Changes in the occlusal function of orthognathic patients with vertical malformations after combined orthodontic surgical therapy: a prospective clinical study.

The aim of this study was to assess the changes in occlusal patterns during combined surgical and orthodontic therapy in patients with vertical jaw malformations. Twenty-six orthognathic patients (18 female, eight male; median age 25 years, interquartile range 11.5 years) and 10 control patients (five female, five male; median age 29.8 years, interquartile range 13.5 years) recruited from neutral configured patients attending the Department of Orthodontics, were investigated. Based on cephalometry, the patients were grouped into vertical skeletal configurations of either open, deep, or natural bite cases. Registrations of the occlusal contacts were taken using a digital occlusal sensor immediately before surgery and at 9 months after the surgical intervention. Before the intervention, open and deep bite patients showed significantly less efficient occlusal patterns than the untreated controls regarding total tooth contact (P < 0.001), time of occlusion (P = 0.002), occlusal asymmetry (P = 0.001), anterior tooth contact (P < 0.001), and posterior tooth contact (P < 0.001). After surgery, the parameters in the deep bite patients were similar to those in the controls; however, in open bite patients, total tooth contact (P = 0.003), occlusal asymmetry (P = 0.011), and posterior tooth contact (P = 0.035) differed significantly. In conclusion, combined orthodontic and surgical correction of vertical malocclusions was found to improve occlusal function in patients with deep bite to the level of controls.

A new approach in three dimensions to define pre- and intraoperative condyle-fossa relationships in orthognathic surgery - is there an effect of general anaesthesia on condylar position?

Incorrect registration of the condylar position in orthognathic surgery is supposed to cause postoperative relapse, condylar resorption and temporomandibular disorders. The aim of this prospective study was to evaluate the influence of general anaesthesia on centric relation (CR). Therefore, CR registered preoperatively in the awake patient and CR registered intraoperatively under general anaesthesia were recorded in 30 patients (14 men, 16 women) undergoing orthognathic surgery (skeletal class I: n=3, II: n=13, III: n=14; symmetric: n=20; asymmetric: n=10). CR records were digitized and, through superimposition on the preoperative cone beam computed tomography of the patient's skull, the superior, anterior and posterior joint space and the volumetric congruence of 120 condyles were analysed. The linear measurements of joint spaces did not demonstrate any clinically relevant discrepancy between the CR measured in the awake and anaesthetized patient. In contrast, volumetric analysis revealed statistically significant differences between both states, with an intraoperative condylar sag predominantly in the posterior-inferior direction. The patient's skeletal class or symmetry had no significant influence on the intraoperative condylar displacement. Thus, the risk of fixing the condyle in an unphysiological position supports the idea of using intraoperative condylar positioning devices to achieve predictable and stable outcomes.

Shallow whole genome sequencing of adenoid cystic carcinomas of the salivary glands identifies specific chromosomal aberrations related to tumor progression.

BACKGROUND AND PURPOSE: Adenoid cystic carcinomas (ACC) are characterized by high rate of local recurrence and late distant metastasis. Chromosomal changes in the evolution from primary tumors to metastatic disease of ACC have not been appointed. Here we investigated the chromosomal alterations of 53 primary tumors from ACC patients with different progressive states by shallow whole genome sequencing to identify potential new markers for metastatic spread. METHODS: Illumina paired-end libraries were generated using DNA from the primary tumor of 53 ACC patients. Fragmented DNA was end-repaired, A-tailed and multiplex sequencing adapters were ligated. Sequence data were mapped to HG19 and a copy-number analysis was conducted using the QDNAseq R package (version 1.10.0). Outliers were removed and data was smoothed by applying the circular binary segmentation algorithm implemented in the R package copynumber version 1.22.0. A modified chromosomal instability (CNI) score was used to analyze deletions and amplifications. RESULTS: Cluster analysis of the whole genome sequencing revealed that the frequency of chromosomal aberrations were increased in ACC with local recurrence and distant metastases in comparison to ACC patients with no metastatic spread. Specifically, chromosome 6 and 12 and exclusively the entire chromosome 4 showed an increased frequency of chromosomal alterations with tumor progression. CONCLUSION: Our data show a molecular evolution from primary tumors to local recurrences and distant metastases and pinpoint the critical chromosomal regions involved in this process. These regions should be in the focus of the search for therapeutic targets of progressive ACC.

Influence of tumour necrosis factor alpha on epithelial-mesenchymal transition of oral cancer cells in co-culture with mesenchymal stromal cells.

Tumour progression in head and neck squamous cell carcinoma (HNSCC) is influenced by the surrounding stroma and inflammatory cytokines such as tumour necrosis factor alpha (TNF-α). The aim of this study was to test the hypothesis that TNF-α modulates the interactions of HNSCC cell line PCI-13 and bone marrow mesenchymal stromal cells (BMSCs) and influences markers of epithelial-mesenchymal transition (EMT). Following induction with TNF-α, mono- and co-cultures of BMSCs and the established HNSCC cell line PCI-13 were analyzed; protein expression of E-cadherin and vimentin and qRT-PCR expression of Snail, Twist, MMP14, vimentin, E-cadherin, and ß-catenin were examined, and changes in cellular AKT signalling were analyzed. TNF-α induced a significant decrease in E-cadherin (64.5±6.0%, P=0.002) and vimentin (10.4±3.5%, P=0.04) protein expression in co-cultured PCI-13, while qRT-PCR showed a significant increase in ß-catenin (BMSCs P<0.0001; PCI-13 P=0.0005) and Snail (BMSCs P=0.009; PCI-13 P=0.01). TNF-α also resulted in a down-regulation of AKT downstream targets S6 (38.7±20.9%, P=0.01), p70S6 (16.7±12%, P=0.05), RSK1 (23.6±28.8%, P=0.02), and mTOR (27.4±17.5%, P=0.004) in BMSC co-cultures. In summary, while reducing the expression of vimentin and AKT-signalling in PCI-13 and BMSC, respectively, TNF-α introduced an inflammatory-driven tumour-stroma transition, marked by an increased expression of markers of EMT.

Quality assessment of systematic reviews on vertical bone regeneration.

The aim of this study was to evaluate and compare the quality of systematic reviews of vertical bone regeneration techniques, using two quality-assessment tools (AMSTAR and ROBIS). An electronic literature search was conducted to identify systematic reviews or meta-analyses that would evaluate at least one of the following outcomes: implant survival, success rates, complications or bone gain after vertical ridge augmentation. Methodological quality assessment was performed by two independent evaluators. Results were compared between reviewers, and reliability measures were calculated using the Holsti's method® and Cohen's kappa. Seventeen systematic reviews were included, of which seven presented meta-analysis. Mean ±95% confidence interval AMSTAR score was 6.35 [4.74;7.97], with higher scores being correlated with a smaller risk of bias (Pearson's correlation coefficient=-0.84; P<0.01). Cohen's inter-examiner kappa showed substantial agreement for both checklists. From the available evidence, we ascertained that, regardless of the technique used, it is possible to obtain vertical bone gains. Implant success in regenerated areas was similar to implants placed in pristine bone with results equating between 61.5% and 100% with guided bone regeneration being considered the most predictable technique regarding bone stability, while distraction osteogenesis achieved the biggest bone gains with the highest risk of possible complications.

Traditional face-bow transfer versus three-dimensional virtual reconstruction in orthognathic surgery.

Face-bow transfer is an essential step in articulator-based orthognathic surgery planning. However, it can be a source of inaccuracy. Virtual computer-based planning avoids this error through the use of direct patient-related three-dimensional imaging data. The aim of this prospective observational study was to determine the error of face-bow transfer three-dimensionally and correlate it to the different types of malocclusion. Orthognathic surgery performed on 38 patients (10 male, 28 female; mean (standard deviation) age 24.7 (6.9) years) was planned twice: first articulator-based with plaster models and second computer-based with surgery planning software. Both models were digitized and compared regarding the angle between the Frankfort horizontal plane and the occlusal plane. In most cases, the angle in the sagittal dimension was higher in the articulator-based model than in the computer-based model. The angle in the transverse dimension was as often under- as over-represented. The type of malocclusion, i.e. skeletal class, vertical relationship, and degree of asymmetry, had no significant impact on the amount of error. In conclusion, this study indicates that computer-based planning should be considered as an advantageous alternative in orthognathic surgery planning.

Do we need retarded delivery of bone growth factors in facial bone repair? An experimental study in rats.

The aim of the present study was to evaluate the effect of different dosages of retarded vs. rapid release of bone morphogenic protein 2 (BMP2) at different recipient sites. Porous composite poly(D,L-lactic acid) (PDLLA)/CaCO3 scaffolds were loaded with three different dosages of rhBMP2 (24 µg, 48 µg and 96 µg) and implanted, together with blank controls, both into non-healing defects of the mandibles and into the gluteal muscles of 24 adult male Wistar rats. After 26 weeks, bone formation and expression of bone specific markers [alkaline phosphatase (AP) and Runx2] were evaluated by histomorphometry and immunohistochemistry. Results showed that the mode of delivery had no quantitative effect on bone formation in mandibular sites. Expression of AP and Runx2 showed significant differences among the three dosage groups. There were significant correlations between the expression of both AP and Runx2 as well as the extent of bone formation, with both retarded and rapid release of rhBMP2. In ectopic sites, retarded release significantly enhanced bone formation in the low and medium dosage groups, compared to rapid release. Expression of AP was significantly higher and Runx2 significantly lower in ectopic sites, compared to mandibular sites. Significant correlations between the expression of bone specific markers and bone formation occurred only in the retarded delivery groups, but not in the rapid release groups. Within the limitations of the experimental model, it was concluded that retarded delivery of BMP2 was effective, preferably in sites with low or non-existing pristine osteogenic activity. Expression of bone specific markers indicated that osteogenic pathways might be different in mandibular vs. ectopic sites.

Presentation of a variation of the chorioallantoic membrane set up as a potential model for individual therapy for squamous cell carcinoma of the oropharynx.

The chorioallantoic membrane of fertilized chicken eggs in an early phase of breeding presents an approved test situation for the growth and treatment of human cancer cells.These models work due to the inoculation of cells into the membrane that stays within the egg shell during the time of investigation. In this study a modification of this model is presented. Samples of native tumors, rather than cell lines, are transplanted into the membrane and the body of the egg is taken out of the shell and placed in a plastic bowl. These modifications lead to an enhanced accessibility to the chorioallantoic membrane and the surrounding vessels thus facilitating intra venous access and application of pharmaceuticals and a focused radiotherapy. With the current modifications the embryo was kept alive and additionally, the vascularized tumor environment was preserved.

Influence of TGF-ß1 on tumor transition in oral cancer cell and BMSC co-cultures.

OBJECTIVES: TGF-ß1 signaling modulates epithelial mesenchymal transitions (EMT) of head and neck squamous cell carcinoma (HNSCC). Bone marrow mesenchymal stromal cells (BMSC) are able to exert a regulating influence on the expression of markers of EMT in HNSCC cells. It was thus the aim of this study to test the hypothesis that TGF-ß1 modulates the interactions of tumor transition between BMSCs and HNSCC, affecting the expression of E-cadherin, Vimentin, Snail, Twist, MMP14 and beta-catenin. Furthermore, we analyzed alterations in the AKT-signaling of tumor and stroma cells. MATERIALS AND METHODS: BMSCs were isolated from iliac bone marrow aspirates and co-cultured in trans-well permeable membrane wells with tumor cells of the established HNSCC cell line PCI-13. Following the induction with TGF-ß1 under serum free conditions the expression of Vimentin and E-Cadherin was assessed via immunofluorescence. A quantitative RT-PCR analysis of tumor transition markers E-cadherin, Vimentin, Snail, Twist, MMP14 and beta-catenin was performed. Changes in AKT-Signaling were identified via protein analysis. RESULTS: In non-induced co-cultures, BMSC were able to suppress Vimentin in PCI-13 as a marker of tumor transition. In TGF-ß1 induced co-cultures PCI-13 significantly increased the expression of Vimentin, Twist, Snail, MMP14, GSK3a, PRAS40, 4E-BP1, and AMPKa compared to monolayer controls. TGF-ß1 co-cultured BMSC demonstrated a significant increase of Snail, PRAS40, mTOR, GSK3a/b, Bad, PDK1 and 4E-BP1. CONCLUSIONS: TGF-ß1 was able to attenuate the modulating influence of BMSC in co-culture and drive the co-culture towards a progressive tumor transition, affecting the expression of markers of EMT, AKT-Signaling and proliferative checkpoints.

Continuous delivery of rhBMP2 and rhVEGF165 at a certain ratio enhances bone formation in mandibular defects over the delivery of rhBMP2 alone--An experimental study in rats.

The aim of the present study was to test the hypothesis that different amounts of vascular endothelial growth factor and bone morphogenic protein differentially affect bone formation when applied for repair of non-healing defects in the rat mandible. Porous composite PDLLA/CaCO3 carriers were fabricated as slow release carriers and loaded with rhBMP2 and rhVEGF165 in 10 different dosage combinations using gas foaming with supercritical carbon dioxide. They were implanted in non-healing defects of the mandibles of 132 adult Wistar rats with additional lateral augmentation. Bone formation was assessed both radiographically (bone volume) and by histomorphometry (bone density). The use of carriers with a ratio of delivery of VEGF/BMP between 0.7 and 1.2 was significantly related to the occurrence of significant increases in radiographic bone volume and/or histologic bone density compared to the use of carriers with a ratio of delivery of ≤ 0.5 when all intervals and all outcome parameters were considered. Moreover, simultaneous delivery at this ratio helped to "save" rhBMP2 as both bone volume and bone density after 13 weeks were reached/surpassed using half the dosage required for rhBMP2 alone. It is concluded, that the combined delivery of rhVEGF165 and rhBMP2 for repair of critical size mandibular defects can significantly enhance volume and density of bone formation over delivery of rhBMP2 alone. It appears from the present results that continuous simultaneous delivery of rhVEGF165 and rhBMP2 at a ratio of approximately 1 is favourable for the enhancement of bone formation.

Can piezoelectric ultrasound osteotomies result in serious noise trauma?

The use of ultrasound to cut bone in oral and craniofacial surgery has increased. There is concern that the application of ultrasound to the craniofacial skeleton might represent a potential hazard to the inner ear because of sound transmission by bone conduction resulting in hearing trauma. Conventional and ultrasound osteotomies were performed on human specimens of temporal bone containing an intact middle and inner ear. The equivalent sound pressure was measured with a microphone at the round window, which had been calibrated with a bone conduction audiometer. Conventional osteotomy with a rose burr resulted in maximum sound pressures of 125dB(A) consisting of major frequency components at 2100, 7600, and 9300Hz. Ultrasound osteotomy resulted in maximum sound pressures of 122dB(A) and exhibited major frequency components at around 10kHz, 20kHz, and 26.5kHz. Ultrasound osteotomies have no acoustic advantage over conventional osteotomies. Both osteotomy techniques can produce noise-induced hearing trauma, especially when applied over longer durations of time. This appears to be more relevant for ultrasound osteotomies, because the bone cutting efficiency is usually poorer than in conventional osteotomies. Surgeons should consider the risk of noise-induced potential damage to the inner ear when selecting the method of osteotomy.

In vivo effect of immobilisation of bone morphogenic protein 2 on titanium implants through nano-anchored oligonucleotides.

The aim of the present study was to test the hypothesis that immobilisation of bone morphogenic proteins on the surface of titanium implants through nano-anchored oligonucleotides can enhance peri-implant bone formation. Non-coding 60-mer DNA oligonucleotides (ODN) were anchored to the surface of custom made sandblasted acid etched (SAE) titanium screw implants through anodic polarisation, gamma-sterilised with a standard dose of 25 kGy, and were hybridised with complementary 30-mer strands of DNA oligonucleotides conjugated to rhBMP2. Blank SAE implants, SAE implants with nano-anchored ODN and SAE implants with nano-anchored ODN and non-conjugated rhBMP2 served as controls. The implants were inserted into the tibiae of 36 Sprague Dawley rats. Perforations at the head and the tip of the implants allowed for bone ingrowth. Bone ingrowth into perforations and bone implant contact (BIC) as well as bone density (BD) at a distance of 200 µm from the implant surface were assessed after 1 , 4 and 13 weeks. Implants with nano-anchored ODN strands hybridised with conjugated rhBMP2 exhibited enhanced bone ingrowth into the perforations and increased BIC after 1 week as well as increased BIC after 4 weeks compared to controls. No difference was seen after 13 weeks. Bone density around the outer implant surface did not differ significantly at any of the intervals. It is concluded that rhBMP2 immobilised on the surface of titanium implants through nano-anchored oligonucleotide strands can enhance bone implant contact. The conditions of sterilisation tested allowed for handling under clinically relevant conditions.

Solvent free production of porous PDLLA/calcium carbonate composite scaffolds improves the release of bone growth factors.

PURPOSE: Incorporation of alkaline nano-/microparticles for neutralization of acidic degradation products into degradable polymer foams requires the use of organic solvents, which may compromise biocompatibility and may be associated with biological hazards. The aim of the present study was to develop and validate a solvent-free method to produce porous poly (DL-lactic acid)/calcium carbonate composite scaffolds (PDLLA/CaCO3) for controlled release of incorporated osteogenic growth factors. METHODS: Composite PDLLA/CaCO3 granules were produced using a milling process and compared to composite material fabricated through a solution precipitation process using organic solvents. Particle size and mineral content were comparable in both groups. Supercritical carbon dioxide pressure was used to incorporate rhBMP2 into both composites. RESULTS: Gas foaming resulted in comparable pore structures in both groups exhibiting a homogenous distribution of CaCO3 microparticles in the polymer scaffolds. The elasticity modulus of both types of scaffolds was not significantly different whereas the bending strength of the solvent-free produced scaffolds was significantly lower. The pH values remained constant between 6.90 and 7.25 during degradation of both composites. Release of BMP2 was significantly higher and the induction of alkaline phosphatase was more reliable in the group of scaffolds produced without organic solvents. CONCLUSION: Solvent-free fabrication of composite PDLLA/CaCO3 scaffolds for controlled release of bone growth factors through gas foaming significantly enhances the release of growth factors and improves the biological efficacy of the incorporated growth factors.

The pathology of bone tissue during peri-implantitis.

Dental implants are one of the most frequently used treatment options for tooth replacement. Approximately 30% of patients with dental implants develop peri-implantitis, which is an oral inflammatory disease that leads to loss of the supporting tissues, predominately the bone. For the development of future therapeutic strategies, it is essential to understand the molecular pathophysiology of human dental peri-implant infections. Here, we describe the gene and protein expression patterns of peri-implantitis bone tissue compared with healthy peri-implant bone tissue. Furthermore, cells from the osteoblastic lineage derived from peri-implantitis samples were immortalized and characterized. We applied microarray, quantitative reverse transcription polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. The levels of typical bone matrix molecules, including SPP1, BGLAP, and COL9A1, in patients with peri-implantitis were reduced, while the inflammation marker interleukin 8 (IL8) was highly expressed. RUNX2, one of the transcription factors of mature osteoblasts, was also decreased in peri-implantitis. Finally, the human telomerase reverse transcriptase immortalized cell line from peri-implantitis exhibited a more fibro-osteoblastic character than did the healthy control.

Interactions of human MSC with head and neck squamous cell carcinoma cell line PCI-13 reduce markers of epithelia-mesenchymal transition.

OBJECTIVES: Cancer progression is influenced by tumor microenvironment and communication of stromal cells and tumor cells. Interactions may enhance epithelial-mesenchymal transition (EMT) of tumor cells through signaling proteins such as Wnt/beta-catenin and matrix metalloproteinases (MMP), as well as loss of cellular integrity, which affects invasion, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC). In this study, we are testing the hypothesis that interactions of human mesenchymal stromal cells (MSCs) with HNSCC might influence the expression of markers of EMT and tumor progression by co-culturing human MSC with the PCI-13 HNSCC line. MATERIALS AND METHODS: Pooled MSCs were derived from the iliac bone marrow of seven patients and co-cultured in transwell permeable membrane wells with tumor cells of the established HNSCC cell line PCI-13 (UICC: T3, N1, M0). MSCs were characterized through fluorescence-activated cell sorting (FACS) analysis. Expression of Wnt3, E-cadherin, beta-catenin, MMP14, cathepsin b, and ETS1 was assessed by quantitative RT-PCR. RESULTS: We were able to show that co-culture of MSCs and PCI-13 leads to a significantly reduced expression of Wnt3, MMP14, and beta-catenin compared to controls, whereas the expression of cathepsin b and ETS1 was not significantly different between co-cultures and controls. CONCLUSION: Our results suggest that the interaction between MSCs and PCI-13 may suppress EMT in cancer cells. CLINICAL RELEVANCE: The influence of MSCs can suppress the onset of EMT in HNSCC, affecting tumor progression and therapy.

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF - an in vitro study.

The aim of the present study was to test the hypothesis that sandblasted and acid etched titanium surfaces can be functionalised with vascular endothelial growth factor (VEGF) using oligonucleotides for anchorage and slow release. rhVEGF165 molecules were conjugated to strands of 30-mer non-coding DNA oligonucleotides (ODN) and hybridised to complementary ODN anchor strands which had been immobilised to the surface of sandblasted/acid etched (SAE) Ti specimens. Specimens with non-conjugated VEGF adsorbed to ODN anchor strands and to blank SAE surfaces served as controls. Specific binding of conjugated VEGF exhibited the highest percentage of immobilised VEGF (71.0 %), whereas non-conjugated VEGF only achieved 53.2 and 30.7 %, respectively. Cumulative release reached 54.0 % of the immobilised growth factor in the group of specifically bound VEGF after 4 weeks, whereas non-conjugated VEGF adsorbed to ODN strands released 78.9% and VEGF adsorbed to SAE Ti surfaces released 97.4 %. Proliferation of human umbilical vein endothelial cells (HUVECs) was significantly increased on the surfaces with specifically bound VEGF compared to the control surfaces and SAE Ti surfaces without VEGF. Moreover, the released conjugated VEGF exhibited biological activity by induction of von Willebrand Factor (vWF) in mesenchymal stem cells. It is concluded that the angiogenic functionalisation of SAE titanium surfaces can be achieved by conjugation of VEGF to ODN strands and hybridisation to complementary ODN strands that are anchored to the titanium surface. The angiogenic effect is exerted both through the immobilised and the released portion of the growth factor.

[Guidelines and recommendations from scientific associations within a European context]. / Leitlinien und Behandlungsempfehlungen wissenschaftlicher Dach- und Fachgesellschaften im europäischen Kontext.

Guidelines and recommendations are increasingly impacting day-to-day clinical care in medicine and dentistry. Although guidelines are only meant to define a range of treatment measures that have been proven to be medically useful, they can have a significant impact on both health care politics and reimbursement strategies as well as be misused to direct particular treatment modalities into the hands of certain specialties. Because these effects tend to not only negatively influence the acceptance but also impair the implementation of guidelines, the process of guideline compilation has to be transparent and based on clearly defined methodology. The German Association of Dental and Craniomandibular Sciences ("Deutsche Gesellschaft für Zahn-, Mund- und Kieferheilkunde", DGZMK) is the umbrella organization of all scientific dental associations in Germany, and initiating new guideline projects as well as continuously updating existing guidelines is one of one of its major tasks. These activities are pursued in cooperation with the "Zahnärztliche Zentralstelle Qualitätssicherung" (ZZQ) and the "Arbeitsgemeinschaft wissenschaftlich medizinischer Fachgesellschaften" (AWMF).

Bone formation in trabecular bone cell seeded scaffolds used for reconstruction of the rat mandible.

This study tested whether different in vitro cultivation techniques for tissue-engineered scaffolds seeded with human trabecular bone cells affect in vivo bone formation when implanted into critical-size defects in rat mandibles. Human trabecular cells were isolated and seeded into three types of scaffolds (porous CaCO(3), mineralized collagen, porous tricalcium phosphate). Four in vitro groups were produced: empty control scaffolds incubated with cell culture medium for 24 h; scaffolds seeded with trabecular bone cells, cultivated under static conditions for 24 h; scaffolds seeded with trabecular bone cells, cultivated for 14 days under static conditions; scaffolds seeded with trabecular bone cells, cultivated for 14 days in a continuous flow perfusion bioreactor. The scaffolds were implanted press fit into non-healing defects, 5 mm diameter, in rat mandibles. After 6 weeks the presence of human cells was assessed; none were detected. Histomorphometric evaluation showed that neither seeding human trabecular bone cells nor the culturing technique increased the amount of early bone formation compared with the level provided by osteoconductive bone ingrowth from the defect edges. It is concluded that human bone marrow stroma cells in tissue-engineered scaffolds and associated in vitro technology are difficult to test in the mandible in animal models.

Ectopic bone formation after implantation of a slow release system of polylactic acid and rhBMP-2.

OBJECTIVES: The present study was conducted to test the hypothesis that preshaped polylactic acid (PLA) implants loaded with recombinant human bone morphogenic protein 2 (rhBMP-2) can induce bone formation in a rat ectopic model. MATERIALS AND METHODS: Two groups of porous cylindrical poly-DL-lactic acid implants of 8-mm diameter were produced by gas foaming with CO(2), incorporating 48 and 96 microg rhBMP-2, respectively, into each implant. Blank PLA implants were used as controls. The release of BMPs and the induction of alkaline phosphatase were assessed in vitro. Osteoinduction in vivo was tested by insertion of 15 implants from each group into the gluteal muscles of Wistar rats. Five implants from each group were retrieved after 6, 13 and 26 weeks and assessed using flat panel volume detector computed tomography and light microscopy. RESULTS: Both groups of implants showed increased release of rhBMP-2 during the first 24-48 h, with a slightly higher amount being released from the implants with 48 microg. Release during subsequent intervals was <100 ng/72 h in the low-concentration group and >100 ng in the group with 96 microg rhBMP-2. Implants with 95 microg rhBMP-2 exhibited bone formation in vivo on the outside of the implants across the observation period of 26 weeks with invasion of bone into the pores, whereas implants with 48 microg rhBMP-2 failed to induce the formation of bone tissue. No bone formation was found in the control implants. CONCLUSIONS: The results suggest that release rates of rhBMP-2 for ectopic bone induction have to be >100 ng/72 h to maintain the osteoinductive activity of the tested porous PLA implants. This slow release system may have impact on alveolar bone augmentation procedures when used as individually preformed osteoinductive implants.

Effect of modifications of dual acid-etched implant surfaces on peri-implant bone formation. Part I: organic coatings.

OBJECTIVE: The aim of the present study was to test the hypothesis that peri-implant bone formation can be improved by modifying dual acid-etched (DAE) implant surfaces using organic coatings that enhance cell adhesion and osteogenic differentiation. MATERIAL AND METHODS: Ten adult female foxhounds received experimental titanium implants in the mandible 3 months after removal of all premolar teeth. Six types of implants were evaluated in each animal: (i) implants with a machined surface (MS), (ii) implants with a DAE surface topography, (iii) implants with an acid-etched surface coated with RGD peptides, (iv) implants with an acid-etched surface coated with collagen I, (v) implants with an acid-etched surface coated with collagen I and chondroitin sulphate (CS), (vi) implants with an acid-etched surface coated with collagen I and CS and recombinant human bone morphogenetic protein-2. Peri-implant bone regeneration was assessed by histomorphometry after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the bone volume density (BVD) of the newly formed peri-implant bone. RESULTS: After 1 month, mean BIC was significantly higher in the coated implants group than in the MS group. There was no significant difference when mean BIC in the DAE group was compared with implants with any of the organic coatings, but the difference was significant when compared with the MS implants. Differences in mean BVD value did not reach significance between any of the surfaces. After 3 months, the same held true for the mean BIC of all the groups except for Coll I. Mean volume density of the newly formed bone was higher in all the surface modifications, albeit without statistical significance. CONCLUSIONS: It is concluded that with the exception of Coll I, the tested organic surface coatings on DAE surfaces did not improve peri-implant bone formation when compared with the DAE surfaces but enhanced BIC when compared with the MSs.