John A Jansen

Publications of John A Jansen

• Regeneration of the periodontium using enamel matrix derivative in combination with an injectable bone cement.

  Authors: Daniël A W Oortgiesen, Gert J Meijer, Antonius L J J Bronckers, X Frank Walboomers, John A Jansen

  Clinical oral investigations. 05/2012;

  OBJECTIVES: Enamel matrix derivative (EMD) has proven to enhance periodontal regeneration; however, its effect is mainly restricted to the soft periodontal tissues. Therefore, to stimulate not onlyOBJECTIVES: Enamel matrix derivative (EMD) has proven to enhance periodontal regeneration; however, its effect is mainly restricted to the soft periodontal tissues. Therefore, to stimulate not only the soft tissues, but also the hard tissues, in this study EMD is combined with an injectable calcium phosphate cement (CaP; bone graft material). The aim was to evaluate histologically the healing of a macroporous CaP in combination with EMD. MATERIALS AND METHODS: Intrabony, three-wall periodontal defects (2 × 2 × 1.7 mm) were created mesial of the first upper molar in 15 rats (30 defects). Defects were randomly treated according to one of the three following strategies: EMD, calcium phosphate cement and EMD, or left empty. The animals were killed after 12 weeks, and retrieved samples were processed for histology and histomorphometry. RESULTS: Empty defects showed a reparative type of healing without periodontal ligament or bone regeneration. As measured with on a histological grading scale for periodontal regeneration, the experimental groups (EMD and CaP/EMD) scored equally, both threefold higher compared with empty defects. However, most bone formation was measured in the CaP/EMD group; addition of CAP to EMD significantly enhanced bone formation with 50 % compared with EMD alone. CONCLUSIONS: Within the limits of this animal study, the adjunctive use of EMD in combination with an injectable cement, although it did not affect epithelial downgrowth, appeared to be a promising treatment modality for regeneration of bone and ligament tissues in the periodontium. CLINICAL RELEVANCE: The adjunctive use of EMD in combination with an injectable cement appears to be a promising treatment modality for regeneration of the bone and ligament tissues in the periodontium.

• Periodontal regeneration using an injectable bone cement combined with BMP-2 or FGF-2.

  Authors: Daniël Aw Oortgiesen, X Frank Walboomers, Antonius Ljj Bronckers, Gert J Meijer, John A Jansen

  Journal of tissue engineering and regenerative medicine. 05/2012;

  Periodontitis is a frequently diagnosed oral disease characterized by bone resorption and soft tissue loss around teeth. Unfortunately, currently available therapies only slow or arrest progress ofPeriodontitis is a frequently diagnosed oral disease characterized by bone resorption and soft tissue loss around teeth. Unfortunately, currently available therapies only slow or arrest progress of the disease. Ideally, treatment of periodontal defects should be focused on complete regeneration of the lost tissues [(bone and periodontal ligament (PDL)]. As a result, this study used intrabony defects to evaluate the regenerative potential of an injectable macroporous calcium phosphate cement (CaP) in combination with bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2). After creating 30 periodontal defects in 15 Wistar rats, three treatment strategies were conducted: application of CaP only, CaP + BMP-2 and CaP + FGF-2. Animals were euthanized after 12 weeks and processed for histology and histomorphometry. Using CaP alone resulted in limited effects on PDL and bone healing. CaP + BMP-2 showed a good response for bone healing; a significant 2.4 fold increase in bone healing score was observed compared to CaP. However, for PDL healing, CaP + BMP-2 treatment showed no difference compared to the CaP group. The best results were observed with the combined treatment of CaP + FGF-2, which showed a significant 3.3 fold increase in PDL healing score compared to CaP + BMP-2 and a significant 2.6 fold increase compared to CaP. For bone healing, CaP +  FGF-2 showed a significant 1.9 fold increase compared to CaP but no significant difference was noted compared to the CaP + BMP-2 group. The combination of a topical application of FGF-2 and an injectable CaP seems to be a promising treatment modality for periodontal regeneration. Copyright © 2012 John Wiley & Sons, Ltd.

• Alkaline phosphatase immobilization onto Bio-Gide(®) and Bio-Oss(®) for periodontal and bone regeneration.

  Authors: Daniël A W Oortgiesen, Adelina S Plachokova, Claudia Geenen, Gert J Meijer, X Frank Walboomers, Jeroen J J P van den Beucken, John A Jansen

  Journal of clinical periodontology. 03/2012;

  AIM: To evaluate the effect of alkaline phosphatase (ALP) immobilization onto Bio-Gide(®) in vitro, and to study the in vivo performance of ALP-enriched Bio-Gide(®) and/or Bio-Oss(®) with the purposeAIM: To evaluate the effect of alkaline phosphatase (ALP) immobilization onto Bio-Gide(®) in vitro, and to study the in vivo performance of ALP-enriched Bio-Gide(®) and/or Bio-Oss(®) with the purpose to enhance periodontal regeneration. MATERIALS AND METHODS: Alkaline phosphatase ALP was immobilized onto Bio-Gide(®) and Bio-Oss(®) . Forty-eight rats received periodontal defects, which were treated according to one of the following strategies: Bio-Gide(®) , Bio-Gide(®) -ALP, Bio-Gide(®) -ALP/Bio-Oss(®) , Bio-Gide(®) /Bio-Oss(®) -ALP, Bio-Gide(®) -ALP/Bio-Oss(®) -ALP, or empty. Micro-CT and histological analysis were performed. RESULTS: A 30 min ALP-deposition time was determined as optimal from mineralization capacity assessment and consequently used as Bio-Gide(®) -ALP membranes in the animal experiment. In vivo results showed that after 2 weeks, the defect and implanted materials were still visible, an inflammatory response was present, and membrane degradation was ongoing. Bone formation, although limited, was observed in the majority of Bio-Gide(®) -ALP specimens and all of the Bio-Gide(®) /Bio-Oss(®) -ALP specimens, and was significantly higher compared with Bio-Gide(®) and empty controls. After 6 weeks, the defects and particles were still visible, whereas membranes were completely degraded. The inflammatory response was decreased and bone formation appeared superior for Bio-Gide(®) -ALP treated defects. CONCLUSION: Immobilization of ALP onto guided tissue regeneration (GTR)/ guided bone regeneration (GBR)-materials (Bio-Gide(®) and Bio-Oss(®) ) can enhance the performance of these materials in GTR/GBR procedures.

• In situ formation of porous space maintainers in a composite tissue defect.

  Authors: Patrick P Spicer, James D Kretlow, Allan M Henslee, Meng Shi, Simon Young, Nagi Demian, John A Jansen, Mark E Wong, Antonios G Mikos, F Kurtis Kasper

  Journal of biomedical materials research. Part A. 03/2012; 100(4):827-33.

  Reconstruction of composite defects involving bone and soft tissue presents a significant clinical challenge. In the craniofacial complex, reconstruction of the soft and hard tissues is critical forReconstruction of composite defects involving bone and soft tissue presents a significant clinical challenge. In the craniofacial complex, reconstruction of the soft and hard tissues is critical for both functional and aesthetic outcomes. Constructs for space maintenance provide a template for soft tissue regeneration, priming the wound bed for a definitive repair of the bone tissue with greater success. However, materials used clinically for space maintenance are subject to poor soft tissue integration, which can result in wound dehiscence. Porous materials in space maintenance applications have been previously shown to support soft tissue integration and to allow for drug release from the implant to further prepare the wound bed for definitive repair. This study evaluated solid and low porosity (16.9% ± 4.1%) polymethylmethacrylate space maintainers fabricated intraoperatively and implanted in a composite rabbit mandibular defect model for 12 weeks. The data analyses showed no difference in the solid and porous groups both histologically, evaluating the inflammatory response at the interface and within the pores of the implants, and grossly, observing the healing of the soft tissue defect over the implant. These results demonstrate the potential of porous polymethylmethacrylate implants formed in situ for space maintenance in the craniofacial complex, which may have implications in the potential delivery of therapeutic drugs to prime the wound site for a definitive bone repair. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

• Local delivery of small and large biomolecules in craniomaxillofacial bone.

  Authors: Wei Ji, Huanan Wang, Jeroen J J P van den Beucken, Fang Yang, X Frank Walboomers, Sander Leeuwenburgh, John A Jansen

  Advanced drug delivery reviews. 03/2012;

  Current state of the art reconstruction of bony defects in the craniomaxillofacial (CMF) area involves transplantation of autogenous or allogenous bone grafts. However, the inherent drawbacks of thisCurrent state of the art reconstruction of bony defects in the craniomaxillofacial (CMF) area involves transplantation of autogenous or allogenous bone grafts. However, the inherent drawbacks of this approach strongly urge clinicians and researchers to explore alternative treatment options. Currently, a wide interest exists in local delivery of biomolecules from synthetic biomaterials for CMF bone regeneration, in which small biomolecules are rapidly emerging in recent years as an interesting adjunct for upgrading the clinical treatment of CMF bone regeneration under compromised healing conditions. This review highlights recent advances in the local delivery small and large biomolecules for the clinical treatment of CMF bone defects. Further, it provides a perspective on the efficacy of biomolecule delivery in CMF bone regeneration by reviewing presently available reports of pre-clinical studies using various animal models.

• Facilitating the mineralization of oligo(poly(ethylene glycol) fumarate) hydrogel by incorporation of hydroxyapatite nanoparticles.

  Authors: M Reza Nejadnik, Antonios G Mikos, John A Jansen, Sander C G Leeuwenburgh

  Journal of biomedical materials research. Part A. 02/2012; 100(5):1316-23.

  Exploring strategies to induce the mineralization of hydrogels is an important step toward the development of hydrogel-based materials for bone regeneration. In the current study, the effect ofExploring strategies to induce the mineralization of hydrogels is an important step toward the development of hydrogel-based materials for bone regeneration. In the current study, the effect of incorporating hydroxyapatite (HA) nanoparticles on the mineralization capacity of an inert poly(ethylene glycol) (PEG)-based hydrogel was investigated. HA nanoparticles were either directly loaded into oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel or loaded into commonly used gelatin microsphere porogens that were subsequently integrated in the OPF matrix. Mineralization of composites after immersion of the samples in simulated body fluid up to 28 days was assessed. In contrast to the blank OPF hydrogel, the HA-containing constructs strongly mineralized such that the average rate of calcium uptake by the material was enhanced by orders of magnitude. The mineral formed was observed to be apatitic and needle shaped. The presented method allows modification of inert PEG-based hydrogels into bioactive biomaterials for applications in bone regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2012.

• Maxillary sinus floor augmentation with injectable calcium phosphate cements: a pre-clinical study in sheep.

  Authors: Jan Willem M Hoekstra, Reinoud J Klijn, Gert J Meijer, Jeroen J J P van den Beucken, John A Jansen

  Clinical oral implants research. 02/2012;

  OBJECTIVES: The aim of this pre-clinical study was to evaluate the biological performance of two injectable calcium phosphate cement (CPC) composite materials containingOBJECTIVES: The aim of this pre-clinical study was to evaluate the biological performance of two injectable calcium phosphate cement (CPC) composite materials containing poly(D,L-lactic-co-glycolic)acid (PLGA) microspheres with different properties in a maxillary sinus floor elevation model in sheep. MATERIALS AND METHODS: PLGA microspheres were made of either low molecular weight (~17 kDa) acid-terminated PLGA (PLGA(L-AT) ) or high molecular weight (~44 kDa) end-capped PLGA (PLGA(H-EC) ) and incorporated in CPC. Eight female Swifter sheep underwent a bilateral maxillary sinus floor elevation procedure via an extra-oral approach. All animals received both materials, alternately injected in the left and right sinus (split-mouth model) and a time point of 12 weeks was used. Analysis of biological performance was based on histology, histomorphometry, and evaluation of sequential fluorochrome labeling. RESULTS: Both types of CPC-PLGA composites showed biocompatibility and direct bone-cement contact. CPC-PLGA(L-AT) showed a significantly higher degradation distance compared to CPC-PLGA(H-EC) (1949 ± 1295 μm vs. 459 ± 267 μm; P = 0.0107). Further, CPC-PLGA(L-AT) showed significantly more bone in the region of interest (26.4 ± 10.5% vs. 8.6 ± 3.9% for PLGA(H-EC) ; P = 0.0009) and significantly less remaining CPC material (61.2 ± 17.7% vs. 81.9 ± 10.9% for PLGA(H-EC) ; P = 0.0192). CONCLUSIONS: Both CPC-PLGA(L-AT) and CPC-PLGA(H-EC) demonstrated to be safe materials for sinus floor elevation procedures in a large animal model, presenting biocompatibility and direct bone contact. In view of material performance, CPC-PLGA(L-AT) showed significantly faster degradation and a significantly higher amount of newly formed bone compared to CPC-PLGA(H-EC) .

• Detection, mapping, and quantification of single walled carbon nanotubes in histological specimens with photoacoustic microscopy.

  Authors: Pramod K Avti, Song Hu, Christopher Favazza, Antonios G Mikos, John A Jansen, Kenneth R Shroyer, Lihong V Wang, Balaji Sitharaman

  PloS one. 01/2012; 7(4):e35064.

  In the present study, the efficacy of multi-scale photoacoustic microscopy (PAM) was investigated to detect, map, and quantify trace amounts [nanograms (ng) to micrograms (µg)] of SWCNTs in a varietyIn the present study, the efficacy of multi-scale photoacoustic microscopy (PAM) was investigated to detect, map, and quantify trace amounts [nanograms (ng) to micrograms (µg)] of SWCNTs in a variety of histological tissue specimens consisting of cancer and benign tissue biopsies (histological specimens from implanted tissue engineering scaffolds). Optical-resolution (OR) and acoustic-resolution (AR) - Photoacoustic microscopy (PAM) was employed to detect, map and quantify the SWCNTs in a variety of tissue histological specimens and compared with other optical techniques (bright-field optical microscopy, Raman microscopy, near infrared (NIR) fluorescence microscopy). Both optical-resolution and acoustic-resolution PAM, allow the detection and quantification of SWCNTs in histological specimens with scalable spatial resolution and depth penetration. The noise-equivalent detection sensitivity to SWCNTs in the specimens was calculated to be as low as ∼7 pg. Image processing analysis further allowed the mapping, distribution, and quantification of the SWCNTs in the histological sections. The results demonstrate the potential of PAM as a promising imaging technique to detect, map, and quantify SWCNTs in histological specimens, and could complement the capabilities of current optical and electron microscopy techniques in the analysis of histological specimens containing SWCNTs.

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• Effect of calcium carbonate on hardening, physicochemical properties, and in vitro degradation of injectable calcium phosphate cements.

  Authors: Kemal Sariibrahimoglu, Sander C G Leeuwenburgh, Joop G C Wolke, Li Yubao, John A Jansen

  Journal of biomedical materials research. Part A. 12/2011; 100(3):712-9.

  The main disadvantage of apatitic calcium phosphate cements (CPCs) is their slow degradation rate, which limits complete bone regeneration. Carbonate (CO₃²⁻) is the common constituent of bone and itThe main disadvantage of apatitic calcium phosphate cements (CPCs) is their slow degradation rate, which limits complete bone regeneration. Carbonate (CO₃²⁻) is the common constituent of bone and it can be used to improve the degradability of the apatitic calcium phosphate ceramics. This study aimed to examine the effect of calcite (CaCO₃) incorporation into CPCs. To this end, the CaCO₃ amount (0-4-8-12 wt %) and its particle size (12.0-μm-coarse or 2.5-μm-fine) were systematically investigated. In comparison to calcite-free CPC, the setting time of the bone substitute was delayed with increasing CaCO₃ incorporation. Reduction of the CaCO₃ particle size in the initial powder increased the injectability time of the paste. During hardening of the cements, the increase in calcium release was inversely proportional to the extent of CO₃²⁻ incorporation into apatites. The morphology of the carbonate-free product consisted of large needle-like crystals, whereas small plate-like crystals were observed for carbonated apatites. Compressive strength decreased with increasing CaCO₃ content. In vitro accelerated degradation tests demonstrated that calcium release and dissolution rate from the set cements increased with increasing the incorporation of CO₃²⁻, whereas differences in CaCO₃ particle size did not affect the in vitro degradation rate under accelerated conditions.

• Biocompatibility and bone formation with porous modified PMMA in normal and irradiated mandibular tissue.

  Authors: Kok Weng Lye, Henk Tideman, Joop C G Wolke, Matthias A W Merkx, Francis K C Chin, John A Jansen

  Clinical oral implants research. 12/2011;

  A cemented mandibular endoprosthesis is a potentially viable option for mandibular reconstruction after ablative surgery. The commonly used PMMA cement has the inherent weakness of a lack ofA cemented mandibular endoprosthesis is a potentially viable option for mandibular reconstruction after ablative surgery. The commonly used PMMA cement has the inherent weakness of a lack of bioactivity. Improvement by the addition of porosities and bioactive compounds like calcium phosphates may resolve this issue. OBJECTIVE: The objective of this study was to assess the bone and tissue response to two modified PMMA cements with post-operative radiation as an additional influencing factor. MATERIALS & METHODS: An in vivo animal study was performed using a mandibular rabbit model. A porous PMMA cement (A) and a porous cement incorporated with Beta-tricalcium phosphate particles (b-TCP) (B) were placed in bilateral mandibular defects with exposed roots and mandibular nerve of 20 animals. Half of the animals underwent additional post-operative radiation. RESULTS: The animals were healthy with only a minor complication in one rabbit. Temperature analysis showed no significant risk of thermal necrosis with the maximal in vivo cement temperature at 37.8°C. Histology demonstrated: (1) good bone ingrowth around the defect as well as within the pores of the cement and defect bridging was achieved in 70% of the specimens after 12-15 weeks of implantation, (2) no pulpal injury with minor secondary cementum response, (3) an intact mandibular nerve with no inflammation, (4) extensive degradation and resorption of the b-TCP particles by 12-15 weeks, and (5) presence of an intervening thin fibrous tissue at the bone-to-cement interface. Histomorphometrical analysis revealed that there was no difference between the different cements and the presence or absence of post-operative radiation. The 12-15 weeks specimens showed significantly more bone ingrowth and bone maturity than the 4-7 weeks specimens. CONCLUSION: Both modified PMMA cements have good biocompatibility, bioactivity and support bone ingrowth and additional post-operative radiation did not show any negative effects.

• Bone response to fast-degrading, injectable calcium phosphate cements containing PLGA microparticles.

  Authors: Rosa P Félix Lanao, Sander C G Leeuwenburgh, Joop G C Wolke, John A Jansen

  Biomaterials. 08/2011; 32(34):8839-47.

  Apatitic calcium phosphate cements (CPC) are frequently used to fill bone defects due to their favourable clinical handling and excellent bone response, but their lack of degradability inhibitsApatitic calcium phosphate cements (CPC) are frequently used to fill bone defects due to their favourable clinical handling and excellent bone response, but their lack of degradability inhibits complete bone regeneration. In order to render these injectable CaP cements biodegradable, hollow microspheres made of poly (D,L-lactic-co-glycolic) acid (PLGA) have been previously used as porogen since these microspheres were shown to be able to induce macroporosity upon degradation as well as to accelerate CPC degradation by release of acid degradation products. Recently, the capacity of PLGA microspheres to form porosity in situ in injectable CPCs was optimized by investigating the influence of PLGA characteristics such as microsphere morphology (dense vs. hollow) and end-group functionalization (acid terminated vs. end-capped) on acid production and corresponding porosity formation in vitro. The current study has investigated the in vivo bone response to CPCs containing two types of microspheres (hollow and dense) made of PLGA with two different end-group functionalizations (end capped and acid terminated). Microspheres were embedded in CPC and injected in the distal femoral condyle of New Zealand White Rabbits for 6 and 12 weeks. Histological results confirmed the excellent biocompatibility and osteoconductivity of all tested materials. Composites containing acid terminated PLGA microspheres displayed considerable porosity and concomitant bone ingrowth after 6 weeks, whereas end capped microspheres only revealed open porosity after 12 weeks of implantation. In addition, it was found that dense PLGA microspheres induced significantly more CPC degradation and bone tissue formation compared to hollow PLGA microspheres. In conclusion, it was shown that PLGA microspheres have a strong capacity to induce fast degradation of injectable CPC and concomitant replacement by bone tissue by controlled release of acid polymeric degradation products without compromising the excellent biocompatibility and osteoconductivity of the CPC matrix.

• Influence of the pore generator on the evolution of the mechanical properties and the porosity and interconnectivity of a calcium phosphate cement.

  Authors: Marco A Lopez-Heredia, Kemal Sariibrahimoglu, Wanxun Yang, Marc Bohner, Daiki Yamashita, Aliz Kunstar, Aart A van Apeldoorn, Ewald M Bronkhorst, Rosa P Félix Lanao, Sander C G Leeuwenburgh, Kiyoshi Itatani, Fang Yang, Phil Salmon, Joop G C Wolke, John A Jansen

  Acta biomaterialia. 08/2011; 8(1):404-14.

  Porosity and interconnectivity are important properties of calcium phosphate cements (CPCs) and bone-replacement materials. Porosity of CPCs can be achieved by adding polymeric biodegradablePorosity and interconnectivity are important properties of calcium phosphate cements (CPCs) and bone-replacement materials. Porosity of CPCs can be achieved by adding polymeric biodegradable pore-generating particles (porogens), which can add porosity to the CPC and can also be used as a drug-delivery system. Porosity affects the mechanical properties of CPCs, and hence is of relevance for clinical application of these cements. The current study focused on the effect of combinations of polymeric mesoporous porogens on the properties of a CPC, such as specific surface area, porosity and interconnectivity and the development of mechanical properties. CPC powder was mixed with different amounts of PLGA porogens of various molecular weights and porogen sizes. The major factors affecting the properties of the CPC were related to the amount of porogen loaded and the porogen size; the molecular weight did not show a significant effect per se. A minimal porogen size of 40 μm in 30 wt.% seems to produce a CPC with mechanical properties, porosity and interconnectivity suitable for clinical applications. The properties studied here, and induced by the porogen and CPC, can be used as a guide to evoke a specific host-response to maintain CPC integrity and to generate an explicit bone ingrowth.

• An injectable calcium phosphate cement for the local delivery of paclitaxel to bone.

  Authors: Marco A Lopez-Heredia, G J Bernard Kamphuis, Peter C Thüne, F Cumhur Öner, John A Jansen, X Frank Walboomers

  Biomaterials. 08/2011; 32(23):5411-6.

  Bone metastases are usually treated by surgical removal, fixation and chemotherapeutic treatment. Bone cement is used to fill the resection voids. The aim of this study was to develop a local drugBone metastases are usually treated by surgical removal, fixation and chemotherapeutic treatment. Bone cement is used to fill the resection voids. The aim of this study was to develop a local drug delivery system using a calcium phosphate cement (CPC) as carrier for chemotherapeutic agents. CPC consisted of alpha-tricalcium phosphate, calcium phosphate dibasic and precipitated hydroxyapatite powders and a 2% Na(2)HPO(4) hardening solution. Scanning electron microscopy (SEM) was used to observe CPC morphology. X-ray diffraction (XRD) was used to follow CPC transformation. The loading/release capacity of the CPC was studied by a bovine serum albumin-loading model. Release/retention was measured by high performance liquid chromatography and X-ray photoelectron spectrometry. For chemotherapeutic loading, paclitaxel (PX) was loaded onto the CPC discs by absorption. Viability of osteosarcoma U2OS and metastatic breast cancer MDA-MB-231 cells was measured by an AlamarBlue assay. Results of SEM and XRD showed changes in CPC due to its transformation. The loading model indicated a high retention behavior by the CPC composition. Cell viability tests indicated a PX minimal lethal dose of 90 μg/ml. PX released from CPC remained active to influence cell viability. In conclusion, this study demonstrated that CPC is a feasible delivery vector for chemotherapeutic agents.

• Translocation of autogenous bone particles to improve peri-implant osteogenesis.

  Authors: Afsheen Tabassum, X Frank Walboomers, Gert J Meijer, John A Jansen

  Journal of tissue engineering and regenerative medicine. 07/2011;

  During the placement of titanium implants into bone, particles are loosened and translocated as a result of the inherent roughness of the surface. Such bone particles have been shown to play aDuring the placement of titanium implants into bone, particles are loosened and translocated as a result of the inherent roughness of the surface. Such bone particles have been shown to play a significant role in new bone formation. Therefore, the aim of the present study was to establish a new regenerative procedure, which can be implemented immediately during surgery, to provide implants with additional autogenous bone particles. Thereafter, we investigated the effect of such 'bone-coated' implants on the healing response. In our model, dental screw-type implants were placed in the iliac crests of goats, following three approaches: (a) implants were placed, then removed while retaining bone debris on the surface, and subsequently placed into freshly prepared holes; (b) new implants were installed in the donor sites from group 1; and (c) control implants were inserted according to the standard protocol. After 3 weeks, microcomputed tomography and histomorphometerical analyses on bone-implant contact (BIC) and bone area (BA) were performed. The results showed that the retained bone debris in group 1 was viable bone-like tissue when cultured in vitro. In vivo histological results showed a significantly higher BIC for the 'bone-coated' (43.42 ± 11.29%) compared to the control (28.15 ± 11.86%) implants. Also, adjacent to the implants a significantly higher BA was found for 'bone-coated' implants (39.51 ± 11.17%) compared to the controls (31.92 ± 10.25%). Notably, no detrimental effects were noticed for the 'donor-site' positions. In conclusion, the transported autogenous bone particles accelerated peri-implant osteogenesis. Clinical studies are needed to evaluate the potential of this procedure in clinical practice. Copyright © 2011 John Wiley & Sons, Ltd.

• Retracted: Effects of pro-inflammatory cytokines on mineralization potential of rat dental pulp stem cells.

  Authors: Xuechao Yang, X Frank Walboomers, Zhuan Bian, John A Jansen, Mingwen Fan

  Journal of tissue engineering and regenerative medicine. 07/2011; 5(9):759.

  The following article from the Journal of Tissue Engineering and Regenerative Medicine, 'Effects of Pro-inflammatory Cytokines on Mineralization Potential of Rat Dental Pulp Stem Cells' by Yang X,The following article from the Journal of Tissue Engineering and Regenerative Medicine, 'Effects of Pro-inflammatory Cytokines on Mineralization Potential of Rat Dental Pulp Stem Cells' by Yang X, Walboomers XF, Bian Z, Jansen JA, Fan M, published online on 11 July 2011 in Wiley Online Library (onlinelibrary.wiley.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, and John Wiley & Sons, Ltd. The retraction has been agreed due to two authors (Walboomers XF, and Jansen JA) not having been involved in the research described, nor made aware of their names being listed on the manuscript, nor told of its submission to the journal.

• In vitro and in vivo evaluation of the inflammatory response to nanoscale grooved substrates.

  Authors: Edwin Lamers, X Frank Walboomers, Maciej Domanski, Ljupcho Prodanov, Jacoline Melis, Regina Luttge, Louis Winnubst, James M Anderson, Han J G E Gardeniers, John A Jansen

  Nanomedicine : nanotechnology, biology, and medicine. 06/2011;

  The immune response to an implanted biomaterial is orchestrated by macrophages. In this study various nanogrooved patterns were created by using laser interference lithography and reactive ionThe immune response to an implanted biomaterial is orchestrated by macrophages. In this study various nanogrooved patterns were created by using laser interference lithography and reactive ion etching. The created nanogrooves mimic the natural extracellular matrix environment. Macrophage cell culture demonstrated that interleukin 1β and TNF-α cytokine production were upregulated on nanogrooved substrates. In vivo subcutaneous implantation in a validated mouse cage model for 14 days demonstrated that nanogrooves enhanced and guided cell adhesion, and few multinucleated cells were formed. In agreement with the in vitro results, cytokine production was found to be nanogroove dependent, as interleukin 1β, TNF-α, TGF-β and osteopontin became upregulated. The results indicate that biomaterial surface texturing, especially at the nanometric scale, can be used to control macrophage activation to induce a wound healing response, rather than a profound inflammatory response.

• Tantalumpentoxide as a radiopacifier in injectable calcium phosphate cements for bone substitution.

  Authors: Jan Willem M Hoekstra, Jeroen J J P van den Beucken, Sander C G Leeuwenburgh, Gert J Meijer, John A Jansen

  Tissue engineering. Part C, Methods. 06/2011; 17(9):907-13.

  The chemical resemblance of calcium phosphate (CaP) cements and the mineral phase of bone is a problem in distinguishing CaP cement from bone tissue by means of common, noninvasive techniques (e.g.,The chemical resemblance of calcium phosphate (CaP) cements and the mineral phase of bone is a problem in distinguishing CaP cement from bone tissue by means of common, noninvasive techniques (e.g., X-ray imaging and microcomputed tomography [μCT]). In this study, the feasibility of using tantalumpentoxide (Ta(2)O(5)) powder as radiopacifier in CaP cements was analyzed. A distal femoral condyle model in male adult Wistar rats was used. After 6 weeks of implantation time, the results were analyzed by means of μCT and histology. Unambiguous distinction of CaP cement from native bone tissue and volumetric measurements of the materials appeared to be possible by means of μCT scanning. Furthermore, there was no evidence of either inflammation or fibrous tissue around the implant materials or at the bone-material interface. In conclusion, the addition of Ta(2)O(5) as a radiopacifying additive to CaP cements allows discrimination between bone substitute and surrounding bone tissue. Consequently, Ta(2)O(5) represents an effective and biocompatible additive in CaP cements for in vivo monitoring purposes.

• Calcium phosphate/poly(D,L-lactic-co-glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical-sized cranial defect.

  Authors: Floor C J van de Watering, Jeroen J J P van den Beucken, X Frank Walboomers, John A Jansen

  Clinical oral implants research. 06/2011; 23(2):151-9.

  The present study aimed to provide temporal information on material degradation and bone formation using composite (C) bone defect filler materials consisting of calcium phosphate cement (CaP) andThe present study aimed to provide temporal information on material degradation and bone formation using composite (C) bone defect filler materials consisting of calcium phosphate cement (CaP) and poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles (20 or 30 wt%) in rat critical-sized cranial defects. Critical-sized bicortical cranial defects were created in 48 rats and CaP/PLGA cement composites were implanted for 4, 8 and 12 weeks (n=8). Histological analysis of the retrieved specimens revealed that implant degradation was significantly faster for C30% (remaining implant up to 89.4 ± 4.4% at 12 weeks) compared with C20% (remaining implant upto 94.8 ± 2.1% at 12 weeks), albeit that overall degradation was limited. Although bone formation was limited in both experimental groups (upto 685765.9 μm(2) for C20% vs. 917603.3 μm(2) for C30%), C30% showed a significant temporal increase of total bone formation. The percentage of defect bridging was comparable for C20% and C30% at all implantation periods (range 40 ± 25.5% at week 4 to 65 ± 20% at week 12 for C20%; range 51.8 ± 7.8% at week 4 to 70.5 ± 16.2% at week 12 for C30%). The amount of PLGA-microparticles in the CaP/PLGA cement composites demonstrated acceleration of material degradation, while bone formation was found not to be influenced. Further optimization of the composite material is necessary to increase control over degradation and tissue ingrowth.

• Effect of nanotubes and apatite on growth factor release from PLLA scaffolds.

  Authors: Meike van der Zande, X Frank Walboomers, Beatriz Olalde, Maria J Jurado, J Iñaki Alava, Otto C Boerman, John A Jansen

  Journal of tissue engineering and regenerative medicine. 06/2011; 5(6):476-82.

  There is an evident clinical need for artificial bone restorative materials. In this respect, novel composites based on poly(L-lactic acid) (PLLA) have been described. The bone response of suchThere is an evident clinical need for artificial bone restorative materials. In this respect, novel composites based on poly(L-lactic acid) (PLLA) have been described. The bone response of such polymer-based composites is usually improved by the addition of bone morphogenetic protein-2 (BMP-2). However, released BMP-2 is cleared almost immediately from the site of implantation by diffusion, whereas a prolonged retention of BMP-2 onto the scaffold has been suggested to be more favourable. Besides the ability to improve the mechanical strength and osteoconductivity of polymeric scaffolds, both carbon nanotubes (CNTs) and microhydroxyapatite (µHA) have been described to facilitate such retention of BMP-2 when incorporated into a composite scaffold. Therefore, in the current study, radiolabelled BMP-2 was loaded onto plain PLLA and composite PLLA-CNT-µHA scaffolds. Subsequently, the scaffolds were implanted subcutaneously for 5 weeks in rats and BMP-2 release was measured. Release started with an initial phase of quick release, followed by a gradual release of BMP-2. Both scaffold types comprised the same in vivo release properties for BMP-2. The bioactivity of the BMP-2 remained unaltered. It can be concluded that incorporated CNTs and µHA did not affect BMP-2 release from composite scaffold materials.

• Effect of implant surface properties on peri-implant bone healing: a histological and histomorphometric study in dogs.

  Authors: Khalid Al-Hamdan, Samar H Al-Moaber, Rüdiger Junker, John A Jansen

  Clinical oral implants research. 04/2011; 22(4):399-405.

  The present study aimed to evaluate and compare two types of implants, i.e. grit-blasted and acid-etched implants (SLActive(®)) with nano-meter-scale hydroxyapatite surface-modified implantsThe present study aimed to evaluate and compare two types of implants, i.e. grit-blasted and acid-etched implants (SLActive(®)) with nano-meter-scale hydroxyapatite surface-modified implants (NanoTite™). For histological and histomorphometrical evaluation, 22 SLActive(®) and 22 Nanotite™ implants were inserted in eleven Beagle dogs. The animals were divided into three groups of healing (A: 2 weeks; B: 4 weeks and C: 8 weeks). Two, 4 and 8 weeks after implantation, the animals were sacrificed and bone-to-implant contact (BIC %), first implant-bone contact (1st BIC) as well as amount of bone (BV) were assessed. For SLActive(®) and Nanotite™ implants, BIC% increased significantly over time. No statistically significant differences in BIC% were found between SLActive(®) and Nanotite™ at all the respective implantation times. Moreover, for the different healing periods, no significant differences for BV between SLActive(®) and Nanotite™ implants were found. The present study showed that SLActive(®) and NanoTite™ implants induce a similar bone response after implantation for 2, 4 and 8 weeks in a non-submerged position in the mandible of dogs.