@article{BruecknerMeiningerGrolletal.2019, author = {Br{\"u}ckner, Theresa and Meininger, Markus and Groll, J{\"u}rgen and K{\"u}bler, Alexander C. and Gbureck, Uwe}, title = {Magnesium Phosphate Cement as Mineral Bone Adhesive}, series = {Materials}, volume = {12}, journal = {Materials}, number = {23}, issn = {1996-1944}, doi = {10.3390/ma12233819}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193052}, year = {2019}, abstract = {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}, 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{HettichSchierjottEppleetal.2019, author = {Hettich, Georg and Schierjott, Ronja A. and Epple, Matthias and Gbureck, Uwe and Heinemann, Sascha and Mozaffari-Jovein, Hadi and Grupp, Thomas M.}, title = {Calcium phosphate bone graft substitutes with high mechanical load capacity and high degree of interconnecting porosity}, series = {Materials}, volume = {12}, journal = {Materials}, number = {21}, issn = {1996-1944}, doi = {10.3390/ma12213471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193233}, pages = {3471}, year = {2019}, abstract = {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}, language = {en} } @article{ElgheznawyOefteringEnglertetal.2023, author = {Elgheznawy, Amro and {\"O}ftering, Patricia and Englert, Maximilian and Mott, Kristina and Kaiser, Friederike and Kusch, Charly and Gbureck, Uwe and B{\"o}sl, Michael R. and Schulze, Harald and Nieswandt, Bernhard and V{\"o}gtle, Timo and Hermanns, Heike M.}, title = {Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formation in vivo}, series = {Frontiers in Immunology}, volume = {14}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2023.1197894}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320154}, year = {2023}, abstract = {Zinc (Zn2+) is considered as important mediator of immune cell function, thrombosis and haemostasis. However, our understanding of the transport mechanisms that regulate Zn2+ homeostasis in platelets is limited. Zn2+ transporters, ZIPs and ZnTs, are widely expressed in eukaryotic cells. Using mice globally lacking ZIP1 and ZIP3 (ZIP1/3 DKO), our aim was to explore the potential role of these Zn2+ transporters in maintaining platelet Zn2+ homeostasis and in the regulation of platelet function. While ICP-MS measurements indicated unaltered overall Zn2+ concentrations in platelets of ZIP1/3 DKO mice, we observed a significantly increased content of FluoZin3-stainable free Zn2+, which, however, appears to be released less efficiently upon thrombin-stimulated platelet activation. On the functional level, ZIP1/3 DKO platelets exhibited a hyperactive response towards threshold concentrations of G protein-coupled receptor (GPCR) agonists, while immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor agonist signalling was unaffected. This resulted in enhanced platelet aggregation towards thrombin, bigger thrombus volume under flow ex vivo and faster in vivo thrombus formation in ZIP1/3 DKO mice. Molecularly, augmented GPCR responses were accompanied by enhanced Ca2+ and PKC, CamKII and ERK1/2 signalling. The current study thereby identifies ZIP1 and ZIP3 as important regulators for the maintenance of platelet Zn2+ homeostasis and function.}, 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{HolzmeisterWeichholdGrolletal.2021, author = {Holzmeister, Ib and Weichhold, Jan and Groll, J{\"u}rgen and Zreiqat,, Hala and Gbureck, Uwe}, title = {Hydraulic reactivity and cement formation of baghdadite}, series = {Journal of the American Ceramic Society}, volume = {104}, journal = {Journal of the American Ceramic Society}, number = {7}, doi = {10.1111/jace.17727}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259457}, pages = {3554-3561}, year = {2021}, abstract = {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.}, language = {en} } @article{GoetzHoleczekGrolletal.2021, author = {G{\"o}tz, Lisa-Marie and Holeczek, Katharina and Groll, J{\"u}rgen and J{\"u}ngst, Tomasz and Gbureck, Uwe}, title = {Extrusion-Based 3D Printing of Calcium Magnesium Phosphate Cement Pastes for Degradable Bone Implants}, series = {Materials}, volume = {14}, journal = {Materials}, number = {18}, issn = {1996-1944}, doi = {10.3390/ma14185197}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246110}, year = {2021}, abstract = {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.}, 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{EwaldFuchsBoegeleinetal.2023, author = {Ewald, Andrea and Fuchs, Andreas and Boegelein, Lasse and Grunz, Jan-Peter and Kneist, Karl and Gbureck, Uwe and Hoelscher-Doht, Stefanie}, title = {Degradation and bone-contact biocompatibility of two drillable magnesium phosphate bone cements in an in vivo rabbit bone defect model}, series = {Materials}, volume = {16}, journal = {Materials}, number = {13}, issn = {1996-1944}, doi = {10.3390/ma16134650}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362824}, year = {2023}, abstract = {The use of bone-cement-enforced osteosynthesis is a growing topic in trauma surgery. In this context, drillability is a desirable feature for cements that can improve fracture stability, which most of the available cement systems lack. Therefore, in this study, we evaluated a resorbable and drillable magnesium-phosphate (MgP)-based cement paste considering degradation behavior and biocompatibility in vivo. Two different magnesium-phosphate-based cement (MPC) pastes with different amounts of phytic acid (IP 6) as setting retarder (MPC 22.5 and MPC 25) were implanted in an orthotopic defect model of the lateral femoral condyle of New Zealand white rabbits for 6 weeks. After explantation, their resorption behavior and material characteristics were evaluated by means of X-ray diffraction (XRD), porosimetry measurement, histological staining, peripheral quantitative computed tomography (pQCT), cone-beam computed tomography (CBCT) and biomechanical load-to-failure tests. Both cement pastes displayed comparable results in mechanical strength and resorption kinetics. Bone-contact biocompatibility was excellent without any signs of inflammation. Initial resorption and bone remodeling could be observed. MPC pastes with IP 6 as setting retardant have the potential to be a valuable alternative in distinct fracture patterns. Drillability, promising resorption potential and high mechanical strength confirm their suitability for use in clinical routine.}, 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{HeiligSandnerJordanetal.2021, author = {Heilig, Philipp and Sandner, Phoebe and Jordan, Martin Cornelius and Jakubietz, Rafael Gregor and Meffert, Rainer Heribert and Gbureck, Uwe and Hoelscher-Doht, Stefanie}, title = {Experimental drillable magnesium phosphate cement is a promising alternative to conventional bone cements}, series = {Materials}, volume = {14}, journal = {Materials}, number = {8}, issn = {1996-1944}, doi = {10.3390/ma14081925}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236633}, year = {2021}, abstract = {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.}, language = {en} } @article{FuchsHeiligMcDonoghetal.2020, author = {Fuchs, Konrad F. and Heilig, Philipp and McDonogh, Miriam and Boelch, Sebastian and Gbureck, Uwe and Meffert, Rainer H. and Hoelscher-Doht, Stefanie and Jordan, Martin C.}, title = {Cement-augmented screw fixation for calcaneal fracture treatment: a biomechanical study comparing two injectable bone substitutes}, series = {Journal of Orthopaedic Surgery and Research}, volume = {15}, journal = {Journal of Orthopaedic Surgery and Research}, doi = {10.1186/s13018-020-02009-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230336}, year = {2020}, abstract = {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.}, language = {en} } @article{DiloksumpandeRuijterCastilhoetal.2020, author = {Diloksumpan, Paweena and de Ruijter, Myl{\`e}ne and Castilho, Miguel and Gbureck, Uwe and Vermonden, Tina and van Weeren, P Ren{\´e} and Malda, Jos and Levato, Riccardo}, title = {Combining multi-scale 3D printing technologies to engineer reinforced hydrogel-ceramic interfaces}, series = {Biofabrication}, volume = {12}, journal = {Biofabrication}, number = {2}, doi = {10.1088/1758-5090/ab69d9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254005}, year = {2020}, abstract = {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.}, language = {en} } @article{FuchsKreczyBrueckneretal.2022, author = {Fuchs, Andreas and Kreczy, Dorothea and Br{\"u}ckner, Theresa and Gbureck, Uwe and Stahlhut, Philipp and Bengel, Melanie and Hoess, Andreas and Nies, Berthold and Bator, Julia and Klammert, Uwe and Linz, Christian and Ewald, Andrea}, title = {Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules}, series = {Clinical Oral Investigations}, volume = {26}, journal = {Clinical Oral Investigations}, number = {3}, issn = {1436-3771}, doi = {10.1007/s00784-021-04231-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268872}, pages = {2619-2633}, year = {2022}, abstract = {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.}, language = {en} }