The Influence of Implant Design Features on the Bone Healing Pathway: An Experimental Study in Sheep.

This study evaluated how implant design features influence osseointegration. Two implant macrogeometries and surface treatments were evaluated: (1) progressive buttress threads with an SLActive surface (SLActive/BL), and (2) inner and outer trapezoidal threads with a nanohydroxyapatite coating over a dual acid-etched surface (Nano/U). Implants were placed in the right ilium of 12 sheep, and histologic and -metric analyses were conducted after 12 weeks. Percentages of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within the threads were quantified. Histologically, the SLActive/BL group showed greater and more intimate BIC than the Nano/U group. In contrast, Nano/U group depicted woven bone formation within the healing chambers, between the osteotomy wall and implant threads, and bone remodeling was evident at the outer thread tip. Significantly higher BAFO was seen in the Nano/U group than the SLActive/BL group at 12 weeks (P < .042). Different implant design features influenced the osseointegration pathway, supporting further investigations to describe the differences and clinical performance.

Bone regeneration at extraction sockets filled with leukocyte-platelet-richfibrin: An experimental pre-clinical study

Background: We aimed to histomorphometrically evaluate the effects of Leucocyte-Platelet-Rich Fibrin (L-PRF),with and without the combination of a bone grafting material, for alveolar ridge preservation using an in vivocanine model.Material and Methods: Seven dogs (Female Beagles, ~18-month-old) were acquired for the study. L-PRF wasprepared from each individual animal by drawing venous blood and spinning them through a centrifuge at 408RCF-clot (IntrasSpin, Intra-Lock, Boca Raton, FL). L-PRF membranes were obtained from XPression fabrication kit (Biohorizons Implant Systems, Inc., AL, USA). A split mouth approach was adopted with the first molarmesial and distal socket defects treated in an interpolated fashion of the following study groups: 1) Empty socket (negative control); 2) OSS filled defect 3) L-PRF membrane; and 4) Mix of Bio-Oss® with L-PRF. After six weeks,samples were harvested, histologically processed, and evaluated for bone area fraction occupancy (BAFO), vertical/horizontal ridge dimensions (VRD and HRD, respectively), and area of coronal soft tissue infiltration.Results: BAFO was statistically lower for the control group in comparison to all treatment groups. Defects treatedwith Bio-Oss® were not statistically different then defects treated solely with L-PRF. Collapsed across all groups,L-PRF exhibited higher degrees of BAFO than groups without L-PRF. Defects filled with Bio-Oss® and Bio-Oss®with L-PRF demonstrated greater maintenance of VRD relative to the control group. Collapsed across all groups,Bio-Oss® maintained the VRD and resulted in less area of coronal soft tissue infiltration compared to the emptydefect. Soft tissue infiltration observed at the coronal area was not statistically different among defects filled withL-PRF, Bio-Oss®, and Bio-Oss® with L-PRF.Conclusions: Inclusion of L-PRF to particulate xenograft did not promote additional bone heading at 6 weeks invivo. ... (AU)

Effect of leukocyte-platelet-rich fibrin in bone healing around dental implants placed in conventional and wide osteotomy sites: A pre-clinical study.

Leukocyte-platelet-rich fibrin (L-PRF) has been suggested for gap management for immediate implant placement when the distance is greater than 2 mm. However, there remains a paucity in hierarchically designed research to support this application. The present study aimed to evaluate the effect of L-PRF on the osseointegration parameters of dental implants placed after conventional osteotomy of surgically created bone defects that simulate post extraction sockets in a canine model after 3, 6, and 12 weeks in vivo. Eighty dental implants (Intra-Lock, Boca Raton, FL) were placed in the radius of 13 beagle dogs. The experiment consisted of 4 groups (n = 20 implants/group): 1) Regular osteotomy (Reg n/L-PRF); 2) Regular osteotomy and implant placement with L-PRF membrane (Reg L-PRF); 3) Wide osteotomy with no gap management performed, where an osteotomy/bony defect (6 mm of diameter and ~5 mm deep) was created to simulate immediate implant placement in post-extraction sockets, and the gap was left for spontaneous healing (Wide nL-PRF); and 4) Wide osteotomy with L-PRF gap management (Wide L-PRF). L-PRF membranes were obtained by blood drawn from each subject and centrifuged at 2700 rpm (408 RCF-clot) for 12 min. In the experimental groups where L-PRF was utilized, the membrane was inserted into the osteotomy site prior to implant placement. Six dogs had implants placed in the radius for 3 weeks; and 7 dogs had implants placed in the left radius for 6 weeks and in the right radius for 12 weeks. At the corresponding experimental time points, samples were harvested, and subjected to histological processing for qualitative and quantitative analyses, via bone-to-implant contact (BIC) and bone-area-fraction occupancy (BAFO). Qualitative analysis demonstrated increased amounts of bone formation around the implant and within the healing chambers over time for all groups. While comparable histological features were observed for both Reg groups (L-PRF and nL-PRF), the gap management performed in Wide L-PRF group resulted in effective gap filling with improved bone growth in close proximity to the implant surface. Quantitative analyses of BIC and BAFO yielded higher values for both variables at 3 weeks for Wide L-PRF (~38% and ~56% respectively) compared to Wide nL-PRF (~20% for BIC and BAFO) (p < .03). No statistical differences were detected between Wide groups at 6 and 12 weeks, neither between Reg groups, independent of the association with or without the L-PRF membrane at all healing times. L-PRF placed within wide osteotomies, prior to implant placement, resulted in increased early bone formation compared to unfilled wide osteotomies at the early healing time (3 weeks in vivo).

The effect of platelet-rich fibrin exudate addition to porous poly(lactic-co-glycolic acid) scaffold in bone healing: An in vivo study.

Bone grafting procedures have been widely utilized as the current state-of-the-art for bone regeneration, with autogenous bone graft being the gold-standard bone reconstructive option. However, the use of autografts may be limited by secondary donor-site comorbidities, a finite amount of donor supply, increased operating time, and healthcare cost impact. Synthetic materials, or alloplasts, such as the polymeric material, poly(lactic-co-glycolic acid) (PLGA) has previously been utilized as a transient scaffold to support healing of bone defects with the potential to locally delivery osteogenic additives. In this study a novel procedure was adopted to incorporate both the dissolved contents and mechanical components of leukocyte- and platelet-rich fibrin (L-PRF) into an PLGA scaffold through a two-step method: (a) extraction of the L-PRF membrane transudate with subsequent immersion of the PLGA scaffold in transudate followed by (b) delivering a fibrin gel as a low-viscosity component that subsequently polymerizes into a highly viscous, gel-like biological material within the pores of the PLGA scaffold. Two, ~0.40 cm3 , submandibular defects (n = 24) were created per side using rotary instrumentation under continuous irrigation in six sheep. Each site received a PLGA scaffold (Intra-Lock R&D, Boca Raton, FL), with one positive control (without L-PRF exudate addition [nL-PRF]), and one experimental (augmented with PLGA/L-PRF Blocks [L-PRF]). Animals were euthanized 6 weeks postoperatively and mandibles retrieved, en bloc, for histological analysis. Histomorphometric evaluation for bone regeneration was evaluated as bone area fraction occupancy (BAFO) within the region of interest of the cortical bone (with specific image analysis software) and data presented as mean values with the corresponding 95% confidence interval values. Qualitative evaluation of nondecalcified histologic sections revealed extensive bone formation for both groups, with substantially more bone regeneration for the L-PRF induced group relative nL-PRF group. Quantitative BAFO within the defect as function of the effect of L-PRF exudate on bone regeneration, demonstrated significantly (p = .018) higher values for the L-PRF group (38.26% ± 8.5%) relative to the nL-PRF group (~28% ± 4.0%). This in vivo study indicated that L-PRF exudate has an impact on the regeneration of bone when incorporated with the PLGA scaffold in a large translational model. Further studies are warranted in order to evaluate the L-PRF exudate added, as well as exploring the preparation methods, in order to facilitate bone regeneration.

Osteogenic parameters surrounding trabecular tantalum metal implants in osteotomies prepared via osseodensification drilling

BACKGROUND: Surgical fixation of implants into bone for the correction of bone deformities or defects is a traditional approach for skeletal stabilization. Important measures of efficacy of implants include implant stability and osseo integration-the direct interaction between living bone and an implant. Osseointegration depends on successful implant placement and subsequent bone remodeling. This study utilized osseo densification drilling (OD) in a low bone density model using trabecular metal (TM) implants. MATERIAL AND METHODS: Three osteotomy sites, Regular, OD-CW (clockwise), and OD-CCW (counterclockwise), were prepared in each ilium of three female sheep. Drilling was performed at 1100rpm with saline irrigation. Trabecular metal (TM) (Zimmer(R), Parsippany, NJ, USA) implants measuring 3.7mm in diameter X 10mm length were placed into respective osteotomies. A three-week period post-surgery was given to allow for healing to take place after which all three sheep were euthanized and the ilia were collected. Samples were prepared, qualitatively and quantitatively analyzed using histology micrographs and image analysis software (ImageJ, NIH, Bethesda, MD). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were quantified to evaluate the osseointegration parameters. RESULTS: All implants exhibit successful bone formation in the peri-implant environment as well as within the open spaces of the trabecular network. Osseointegration within the TM (quantified by %BIC) as a function of drilling technique was more pronounced in OD samples (p > 0.05). The %BAFO however shows a significant difference (p = 0.036) between the CCW and R samples. Greater bone volume and frequency of bone chips are observed in OD samples. CONCLUSION: The utilization of OD as a design for improved fixation of hardware was supported by increased levels of stability, both primary and secondary. Histological data with OD provided notably different results from those of the regular drilling method

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Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone.

BACKGROUND: Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. METHODS: Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of ß-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 µM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. RESULTS: Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. CONCLUSION: Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment.

Alveolar Ridge Expansion: Comparison of Osseodensification and Conventional Osteotome Techniques.

OBJECTIVE: The aim of this in vivo study is to compare the osseointegration of endosteal implants placed in atrophic mandibular alveolar ridges with alveolar ridge expansion surgical protocol via an experimental osseodensification drilling versus conventional osteotome technique. METHODS: Twelve endosteal implants, 4 mm × 13 mm, were placed in porcine models in horizontally atrophic mandibular ridges subsequent to prior extraction of premolars. Implants were placed with osseodensification drilling technique as the experimental group (n = 6) and osteotome site preparation as the control group (n = 6). After 4 weeks of healing, samples were retrieved and stained with Stevenel's Blue and Van Gieson's Picro Fuschin for histologic evaluation. Quantitative analysis via bone-to-implant contact (BIC%) and bone area fraction occupancy (BAFO%) were obtained as mean values with corresponding 95% confidence interval. A significant omnibus test, post-hoc comparison of the 2 drilling techniques' mean values was accomplished using a pooled estimate of the standard error with P-value set at 0.05. RESULTS: The mean BIC% value was approximately 62.5% in the osseodensification group, and 31.4% in the regular instrumentation group. Statistical analysis showed a significant effect of the drilling technique (P = 0.018). There was no statistical difference in BAFO as a function of drilling technique (P = 0.198). CONCLUSION: The combined osseodensification drilling-alveolar ridge expansion technique showed increased evidence of osseointegration and implant primary stability from a histologic and biomechanical standpoint, respectively. Future studies will focus on expanding the sample size as well as the timeline of the study to allow investigation of long-term prognosis of this novel technique.

In vivo evaluation of resorbable supercritical CO2 -treated collagen membranes for class III furcation-guided tissue regeneration.

The study evaluated the effects of a Supercritical CO2 (scCO2 ) on a commercially available decellularized/delipidized naturally derived porcine pericardium collagen membrane, Vitala®. The Vitala® and scCO2 treated experimental membranes were evaluated for guided tissue regeneration (GTR) of periodontal tissue in class III furcation defects utilizing a dog model. Physical material characterization was performed by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The in vivo portion of the study was allocated to three-time points (6, 12, and 24-weeks) using standardized class III furcation defects created in the upper second and third premolars. The experimental defects (n = 5) were covered with either a collagen membrane (positive control), scCO2 -treated collagen membrane (experimental) or no membrane (negative control). Following sacrifice, histologic serial sections were performed from cervical to apical for morphologic/morphometric evaluation. Morphometric evaluation was carried out by ranking the presence of collagen membrane, amount of bone formation within the defect site and inflammatory cell infiltrate content. SEM showed the experimental scCO2 -treated membrane to have a similar gross fibrous appearance and chemical structure in comparison to the Vitala® Collagen membrane. A significant increase in membrane thickness was noted in the scCO2 -treated membranes (366 ± 54 µm) vs non-treated membranes (265 ± 75 µm). TGA and DSC spectra indicated no significant qualitative differences between the two membranes. For the in vivo results, both membranes indicated significantly greater amounts of newly formed bone (scCO2 : 2.85 ± 1.1; Vitala®: 2.80 ± 1.0) within the covered defects relative to uncovered controls (0.8 ± 0.27) at 24 weeks. Both membrane types gradually degraded as time elapsed in vivo from 6 to 12 weeks, and presented nearly complete resorption at 24 weeks. The inflammatory infiltrate at regions in proximity with the membranes was commensurate with healthy tissue levels from 6 weeks in vivo on, and periodontal ligament regeneration onset was detected at 12 weeks in vivo. The effect of the supplementary scCO2 treatment step on the collagen membrane was demonstrated to be biocompatible, allowing for the infiltration of cells and degradation over time. The treated membranes presented similar performance in GTR to non-treated samples in Class III furcation lesions. Defects treated without membranes failed to achieve regeneration of the native periodontium. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1320-1328, 2019.

Synergistic Effects of Implant Macrogeometry and Surface Physicochemical Modifications on Osseointegration: An In Vivo Experimental Study in Sheep.

This study evaluates the influence of two surface physicochemical modifications on osseointegration parameters of a healing chamber implant design. We examine dental implants with internal and external trapezoidal threads that have the following surface modifications: dual acid etching (DAE) and nano-hydroxyapatite (HA) coating over DAE surface (Nano). We installed implants in the right ilium of sheep and conducted histologic/metric analyses after 3 and 12 wk in vivo. We quantified the percentage of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO) within implant threads. Histologic micrographs indicate early bone formation within the healing chambers of implants with Nano surface relative to DAE surface. Histomorphometric analysis demonstrates there to be no significant differences in %BIC between 3 and 12 wk (p = 0.298). Compared to DAE, Nano shows more bone formation in contact with implant, regardless of time (p < 0.025). We observe > %BAFO at 12 wk relative to 3 wk, which differs significantly for Nano (p < 0.038). Implant surface treatment affects the amounts of bone formation within healing chambers, with Nano significantly outperforming DAE at 12 wk (p < 0.025). Nano presents a synergistic effect with implant design, improving osseointegration parameters.

Early Healing Evaluation of Commercially Pure Titanium and Ti-6Al-4V Presenting Similar Surface Texture: An In Vivo Study.

OBJECTIVE: This study evaluated the osseointegration of commercially pure titanium (Ti) grade-2 (G2) and Ti-6Al-4V alloy (G5) implants with the same geometry and surface treatment. MATERIALS AND METHODS: Thirty-six dental implants with a grit-blasted acid-etched surface were used (n = 18, each). Two implants, one per group, were installed in each subject, in the radius diaphysis (n = 18 beagle dogs), with interchanged fixture position (proximal-distal) between animals for a balanced number of devices per group and time in vivo (1, 3, and 6 weeks). RESULTS: Similar topographical parameters between G2 and G5 were observed for average surface roughness, root mean square, developed surface ratio, maximum height of surface, and density of summits. Removal torque was significantly higher for G5 than for G2. No differences were observed for bone-to-implant contact and bone-area-fraction occupancy. Removal torque significantly increased with time for both groups. At 1 week, new bone formation in direct contact with the implant surface and osteogenic tissue migration was observed with an increase in woven bone formation at 3 weeks followed by the onset of lamellar bone formation at 6 weeks. CONCLUSION: Although both surfaces were biocompatible and osteoconductive, increased removal torque was observed for Ti-6Al-4V compared with commercially pure Ti implants.

The Effect of Laser-Etched Surface Design on Soft Tissue Healing of Two Different Implant Abutment Systems: An Experimental Study in Dogs.

This study describes the early soft tissue morphology around two different implant systems that received either smooth or laser-etched abutments in a beagle dog model. Implants were placed in the healed mandibular molar region of eight beagle dogs and allowed to heal for 7 weeks. When the most apical aspect of the junctional epithelium (JE) was above or within the upper half of the laser-etched region, fibers were oriented perpendicular to the abutment surface. In contrast, JE positioned within the lower half of the laser-etched region or within or below the implant-abutment gap level presented fibers oriented parallel to the abutment surface.

Effect of Simplified One-Step Drilling Protocol on Osseointegration.

This study was designed to compare the combined effect of two different drilling techniques (conventional expansion and one-step) and four different implant geometries in a beagle dog model. The nondecalcified bone-implant samples underwent histologic/metric analysis at 2 and 6 weeks. Morphologic analysis showed similarities between different drilling technique groups and implant geometries. Histomorphometric parameters, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) were analyzed, and no statistical difference between drilling groups and/or implant geometry was found. Time was the only variable that affected BIC and BAFO, suggesting that the two protocols are equally biocompatible and osseoconductive.

Histomorphological and Histomorphometric Analyses of Grade IV Commercially Pure Titanium and Grade V Ti-6Al-4V Titanium Alloy Implant Substrates: An In Vivo Study in Dogs.

PURPOSE: To evaluate the bone response to grade IV commercially pure titanium (G4) relative to Ti-6Al-4V (G5). MATERIALS AND METHODS: Implant surface topography was characterized by optical interferometry and scanning electron microscopy (SEM). Thirty-six implants (Signo Vinces, n = 18 per group) were installed in the radius of 18 dogs. The animals were killed at 1, 3, and 6 weeks, resulting in 6 implants per group and time in vivo for bone morphology, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) evaluation. RESULTS: SEM depicted a more uniform topography of G4 than G5. Surfaces were statistically homogeneous for Sa, Sq, and Sdr. At 1 week, new bone formation was observed within the healing connective tissue in contact with the implant surface. At 3 weeks, new bone in direct contact with the implant surface was observed at all bone regions. At 6 weeks, the healing chambers filled with woven bone depicted an onset of replacement by lamellar bone. No significant effect of substrate was detected. Time presented an effect on BIC and BAFO (P < 0.001). CONCLUSION: Both titanium substrates were biocompatible and osseoconductive at the bone tissue level.

Guidelines for Clinical Management of Laser-Etched (Laser-Lok) Abutments in Two Different Clinical Scenarios: A Preclinical Laboratory Soft Tissue Assessment Study.

One-stage implants were placed in the mandibles of eight beagle dogs with laser-etched (LL) and machined abutments. After 4 weeks, half of the LL abutments were disconnected and reconnected after 10 minutes of saline storage, and the other half were replaced with a new LL abutment (impression simulation) with or without sulcus de-epithelialization. After abutment change, systems remained in vivo for 3 weeks. Results showed that LL abutments can be reconnected and that sulcus scoring prior to LL placement of one-stage implants receiving machined abutments may be beneficial.

The effect of controlled microrobotized blasting on implant surface texturing and early osseointegration.

Surface topography modifications have become a key strategy for hastening the host-to-implant response to implantable materials. The present study evaluated the effect of three different carefully controlled surface texture patterns achieved through microrobotized blasting (controlled to high, medium and low roughness) relative to a larger scale blasting procedure (control) in early osseointegration in a canine model. Four commercially pure grade 2 titanium alloy implants (one of each surface) were bilaterally placed in the radii of six beagle dogs and allowed end points of 1 and 6 weeks in vivo. Following sacrifice, implants in bone were non-decalcified processed for bone morphologic and histometric (bone-to-implant contact; bone area fraction occupancy) evaluation. Surface topography was characterized by scanning electron microscopy and optical interferometry. Results showed initial osteogenic tissue interaction at one week and new bone in intimate contact with all implant surfaces at 6 weeks. At 1 and 6 weeks in vivo, higher bone-to-implant and bone area fraction occupancy were observed for the high texture pattern microrobotized blasted surface relative to others.

Microrobotized blasting improves the bone-to-textured implant response. A preclinical in vivo biomechanical study.

This study evaluated the effect of microrobotized blasting of titanium endosteal implants relative to their manually blasted counterparts. Two different implant systems were utilized presenting two different implant surfaces. Control surfaces (Manual) were fabricated by manually grit blasting the implant surfaces while experimental surfaces (Microblasted) were fabricated through a microrobotized system that provided a one pass grit blasting routine. Both surfaces were created with the same ~50µm average particle size alumina powder at ~310KPa. Surfaces were then etched with 37% HCl for 20min, washed, and packaged through standard industry procedures. The surfaces were characterized through scanning electron microscopy (SEM) and optical interferometry, and were then placed in a beagle dog radius model remaining in vivo for 3 and 6 weeks. The implant removal torque was recorded and statistical analysis evaluated implant system and surface type torque levels as a function of time in vivo. Histologic sections were qualitatively evaluated for tissue response. Electron microscopy depicted textured surfaces for both manual and microblasted surfaces. Optical interferometry showed significantly higher Sa, Sq, values for the microblasted surface and no significant difference for Sds and Sdr values between surfaces. In vivo results depicted that statistically significant gains in biomechanical fixation were obtained for both implant systems tested at 6 weeks in vivo, while only one system presented significant biomechanical gain at 3 weeks. Histologic sections showed qualitative higher amounts of new bone forming around microblasted implants relative to the manually blasted group. Microrobotized blasting resulted in higher biomechanical fixation of endosteal dental implants and should be considered as an alternative for impant surface manufacturing.

Progressive plateau root form dental implant osseointegration: A human retrieval study.

Although preclinical and sparse human histology retrieval studies have shown that the interface between implant and bone is constantly remodeling, no human retrieval database has been developed to determine the effect of functional loading time and other clinical/implant design variables on osseointegration. The present study tested the hypothesis that bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) increase over functional loading time around dental implants. Due to prosthetic retreatment reasons, 93 human implant retrievals from the same manufacturer (Bicon LLC, Boston, MA, USA) were obtained over a period of approximately 15 years. The retrieved implants were under functional loading from 120 days to ∼18 years and were histomorphologic/metrically evaluated. BIC/BAFO were assessed as a function of multiple independent variables: implant surface type, diameter, length, jaw (maxilla/mandible), region (anterior/posterior), and time of functional loading. The results showed that both BIC and BAFO increased over time independently of implant design/clinical variables, supporting the postulated hypothesis.