@article{SzalayHillStritzkeretal.2011,
  author    = {Szalay, Aladar A. and Hill, Philip J. and Stritzker, Jochen and Scadeng, Miriam and Geissinger, Ulrike and Haddad, Daniel and Basse-L{\"u}sebrink, Thomas C. and Gbureck, Uwe and Jakob, Peter},
  title     = {Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing Escherichia coli},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75789},
  year      = {2011},
  abstract  = {Background: Recent studies have shown that human ferritin can be used as a reporter of gene expression for magnetic resonance imaging (MRI). Bacteria also encode three classes of ferritin-type molecules with iron accumulation properties. Methods and Findings: Here, we investigated whether these bacterial ferritins can also be used as MRI reporter genes and which of the bacterial ferritins is the most suitable reporter. Bacterial ferritins were overexpressed in probiotic E. coli Nissle 1917. Cultures of these bacteria were analyzed and those generating highest MRI contrast were further investigated in tumor bearing mice. Among members of three classes of bacterial ferritin tested, bacterioferritin showed the most promise as a reporter gene. Although all three proteins accumulated similar amounts of iron when overexpressed individually, bacterioferritin showed the highest contrast change. By site-directed mutagenesis we also show that the heme iron, a unique part of the bacterioferritin molecule, is not critical for MRI contrast change. Tumor-specific induction of bacterioferritin-expression in colonized tumors resulted in contrast changes within the bacteria-colonized tumors. Conclusions: Our data suggest that colonization and gene expression by live vectors expressing bacterioferritin can be monitored by MRI due to contrast changes},
  subject      = {Escherichia coli},
  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{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{SeifertGrollWeichholdetal.2021,
  author    = {Seifert, Annika and Groll, J{\"u}rgen and Weichhold, Jan and Boehm, Anne V. and M{\"u}ller, Frank A. and Gbureck, Uwe},
  title     = {Phase Conversion of Ice-Templated α-Tricalcium Phosphate Scaffolds into Low-Temperature Calcium Phosphates with Anisotropic Open Porosity},
  series = {Advanced Engineering Materials},
  volume    = {23},
  journal   = {Advanced Engineering Materials},
  number    = {5},
  doi       = {10.1002/adem.202001417},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256311},
  year      = {2021},
  abstract  = {The current study aims to extend the material platform for anisotropically structured calcium phosphates to low-temperature phases such as calcium-deficient hydroxyapatite (CDHA) or the secondary phosphates monetite and brushite. This is achieved by the phase conversion of highly porous α-tricalcium phosphate (α-TCP) scaffolds fabricated by ice-templating into the aforementioned phases by hydrothermal treatment or incubation in phosphoric acid. Prior to these steps, α-TCP scaffolds are either sintered for 8 h at 1400 °C or remain in their original state. Both nonsintered and sintered α-TCP specimens are converted into CDHA by hydrothermal treatment, while a transformation into monetite and brushite is achieved by incubation in phosphoric acid. Hydrothermal treatment for 72 h at 175 °C increases the porosity in nonsintered samples from 85\% to 88\% and from 75\% to 88\% in the sintered ones. An increase in the specific surface area from (1.102 ± 0.005) to (9.17 ± 0.01) m2 g-1 and from (0.190 ± 0.004) to (2.809 ± 0.002) m2 g-1 due to the phase conversion is visible for both the nonsintered and sintered samples. Compressive strength of the nonsintered samples increases significantly from (0.76 ± 0.11) to (5.29 ± 0.94) MPa due to incubation in phosphoric acid.},
  language  = {en}
}
@article{SchmitzJannaschWeigeletal.2020,
  author    = {Schmitz, Tobias and Jannasch, Maren and Weigel, Tobias and Moseke, Claus and Gbureck, Uwe and Groll, J{\"u}rgen and Walles, Heike and Hansmann, Jan},
  title     = {Nanotopographical Coatings Induce an Early Phenotype-Specific Response of Primary Material-Resident M1 and M2 Macrophages},
  series = {Materials},
  volume    = {13},
  journal   = {Materials},
  number    = {5},
  issn      = {1996-1944},
  doi       = {10.3390/ma13051142},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203378},
  year      = {2020},
  abstract  = {Implants elicit an immunological response after implantation that results in the worst case in a complete implant rejection. This biomaterial-induced inflammation is modulated by macrophages and can be influenced by nanotopographical surface structures such as titania nanotubes or fractal titanium nitride (TiN) surfaces. However, their specific impact on a distinct macrophage phenotype has not been identified. By using two different levels of nanostructures and smooth samples as controls, the influence of tubular TiO2 and fractal TiN nanostructures on primary human macrophages with M1 or M2-phenotype was investigated. Therefore, nanotopographical coatings were either, directly generated by physical vapor deposition (PVD) or by electrochemical anodization of titanium PVD coatings. The cellular response of macrophages was quantitatively assessed to demonstrate a difference in biocompatibility of nanotubes in respect to human M1 and M2-macrophages. Depending on the tube diameter of the nanotubular surfaces, low cell numbers and impaired cellular activity, was detected for M2-macrophages, whereas the impact of nanotubes on M1-polarized macrophages was negligible. Importantly, we could confirm this phenotypic response on the fractal TiN surfaces. The results indicate that the investigated topographies specifically impact the macrophage M2-subtype that modulates the formation of the fibrotic capsule and the long-term response to an implant.},
  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{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{RennerOttoKuebleretal.2023,
  author    = {Renner, Tobias and Otto, Paul and K{\"u}bler, Alexander C. and H{\"o}lscher-Doht, Stefanie and Gbureck, Uwe},
  title     = {Novel adhesive mineral-organic bone cements based on phosphoserine and magnesium phosphates or oxides},
  series = {Journal of Materials Science: Materials in Medicine},
  volume    = {34},
  journal   = {Journal of Materials Science: Materials in Medicine},
  doi       = {10.1007/s10856-023-06714-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357342},
  year      = {2023},
  abstract  = {Present surgical situations require a bone adhesive which has not yet been developed for use in clinical applications. Recently, phosphoserine modified cements (PMC) based on mixtures of o-phosphoserine (OPLS) and calcium phosphates, such as tetracalcium phosphate (TTCP) or α-tricalcium phosphate (α-TCP) as well as chelate setting magnesium phosphate cements have gained increasing popularity for their use as mineral bone adhesives. Here, we investigated new mineral-organic bone cements based on phosphoserine and magnesium phosphates or oxides, which possess excellent adhesive properties. These were analyzed by X-ray diffraction, Fourier infrared spectroscopy and electron microscopy and subjected to mechanical tests to determine the bond strength to bone after ageing at physiological conditions. The novel biomineral adhesives demonstrate excellent bond strength to bone with approximately 6.6-7.3 MPa under shear load. The adhesives are also promising due to their cohesive failure pattern and ductile character. In this context, the new adhesive cements are superior to currently prevailing bone adhesives. Future efforts on bone adhesives made from phosphoserine and Mg2+ appear to be very worthwhile.},
  language  = {en}
}
@article{RathBrandlHilleretal.2014,
  author    = {Rath, Subha N. and Brandl, Andreas and Hiller, Daniel and Hoppe, Alexander and Gbureck, Uwe and Horch, Raymund E. and Boccaccini, Aldo R. and Kneser, Ulrich},
  title     = {Bioactive Copper-Doped Glass Scaffolds Can Stimulate Endothelial Cells in Co-Culture in Combination with Mesenchymal Stem Cells},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {12},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0113319},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114339},
  year      = {2014},
  abstract  = {Bioactive glass (BG) scaffolds are being investigated for bone tissue engineering applications because of their osteoconductive and angiogenic nature. However, to increase the in vivo performance of the scaffold, including enhancing the angiogenetic growth into the scaffolds, some researchers use different modifications of the scaffold including addition of inorganic ionic components to the basic BG composition. In this study, we investigated the in vitro biocompatibility and bioactivity of Cu2+-doped BG derived scaffolds in either BMSC (bone-marrow derived mesenchymal stem cells)-only culture or co-culture of BMSC and human dermal microvascular endothelial cells (HDMEC). In BMSC-only culture, cells were seeded either directly on the scaffolds (3D or direct culture) or were exposed to ionic dissolution products of the BG scaffolds, kept in permeable cell culture inserts (2D or indirect culture). Though we did not observe any direct osteoinduction of BMSCs by alkaline phosphatase (ALP) assay or by PCR, there was increased vascular endothelial growth factor (VEGF) expression, observed by PCR and ELISA assays. Additionally, the scaffolds showed no toxicity to BMSCs and there were healthy live cells found throughout the scaffold. To analyze further the reasons behind the increased VEGF expression and to exploit the benefits of the finding, we used the indirect method with HDMECs in culture plastic and Cu2+-doped BG scaffolds with or without BMSCs in cell culture inserts. There was clear observation of increased endothelial markers by both FACS analysis and acetylated LDL (acLDL) uptake assay. Only in presence of Cu2+-doped BG scaffolds with BMSCs, a high VEGF secretion was demonstrated by ELISA; and typical tubular structures were observed in culture plastics. We conclude that Cu2+-doped BG scaffolds release Cu2+, which in turn act on BMSCs to secrete VEGF. This result is of significance for the application of BG scaffolds in bone tissue engineering approaches.},
  language  = {en}
}
@article{OuhaddiCharbonnierPorgeetal.2023,
  author    = {Ouhaddi, Yassine and Charbonnier, Baptiste and Porge, Juliette and Zhang, Yu-Ling and Garcia, Isadora and Gbureck, Uwe and Grover, Liam and Gilardino, Mirko and Harvey, Edward and Makhoul, Nicholas and Barralet, Jake},
  title     = {Development of neovasculature in axially vascularized calcium phosphate cement scaffolds},
  series = {Journal of Functional Biomaterials},
  volume    = {14},
  journal   = {Journal of Functional Biomaterials},
  number    = {2},
  issn      = {2079-4983},
  doi       = {10.3390/jfb14020105},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304026},
  year      = {2023},
  abstract  = {Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical proof of concept for biomaterial-induced luminal sprouting of large-diameter vessels. In this study, we investigated if sprouting was a general response to surgical injury or placement of an inorganic construct around the vessel. Cylindrical biocement scaffolds of differing chemistries were placed around the femoral vein. A contrast agent was used to visualize vessel ingrowth into the scaffolds. Cell populations in the scaffold were mapped using immunohistochemistry. Calcium phosphate scaffolds induced 2.7-3 times greater volume of blood vessels than calcium sulphate or magnesium phosphate scaffolds. Macrophage and vSMC populations were identified that changed spatially and temporally within the scaffold during implantation. NLRP3 inflammasome activation peaked at weeks 2 and 4 and then declined; however, IL-1β expression was sustained over the course of the experiment. IL-8, a promoter of angiogenesis, was also detected, and together, these responses suggest a role of sterile inflammation. Unexpectedly, the effect was distinct from an injury response as a result of surgical placement and also was not simply a foreign body reaction as a result of placing a rigid bioceramic next to a vein, since, while the materials tested had similar microstructures, only the calcium phosphates tested elicited an angiogenic response. This finding then reveals a potential path towards a new strategy for creating better pro-regenerative biomaterials.},
  language  = {en}
}