Effects of implant design on marginal bone changes around early loaded, chemically modified, sandblasted Acid-etched-surfaced implants: a histologic analysis in dogs

A minimal marginal bone loss around implants during early healing has been considered acceptable. However, the preservation of the marginal bone is related to soft tissue stability and esthetics. Implant designs and surfaces were evaluated to determine their impact on the behavior of the crestal bone. The purpose of this study is to evaluate histologic marginal bone level changes around early loaded, chemically modified, sandblasted acid-etched-surfaced implants with a machined collar (MC) or no MC (NMC).

Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs

OBJECTIVE: The purpose was to qualitatively and quantitatively compare the bone formation and graft resorption of two different bone substitutes used in both orthopedic and oral surgery, with autogenous bone as a positive control. MATERIALS AND METHODS: Three standardized bone defects were prepared in both mandibular angles of 12 adult minipigs. The defects were grafted with either autograft, anorganic bovine bone (ABB), or synthetic beta-tricalcium phosphate (beta-TCP). Sacrifice was performed after 1, 2, 4, and 8 weeks for histologic and histomorphometric analysis. RESULTS: At 2 weeks, more new bone formation was seen in defects filled with autograft than with ABB (P approximately 0.0005) and beta-TCP (P approximately 0.002). After 4 weeks, there was no significant difference between beta-TCP and the two other materials. Defects grafted with ABB still exhibited less bone formation as compared with autograft (P approximately 0.004). At 8 weeks, more bone formation was observed in defects grafted with autograft (P approximately 0.003) and beta-TCP (P approximately 0.00004) than with ABB. No difference could be demonstrated between beta-TCP and autograft. beta-TCP resorbed almost completely over 8 weeks, whereas ABB remained stable. CONCLUSION: Both bone substitutes seemed to decelerate bone regeneration in the early healing phase as compared with autograft. All defects ultimately regenerated with newly formed bone and a developing bone marrow. The grafting materials showed complete osseous integration. Both bone substitutes may have a place in reconstructive surgery where different clinical indications require differences in biodegradability.

Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model

Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a self-polymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 months after repair. Cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, collagen type I and type II immunohistochemistry, collagen type II in situ hybridization, and matrix biochemical assays. Arthroscopic scores for MSC-implanted defects were significantly improved at the 30-day arthroscopic assessment. Biopsy showed MSC-implanted defects contained increased fibrous tissue with several defects containing predominantly type II collagen. Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects. Collagen type II and proteoglycan content in MSC-implanted and control defects were similar. Mesenchymal stem cell grafts improved the early healing response, but did not significantly enhance the long-term histologic appearance or biochemical composition of full-thickness cartilage lesions.

Lack of influence of the Schneiderian membrane in forming new bone apical to implants simultaneously installed with sinus floor elevation: an experimental study in monkeys

Aim: To describe the early healing processes around the implants installed after elevation of the sinus mucosa applying the lateral access technique without the use of grafting material.Material and methods: Immediately after the elevation of the maxillary sinus Schneiderian membrane by the lateral approach in eight monkeys, implants were installed without the use of grafting material. The healing of the tissue around the implants was evaluated after 4, 10, 20 and 30 days. Ground sections were prepared and analyzed histologically.Results: After 4 days of healing, the formation of coagulum and provisional matrix was documented within the elevated area. At 10-day interval, sprouts of woven bone were in continuity with the parent bone, and partly in contact with the implant surface at the base of the augmented area. While bone-to-implant contact increased after 20 and 30 days, the area underneath the Schneiderian membrane appeared reduced in volume and condensed toward the apex of the implants. The sinus mucosa was to some extent collapsed onto the implant surface and on the newly formed bone.Conclusions: The void initially occupied by the coagulum after sinus membrane elevation shrank substantially during the observation period. A lack of influence of the Schneiderian membrane in bone formation apical to implants was documented in the early phase of healing.

Biomechanical effect of one session of low-level laser on the bone-titanium implant interface

Low-level laser (LLL) has been used on peri-implant tissues for accelerating bone formation. However, the effect of one session of LLL in the strength of bone-implant interface during early healing process remains unclear. The present study aims to evaluate the removal torque of titanium implants irradiated with LLL during surgical preparation of implant bed, in comparison to non-irradiation. Sixty-four Wistar rats were used. Half of the animals were included in LLL group, while the other half remained as control. All animals had the tibia prepared with a 2 mm drill, and a titanium implant (2.2 × 4 mm) was inserted. Animals from LLL group were irradiated with laser (gallium aluminum arsenide), with a wavelength of 808 nm, a measured power output of 50 mW, to emit radiation in collimated beams (0.4 cm2), for 1 min and 23 s, and an energy density of 11 J/cm2. Two applications (22 J/cm 2) were performed immediately after bed preparation for implant installation. Flaps were sutured, and animals from both groups were sacrificed 7, 15, 30, and 45 days after implant installation, when load necessary for removing implant from bone was evaluated by using a torquimeter. In both groups, torque values tended to increase overtime; and at 30 and 45 days periods, values were statistically higher for LLL group in comparison to control (ANOVA test, p < 0.0001). Thus, it could be suggested that a single session of irradiation with LLL was beneficial to improve bone-implant interface strength, contributing to the osseointegration process. © 2012 Springer-Verlag London Ltd.

Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immediate loading of implants installed in a healed alveolar bony ridge or immediately after tooth extraction: an experimental study in dogs

ObjectiveTo compare the sequential healing at immediately loaded implants installed in a healed alveolar bony ridge or immediately after tooth extraction.Material and methodsIn the mandible of 12 dogs, the second premolars were extracted. After 3months, the mesial roots of the third premolars were endodontically treated and the distal roots extracted. Implants were placed immediately into the extraction sockets (test) and in the second premolar region (control). Crowns were applied at the second and third maxillary premolars, and healing abutments of appropriate length were applied at both implants placed in the mandible and adapted to allow occlusal contacts with the crowns in the maxilla. The time of surgery and time of sacrifices were planned in such a way to obtain biopsies representing the healing after 1 and 2weeks and 1 and 3months. Ground sections were prepared for histological analyses.ResultsAt the control sites, a resorption of the buccal bone of 1mm was found after 1week and remained stable thereafter. At the test sites, the resorption was 0.4mm at 1-week period and further loss was observed after 1month. The height of the peri-implant soft tissue was 3.8mm both at test and control sites. Higher values of mineralized bone-to-implant contact and bone density were seen at the controls compared with the test sites. The differences, however, were not statistically significant.ConclusionsDifferent patterns of sequential early healing were found at implants installed in healed alveolar bone or in alveolar sockets immediately after tooth extractions. However, three months after implant installation, no statistically significant differences were found for the hard- and soft-tissue dimensions.

Transcriptional profiling of osseointegration in humans

To determine the temporal gene expression profile associated with the early healing events during osseointegration in a human model.

A phase IIa randomized controlled pilot study evaluating the safety and clinical outcomes following the use of rhGDF-5/β-TCP in regenerative periodontal therapy

To present the safety profile, the early healing phase and the clinical outcomes at 24 weeks following treatment of human intrabony defects with open flap debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier. Twenty chronic periodontitis patients, each with at least one tooth exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥4 mm entered the study. Ten subjects (one defect/patient) were randomized to receive OFD alone (control) and ten subjects OFD combined with rhGDF-5/β-TCP. Blood samples were collected at screening, and at weeks 2 and 24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels, and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on probing, probing depth, clinical attachment level, and radiographs were recorded pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5 plasma levels were detected in any patient. At 6 months, treatment with OFD + rhGDF-5/β-TCP resulted in higher but statistically not significant PD reduction (3.7 ± 1.2 vs. 3.1 ± 1.8 mm; p = 0.26) and CAL gain (3.2 ± 1.7 vs. 1.7 ± 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration, the use of rhGDF-5/β-TCP appeared to be safe and the material possesses a sound biological rationale. Thus, further adequately powered, randomized controlled clinical trials are warranted to confirm the clinical relevance of this new approach in regenerative periodontal therapy. rhGDF-5/β-TCP may represent a promising new techology in regenerative periodontal therapy.

Comparative study of biphasic calcium phosphates with different HA/TCP ratios in mandibular bone defects. A long-term histomorphometric study in minipigs

Three biphasic calcium phosphate (BCP) bone substitute materials with hydroxyapatite (HA)/tricalcium phosphate (TCP) ratios of 20/80, 60/40, and 80/20 were compared to coagulum, particulated autogenous bone, and deproteinized bovine bone mineral (DBBM) in membrane-protected bone defects. The defects were prepared in the mandibles of 24 minipigs that were divided into four groups of six with healing times of 4, 13, 26, and 52 weeks, respectively. The histologic and histomorphometric evaluation focused on differences in amount and pattern of bone formation, filler degradation, and the interface between bone and filler. Collapse of the expanded polytetrafluoroethylene barrier membrane into the coagulum defects underlined the necessity of a filler material to maintain the augmented volume. Quantitatively, BCP 20/80 showed bone formation and degradation of the filler material similar to autografts, whereas BCP 60/40 and BCP 80/20 rather equaled DBBM. Among the three BCP's, the amount of bone formation and degradation of filler material seemed to be inversely proportional to the HA/TCP ratio. The fraction of filler surface covered with bone was highest for autografts at all time points and was higher for DBBM than BCP 80/20 and 60/40 at the early healing phase. TRAP-positive multinucleated cells were identified on BCP and DBBM surfaces without showing typical signs of resorption lacunae.

Efeito da geometria do implante dentário e do protocolo de fresagem óssea na estabilidade primária e na osseointegração inicial: estudo experimental em cães

CHAPTER 1 - This study histologically evaluated two implant designs: a classic thread design versus another specifically designed for healing chamber formation placed with two drilling protocols. Forty dental implants (4.1 mm diameter) with two different macrogeometries were inserted in the tibia of 10 Beagle dogs, and maximum insertion torque was recorded. Drilling techniques were: until 3.75 mm (regular-group); and until 4.0 mm diameter (overdrillinggroup) for both implant designs. At 2 and 4 weeks, samples were retrieved and processed for histomorphometric analysis. For torque and BIC (bone-to-implant contact) and BAFO (bone area fraction occupied), a general-linear model was employed including instrumentation technique and time in vivo as independent. The insertion torque recorded for each implant design and drilling group significantly decreased as a function of increasing drilling diameter for both implant designs (p<0.001). No significant differences were detected between implant designs for each drilling technique (p>0.18). A significant increase in BIC was observed from 2 to 4 weeks for both implants placed with the overdrilling technique (p<0.03) only, but not for those placed in the 3.75 mm drilling sites (p>0.32). Despite the differences between implant designs and drilling technique an intramembranous-like healing mode with newly formed woven bone prevailed. CHAPTER 2 - The objective of this preliminary histologic study was to determine whether the alteration of drilling protocols (oversized, intermediate, undersized drilling) present different biologic responses at early healing periods of 2 weeks in vivo in a beagle dog model. Ten beagle dogs were acquired and subjected to surgeries in the tibia 2 weeks before euthanasia. During surgery, 3 implants, 4 mm in diameter by 10 mm in length, were placed in bone sites drilled to 3.5 mm, 3.75 mm, and 4.0 mm in final diameter. The insertion and removal torque was recorded for all samples. Statistical significance was set to 95% level of confidence and the number of dogs was considered as the statistical unit for all comparisons. For the torque and BIC and BAFO, a general linear model was employed including instrumentation technique and time in vivo as independent. Overall, the insertion torque increased as a function of drilling diameter from 4.0 mm, to 3.75 mm, to 3.5 mm, with a significant difference in torque levels between all groups (p<0.001). Statistical assessment of BIC and BAFO showed significantly higher values for the 3.75 mm (recommended) drilling group was observed relative to the other two groups (p<0.001). Different drilling dimensions resulted in variations in insertion torque values (primary stability) and different pattern of healing and interfacial remodeling was observed for the different groups. CHAPTER 3 - The present study evaluated the effect of different drilling dimensions (undersized, regular, and oversized) in the insertion and removal torques of dental implants in a beagle dog model. Six beagle dogs were acquired and subjected to bilateral surgeries in the radii 1 and 3 weeks before euthanasia. During surgery, 3 implants, 4 mm in diameter by 10 mm in length, were placed in bone sites drilled to 3.2 mm, 3.5 mm, and 3.8 mm in final diameter. The insertion and removal torque was recorded for all samples. Statistical analysis was performed by paired t tests for repeated measures and by t tests assuming unequal variances (all at the 95% level of significance). Overall, the insertion torque and removal torque levels obtained were inversely proportional to the drilling dimension, with a significant difference detected between the 3.2 mm and 3.5 mm relative to the 3.8 mm groups (P < 0.03). Although insertion torque–removal torque paired observations was statis- tically maintained for the 3.5 mm and 3.8 mm groups, a significant decrease in removal torque values relative to insertion torque levels was observed for the 3.2 mm group. A different pattern of healing and interfacial remodeling was observed for the different groups. Different drilling dimensions resulted in variations in insertion torque values (primary stability) and stability maintenance over the first weeks of bone healing.

Osteoclastic activity begins early and increases over the course of bone healing

Osteoclasts are specialised bone-resorbing cells. This particular ability makes osteoclasts irreplaceable for the continual physiological process of bone remodelling as well as for the repair process during bone healing. Whereas the effects of systemic diseases on osteoclasts have been described by many authors, the spatial and temporal distribution of osteoclasts during bone healing seems to be unclear so far. In the present study, healing of a tibial osteotomy under standardised external fixation was examined after 2, 3, 6 and 9 weeks (n = 8) in sheep. The osteoclastic number was counted, the area of mineralised bone tissue was measured histomorphometrically and density of osteoclasts per square millimetre mineralised tissue was calculated. The osteoclastic density in the endosteal region increased, whereas the density in the periosteal region remained relatively constant. The density of osteoclasts within the cortical bone increased slightly over the first 6 weeks, however, there was a more rapid increase between the sixth and ninth weeks. The findings of this study imply that remodelling and resorption take place already in the very early phase of bone healing. The most frequent remodelling process can be found in the periosteal callus, emphasising its role as the main stabiliser. The endosteal space undergoes resorption in order to recanalise the medullary cavity, a process also started in the very early phase of healing at a low level and increasing significantly during healing. The cortical bone adapts in its outward appearance to the surrounding callus structure. This paradoxic loosening is caused by the continually increasing number and density of osteoclasts in the cortical bone ends. This study clearly emphasises the osteoclastic role especially during early bone healing. These cells do not simply resorb bone but participate in a fine adjusted system with the bone-producing osteoblasts in order to maintain and improve the structural strength of bone tissue.

Computational simulation of the early stage of bone healing under different configurations of locking compression plates

Flexible fixation or the so-called ‘biological fixation’ has been shown to encourage the formation of fracture callus, leading to better healing outcomes. However, the nature of the relationship between the degree of mechanical stability provided by a flexible fixation and the optimal healing outcomes has not been fully understood. In this study, we have developed a validated quantitative model to predict how cells in fracture callus might respond to change in their mechanical microenvironment due to different configurations of locking compression plate (LCP) in clinical practice, particularly in the early stage of healing. The model predicts that increasing flexibility of the LCP by changing the bone–plate distance (BPD) or the plate working length (WL) could enhance interfragmentary strain in the presence of a relatively large gap size (.3 mm). Furthermore, conventional LCP normally results in asymmetric tissue development during early stage of callus formation, and the increase of BPD or WL is insufficient to alleviate this problem.