the cooling surfaces. In addition, the effect of material properties such as molecular weight, solution concentration, or viscosity on the sample morphology is investigated. By selecting appropriate temperature gradients and cooling surface temperatures, aligned pores ranging in size between (50 ± 22) μm and (144 ± 56) μm are observed in the alginate samples, whereas the pore orientation is influenced by altering the external temperature gradient. As this gradient increases, the pores are increasingly oriented perpendicular to the sample surface. This is also observed in the chitosan samples. However, if the overall system is too cold, that is, using temperatures of the lower cooling surface down to -60 °C combined with low temperatures of the upper cooling surface, control over pore orientation is lost. This is also found when viscosity of chitosan solutions is above ≈5 Pas near the freezing point.},
  language  = {en}
}
@article{StuckensenLamoEspinosaMuinosLopezetal.2019,
  author    = {Stuckensen, Kai and Lamo-Espinosa, Jos{\´e} M. and Mui{\~n}os-L{\´o}pez, Emma and Ripalda-Cembor{\´a}in, Purificaci{\´o}n and L{\´o}pez-Mart{\´i}nez, Tania and Iglesias, Elena and Abizanda, Gloria and Andreu, Ion and Flandes-Iparraguirre, Mar{\´i}a and Pons-Villanueva, Juan and Elizalde, Reyes and Nickel, Joachim and Ewald, Andrea and Gbureck, Uwe and Pr{\´o}sper, Felipe and Groll, J{\"u}rgen and Granero-Molt{\´o}, Froil{\´a}n},
  title     = {Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP-2 and enhanced bone regeneration},
  series = {Materials},
  volume    = {12},
  journal   = {Materials},
  number    = {19},
  issn      = {1996-1944},
  doi       = {10.3390/ma12193105},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195966},
  year      = {2019},
  abstract  = {In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP-2, BMP-7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP-2. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP-2 mediated bone healing.},
  language  = {en}
}
@article{DoganScheuringWagneretal.2021,
  author    = {Dogan, Leyla and Scheuring, Ruben and Wagner, Nicole and Ueda, Yuichiro and Schmidt, Sven and W{\"o}rsd{\"o}rfer, Philipp and Groll, J{\"u}rgen and Erg{\"u}n, S{\"u}leyman},
  title     = {Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels},
  series = {Biofabrication},
  volume    = {13},
  journal   = {Biofabrication},
  number    = {4},
  doi       = {10.1088/1758-5090/ac26ac},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254046},
  year      = {2021},
  abstract  = {Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type I bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimics the embryonic steps of vessel formation during vasculogenesis. Histological evaluations at different time points of extrusion revealed the initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, endothelial cells in capillary-like vessel structures deposited a basement membrane-like matrix at the basal side between the vessel wall and the alginate-collagen matrix. After transplantation of the printed constructs into the chicken chorioallantoic membrane (CAM) the printed vessels connected to the CAM blood vessels and get perfused in vivo. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.},
  language  = {en}
}