Calcium Phosphate Cement Paste Research Articles

Self-setting calcium phosphate cement scaffolds with pre-forming and in-situ forming interconnected macropores: Comparative study in vitro and in vivo

Creating interconnected macropores in calcium phosphate cement (CPC) is an effective strategy to promote its degradation and osteogenesis. However, little attention has been given to the osteogenic effect of the CPC scaffolds with pre-forming and in-situ forming interconnected macropores. Herein, two types of CPC scaffolds were prepared by infiltrating CPC pastes into 3D-printed polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) networks. Meanwhile, the sacrificial PCL network within CPC was dissolved to obtain the CPC scaffold with approximately 300 μm macropores, whereas the PLGA network was retained within the CPC to obtain the PLGA/CPC scaffold. The results indicated that the PLGA/CPC scaffold showed higher degradation rate and compressive strength compared to the CPC scaffold with pre-forming interconnected macropores. However, the proliferation rate and alkaline phosphatase activity of mouse bone mesenchymal stem cells cultured with the CPC scaffold were superior to those cultured with the PLGA/CPC scaffold. In addition, greater formation of new bone and material degradation in the CPC scaffold compared to the PLGA/CPC scaffold after implanted in the rabbit femoral defects.

Composite grafts made of polycaprolactone fiber mats and oil-based calcium phosphate cement pastes for the reconstruction of cranial and maxillofacial defects

ObjectivesSynthetic bone substitutes which can be adapted preoperatively and patient specific may be helpful in various bony defects in the field of oral- and maxillofacial surgery. For this purpose, composite grafts made of self-setting and oil-based calcium phosphate cement (CPC) pastes, which were reinforced with 3D-printed polycaprolactone (PCL) fiber mats were manufactured.Materials and methodsBone defect models were acquired using patient data from real defect situations of patients from our clinic. Using a mirror imaging technique, templates of the defect situation were fabricated via a commercially available 3D-printing system. The composite grafts were assembled layer by layer, aligned on top of these templates and fitted into the defect situation. Besides, PCL-reinforced CPC samples were evaluated regarding their structural and mechanical properties via X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM), and 3-point-bending testing.ResultsThe process sequence including data acquisition, template fabrication, and manufacturing of patient specific implants proved to be accurate and uncomplicated. The individual implants consisting mainly of hydroxyapatite and tetracalcium phosphate displayed good processability and a high precision of fit. The mechanical properties of the CPC cements in terms of maximum force and stress load to material fatigue were not negatively affected by the PCL fiber reinforcement, whereas clinical handling properties increased remarkably.ConclusionPCL fiber reinforcement of CPC cements enables the production of very freely modelable three-dimensional implants with adequate chemical and mechanical properties for bone replacement applications.Clinical relevanceThe complex bone morphology in the region of the facial skull often poses a great challenge for a sufficient reconstruction of bony defects. A full-fledged bone replacement here often requires the replication of filigree three-dimensional structures partly without support from the surrounding tissue. With regard to this problem, the combination of smooth 3D-printed fiber mats and oil-based CPC pastes represents a promising method for fabricating patient specific degradable implants for the treatment of various craniofacial bone defects.

Preparation and Properties of Self‐Setting Calcium Phosphate Scaffolds: Effect of Pore Architecture

Self‐setting calcium phosphate cement (CPC) scaffold with interconnected macropores is hard to prepare without compromising its hydration reaction. Herein, an indirect 3D printing method is using to prepare CPC scaffolds. Detailedly, polycaprolactone (PCL)‐sacrificed models with different strut sizes are first printed by 3D plotting technique, and then the CPC pastes are perfused into the PCL models and then self‐setting. After the removal of the PCL models, the CPC scaffolds with different pore sizes are obtained. It is showed in the results that the prepared CPC scaffolds had uniform shape and 3D interconnected macropore structure. Meanwhile, the compressive strength of CPC scaffolds all meets the requirements of repairing cancellous bone. More interestingly, the CPC scaffold with about 300 μm in macropore size is more conducive to the ingrowth and osteogenesis differentiation of mouse bone marrow mesenchymal stem cells. As a whole, the indirect 3D printing method is a promising strategy for preparing CPC scaffolds, which are hard to form directly by 3D printing technique.

Automatic computation of bone defective volume from tomographic images

One of the most difficult aims of modern biomaterial science is predicting the shape and volume of a bone defect and adjusting the implementation of a bone substitute. Prior to implantation, practitioners must carefully identify the architecture and volume of the defective bone to be filled. This information is often accessed via imaging techniques. The defective bone is frequently confused with its surroundings and the image background. The use of conventional segmentation for the selection and isolation of the cavity to be filled proves to be difficult. In this work, a defect in a dead bone is created and then imaged with the microtomography technique (343 cuts generated). The goal is to separate the defect's shape and volume from both the bone and the background image. An adaptive morphological operation technique was employed to complete these tasks. The proposed method allows for exact segmentation and calculation of the volume of the cavity to be filled. Using several calculated phantoms, the approach is subjectively and quantitatively evaluated: Compared to the high error value of the conventional method, the error value of the proposed one has no bearing on the overall data. The method's accuracy was also confirmed by comparing the calculated volume of the bone defect (0.91 cm3) and the volume of prepared calcium phosphate cement paste necessary for its filling (0.87 cm3). To challenge the method even further, another direct application on a mandibular bone is realized with an advanced number of cuts (1236 cuts). The result of this application proved that the proposed algorithm overcomes the performance of the classical approaches of segmentation with a gain of 2 min on average. A comparison study between the proposed method and other classical segmentation approaches is also presented. The effectiveness of the method is proved by the various reports and metrics generated.The automated procedure can be beneficial in implantology for realizing and guiding surgical acts, as well as in computer-aided scaffolding techniques.

Confirmation of Calcium Phosphate Cement Biodegradation after Jawbone Augmentation around Dental Implants Using Three-Dimensional Visualization and Segmentation Software.

The use of autologous bone graft for oral rehabilitation of bone atrophy is considered the gold standard. However, the available grafts do not allow a fast loading of dental implants, as they require a long healing time before full functionality. Innovative bioactive materials provide an easy-to-use solution to this problem. The current study shows the feasibility of calcium phosphate cement paste (Paste-CPC) in the sinus. Long implants were placed simultaneously with the cement paste, and provisional prosthetics were also mounted in the same sessions. Final prosthetics and the full loading took place within the same week. Furthermore, the study shows for the first time the possibility to monitor not only healing progression using Cone Beam Computer tomography (CBCT) but also material retention, over two years, on a case study example. The segmented images showed a 30% reduction of the cement size and an increased mineralized tissue in the sinus. Mechanical testing was performed qualitatively using reverse torque after insertion and cement solidification to indicate clinical feasibility. Both functional and esthetic satisfaction remain unchanged after one year. This flowable paste encourages the augmentation procedure with less invasive measure through socket of removed implants. However, this limitation can be addressed in future studies.

Soluble phosphate salts as setting aids for premixed calcium phosphate bone cement pastes

Recently, premixed calcium phosphate cement pastes have been proposed as biomaterials for bone tissue repair and regeneration. Use of premixed pastes saves the time and removes an extra step during a medical operation. α-Tricalcium phosphate (α-TCP) based cements set to form calcium deficient hydroxyapatite which has a moderate bioresorbtion speed. α-TCP cements require a setting aid, usually a sodium or potassium phosphate salt, to speed up the setting process. Within the current research we investigated which setting aid has significant advantage, if α-TCP is used in form of non-aqueous premixed paste. This approach offers the application of simple ingredients to produce a premixed calcium phosphate cement. The following properties of cement formulations were evaluated: cohesion, phase composition, microstructure, pH value of the liquid surrounding the cement, and compressive strength.Compositions using mixture of basic and acidic potassium phosphate salts (KH2PO4 and K2HPO4) in sufficient amounts give the best overall results (adequate cohesion and pH of the surrounding liquid, hydrolysis of starting materials within 48 h, and compressive strength of 12 ± 3 MPa). Cement prepared with basic sodium phosphate salt (Na2HPO4) as setting aid had considerably higher compressive strength 22 ± 1 MPa, but the pH of the surrounding liquid was basic (9.0).

Effects of zirconia additives on β-tricalcium-phosphate cement for high strength and high injectability

Injectable calcium phosphate cements (CPCs) exhibit many advantages as bone substitution materials. However, the strength of injectable CPCs after setting are often insufficient. In our previous studies, mechano-chemically modification of β-tricalcium phosphate cement powder through a planetary ball-milling process exhibited simultaneous improvement in the strength and injectability of CPC. Two plausible effects of this process are: changes in the CPC powder properties and zirconia abrasion powder contamination from the milling pot and balls. The objective of the present study is to separately evaluate these two effects on the strength and injectability of CPCs.The calculated injectability of the cement paste with and without the addition of zirconia powder were higher than 65% at 6 h after mixing. These values were much higher than that of the CPC paste without mechano-chemically modification, and similar to that of CPC with zirconia abrasion powder contamination. By contrast, the compression strength of the set CPC with zirconia powder additives were higher than that without the addition, and similar to that of CPC with zirconia abrasion powder contamination. These results suggest that the changes in the CPC powder properties due to mechano-chemically modification mainly affected the injectability of the CPC paste, and the zirconia abrasion powder contamination of the CPC powder affected the strength of the set CPC.

Development and Characterization of Composites Consisting of Calcium Phosphate Cements and Mesoporous Bioactive Glass for Extrusion-Based Fabrication.

Calcium phosphate cements (CPC) and mesoporous bioactive glasses (MBG) are two degradable biomaterial groups widely under investigation concerning their applicability to treat bone defects. MBG-CPC composites were recently shown to possess enhanced degradation properties in comparison to pure CPC. In addition, modification of MBG allows an easy incorporation of therapeutically effective ions. Additive manufacturing of such composites enables the fabrication of patient-specific geometries with further improved degradation behavior due to control over macroporosity. In this study, we developed composites prepared from a non-aqueous carrier-liquid (cl) based CPC paste and MBG particles suitable for extrusion-based additive manufacturing (3D plotting). CPC with the addition of up to 10 wt % MBG were processible by adjusting the amount of cl. Scaffolds consisting of a 4, 6 and 8%-MBG-CPC composite were successfully manufactured by 3D plotting. While mechanically characterization of the scaffolds showed an influence of the MBG, no changes of microstructure were observed. During degradation of the composite, the release of Ca2+ and Sr2+ ions could be controlled by the MBG composition and plotted scaffolds with macropores showed a significant higher release than bulk samples of comparable mass. These findings demonstrate a high flexibility regarding ion release of the developed composites and suggest utilizing the drug binding capacities of MBG as a prospective delivery system for biologically active proteins.

Biomechanical in vitro evaluation of a ready-to-use calcium phosphate cement implanted to augment intramedullary nail fixation of a three-part humeral head fracture model.

The aim of this study was the dynamic biomechanical evaluation of a ready-to-use oil-based calcium phosphate cement paste implanted to augment intramedullary nail fixation of a three-part humeral head fracture model. Fractures in the osteoporotic bone are often fractures of the proximal humerus. Secondary fracture displacements due to cut-out in osteoporotic bone have been observed in up to 13% of cases. Procedures have been developed to augment fracture fixation with polymethylmethacrylate to increase stability, but there are still unsolved challenges relating to its material-specific properties. Calcium phosphate cement could be a biological alternative in the augmentation of osteoporotic fractures because of its more favourable material properties. Fracture fixation was performed on eight pairs of human cadaveric bones to stabilize a standardized three-part humeral head fracture model by implantation of the Targon® PH (Braun-Aesculap AG, Tuttlingen, Germany) intramedullary nail and insertion of three head screws and two bicortical shaft screws. The procedure was randomized, and one bone of each pair received calcium phosphate cement augmentation. Custom-made cannulated screws with an open lateral slot facilitated augmentation, making it possible to cement the threaded portion of the screw (1-mL calcium phosphate cement/screw). After the calcium phosphate cement had hardened, the humeri were subjected to dynamic axial loading. Load was progressively increased, monitored by ultrasound-based motion analysis, and total deformation was recorded. Load testing continued until implant failure. The augmented group withstood significantly more cycles before implant failure. The average initial stiffness showed a significant difference between the two study groups. Ultrasonic sensor technology was used to measure angular displacement during testing and a significant difference was found. Calcium phosphate cement offers a potential alternative to implant augmentation in the treatment of osteoporotic humeral head fractures. Future studies are required to confirm these observations clinically in vivo.

Improving the anti-washout property of calcium phosphate cement by introducing konjac glucomannan/κ-carrageenan blend.

Anti-washout calcium phosphate cement (CPC) was prepared by dissolving water-soluble konjac glucomannan (KGM) and κ-carrageenan (KC) blend in the cement liquid. The anti-washout property, setting time, compressive strength and in vitro cytocompatibility of the CPC modified with KGM/KC blend were evaluated. The results indicated that the CPC pastes modified with KGM/KC blend exhibited excellent anti-washout property. The addition of KGM/KC blend shortened the setting time and increased the injectability of CPC. Although the introduction of KGM/KC blend reduced the compressive strength of CPC, the compressive strength still surpassed that of human cancellous bone. The optimal KGM/KC mass ratio was 2:8, with which the modified cement exhibited the most efficient washout resistance and the highest compressive strength. The introduction of KGM/KC blend obviously promoted the proliferation of mouse bone marrow mesenchymal stem cells. This anti-washout CPC modified by KGM/KC blend with excellent in vitro cytocompatibility will have good prospects for application in bone defect repair.

Invitro and invivo analysis of the biocompatibility of two novel and injectable calcium phosphate cements.

Calcium phosphate cements (CPCs) have been widely used as bone graft substitutes for many years. The aim of this study was to evaluate the biocompatibility of two novel injectable, bioactive cements: β-tricalcium phosphate (β-TCP)/CPC and chitosan microsphere/CPC in vitro and in vivo. This was accomplished by culturing mouse pre-osteoblastic cells (MC3T3-E1) on discs and pastes of CPCs. Cell growth, adhesion, proliferation and differentiation were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and alkaline phosphatase assays as well as by scanning electron microscopy and fluorescence. The effect of CPC paste curing was also evaluated. Implantation of two materials into the muscle tissue of rabbits was also studied and evaluated by histological analysis. Cell analysis indicated good biocompatibility in vitro. The fluorescence assay suggested that the cured material discs had no obvious effect on cell growth, while the curing process did. Histological examination showed no inflammatory cell infiltration into soft tissue. These data suggest that β-TCP/CPC and chitosan microsphere/CPC composites may be promising injectable material for bone tissue engineering.

Neutral Liquid Containing Chitosan and Polyol for Calcium Phosphate Cement

The self-hardening calcium phosphate cement (CPC) has widely been used in bone defect repairs. CPC tends to decay or disintegrate upon early contact with blood or body fluids, and the gelation of CPC paste using sodium alginate, chitosan, or collagen may overcome such a wash-out property. The incorporation of chitosan in CPC paste increased the compressive strength and work-of-fracture. However, the viscosity of CPC paste increased with an increase of chitosan content, and acidic liquid is not favorable, as chitosan must be dissolved in an acidic solution. The CPC paste using the liquid prepared from freeze-dried chitosan powder was easily push out from the syringe, but the content of chitosan was reduced. An addition of polyol-phosphate salt to chitosan solution produces a transparent liquid at physiological pH, and the chitosan content was found to be increased. Chitosan content of liquid was increased from 0.09% to 0.54 % by adding polyol to liquid, and the compressive strength of CPC was also increased.

Calcium Phosphate Cement Paste Injection as a Fiducial Marker of Cervical Cancer

Calcium phosphate cement (CPC) is used to fill bone voids in dental, orthopedic, and craniofacial applications. This study evaluated CPC marker as an injectable non-metallic fiducial marker. Six patients received 3-5 injections of CPC paste placed at a depth of 10 mm into tumors of the cervix before treatment planning CT (TPCT). Patients were treated with external-beam radiotherapy (EBRT) and high-dose rate brachytherapy (BT). We investigated marker visibility on cone-beam CT (CBCT), T2-weighted MRI, and interfraction of the marker motion for cervical cancer patients. Of a total of 22 visible CPC markers at TPCT, 17 CPC markers were visible on the first CBCT. Excluding one patient, all markers were visible on CBCT during EBRT. Of 16 visible CPC markers on CBCT, 13 CPC markers were visible on the magnetic resonance imaging (MRI) obtained before BT. For CPC marker centroid movement, the mean-of-means/systematic variation/random variation were 0.2/0.4/1.4, -1.6/5.1/4.1, and -3.4/2.1/2.8 mm for the left-right, dorsal-ventral, and cranial-caudal directions, respectively. This is the first report of a CPC marker injected into tumors of the cervix. It can be visualized on CBCT and MRI with reductions in marker loss and artifacts.

Novel Injectable Calcium Phosphate Bone Cement from Wet Chemical Precipitation Method

Calcium phosphate cement has been prepared via chemical precipitation method for injectable bone filling materials. Calcium hydroxide, Ca(OH)2, and diammonium hydrogen phosphate, (NH4)2HPO4, were used as calcium and phosphorus precursors respectively. The synthesized powder was mixed with water at different powder-to-liquid (P/L) ratios, which was adjusted at 0.8, 0.9, 1.0, 1.1 and 1.2. The influence of P/L ratio on the injectability, setting time and mechanical strength of calcium phosphate cement paste has been evaluated. The synthesized powder appeared as purely hydroxyapatite with nanosized and agglomerated spherical particles. All cement pastes show excellent injectability except for the paste with P/L ratio 1.2. Calcium phosphate cement with P/L ratio 1.1 shows the ideal cement for bone filler application with good injectability, the initial and final setting times of 30 min and 160 min, and the compression strength of 2.47 MPa. The result indicated that the newly developed calcium phosphate cement is physically suitable for bone filler application. This paper presents our investigation on the effect of P/L ratio on the handling and mechanical properties of calcium phosphate cement prepared via wet chemical precipitation method.

Engineering bone regeneration with novel cell-laden hydrogel microfiber-injectable calcium phosphate scaffold

Cell-based tissue engineering is promising to create living functional tissues for bone regeneration. The implanted cells should be evenly distributed in the scaffold, be fast-released to the defect and maintain high viability in order to actively participate in the regenerative process. Herein, we report an injectable calcium phosphate cement (CPC) scaffold containing cell-encapsulating hydrogel microfibers with desirable degradability that could deliver cells in a timely manner and maintain cell viability. Microfibers were synthesized using partially-oxidized alginate with various concentrations (0–0.8%) of fibrinogen to optimize the degradation rate of the alginate-fibrin microfibers (Alg-Fb MF). A fibrin concentration of 0.4% in Alg-Fb MF resulted in the greatest enhancement of cell migration, release and proliferation. Interestingly, a significant amount of cell–cell contact along the long-axis of the microfibers was established in Alg-0.4%Fb MF as early as day 2. The injectable tissue engineered construct for bone reconstruct was fabricated by mixing the fast-degradable Alg-0.4%Fb MF with CPC paste at 1:1 volume ratio. In vitro study showed that cells re-collected from the construct maintained good viability and osteogenic potentials. In vivo study demonstrated that the hBMSC-encapsulated CPC-MF tissue engineered construct displayed a robust capacity for bone regeneration. At 12weeks after implantation, osseous bridge in the rat mandibular defect was observed in CPC-MF-hBMSCs group with a new bone area fraction of (42.1±7.8) % in the defects, which was >3-fold that of the control group. The novel tissue-engineered construct presents an excellent prospect for a wide range of dental, craniofacial and orthopedic applications.

Preparation, characterization and in vitro cell performance of anti-washout calcium phosphate cement modified by sodium polyacrylate

The anti-washout ability of calcium phosphate cement (CPC) is essential for its application in massive hemorrhage regions. Sodium polyacrylate (PAAS) could be used to improve the anti-washout property of CPC paste.

Calcium Phosphate Cement Paste Injection as a Marker of Cervical Cancer

Calcium Phosphate Cement Paste Injection as a Marker of Cervical Cancer

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

The aim of this study was to evaluate a calcium phosphate cement (CPC) marker as an injectable nonmetallic fiducial marker. We investigated interfraction cervical motion with cone beam CT (CBCT) images using a CPC marker and marker visibility on T2-weighted MRI for cervical cancer patients. Our commercially available CPC, widely used as a bone substitute, was prepared by mixing a powder component and liquid. A volume of 0.1-0.2 cc of the paste was injected by a disposable syringe with a 19-gauge long needle. This paste was self-hardening and recrystallizes to calcium hydroxyapatite in a living body. Six patients received 3-4 injections of CPC paste placed at a depth of 10 mm into a tumor of the cervix before planning CT. Patients were first treated with external beam radiation therapy to the whole pelvis with a total prescribed dose of 48.6-50.4 Gy delivered in 27-28 fractions. Three fractionated high-dose rate brachytherapy treatments were performed with a prescribed dose per fraction of 6 Gy to Point A. Concurrent chemotherapy was delivered to all except one patient. In each fraction, a CBCT scan was acquired before dose delivery. Position verification was based on registration of the bony structures in the CBCT images corresponding to planning CT images. Systematic and random displacement of the marker centroid analysis were performed in 3 directions. Visibility of the markers using T2-weighted MRI before final brachytherapy was also assessed. The procedure was well-tolerated. There was no interruption of the implantation due to pain or hemorrhage. There were no other procedure-related complications during or after CPC marker injection. Comparing the initial and final CBCT images, one patient had lost all three markers and one patient lost one marker. Gross tumor volumes (GTV) before radiation therapy of these patients were 250.7 and 91.7 cc, and GTV before final brachytherapy were 7.5 and 1.1 cc, respectively. The initial GTV of patients with no marker loss ranged from 49.1-67.2 cc, and GTV before the final brachytherapy ranged from 2.4-8.4 cc. Of 15 markers in the final CBCT images, 11 markers with a size >0.15 cc on planning CT images were visible on T2-weighted MRI. For CPC marker movement with rigid bony anatomy registration, the mean-of-means/systematic variation/random variation were 0.6/2.4/0.5, 1.5/4.6/1.9, and 3.4/2.6/1.1 mm for the left-right, anterior-posterior, and cranial-caudal directions, respectively. The injection of CPC paste into the cervix was feasible and safe. More than 0.15 cc of CPC paste was required to be visualized with T2-weighted MRI. For patients with a large cervical tumor, technical improvements in CPC marker placement are necessary.

Design and Fabrication of Complex Scaffolds for Bone Defect Healing: Combined 3D Plotting of a Calcium Phosphate Cement and a Growth Factor-Loaded Hydrogel

Additive manufacturing enables the fabrication of scaffolds with defined architecture. Versatile printing technologies such as extrusion-based 3D plotting allow in addition the incorporation of biological components increasing the capability to restore functional tissues. We have recently described the fabrication of calcium phosphate cement (CPC) scaffolds by 3D plotting of an oil-based CPC paste under mild conditions. In the present study, we have developed a strategy for growth factor loading based on multichannel plotting: a biphasic scaffold design was realised combining CPC with VEGF-laden, highly concentrated hydrogel strands. As hydrogel component, alginate and an alginate-gellan gum blend were evaluated; the blend exhibited a more favourable VEGF release profile and was chosen for biphasic scaffold fabrication. After plotting, two-step post-processing was performed for both, hydrogel crosslinking and CPC setting, which was shown to be compatible with both materials. Finally, a scaffold was designed and fabricated which can be applied for testing in a rat critical size femur defect. Optimization of CPC plotting enabled the fabrication of highly resolved structures with strand diameters of only 200µm. Micro-computed tomography revealed a precise strand arrangement and an interconnected pore space within the biphasic scaffold even in swollen state of the hydrogel strands.

Multichannel 3D plotting for complex tissue equivalents and implants for defects at tissue interfaces

Event Abstract Back to Event Multichannel 3D plotting for complex tissue equivalents and implants for defects at tissue interfaces Michael Gelinsky1, Ashwini R. Akkineni1, Kathleen Schütz1, Tilman Ahlfeld1, Yvonne Förster1, Falko Doberenz1, Maja Brückner1 and Anja Lode1 1 TU Dresden, Centre for Translational Bone, Joint and Soft Tissue Research, Germany Introduction: Additive Manufacturing (AM) opens up fascinating possibilities for the generation of implants and tissue engineering (TE) constructs. 3D plotting, i. e. extrusion of pasty biomaterials at room or physiological temperature, allows utilization of a great variety of materials and incorporation of sensitive substances like drugs, growth factors or even living cells. Multichannel-3D plotting enables processing of more than one material within one construct and therefore manufacturing of complex specimens, e.g. for application at tissue interfaces and/or generation of improved tissue equivalents which closer mimic natural tissues than conventional TE strategies. We wanted to investigate whether we can load calcium phosphate cement (CPC) pastes with growth factors and combine them with biopolymer hydrogels for AM of complex scaffolds. Further questions were whether live cells can be included within the hydrogels and both materials combined in joint strands with core/shell morphology. Materials and Methods: For 3D plotting BioScaffolder 2.1 from GeSiM (Grosserkmannsdorf, Germany) was used. As CPC paste an hydroxyapatite (HA) forming α-tricalcium phosphate-based precursor mixture, suspended in a biocompatible oily phase[1], was utilized. Blends of alginate (3%) and methylcellulose (9%)[2] were used as hydrogel material. Before scaffold preparation, all materials were sterilized. After plotting of the scaffolds in air they were stabilized by immersion in 100 mM CaCl2 solution. As growth factor, VEGF (vascular endothelial GF) was used and human mesenchymal stroma cells (hMSC) for embedding experiments. For preparation of core/shell strands self-made double-nozzle extruders were applied, mounted onto the 3D plotter. The scaffolds were fully characterized including morphology, mechanical properties, VEGF release (ELISA and bioassay), cell survival (live/dead and MTT staining) and osteogenic differentiation. One type of scaffold was tested in a pilot animal study in a 5 mm femur defect in rat, stabilized with a metal plate. Results and Discussion: Combination of CPC and biopolymer hydrogel strands within one scaffold was possible. Immersion of the scaffolds after plotting in calcium ion containing media led to CPC setting and simultaneously to alginate crosslinking. Methylcellulose which improved viscosity and therefore plottability of the hydrogel paste slowly dissolves during further storage in aqueous media, creating an additional microporosity (besides the macropores = space between the strands). We could demonstrate that VEGF could be successfully incorporated in CPC as well as hydrogel strands; for mixing with CPC binding of the GF to chitosan microparticles was advantageous. GF release was much faster from hydrogel compared to CPC – and retained biological activity of released VEGF was proven with an bioassay using endothelial cells. Human MSC could be mixed into the biopolymer hydrogel blend and survived extrusion, scaffold crosslinking and additional 3 weeks of culture. Osteogenic differentiation could be induced by applying common supplements. In addition, the animal pilot study proved biocompatibility of the new type of scaffold and biological activity of the released VEGF in vivo. A novel type of core/shell strands with a stiff shell (CPC) and soft core (hydrogel) and 3D scaffolds made thereof could be manufactured using double-nozzle extruders. Such material combinations within one extruded strand open up new possibilities for dual drug loading and release. Conclusion: Multichannel 3D plotting is a versatile AM technology and allows combination of such different biomaterials like a calcium phosphate cement and a biopolymer hydrogel. Due to the mild processing conditions sensitive components like GF and living cells can be incorporated. Of special interest is the combination of different biomaterials in strands with core/shell morphology. This technology can be further developed towards more complex tissue and organ models. Saxon State Ministry for Higher Education, Research and the Arts (SMWK) for funding