Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model.

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

Diagnosing peri-implant disease using the tongue as a 24/7 detector.

Our ability of screening broad communities for clinically asymptomatic diseases critically drives population health. Sensory chewing gums are presented targeting the tongue as 24/7 detector allowing diagnosis by "anyone, anywhere, anytime". The chewing gum contains peptide sensors consisting of a protease cleavable linker in between a bitter substance and a microparticle. Matrix metalloproteinases in the oral cavity, as upregulated in peri-implant disease, specifically target the protease cleavable linker while chewing the gum, thereby generating bitterness for detection by the tongue. The peptide sensors prove significant success in discriminating saliva collected from patients with peri-implant disease versus clinically asymptomatic volunteers. Superior outcome is demonstrated over commercially available protease-based tests in saliva. "Anyone, anywhere, anytime" diagnostics are within reach for oral inflammation. Expanding this platform technology to other diseases in the future features this diagnostic as a massive screening tool potentially maximizing impact on population health.Early detection of gum inflammation caused by dental implants helps prevent tissue damage. Here, the authors present a peptide sensor that generates a bitter taste when cleaved by proteases present in peri-implant disease, embed it in a chewing gum, and compare the probe to existing sensors using patient saliva.

Ultrasound melted polymer sleeve for improved screw anchorage in trabecular bone--A novel screw augmentation technique.

BACKGROUND: Screw anchorage in osteoporotic bone is still limited and makes treatment of osteoporotic fractures challenging for surgeons. Conventional screws fail in poor bone quality due to loosening at the screw-bone interface. A new technology should help to improve this interface. In a novel constant amelioration process technique, a polymer sleeve is melted by ultrasound in the predrilled screw hole prior to screw insertion. The purpose of this study was to investigate in vitro the effect of the constant amelioration process platform technology on primary screw anchorage. METHODS: Fresh frozen femoral heads (n=6) and vertebrae (n=6) were used to measure the maximum screw insertion torque of reference and constant amelioration process augmented screws. Specimens were cut in cranio-caudal direction, and the screws (reference and constant amelioration process) were implanted in predrilled holes in the trabecular structure on both sides of the cross section. This allowed the pairwise comparison of insertion torque for constant amelioration process and reference screws (femoral heads n=18, vertebrae n=12). Prior to screw insertion, a micro-CT scan was made to ensure comparable bone quality at the screw placement location. FINDINGS: The mean insertion torque for the constant amelioration process augmented screws in both, the femoral heads (44.2 Ncm, SD 14.7) and the vertebral bodies (13.5 Ncm, SD 6.3) was significantly higher than for the reference screws of the femoral heads (31.7 Ncm, SD 9.6, p<0.001) and the vertebral bodies (7.1 Ncm, SD 4.5, p<0.001). INTERPRETATION: The interconnection of the melted polymer sleeve with the surrounding trabecular bone in the constant amelioration process technique resulted in a higher screw insertion torque and can improve screw anchorage in osteoporotic trabecular bone.

Osseointegration of biochemically modified implants in an osteoporosis rodent model.

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), peri-implant bone area (BA), bone volume/tissue volume (BV/TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Histological and histomorphometric evaluation of immediate implant placement on a dog model with a new implant surface treatment.

PURPOSE: The aim of this study was to evaluate crestal bone resorption and bone apposition resulting from immediate post-extraction implants in the canine mandible, comparing a conditioned sandblasted acid-etched implant surface with a non-conditioned standard sandblasted implant surface. MATERIAL AND METHODS: In this experimental study, third and fourth premolars and distal roots of first molars were extracted bilaterally from six Beagle dog mandibles. Each side of the mandible received three assigned dental implants, with the conditioned surface (CS) on the right side and the non-conditioned surface (NCS) on the left. The dogs were sacrificed at 2 (n=2), 4 (n=2) and 12 weeks (n=2) after implant placement. RESULTS: The microscopic healing patterns at 2, 4 and 12 weeks for both implant types (CS and NCS) yielded similar qualitative bone findings. The mean crestal bone resorption was found to be greater for all implants with NCS (2.28+/-1.9 mm) than CS (1.21+/-1.05 mm) at 12 weeks. The mean percentage of newly formed bone in contact with implants was greater in implants CS (44.67+/-0.19%) than with the NCS (36,6+/-0.11%). There was less bone resorption with the CS than the NCS. CONCLUSION: The data show significantly more bone apposition (8% more) and less crestal bone resorption (1.07 mm) with the CS than with the NCS after 12 weeks of healing. This CS can reduce the healing period and increase bone apposition in immediate implant placements.

How is wettability of titanium surfaces influenced by their preparation and storage conditions?

The effect of two different etching procedures with inorganic acids (HSE and CSE)-one using additionally strongly oxidising conditions due to the presence of CrO(3) (CSE)-and consecutive storage conditions (dry methanol and air) for previous corundum blasted titanium surfaces is compared with respect to their wettability behaviour and the potential of the etching processes for removing remaining blasting material. The etching procedures result in distinct different surface morphologies. Whereas the HSE surface shows sub-mm to sub-mum structures but neither porosity nor undercuts, the CSE surface is extremely rugged and porous with structures protruding the more homogeneously attacked areas by several micrometers. By EDX analysis both remaining blasting material and chromium and sulphur from the etching treatment has been detected on the CSE surfaces only. Both surfaces states show super-hydrophilic behaviour immediately after etching and storage up to 28 days in dry methanol. Whereas contact with air does not change super-hydrophilicity for the CSE samples, wettings angles of the HSE samples increase within minutes and reach about angles of about 60 degrees and 90 degrees after one and 2 days exposure to air, respectively. The increasing hydrophobicity is discussed with respect to the formation of a surface coverage from hydrocarbons originating from aromatic compounds present in traces in air.

Comparison of chemically and pharmaceutically modified titanium and zirconia implant surfaces in dentistry: a study in sheep.

Advanced surface modifications and materials were tested on the same implant geometry. Six types of dental implants were tested for osseointegration after 2, 4 and 8 weeks in a sheep pelvis model. Four titanium implant types were treated with newly developed surface modifications, of which two were chemically and two were pharmacologically modified. One implant was made of zirconia. A sandblasted and acid-etched titanium surface was used as reference. The chemically modified implants were plasma-anodized or coated with calcium phosphate. The pharmacological coatings contained either bisphosphonate or collagen type I with chondroitin sulphate. The implants were evaluated using macroscopic, radiographic and histomorphometric methods. All implants were well osseointegrated at the time of death. All titanium implants had similar bone implant contact (BIC) at 2 weeks (57-61%); only zirconia was better (77%). The main BIC increase was between 2 and 4 weeks. The pharmacologically coated implants (78-79%) and the calcium phosphate coating (83%) showed similar results compared with the reference implant (80%) at 8 weeks. There were no significant differences in BIC. Compared with previous studies the results of all implants were comparatively good.

Anodic plasma-chemical treatment of CP titanium surfaces for biomedical applications.

The anodic plasma-chemical (APC) process was used to modify CP titanium surfaces for biomedical applications. This technique allows for the combined chemical and morphological modification of titanium surfaces in a single process step. The resulting conversion coatings, typically several micrometer thick, consist mainly of titanium oxide and significant amounts of electrolyte constituents. In this study, a new electrolyte was developed containing both calcium-stabilized by complexation with EDTA-and phosphate ions at pH 14. The presence of the Ca-EDTA complex, negatively charged at high pH, favors incorporation of high amounts of calcium into the APC coatings during the anodic (positive) polarization. The coating properties were evaluated as a function of the process variables by XPS, GD-OES, Raman spectroscopy, SEM and tensile testing, and compared to those of calcium-free APC coatings and uncoated CP titanium surfaces. The maximal Ca/P atomic ratio in the coating produced with the new APC electrolyte was approximately 1.3, with higher Ca concentrations than reported in conventional APC coatings. The dissolution behavior of the incorporated, amorphous CaP phases was investigated by exposure to a diluted EDTA solution. The coatings produced in the new electrolyte system exhibit favorable mechanical stability. The new APC technology is believed to be a versatile and cost-effective coating technique to render titanium implant surfaces bioactive.

Characterization of anodic spark-converted titanium surfaces for biomedical applications.

The aim of the present study was to characterize the surface morphology, microstructure and the chemical composition of anodic spark-converted titanium surfaces. The coatings were prepared in an electrochemical cell by the anodic spark deposition technique in an aqueous solution of Ca(H2PO4)2. The coatings were characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), electron probe microanalysis (EPMA) and X-ray diffraction (XRD). The properties of the coatings are described in terms of morphology.