TY - JOUR A1 - Hill, Philip J. A1 - Stritzker, Jochen A1 - Scadeng, Miriam A1 - Geissinger, Ulrike A1 - Haddad, Daniel A1 - Basse-Lüsebrink, Thomas C. A1 - Gbureck, Uwe A1 - Jakob, Peter A1 - Szalay, Aladar A. T1 - Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing \(Escherichia\) \(coli\) JF - PLoS ONE N2 - 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. KW - Blood-brain barrier KW - Gene-expression KW - Salmonella-typhimurium KW - Sugar-transport KW - Breast-tumors KW - MRI reporter KW - Iron-uptake KW - Proteins KW - Therapy KW - Mice Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140920 VL - 6 IS - 10 ER - TY - JOUR A1 - Geffers, Martha A1 - Groll, Jürgen A1 - Gbureck, Uwe T1 - Reinforcement strategies for load-bearing calcium phosphate biocements JF - Materials N2 - 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. KW - in vitro KW - synergistic reinforcement KW - dihydrate cement KW - porosity KW - mechanical properties KW - dual setting KW - calcium phosphate cements KW - fiber reinforcement KW - polyacrylic acid KW - compressive strength KW - balloon kyphoplasty KW - brushite cement KW - bone cement Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148636 VL - 8 ER - TY - JOUR A1 - Szalay, Aladar A. A1 - Hill, Philip J. A1 - Stritzker, Jochen A1 - Scadeng, Miriam A1 - Geissinger, Ulrike A1 - Haddad, Daniel A1 - Basse-Lüsebrink, Thomas C. A1 - Gbureck, Uwe A1 - Jakob, Peter T1 - Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing Escherichia coli N2 - 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 KW - Escherichia coli Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75789 ER - TY - JOUR A1 - Rath, Subha N. A1 - Brandl, Andreas A1 - Hiller, Daniel A1 - Hoppe, Alexander A1 - Gbureck, Uwe A1 - Horch, Raymund E. A1 - Boccaccini, Aldo R. A1 - Kneser, Ulrich T1 - Bioactive Copper-Doped Glass Scaffolds Can Stimulate Endothelial Cells in Co-Culture in Combination with Mesenchymal Stem Cells JF - PLOS ONE N2 - 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. KW - arteriovenous loop KW - calcium-phosphate KW - iron release KW - bone KW - angiogenesis KW - expression KW - differentation KW - proliferation KW - osteoblasts KW - growth Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114339 SN - 1932-6203 VL - 9 IS - 12 ER - TY - JOUR A1 - Rödel, Michaela A1 - Teßmar, Jörg A1 - Groll, Jürgen A1 - Gbureck, Uwe T1 - Tough and Elastic alpha-Tricalcium Phosphate Cement Composites with Degradable PEG-Based Cross-Linker JF - Materials N2 - 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. KW - dual setting system KW - bending strength KW - calcium phosphate cement KW - composite material KW - HEMA KW - hydroxyapatite KW - free radical polymerization Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226437 VL - 12 IS - 53 ER - TY - JOUR A1 - Rödel, Michaela A1 - Baumann, Katrin A1 - Groll, Jürgen A1 - Gbureck, Uwe T1 - Simultaneous structuring and mineralization of silk fibroin scaffolds JF - Journal of Tissue Engineering N2 - 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. KW - Brushite KW - calcium phosphate KW - cryostructuring KW - hydrogel KW - mineralization KW - silk fibroin scaffolds Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226427 VL - 9 ER - TY - JOUR A1 - Seifert, Annika A1 - Gruber, Julia A1 - Gbureck, Uwe A1 - Groll, Jürgen T1 - Morphological control of freeze‐structured scaffolds by selective temperature and material control in the ice‐templating process JF - Advanced Engineering Materials N2 - 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. KW - unidirectional freezing KW - anisotropic porous structures KW - morphology controls KW - systematic investigations Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256330 VL - 24 IS - 3 ER - TY - JOUR A1 - Stuckensen, Kai A1 - Lamo-Espinosa, José M. A1 - Muiños-López, Emma A1 - Ripalda-Cemboráin, Purificación A1 - López-Martínez, Tania A1 - Iglesias, Elena A1 - Abizanda, Gloria A1 - Andreu, Ion A1 - Flandes-Iparraguirre, María A1 - Pons-Villanueva, Juan A1 - Elizalde, Reyes A1 - Nickel, Joachim A1 - Ewald, Andrea A1 - Gbureck, Uwe A1 - Prósper, Felipe A1 - Groll, Jürgen A1 - Granero-Moltó, Froilán T1 - Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP−2 and enhanced bone regeneration JF - Materials N2 - 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. KW - rhBMP–2 KW - collagen sponge KW - cryostructured scaffolds KW - bone critical size defect Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195966 SN - 1996-1944 VL - 12 IS - 19 ER - TY - JOUR A1 - Heilig, Philipp A1 - Sandner, Phoebe A1 - Jordan, Martin Cornelius A1 - Jakubietz, Rafael Gregor A1 - Meffert, Rainer Heribert A1 - Gbureck, Uwe A1 - Hoelscher-Doht, Stefanie T1 - Experimental drillable magnesium phosphate cement is a promising alternative to conventional bone cements JF - Materials N2 - Clinically used mineral bone cements lack high strength values, absorbability and drillability. Therefore, magnesium phosphate cements have recently received increasing attention as they unify a high mechanical performance with presumed degradation in vivo. To obtain a drillable cement formulation, farringtonite (Mg\(_3\)(PO\(_4\))\(_2\)) and magnesium oxide (MgO) were modified with the setting retardant phytic acid (C\(_6\)H\(_{18}\)O\(_{24}\)P\(_6\)). In a pre-testing series, 13 different compositions of magnesium phosphate cements were analyzed concentrating on the clinical demands for application. Of these 13 composites, two cement formulations with different phytic acid content (22.5 wt% and 25 wt%) were identified to meet clinical demands. Both formulations were evaluated in terms of setting time, injectability, compressive strength, screw pullout tests and biomechanical tests in a clinically relevant fracture model. The cements were used as bone filler of a metaphyseal bone defect alone, and in combination with screws drilled through the cement. Both formulations achieved a setting time of 5 min 30 s and an injectability of 100%. Compressive strength was shown to be ~12–13 MPa and the overall displacement of the reduced fracture was <2 mm with and without screws. Maximum load until reduced fracture failure was ~2600 N for the cements only and ~3800 N for the combination with screws. Two new compositions of magnesium phosphate cements revealed high strength in clinically relevant biomechanical test set-ups and add clinically desired characteristics to its strength such as injectability and drillability. KW - magnesium phosphate cement KW - phytic acid KW - inositol hexaphosphate KW - drillable bone cement KW - tibial head depression fracture KW - synbones KW - artificial bones KW - biomechanical evaluation KW - cyclic testing KW - load to failure testing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236633 SN - 1996-1944 VL - 14 IS - 8 ER - TY - JOUR A1 - Fuchs, Konrad F. A1 - Heilig, Philipp A1 - McDonogh, Miriam A1 - Boelch, Sebastian A1 - Gbureck, Uwe A1 - Meffert, Rainer H. A1 - Hoelscher-Doht, Stefanie A1 - Jordan, Martin C. T1 - Cement-augmented screw fixation for calcaneal fracture treatment: a biomechanical study comparing two injectable bone substitutes JF - Journal of Orthopaedic Surgery and Research N2 - Background The role of cement-augmented screw fixation for calcaneal fracture treatment remains unclear. Therefore, this study was performed to biomechanically analyze screw osteosynthesis by reinforcement with either a calcium phosphate (CP)-based or polymethylmethacrylate (PMMA)-based injectable bone cement. Methods A calcaneal fracture (Sanders type IIA) including a central cancellous bone defect was generated in 27 synthetic bones, and the specimens were assigned to 3 groups. The first group was fixed with four screws (3.5 mm and 6.5 mm), the second group with screws and CP-based cement (Graftys (R) QuickSet; Graftys, Aix-en-Provence, France), and the third group with screws and PMMA-based cement (Traumacem (TM) V+; DePuy Synthes, Warsaw, IN, USA). Biomechanical testing was conducted to analyze peak-to-peak displacement, total displacement, and stiffness in following a standardized protocol. Results The peak-to-peak displacement under a 200-N load was not significantly different among the groups; however, peak-to-peak displacement under a 600- and 1000-N load as well as total displacement exhibited better stability in PMMA-augmented screw osteosynthesis compared to screw fixation without augmentation. The stiffness of the construct was increased by both CP- and PMMA-based cements. Conclusion Addition of an injectable bone cement to screw osteosynthesis is able to increase fixation strength in a biomechanical calcaneal fracture model with synthetic bones. In such cases, PMMA-based cements are more effective than CP-based cements because of their inherently higher compressive strength. However, whether this high strength is required in the clinical setting for early weight-bearing remains controversial, and the non-degradable properties of PMMA might cause difficulties during subsequent interventions in younger patients. KW - arthritis KW - bone KW - calcaneus KW - cement KW - fracture KW - fixation KW - osteoporosis KW - sanders KW - screw Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230336 VL - 15 ER - TY - JOUR A1 - Diloksumpan, Paweena A1 - de Ruijter, Mylène A1 - Castilho, Miguel A1 - Gbureck, Uwe A1 - Vermonden, Tina A1 - van Weeren, P René A1 - Malda, Jos A1 - Levato, Riccardo T1 - Combining multi-scale 3D printing technologies to engineer reinforced hydrogel-ceramic interfaces JF - Biofabrication N2 - Multi-material 3D printing technologies that resolve features at different lengths down to the microscale open new avenues for regenerative medicine, particularly in the engineering of tissue interfaces. Herein, extrusion printing of a bone-biomimetic ceramic ink and melt electrowriting (MEW) of spatially organized polymeric microfibres are integrated for the biofabrication of an osteochondral plug, with a mechanically reinforced bone-to-cartilage interface. A printable physiological temperature-setting bioceramic, based on α-tricalcium phosphate, nanohydroxyapatite and a custom-synthesized biodegradable and crosslinkable poloxamer, was developed as bone support. The mild setting reaction of the bone ink enabled us to print directly within melt electrowritten polycaprolactone meshes, preserving their micro-architecture. Ceramic-integrated MEW meshes protruded into the cartilage region of the composite plug, and were embedded with mechanically soft gelatin-based hydrogels, laden with articular cartilage chondroprogenitor cells. Such interlocking design enhanced the hydrogel-to-ceramic adhesion strength >6.5-fold, compared with non-interlocking fibre architectures, enabling structural stability during handling and surgical implantation in osteochondral defects ex vivo. Furthermore, the MEW meshes endowed the chondral compartment with compressive properties approaching those of native cartilage (20-fold reinforcement versus pristine hydrogel). The osteal and chondral compartment supported osteogenesis and cartilage matrix deposition in vitro, and the neo-synthesized cartilage matrix further contributed to the mechanical reinforcement at the ceramic-hydrogel interface. This multi-material, multi-scale 3D printing approach provides a promising strategy for engineering advanced composite constructs for the regeneration of musculoskeletal and connective tissue interfaces. KW - biofabrication KW - melt electrowriting KW - bioinspired interface KW - bone and cartilage tissue engineering KW - microfibres KW - ceramics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254005 VL - 12 IS - 2 ER - TY - JOUR A1 - Fuchs, Andreas A1 - Kreczy, Dorothea A1 - Brückner, Theresa A1 - Gbureck, Uwe A1 - Stahlhut, Philipp A1 - Bengel, Melanie A1 - Hoess, Andreas A1 - Nies, Berthold A1 - Bator, Julia A1 - Klammert, Uwe A1 - Linz, Christian A1 - Ewald, Andrea T1 - Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules JF - Clinical Oral Investigations N2 - Objectives Magnesium phosphate-based cements begin to catch more attention as bone substitute materials and especially as alternatives for the more commonly used calcium phosphates. In bone substitutes for augmentation purposes, atraumatic materials with good biocompatibility and resorbability are favorable. In the current study, we describe the in vivo testing of novel bone augmentation materials in form of spherical granules based on a calcium-doped magnesium phosphate (CaMgP) cement. Materials and Methods Granules with diameters between 500 and 710 μm were fabricated via the emulsification of CaMgP cement pastes in a lipophilic liquid. As basic material, two different CaMgP formulations were used. The obtained granules were implanted into drill hole defects at the distal femoral condyle of 27 New Zealand white rabbits for 6 and 12 weeks. After explantation, the femora were examined via X-ray diffraction analysis, histological staining, radiological examination, and EDX measurement. Results Both granule types display excellent biocompatibility without any signs of inflammation and allow for proper bone healing without the interposition of connective tissue. CaMgP granules show a fast and continuous degradation and enable fully adequate bone regeneration. Conclusions Due to their biocompatibility, their degradation behavior, and their completely spherical morphology, these CaMgP granules present a promising bone substitute material for bone augmentation procedures, especially in sensitive areas. Clinical Relevance The mostly insufficient local bone supply after tooth extractions complicates prosthetic dental restoration or makes it even impossible. Therefore, bone augmentation procedures are oftentimes inevitable. Spherical CaMgP granules may represent a valuable bone replacement material in many situations. KW - implantation KW - calcium-magnesium phosphate cement KW - cement pastes KW - prefabricated granules KW - bone replacement material Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268872 SN - 1436-3771 VL - 26 IS - 3 ER - TY - JOUR A1 - Holzmeister, Ib A1 - Weichhold, Jan A1 - Groll, Jürgen A1 - Zreiqat,, Hala A1 - Gbureck, Uwe T1 - Hydraulic reactivity and cement formation of baghdadite JF - Journal of the American Ceramic Society N2 - In this study, the hydraulic reactivity and cement formation of baghdadite (Ca\(_{3}\)ZrSi\(_{2}\)O\(_{9}\)) was investigated. The material was synthesized by sintering a mixture of CaCO\(_{3}\), SiO\(_{2}\), and ZrO\(_{2}\) and then mechanically activated using a planetary mill. This leads to a decrease in particle and crystallite size and a partial amorphization of baghdadite as shown by X-ray powder diffraction (XRD) and laser diffraction measurements. Baghdadite cements were formed by the addition of water at a powder to liquid ratio of 2.0 g/ml. Maximum compressive strengths were found to be ~2 MPa after 3-day setting for a 24-h ground material. Inductively coupled plasma mass spectrometry (ICP-MS) measurements showed an incongruent dissolution profile of set cements with a preferred dissolution of calcium and only marginal release of zirconium ions. Cement formation occurs under alkaline conditions, whereas the unground raw powder leads to a pH of 11.9 during setting, while prolonged grinding increased pH values to approximately 12.3. KW - baghdadite KW - bone cement KW - hydraulic reactivity KW - mechanical activation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259457 VL - 104 IS - 7 ER - TY - JOUR A1 - Götz, Lisa-Marie A1 - Holeczek, Katharina A1 - Groll, Jürgen A1 - Jüngst, Tomasz A1 - Gbureck, Uwe T1 - Extrusion-Based 3D Printing of Calcium Magnesium Phosphate Cement Pastes for Degradable Bone Implants JF - Materials N2 - This study aimed to develop printable calcium magnesium phosphate pastes that harden by immersion in ammonium phosphate solution post-printing. Besides the main mineral compound, biocompatible ceramic, magnesium oxide and hydroxypropylmethylcellulose (HPMC) were the crucial components. Two pastes with different powder to liquid ratios of 1.35 g/mL and 1.93 g/mL were characterized regarding their rheological properties. Here, ageing over the course of 24 h showed an increase in viscosity and extrusion force, which was attributed to structural changes in HPMC as well as the formation of magnesium hydroxide by hydration of MgO. The pastes enabled printing of porous scaffolds with good dimensional stability and enabled a setting reaction to struvite when immersed in ammonium phosphate solution. Mechanical performance under compression was approx. 8–20 MPa as a monolithic structure and 1.6–3.0 MPa for printed macroporous scaffolds, depending on parameters such as powder to liquid ratio, ageing time, strand thickness and distance. KW - magnesium phosphate cement KW - extrusion-based 3D printing KW - degradable implant Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246110 SN - 1996-1944 VL - 14 IS - 18 ER - TY - JOUR A1 - Schmitz, Tobias A1 - Jannasch, Maren A1 - Weigel, Tobias A1 - Moseke, Claus A1 - Gbureck, Uwe A1 - Groll, Jürgen A1 - Walles, Heike A1 - Hansmann, Jan T1 - Nanotopographical Coatings Induce an Early Phenotype-Specific Response of Primary Material-Resident M1 and M2 Macrophages JF - Materials N2 - 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. KW - nanotopographical surfaces KW - combination of physical vapor deposition and electrochemical etching KW - defined humanized test system KW - inflammatory response Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203378 SN - 1996-1944 VL - 13 IS - 5 ER - TY - JOUR A1 - Boehm, Anne A1 - Meininger, Susanne A1 - Tesch, Annemarie A1 - Gbureck, Uwe A1 - Müller, Frank A. T1 - The mechanical properties of biocompatible apatite bone cement reinforced with chemically activated carbon fibers JF - Materials N2 - Calcium phosphate cement (CPC) is a well-established bone replacement material in dentistry and orthopedics. CPC mimics the physicochemical properties of natural bone and therefore shows excellent in vivo behavior. However, due to their brittleness, the application of CPC implants is limited to non-load bearing areas. Generally, the fiber-reinforcement of ceramic materials enhances fracture resistance, but simultaneously reduces the strength of the composite. Combining strong C-fiber reinforcement with a hydroxyapatite to form a CPC with a chemical modification of the fiber surface allowed us to adjust the fiber–matrix interface and consequently the fracture behavior. Thus, we could demonstrate enhanced mechanical properties of CPC in terms of bending strength and work of fracture to a strain of 5% (WOF5). Hereby, the strength increased by a factor of four from 9.2 ± 1.7 to 38.4 ± 1.7 MPa. Simultaneously, the WOF5 increased from 0.02 ± 0.004 to 2.0 ± 0.6 kJ∙m−2, when utilizing an aqua regia/CaCl2 pretreatment. The cell proliferation and activity of MG63 osteoblast-like cells as biocompatibility markers were not affected by fiber addition nor by fiber treatment. CPC reinforced with chemically activated C-fibers is a promising bone replacement material for load-bearing applications. KW - calcium phosphate cement KW - damage tolerant cement KW - carbon fiber reinforcement KW - interface control KW - fiber–matrix interaction Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197808 SN - 1996-1944 VL - 11 IS - 2 ER - TY - JOUR A1 - Meininger, Susanne A1 - Blum, Carina A1 - Schamel, Martha A1 - Barralet, Jake E. A1 - Ignatius, Anita A1 - Gbureck, Uwe T1 - Phytic acid as alternative setting retarder enhanced biological performance of dicalcium phosphate cement in vitro JF - Scientific Reports N2 - Dicalcium phosphate cement preparation requires the addition of setting retarders to meet clinical requirements regarding handling time and processability. Previous studies have focused on the influence of different setting modifiers on material properties such as mechanical performance or injectability, while ignoring their influence on biological cement properties as they are used in low concentrations in the cement pastes and the occurrence of most compounds in human tissues. Here, analyses of both material and biological behavior were carried out on samples with common setting retardants (citric acid, sodium pyrophosphate, sulfuric acid) and novel (phytic acid). Cytocompatibility was evaluated by in vitro tests with osteoblastic (hFOB 1.19) and osteoclastic (RAW 264.7) cells. We found cytocompatibility was better for sodium pyrophosphate and phytic acid with a three-fold cell metabolic activity by WST-1 test, whereas samples set with citric acid showed reduced cell number as well as cell activity. The compressive strength (CS) of cements formed with phytic acid (CS = 13 MPa) were nearly equal to those formed with citric acid (CS = 15 MPa) and approximately threefold higher than for other setting retardants. Due to a proven cytocompatibility and high mechanical strength, phytic acid seems to be a candidate replacement setting retardant for dicalcium phosphate cements. KW - implants KW - biomedical materials KW - dicalcium phosphate cement KW - phytic acid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171047 VL - 7 IS - 558 ER - TY - JOUR A1 - No, Young Jung A1 - Holzmeister, Ib A1 - Lu, Zufu A1 - Prajapati, Shubham A1 - Shi, Jeffrey A1 - Gbureck, Uwe A1 - Zreiqat, Hala T1 - Effect of Baghdadite Substitution on the Physicochemical Properties of Brushite Cements JF - Materials N2 - Brushite cements have been clinically used for irregular bone defect filling applications, and various strategies have been previously reported to modify and improve their physicochemical properties such as strength and injectability. However, strategies to address other limitations of brushite cements such as low radiopacity or acidity without negatively impacting mechanical strength have not yet been reported. In this study, we report the effect of substituting the beta-tricalcium phosphate reactant in brushite cement with baghdadite (Ca\(_3\)ZrSi\(_2\)O\(_9\)), a bioactive zirconium-doped calcium silicate ceramic, at various concentrations (0, 5, 10, 20, 30, 50, and 100 wt%) on the properties of the final brushite cement product. X-ray diffraction profiles indicate the dissolution of baghdadite during the cement reaction, without affecting the crystal structure of the precipitated brushite. EDX analysis shows that calcium is homogeneously distributed within the cement matrix, while zirconium and silicon form cluster-like aggregates with sizes ranging from few microns to more than 50 µm. X-ray images and µ-CT analysis indicate enhanced radiopacity with increased incorporation of baghdadite into brushite cement, with nearly a doubling of the aluminium equivalent thickness at 50 wt% baghdadite substitution. At the same time, compressive strength of brushite cement increased from 12.9 ± 3.1 MPa to 21.1 ± 4.1 MPa with 10 wt% baghdadite substitution. Culture medium conditioned with powdered brushite cement approached closer to physiological pH values when the cement is incorporated with increasing amounts of baghdadite (pH = 6.47 for pure brushite, pH = 7.02 for brushite with 20 wt% baghdadite substitution). Baghdadite substitution also influenced the ionic content in the culture medium, and subsequently affected the proliferative activity of primary human osteoblasts in vitro. This study indicates that baghdadite is a beneficial additive to enhance the radiopacity, mechanical performance and cytocompatibility of brushite cement KW - baghdadite KW - calcium phosphate cement KW - radiopacity KW - setting reaction KW - mechanical performance Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196980 SN - 1996-1944 VL - 12 IS - 10 ER - TY - JOUR A1 - Brückner, Theresa A1 - Meininger, Markus A1 - Groll, Jürgen A1 - Kübler, Alexander C. A1 - Gbureck, Uwe T1 - Magnesium Phosphate Cement as Mineral Bone Adhesive JF - Materials N2 - Mineral bone cements were actually not developed for their application as bone-bonding agents, but as bone void fillers. In particular, calcium phosphate cements (CPC) are considered to be unsuitable for that application, particularly under moist conditions. Here, we showed the ex vivo ability of different magnesium phosphate cements (MPC) to adhere on bovine cortical bone substrates. The cements were obtained from a mixture of farringtonite (Mg\(_3\)(PO\(_4\))\(_2\)) with different amounts of phytic acid (C\(_6\)H\(_{18}\)O\(_{24}\)P\(_6\), inositol hexaphosphate, IP6), whereas cement setting occurred by a chelation reaction between Mg\(^{2+}\) ions and IP6. We were able to show that cements with 25% IP6 and a powder-to-liquid ratio (PLR) of 2.0 g/mL resulted in shear strengths of 0.81 ± 0.12 MPa on bone even after 7 d storage in aqueous conditions. The samples showed a mixed adhesive–cohesive failure with cement residues on the bone surface as indicated by scanning electron microscopy and energy-dispersive X-ray analysis. The presented material demonstrated appropriate bonding characteristics, which could enable a broadening of the mineral bone cements’ application field to bone adhesives KW - magnesium phosphate cement KW - phytic acid KW - bone adhesive Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193052 SN - 1996-1944 VL - 12 IS - 23 ER - TY - JOUR A1 - Seifert, Annika A1 - Groll, Jürgen A1 - Weichhold, Jan A1 - Boehm, Anne V. A1 - Müller, Frank A. A1 - Gbureck, Uwe T1 - Phase Conversion of Ice‐Templated α‐Tricalcium Phosphate Scaffolds into Low‐Temperature Calcium Phosphates with Anisotropic Open Porosity JF - Advanced Engineering Materials N2 - 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. KW - phase conversion KW - α-tricalcium phosphate Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256311 VL - 23 IS - 5 ER - TY - JOUR A1 - Hettich, Georg A1 - Schierjott, Ronja A. A1 - Epple, Matthias A1 - Gbureck, Uwe A1 - Heinemann, Sascha A1 - Mozaffari-Jovein, Hadi A1 - Grupp, Thomas M. T1 - Calcium phosphate bone graft substitutes with high mechanical load capacity and high degree of interconnecting porosity JF - Materials N2 - Bone graft substitutes in orthopedic applications have to fulfill various demanding requirements. Most calcium phosphate (CaP) bone graft substitutes are highly porous to achieve bone regeneration, but typically lack mechanical stability. This study presents a novel approach, in which a scaffold structure with appropriate properties for bone regeneration emerges from the space between specifically shaped granules. The granule types were tetrapods (TEPO) and pyramids (PYRA), which were compared to porous CaP granules (CALC) and morselized bone chips (BC). Bulk materials of the granules were mechanically loaded with a peak pressure of 4 MP; i.e., comparable to the load occurring behind an acetabular cup. Mechanical loading reduced the volume of CALC and BC considerably (89% and 85%, respectively), indicating a collapse of the macroporous structure. Volumes of TEPO and PYRA remained almost constant (94% and 98%, respectively). After loading, the porosity was highest for BC (46%), lowest for CALC (25%) and comparable for TEPO and PYRA (37%). The pore spaces of TEPO and PYRA were highly interconnected in a way that a virtual object with a diameter of 150 µm could access 34% of the TEPO volume and 36% of the PYRA volume. This study shows that a bulk of dense CaP granules in form of tetrapods and pyramids can create a scaffold structure with load capacities suitable for the regeneration of an acetabular bone defect KW - calcium phosphate KW - granules KW - biomechanics KW - bone graft substitutes Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193233 SN - 1996-1944 VL - 12 IS - 21 ER - TY - JOUR A1 - Ouhaddi, Yassine A1 - Charbonnier, Baptiste A1 - Porge, Juliette A1 - Zhang, Yu-Ling A1 - Garcia, Isadora A1 - Gbureck, Uwe A1 - Grover, Liam A1 - Gilardino, Mirko A1 - Harvey, Edward A1 - Makhoul, Nicholas A1 - Barralet, Jake T1 - Development of neovasculature in axially vascularized calcium phosphate cement scaffolds JF - Journal of Functional Biomaterials N2 - 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. KW - angiogenesis KW - axial vascularization KW - bioceramic KW - bioinorganic KW - calcium phosphate KW - NLRP3 KW - inflammation Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304026 SN - 2079-4983 VL - 14 IS - 2 ER -