J A Jansen

Publications of J A Jansen

• Bulk properties and bioactivity assessment of porous polymethylmethacrylate cement loaded with calcium phosphates under simulated physiological conditions.

  Authors: M A Lopez-Heredia, Y Sa, P Salmon, J R de Wijn, J G C Wolke, J A Jansen

  Acta biomaterialia. 05/2012;

  Polymethylmethacrylate (PMMA) cements are amply used in spinal surgery. Nevertheless, these type of cements present some documented drawbacks. Efforts are made to improve the properties andPolymethylmethacrylate (PMMA) cements are amply used in spinal surgery. Nevertheless, these type of cements present some documented drawbacks. Efforts are made to improve the properties and biological performance of solid PMMA. A porous structure would seem to be advantageous for anchoring purposes. This work studied the bulk physicochemical, mechanical and interconnectivity properties of porous PMMA cements loaded with several percentages of calcium phosphate (CaP). As a measure of bioactivity, changes of PMMA cements under simulated physiological conditions were studied in a calcium phosphate solution for 0, 3, 7, 14, 21 and 28 days. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), micro-computed tomography (μ-CT) and mechanical compression tests were performed to characterize the morphology, crystallographic and chemical composition, interconnectivity and mechanical properties, respectively. SEM allowed observing the result of loading CaP into the porous PMMA, which was corroborated by XRD, FTIR and μ-CT. No interference of the CaP with the PMMA was detected. μ-CT described similar interconnectivity and pore distribution for all CaP percentages. Mechanical properties were not significantly altered by the CaP percentages or the immersion time. Hence, porous PMMA was effectively loaded with CaP, which provided the material with properties for potential osteoconductivity.

• Submicron-patterning of bulk titanium by nanoimprint lithography and reactive ion etching.

  Authors: M Domanski, R Luttge, E Lamers, X F Walboomers, L Winnubst, J A Jansen, J G E Gardeniers

  Nanotechnology. 02/2012; 23(6):065306.

  Nanopatterns on titanium may enhance endosseous implant biofunctionality. To enable biological studies to prove this hypothesis, we developed a scalable method of fabricating nanogrooved titaniumNanopatterns on titanium may enhance endosseous implant biofunctionality. To enable biological studies to prove this hypothesis, we developed a scalable method of fabricating nanogrooved titanium substrates. We defined nanogrooves by nanoimprint lithography (NIL) and a subsequent pattern transfer to the surface of ASTM grade 2 bulk titanium applying a soft-mask for chlorine-based reactive ion etching (RIE). With respect to direct write lithographic techniques the method introduced here is fast and capable of delivering uniformly patterned areas of at least 4 cm(2). A dedicated silicon nanostamp process has been designed to generate the required thickness of the soft-mask for the NIL-RIE pattern transfer. Stamps with pitch sizes from 1000 nm down to 300 nm were fabricated using laser interference lithography (LIL) and deep cryogenic silicon RIE. Although silicon nanomachining was proven to produce smaller pitch sizes of 200 nm and 150 nm respectively, successful pattern transfer to titanium was only possible down to a pitch of 300 nm. Hence, the smallest nanogrooves have a width of 140 nm. An x-ray photoelectron spectroscopy study showed that only very few contaminations arise from the fabrication process and a cytotoxicity assay on the nanopatterned surfaces confirmed that the obtained nanogrooved titanium specimens are suitable for in vivo studies in implantology research.

• Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2.

  Authors: F C J van de Watering, J J J P van den Beucken, S P van der Woning, A Briest, A Eek, H Qureshi, L Winnubst, O C Boerman, J A Jansen

  Journal of controlled release : official journal of the Controlled Release Society. 01/2012;

  Bone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems areBone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems are non-glycosylated (ng) whereas native and recombinant equivalents produced in mammalian cell expression systems are glycosylated (g) proteins. ngBMP-2 is less soluble, resulting in lower BMP-2 release from carriers as used as bone substitute materials. This seems promising for reducing the amount of included growth factor in bone substitute materials. Hence, it was hypothesized that ngBMP-2 would induce formation of the same amount of bone at an ectopic site at lower dosage as gBMP-2. To that end, gBMP-2 and ngBMP-2 were firstly in vitro comparatively evaluated for biological activity and release from a calcium phosphate (CaP) based bone substitute material. Thereafter, an ectopic implantation model in rats was used, in which gBMP-2 and ngBMP2 were loaded in various dosages (2-20μg/implant) on the CaP-based bone substitute material and implanted for 4 and 12weeks. The results revealed that both the in vitro biological activity of and the in vitro release of ngBMP-2 are lower compared to gBMP2. Upon ectopic implantation, however, ngBMP-2 loaded implants induced more bone formation at lower concentrations from 4-weeks onward compared to gBMP-2 equivalents, indicating the value of ngBMP-2 as a potential alternative for mammalian produced recombinant BMP-2 for bone regenerative therapies.

• Dynamic cell adhesion and migration on nanoscale grooved substrates.

  Authors: E Lamers, J Te Riet, M Domanski, R Luttge, C G Figdor, J Ge Gardeniers, X F Walboomers, J A Jansen

  European cells & materials. 01/2012; 23:182-94.

  Organised nanotopography mimicking the natural extracellular matrix can be used to control morphology, cell motility, and differentiation. However, it is still unknown how specific cell types reactOrganised nanotopography mimicking the natural extracellular matrix can be used to control morphology, cell motility, and differentiation. However, it is still unknown how specific cell types react with specific patterns. Both initial adhesion and preferential cell migration may be important to initiate and increase cell locomotion and coverage with cells, and thus achieve an enhanced wound healing response around an implantable material. Therefore, the aim of this study was to evaluate how MC3T3-E1 osteoblast initial adhesion and directional migration are influenced by nanogrooves with pitches ranging from 150 nm up to 1000 nm. In this study, we used a multi-patterned substrate with five different groove patterns and a smooth area with either a concentric or radial orientation. Initial cell adhesion measurements after 10 s were performed using atomic force spectroscopy-assisted single-cell force spectroscopy, and demonstrated that nascent cell adhesion was highly induced by a 600 nm pitch and reduced by a 150 nm pitch. Addition of RGD peptide significantly reduced adhesion, indicating that integrins and cell adhesive proteins (e.g. fibronectin or vitronectin) are key factors in specific cell adhesion on nanogrooved substrates. Also, cell migration was highly dependent on the groove pitch; the highest directional migration parallel to the grooves was observed on a 600 nm pitch, whereas a 150 nm pitch restrained directional cell migration. From this study, we conclude that grooves with a pitch of 600 nm may be favourable to enhance fast wound closure, thereby promoting tissue regeneration.

• Predictive value of ridge dimensions on autologous bone graft resorption in staged maxillary sinus augmentation surgery using Cone-Beam CT.

  Authors: R J Klijn, J J J P van den Beucken, E M Bronkhorst, S J Berge, G J Meijer, J A Jansen

  Clinical oral implants research. 10/2011; 23(4):409-15.

  No studies are available that provide predictive parameters regarding the expected amount of resorption after maxillary sinus augmentation surgery using autologous bone grafts. Therefore, the aim ofNo studies are available that provide predictive parameters regarding the expected amount of resorption after maxillary sinus augmentation surgery using autologous bone grafts. Therefore, the aim of this study was to determine parameters influencing the outcome of the bone graft resorption process. In 20 patients, three-dimensional analysis of alveolar ridge dimensions and bone graft volume change in the atrophic posterior maxilla was performed by Cone-Beam Computerized Tomography imaging. Ridge dimensions were assessed before maxillary sinus augmentation surgery. Bone graft volumes were compared after maxillary sinus floor augmentation surgery and a graft healing interval of several months. To analyze the relation between bone volume changes with the independent variables, patients' gender, age, alveolar crest height and width, and graft healing time interval, a multi-level extension of linear regression was applied. A residual bone height of 6.0 mm (SD = 3.6 mm) and 6.2 mm (SD = 3.6 mm) was found at the left and right sides, respectively. Moreover, alveolar bone widths of 6.5 mm (SD = 2.2 mm) and 7.0 mm (SD = 2.3 mm) at the premolars, and 8.8 mm (SD = 2.2 mm) and 8.9 mm (SD = 2.5 mm) at the molars regions were found at the left and right site, respectively. Bone graft volume decreased by 25.0% (SD = 21.0%) after 4.7 months (SD = 2.7, median = 4.0 months) of healing time. The variables "age" (P = 0.009) and mean alveolar crest "bone height" (P = 0.043), showed a significant influence on bone graft resorption. A decrease of 1.0% (SE = 0.3%) of bone graft resorption was found for each year the patient grew older, and an increase in bone graft resorption of 1.8% (SE = 0.8%) was found for each mm of original bone height before sinus floor augmentation. Graft resorption occurs when using autologous bone grafts for maxillary sinus augmentation. Alveolar crest bone height and patient age have a significant effect on graft resorption, with increased resorption for higher alveolar crest bone height and decreased resorption for older patients. Consequently, patient characteristics that affect the process of bone graft resorption should be given full consideration, when performing sinus augmentation surgery.

• The effect of ball milling grinding pathways on the bulk and reactivity properties of calcium phosphate cements.

  Authors: M A Lopez-Heredia, M Bohner, W Zhou, A J A Winnubst, J G C Wolke, J A Jansen

  Journal of biomedical materials research. Part B, Applied biomaterials. 07/2011; 98(1):68-79.

  Calcium phosphate cements (CPCs) are significant alternatives to autologous bone grafting. CPCs can be composed of biphasic or multiphase calcium phosphate (CaP) compounds. A common way to processCalcium phosphate cements (CPCs) are significant alternatives to autologous bone grafting. CPCs can be composed of biphasic or multiphase calcium phosphate (CaP) compounds. A common way to process CPCs is by ball milling. Ball milling can be used for grinding or mechanosynthesis. The aim of this study was to determine the effect of well-defined ball milling grinding parameters, applied via different milling pathways, on the properties of CPCs. Starting CaP compounds used included α-tricalcium phosphate, dicalcium phosphate anhydrous and precipitated hydroxyapatite. Scanning electron microscopy showed changes in the powder morphology, which were related to the behavior of the starting CaP materials. Specific surface area (SSA) and particle size (PS) measurements exposed the effect of ball milling on the CaP compounds and CPC powders. X-ray diffraction revealed no effect of ball milling pathways or milling time on the composition of CPCs or the starting materials, but affected their crystallographic properties. No contamination of the milling media or transformation into an amorphous calcium phosphate compound was found. The milling pathways affected setting and cohesion. Fourier transform infrared spectroscopy (FTIR) revealed differences on the CPC v₄-PO₄³⁻ bands according to the interaction, created between the CaP compounds by the milling pathways. FTIR confirmed that the milling pathways changed the crystallographic properties. This study demonstrates that the pathways used for milling grinding modify the PS, SSA, and crystallographic properties of the powders, without affecting their composition. These modifications affected the bulk and reactivity properties of the CPCs by creating different setting and cohesion behaviors.

• Biodegradable composite scaffolds incorporating an intramedullary rod and delivering bone morphogenetic protein-2 for stabilization and bone regeneration in segmental long bone defects.

  Authors: A M Henslee, P P Spicer, D M Yoon, M B Nair, V V Meretoja, K E Witherel, J A Jansen, A G Mikos, F K Kasper

  Acta biomaterialia. 06/2011; 7(10):3627-37.

  In this study, a two-part bone tissue engineering scaffold was investigated. The scaffold consists of a solid poly(propylene fumarate) (PPF) intramedullary rod for mechanical support surrounded by aIn this study, a two-part bone tissue engineering scaffold was investigated. The scaffold consists of a solid poly(propylene fumarate) (PPF) intramedullary rod for mechanical support surrounded by a porous PPF sleeve for osseointegration and delivery of poly(dl-lactic-co-glycolic acid) (PLGA) microspheres with adsorbed recombinant human bone morphogenetic protein-2 (rhBMP-2). Scaffolds were implanted into critical size rat segmental femoral defects with internal fixation for 12 weeks. Bone formation was assessed throughout the study via radiography, and following euthanasia, via microcomputed tomography and histology. Mechanical stabilization was evaluated further via torsional testing. Experimental implant groups included the PPF rod alone and the rod with a porous PPF sleeve containing PLGA microspheres with 0, 2 or 8 μg of rhBMP-2 adsorbed onto their surface. Results showed that presence of the scaffold increased mechanical stabilization of the defect, as evidenced by the increased torsional stiffness of the femurs by the presence of a rod compared to the empty defect. Although the presence of a rod decreased bone formation, the presence of a sleeve combined with a low or high dose of rhBMP-2 increased the torsional stiffness to 2.06 ± 0.63 and 1.68 ± 0.56 N·mm, respectively, from 0.56 ± 0.24 N·mm for the rod alone. The results indicate that, while scaffolds may provide structural support to regenerating tissues and increase their mechanical properties, the presence of scaffolds within defects may hinder overall bone formation if they interfere with cellular processes.

• In vitro degradation rate of apatitic calcium phosphate cement with incorporated PLGA microspheres.

  Authors: R P Félix Lanao, S C G Leeuwenburgh, J G C Wolke, J A Jansen

  Acta biomaterialia. 06/2011; 7(9):3459-68.

  Calcium phosphate cements (CPCs) are frequently used as bone substitute material. Despite their superior clinical handling and excellent biocompatibility, they exhibit poor degradability, whichCalcium phosphate cements (CPCs) are frequently used as bone substitute material. Despite their superior clinical handling and excellent biocompatibility, they exhibit poor degradability, which limits bone ingrowth into the implant. Microspheres were prepared from poly(d,l-lactic-co-glycolic acid) (PLGA) and included in injectable CPCs as porogens in order to enhance its macroporosity after the polymeric microspheres had degraded. Upon degradation of the PLGA microspheres, acid is produced that enhances the dissolution rate of the CPC. However, the effect of the characteristics of PLGA microspheres on the degradation rate of CPCs has never been studied before. Therefore, the purpose of the current study was to investigate the dependence of CPC degradation on the chemical and morphological characteristics of incorporated PLGA microspheres. With respect to the chemical characteristics of the PLGA microspheres, the effects of both PLGA molecular weight (5, 17 and 44kDa) and end-group functionalization (acid-terminated or end-capped) were studied. In addition, two types of PLGA microspheres, differing in morphology (hollow vs. dense), were tested. The results revealed that, although both chemical parameters clearly affected the polymer degradation rate when embedded as hollow microspheres in CPC, the PLGA and CPC degradation rates were mainly dependent on the end-group functionalization. Moreover, it was concluded that dense microspheres were more efficient porogens than hollow ones by increasing the CPC macroporosity during in vitro incubation. By combining all test parameters, it was concluded that dense PLGA microspheres consisting of acid-terminated PLGA of 17kDa exhibited the highest and fastest acid-producing capacity and correspondingly the highest and fastest amount of porosity. In conclusion, the data presented here indicate that the combination of dense, acid-terminated PLGA microspheres with CPC emerges as a successful combination to achieve enhanced apatitic CPC degradation.

• Maxillary sinus augmentation with microstructured tricalcium phosphate ceramic in sheep.

  Authors: R J Klijn, J W M Hoekstra, J J J P Van Den Beucken, G J Meijer, J A Jansen

  Clinical oral implants research. 04/2011; 23(3):274-80.

  Objective: The objective of this study was to evaluate the biological performance of osteoinductive microstructured tricalcium phosphate (MSTCP) particles in maxillary sinus floor augmentationObjective: The objective of this study was to evaluate the biological performance of osteoinductive microstructured tricalcium phosphate (MSTCP) particles in maxillary sinus floor augmentation surgery in sheep. Material and methods: Sinus floor augmentation was performed in eight Swifter sheep. In each animal, the maxillary sinus floor was unilaterally augmented with MSTCP particles. Computed tomography (CT) imaging and histological analyses were performed after 12 weeks of implantation. Results: Maxillofacial CT, histology, histomorphometrical analysis and sequential polychrome fluorescent labeling indicated that MSTCP particles provided a scaffold for cell ingrowth and bone formation. After a 12-week implantation period, the sinuses grafted with MSTCP showed an increased bone height of 6 mm and a mean total bone volume of 43%, with significant degradation of MSTCP particles. Conclusion: MSTCP particles represent a suitable bone substitute material for maxillary sinus floor augmentation surgery. To cite this article: Klijn RJ, Hoekstra JWM, Van Den Beucken JJJP, Meijer GJ, Jansen JA. Maxillary sinus augmentation with microstructured tricalcium phosphate ceramic in sheep. Clin. Oral Impl. Res. 23, 2012; 274-280. doi: 10.1111/j.1600-0501.2011.02190.x.

• Biomimetic modification of synthetic hydrogels by incorporation of adhesive peptides and calcium phosphate nanoparticles: in vitro evaluation of cell behavior.

  Authors: M Bongio, J J J P van den Beucken, M R Nejadnik, S C G Leeuwenburgh, L A Kinard, F K Kasper, A G Mikos, J A Jansen

  European cells & materials. 01/2011; 22:359-76.

  The ultimate goal of this work was to develop a biocompatible and biomimetic in situ crosslinkable hydrogel scaffold with an instructive capacity for bone regenerative treatment. To this end,The ultimate goal of this work was to develop a biocompatible and biomimetic in situ crosslinkable hydrogel scaffold with an instructive capacity for bone regenerative treatment. To this end, synthetic hydrogels were functionalized with two key components of the extracellular matrix of native bone tissue, i.e. the three-amino acid peptide sequence RGD (which is the principal integrin-binding domain responsible for cell adhesion and survival of anchorage-dependent cells) and calcium phosphate (CaP) nanoparticles in the form of hydroxyapatite (which are similar to the inorganic phase of bone tissue). Rat bone marrow osteoblast-like cells (OBLCs) were encapsulated in four different biomaterials (plain oligo(poly(ethylene glycol) fumarate) (OPF), RGD-modified OPF, OPF enriched with CaP nanoparticles and RGD-modified OPF enriched with CaP nanoparticles) and cell survival, cell spreading, proliferation and mineralized matrix formation were determined via cell viability assay, histology and biochemical analysis for alkaline phosphatase activity and calcium. This study showed that RGD peptide sequences promoted cell spreading in OPF hydrogels and hence play a crucial role in cell survival during the early stage of culture, whereas CaP nanoparticles significantly enhanced cell-mediated hydrogel mineralization. Although cell spreading and proliferation activity were inhibited, the combined effect of RGD peptide sequences and CaP nanoparticles within OPF hydrogel systems elicited a better biological response than that of the individual components. Specifically, both a sustained cell viability and mineralized matrix production mediated by encapsulated OBLCs were observed within these novel biomimetic composite systems.

• Temperature changes in a cemented mandibular endoprosthesis: in vitro and in vivo studies.

  Authors: K W Lye, S Lee, H Tideman, M A W Merkx, J A Jansen

  International journal of oral and maxillofacial surgery. 11/2010; 40(1):86-93.

  Using polymethylmethacrylate (PMMA) cement in cemented endoprostheses may cause heat necrosis and prosthesis failure due to the highly exothermic reaction. This study determined the magnitude andUsing polymethylmethacrylate (PMMA) cement in cemented endoprostheses may cause heat necrosis and prosthesis failure due to the highly exothermic reaction. This study determined the magnitude and duration of temperature change during the cementation of a mandibular endoprosthesis in an in vitro and in vivo Macaca fasicularis model. In the in vivo study the median maximum temperature (T(max)) around the mandible-prosthesis unit (MPU) was 31.0°C with the peak T(max) at hole 1 (1mm from stem). The in vitro study recorded a lower T(max) and indicated a trend that increased spacing (groove) around the prosthesis results in a higher T(max). All the T(max) MPU measurements were lower than normal body temperature (38°C). In the in vivo study the median maximum temperature change (T(maxΔ)) was 1.8°C; in the vitro study, the T(maxΔ) of the 4mm groove width was significantly higher than all others. Temperature increases were transient, with the temperature returning to baseline a median of 6.0min after T(max). Histological analysis showed surrounding tissue at the cement-bone interface with mild inflammation. Within the parameters tested, there was minimal risk of thermal damage. The temperature changes were influenced by the quantity of cement used and the distance from the prosthesis stem.

• Bone reaction adjacent to microplasma-sprayed CaP-coated oral implants subjected to occlusal load, an experimental study in the dog. Part I: short-term results.

  Authors: R Junker, P J D Manders, J Wolke, Y Borisov, J A Jansen

  Clinical oral implants research. 11/2010; 21(11):1251-63.

  A new microplasma spraying equipment (MSE) to deposit calcium phosphate ceramic (CaP) coatings onto titanium substrates has been developed. With this system, it is possible to spray fine particlesA new microplasma spraying equipment (MSE) to deposit calcium phosphate ceramic (CaP) coatings onto titanium substrates has been developed. With this system, it is possible to spray fine particles and to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate is diminished. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying for dental implants. Also, the low level of noise (25-50 dB) and hardly any dust makes it possible to operate MSE under conditions of normal workrooms. The aim was to investigate, in a mandibular dog model, bone biological properties and the occlusal loading effects of titanium implants provided with newly developed microplasma-sprayed CaP coatings. For histomorphometrical evaluation, 48 screw-type titanium implants were inserted into the mandibles of six adult beagle dogs. The implants were either acid etched without additional coating, coated with a conventionally plasma-sprayed CaP ceramic, coated with a microplasma-sprayed CaP ceramic or with a microplasma-sprayed coating at the apical part only. To assess the effect of occlusal loading, a split-mouth design was used. Six weeks after implantation, the implants in one half of the mandible of each dog were functionally loaded, while the contra lateral implants served as control. Six weeks after loading, the animals were sacrificed and bone-to-implant contact as well as the amount of bone around the implants were assessed. Irrespective of surface and functional load, no statistically significant differences (P>0.05) were found either for bone-to-implant contact or for the amount of bone between the various implant surfaces. On the other hand, functional loading of the non-coated implants was associated with a tendency towards crestal bone loss. Within the limits of the experiment, we conclude that functional loading of MPS CaP coatings induces a favorable bone response, and furthermore, that the bone response, irrespective of the loading condition, does not differ from conventional plasma-sprayed CaP coatings.

• Loaded microplasma-sprayed CaP-coated implants in vivo.

  Authors: R Junker, P J D Manders, J Wolke, Y Borisov, I Braceras, J A Jansen

  Journal of dental research. 10/2010; 89(12):1489-93.

  Microplasma spray equipment to deposit calcium phosphate ceramic (CaP) coatings has been developed. Fifty-six titanium implants were inserted into the mandibles of 7 adult beagle dogs. The implantsMicroplasma spray equipment to deposit calcium phosphate ceramic (CaP) coatings has been developed. Fifty-six titanium implants were inserted into the mandibles of 7 adult beagle dogs. The implants were either acid-etched (NC), conventionally plasma-sprayed (PS), micro-plasma-sprayed (MPS), or micro-plasma-sprayed (aMPS) only at the apical part. After 6 weeks, implants in one half of the mandible were subjected to load. Fifty-two weeks thereafter, the animals were killed. Regardless of load, bone healing was comparable for all surfaces tested. It was concluded that loading of MPS CaP-coated implants evokes a favorable bone response, and that the bone response does not differ from that of PS CaP-coated implants. However, functional loading of PS as well as MPS CaP-coated implants might be associated with increased crestal bone maintenance as compared with non-coated implants.

• A novel implantation model for evaluation of bone healing response to dental implants: the goat iliac crest.

  Authors: C Schouten, G J Meijer, J J J P van den Beucken, P H M Spauwen, J A Jansen

  Clinical oral implants research. 04/2010; 21(4):414-23.

  Despite the availability of numerous animal models for testing the biological performance of dental and orthopedic implants, the selection of a suitable model is complex. This paper presents a newDespite the availability of numerous animal models for testing the biological performance of dental and orthopedic implants, the selection of a suitable model is complex. This paper presents a new model for objective and standardized evaluation of bone responses to implants using the iliac crest in goats. The feasibility of the iliac crest model regarding anatomy and implant positioning was determined using two cadaveric specimens and the bone structure was evaluated and compared with that of the goat femoral condyle. Additionally, the validity of the model was tested by performing an in vivo study. By means of a rather simple, safe, fast and reproducible surgical procedure, the iliac crest in goats could be approached and allowed the implantation of maximally five dental implants per iliac crest. Because of the bilateral implantation possibility, statistical comparisons between groups on either side of the goat could be performed, resulting in a high statistical power, and hence a reduction in the number of animals required to obtain significant data. In terms of surgical approach, anatomy and implant positioning, the iliac crest is the preferred model over the femoral condyle model. The iliac crest implantation model is suitable for evaluation of the osteogenic response to bone implant materials and represents a justified and deliberate alternative to the already existing animal models.

• The effect of platelet-rich plasma on early and late bone healing using a mixture of particulate autogenous cancellous bone and Bio-Oss: an experimental study in goats.

  Authors: R E C M Mooren, A C A Dankers, M A W Merkx, E M Bronkhorst, J A Jansen, P J W Stoelinga

  International journal of oral and maxillofacial surgery. 04/2010; 39(4):371-8.

  Platelet-rich plasma (PRP), containing various growth factors, may speed up wound and bone healing. Using osteoconductive alloplastic materials in reconstructive surgery, the amount of autogenousPlatelet-rich plasma (PRP), containing various growth factors, may speed up wound and bone healing. Using osteoconductive alloplastic materials in reconstructive surgery, the amount of autogenous bone needed can be reduced. The purpose of this experiment was to study the effect of PRP on a mixture of autogenous bone and deproteinized bovine bone mineral (Bio-Oss) particles in goats. Four, round, critical size defects were made in the foreheads of 20 goats. In all goats the defects were filled with a mixture of autogenous particulate cancellous bone and (Bio-Oss) particles, in which 1 ml of PRP was added in two of the four defects. The goats were allocated to four subgroups each containing five goats, which were killed after 1, 2, 6 and 12 weeks. The results of the histological and histomorphometric examination showed that early and late bone healing were not enhanced when PRP was used.

• Bone particles and the undersized surgical technique.

  Authors: A Tabassum, X F Walboomers, J G C Wolke, G J Meijer, J A Jansen

  Journal of dental research. 03/2010; 89(6):581-6.

  During the installation of implants, osteogenic bone particles are translocated along the surface. These particles may contribute to peri-implant bone healing. Based on this phenomenon, it isDuring the installation of implants, osteogenic bone particles are translocated along the surface. These particles may contribute to peri-implant bone healing. Based on this phenomenon, it is hypothesized that implants placed with undersized drilling, besides showing higher primary-implant stability, also enhance the amount and osteogenic responses of these bone particles. Biocomp implants were inserted into bicortical fresh-cadaver bone by a press-fit or an undersized surgical technique, and peak-insertion torque values (ITV) were measured. After explantation, the implants were incubated in culture medium up to 24 days. Histology, bone-implant contact (BIC), micro-CT, scanning electron microscopy (SEM), and calcium (Ca) measurements were performed. ITV were significantly higher for implants placed with an undersized technique. Moreover, histology, BIC, micro-CT, SEM, and Ca measurements confirmed the presence of more bone-like tissue on implants inserted with an undersized technique. The undersized surgical technique not only results in higher primary-implant stability, but also induces more translocated bone particles, thus having a positive influence on the osteogenic response.

• The influence of nanoscale topographical cues on initial osteoblast morphology and migration.

  Authors: E Lamers, R van Horssen, J te Riet, F Cmjm van Delft, R Luttge, X F Walboomers, J A Jansen

  European cells & materials. 01/2010; 20:329-43.

  The natural environment of a living cell is not only organized on a micrometer, but also on a nanometer scale. Mimicking such a nanoscale topography in implantable biomaterials is critical to guideThe natural environment of a living cell is not only organized on a micrometer, but also on a nanometer scale. Mimicking such a nanoscale topography in implantable biomaterials is critical to guide cellular behavior. Also, a correct positioning of cells on biomaterials is supposed to be very important for promoting wound healing and tissue regeneration. The exact mechanism by which nanotextures can control cellular behavior are thus far not well understood and it is thus far unknown how cells recognize and respond to certain surface patterns, whereas a directed response appears to be absent on other pattern types. Focal adhesions (FAs) are known to be involved in the process of specific pattern recognition and subsequent response by cells. In this study, we used a high throughput screening "Biochip" containing 40 different nanopatterns to evaluate the influence of several nanotopographical cues like depth, width, (an)isotropy and spacing (ridge-groove ratio) on osteoblast behavior. Microscopical analysis and time lapse imaging revealed that an isotropic topography did not alter cell morphology, but it highly induced cell motility. Cells cultured on anisotropic topographies on the other hand, were highly elongated and aligned. Time-lapse imaging revealed that cell motility is highly dependent on the ridge-groove ratio of anisotropic patterns. The highest motility was observed on grooves with a ratio of 1:3, whereas the lowest motility was observed on ratios of 1:1 and 3:1. FA measurements demonstrated that FA-length decreased with increasing motility. From the study it can be concluded that osteoblast behavior is tightly controlled by nanometer surface features.

• In vivo degradation of calcium phosphate cement incorporated with biodegradable microspheres.

  Authors: W J E M Habraken, H B Liao, Z Zhang, J G C Wolke, D W Grijpma, A G Mikos, J Feijen, J A Jansen

  Acta biomaterialia. 12/2009;

  In this study we investigated the influence of the microsphere degradation or erosion mechanism on the in vivo degradation of microsphere/calcium phosphate cement composites (microsphere CPCs) forIn this study we investigated the influence of the microsphere degradation or erosion mechanism on the in vivo degradation of microsphere/calcium phosphate cement composites (microsphere CPCs) for tissue engineering. Therefore, microspheres composed of poly(lactic-co-glycolic acid) (PLGA), gelatin and poly(trimethylene carbonate) (PTMC) were used as model and the resulting microsphere CPCs were implanted subcutaneously for 4, 8 and 12 weeks in the back of New Zealand white rabbits. Besides degradation, the soft tissue response to these formulations was evaluated. After retrieval, specimens were analyzed by physicochemical characterization and histological analysis. RESULTS: showed that all microsphere CPCs exhibited microsphere degradation after 12 weeks of subcutaneous implantation, which was accompanied by decreasing compression strength. The PLGA microspheres exhibited bulk erosion instantly through the whole composite, whereas with gelatin type B degradation of the microspheres proceeded from the outside to the center of the composite. High molecular weight PTMC microspheres exhibited surface erosion resulting in decreasing microsphere sizes. Furthermore, all composites showed a similar tissue response with a decreasing capsule thickness over time and a persisting moderate inflammatory response at the implant interface. In conclusion: microsphere CPCs can be used to generate porous scaffolds in an in vivo environment after degradation of microspheres with various degradation/erosion mechanisms.

• Healing of bone defects in the goat mandible, using COLLOSS(R) E and beta-tricalciumphosphate.

  Authors: M E L Nienhuijs, X F Walboomers, A Briest, M A W Merkx, P J W Stoelinga, J A Jansen

  Journal of biomedical materials research. Part B, Applied biomaterials. 12/2009;

  COLLOSS(R) E, an equine extracellular matrix product containing native transforming growth factor beta1 and several bone morphogenetic proteins, has shown osteoinductive properties in ectopic sites.COLLOSS(R) E, an equine extracellular matrix product containing native transforming growth factor beta1 and several bone morphogenetic proteins, has shown osteoinductive properties in ectopic sites. This study was set up to examine its properties in an orthotoptic site in conjunction with a beta-tricalciumphosphate (beta-TCP) scaffolding material. Thirty-two 17-mm circular defects in goat mandibles were filled with COLLOSS E, beta-TCP, COLLOSS E + beta-TCP, or left empty. After 9 weeks the results were quantified by micro-computed tomography and histology. The empty defects contained the highest percentage of new bone (62%). The beta-TCP scaffold resulted in 38% (p = 0.0029), the mixture of beta-TCP/COLLOSS E resulted in 36% (p = 0.0057), while the use of COLLOSS E alone resulted in 55% (not significant p = 0.34). These results show that addition of TCP did not result in the expected synergy with regard to the healing of the defect and seemed even to inhibit the healing process. On the other hand, the addition of COLLOSS E induced the formation of small islands of new bone, not connected to the defect edges. This was not observed in the specimens not containing COLLOSS E (4.61% of bone formation centrally in the defect vs. 0.56%; p = 0.042). In conclusion, the results of the present study are somewhat unexpected in that the empty defects showed the most bone ingrowth; however, this ingrowth was always connected to the defect edges. In contrast, the application of COLLOSS E with or without beta-TCP induced bone formation in the center of the defects also. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.

• Bone-supportive behavior of microplasma-sprayed CaP-coated implants: mechanical and histological outcome in the goat.

  Authors: R Junker, P J D Manders, J Wolke, Y Borisov, J A Jansen

  Clinical oral implants research. 12/2009;

  Background: New microplasma spray (MPS) equipment to deposit calcium phosphate (CaP) ceramic coatings onto titanium substrates has been developed. With this apparatus, it is possible to spray fineBackground: New microplasma spray (MPS) equipment to deposit calcium phosphate (CaP) ceramic coatings onto titanium substrates has been developed. With this apparatus, it is possible to spray fine particles, as well as to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate is reduced. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying of dental implants. Additionally, the low level of noise (25-50 dB) and hardly any dust makes it possible to operate the MSE under normal workroom conditions. Objective: The aim of this study was to examine the biological properties of different MPS - CaP coatings on titanium implants when inserted into the femoral condyle of goats. Material and methods: For histomorphometrical evaluation as well as mechanical testing, 48 screw-type titanium implants were inserted into the femoral condyles of 12 goats each. The implants were either coated with a conventionally plasma-sprayed CaP ceramic, MPS CaP ceramic, or acid-etched without an additional CaP coating. Six and 12 weeks after implantation, the animals were sacrificed and bone-to-implant contact, amount of bone, as well as mechanical bone fixation were evaluated. Results: For bone-to-implant contact no statistically significant difference was found between the different CaP coatings. However, statistically significant differences were found between non-coated, acid-etched titanium implants and CaP-coated implants after 6 and 12 weeks of healing. The bone values were not statistically significantly different between the different CaP coatings at 6 and 12 weeks. Furthermore, CaP ceramic-coated implants showed statistically significantly higher torque values compared with the non-coated implants after 6 and at 12 weeks of healing. No significant differences existed between the various types of CaP coatings. Conclusion: On the basis of our observations, we conclude that conventionally plasma-sprayed CaP ceramic-coated implants, as well as MPS-coated implants have a comparable effect on adjacent bone response. To cite this article: Junker R, Manders PJD, Wolke J, Borisov Y, Jansen JA. Bone-supportive behavior of microplasma-sprayed CaP-coated implants: mechanical and histological outcome in the goat.