Cementum and enamel surface mimicry influences soft tissue cell behavior.

AIMS: To test whether titanium surface roughness disparity might be used to specifically guide the behavior of gingiva fibroblasts and keratinocytes, thereby improving the quality of soft tissue (ST) integration around abutments. METHODS: Titanium discs resembling the roughness of enamel (M) or cementum (MA) were created with normal or increased hydrophilicity and used as substrates for human fibroblasts and keratinocytes. Adhesion and proliferation assays were performed to assess cell-type specific responses upon encountering the different surfaces. Additionally, immunofluorescence and qPCR analyses were performed to study more in depth the behavior of fibroblasts and keratinocytes on MA and M surfaces, respectively. RESULTS: While enamel-like M surfaces supported adhesion, growth and a normal differentiation potential of keratinocytes, cementum-emulating MA surfaces specifically impaired the growth of keratinocytes. Vice versa, MA surfaces sustained regular adhesion and proliferation of fibroblasts. Yet, a more intimate adhesion between fibroblasts and titanium was achieved by an increased hydrophilicity of MA surfaces, which was associated with an increased expression of elastin. CONCLUSION: The optimal titanium implant abutment might be achieved by a bimodal roughness design, mimicking the roughness of enamel (M) and cementum with increased hydrophilicity (hMA), respectively. These surfaces can selectively elicit cell responses favoring proper ST barrier by impairing epithelial downgrowth and promoting firm adhesion of fibroblasts.

Histological evaluation of osseointegration between conventional and novel bone-level tapered implants in healed bone-A preclinical study.

AIMS: To histologically compare osseointegration and crestal bone healing between newly introduced tapered, self-cutting bone-level test implants and tapered bone-level control implants in sites with fully healed sites. METHODS: Sixty-six implants (33 test, 33 control) were placed 1 mm subcrestally in a minipig model and underwent qualitative histologic and quantitative histometric analyses after 3, 6 and 12 weeks of submerged healing. The primary and secondary outcomes were the bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC). Outcomes between the test and control implants were statistically compared. RESULTS: The BIC values of the test implants were comparable and non-inferior over the time points studied, except for the 12 weeks time point which showed statistically significantly higher BIC values of the test (88.07 ± 5.35%) compared to the control implants (80.88 ± 7.51%) (p = .010). Similarly comparable and non-inferior were the fBIC values, except for the 6-week outcome, which showed statistically higher values for the test (-546.5 ± 450.80 µm) compared to the control implants (-75.7 ± 100.59 µm). fBIC results for the test implants were qualitatively more stable and consistent between test time points. CONCLUSION: Novel self-cutting bone-level test implants demonstrated superior osseointegration and similar bone levels compared to conventional bone-level implants after a healing period of 12 weeks in healed ridges.

Primary stability and osseointegration comparing a novel tapered design tissue-level implant with a parallel design tissue-level implant. An experimental in vivo study.

OBJECTIVES: The aim of the present study was to compare a novel tapered, double-threaded self-tapping tissue-Level design implant (TLC) to a well-established parallel walled tissue-level (TL) implant in terms of primary and secondary stability over time. MATERIALS AND METHODS: Test TLC (n = 10/per timepoint) and control TL (n = 10/per timepoint) implants were placed in the mandible of minipigs and left for submerged healing for 3, 6, and 12 weeks. Maximum insertion torque and implant stability quotient (ISQ) were measured for each implant at placement. Osseointegration and cortical bone maintenance were histologically evaluated by measuring total bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC). RESULTS: A significantly higher maximum insertion torque was measured for the test implant TLC compared to the control TL implant (57.83 ± 24.73 Ncm and 22.62 ± 23.16 Ncm, respectively; p < .001). The mean ISQ values were comparable between the two implant types (75.00 ± 6.70 for TL compared to 75.40 ± 3.20 for TLC, p = .988). BIC was comparable between both implant types at each of the evaluated time points. The fBIC was found to be significantly more coronal at 12 weeks for the TLC implant compared to the TL implant (0.31 ± 0.83 mm for TLC compared to -0.22 ± 0.85 for TL, p = .027). CONCLUSION: The novel tapered tissue level design implant showed improved primary stability and an overall improved crestal bone height maintenance compared to the parallel walled design at 12 weeks.

Comparative osseointegration of hydrophobic tissue-level tapered implants-A preclinical in vivo study.

PURPOSE: To histometrically compare the osseointegration and crestal bone healing of a novel tapered, self-cutting tissue-level test implant with a standard tissue-level control implant in a submerged healing regimen. MATERIALS AND METHODS: In a mandibular minipig model, implants were inserted and evaluated histometrically after a healing period of 3, 6, and 12 weeks. The primary outcome was the evaluation of bone-to-implant contact (BIC) and secondary outcomes were primary stability as per insertion torque and first BIC (fBIC). Outcomes for the test and control implants were compared using Wilcoxon signed-rank tests and mixed linear regression models. RESULTS: Insertion torque values were significantly higher for the test (50.0 ± 26.4 Ncm) compared to the control implants (35.2 ± 19.7 Ncm, p = .0071). BIC values of test implants were non-inferior to those of control implants over the investigated study period. After 12 weeks, the corresponding values measured were 81.62 ± 11.12% and 90.41 ± 4.81% (p = .1763) for test and control implants, respectively. Similarly, no statistical difference was found for fBIC values, except for the 12 weeks outcome that showed statistically lower values for the test (-675.58 ± 590.88 µm) compared to control implants (-182.75 ± 197.40 µm, p = .0068). CONCLUSIONS: Novel self-cutting tissue-level implants demonstrated noninferior osseointegration and crestal bone height maintenance to the tissue-level implants. Histometric outcomes between both implants demonstrated test implants were statistically noninferior to control implants, despite substantial differences in the bone engagement mechanism and resulting differences in insertion torque and qualitative bone healing patterns.

Influence of loading and grafting on hard- and soft-tissue healing at immediately placed implants: An experimental study in minipigs.

AIM: To histologically evaluate the influence of (1) loading and (2) grafting on osseointegration and peri-implant soft-tissue healing at immediately placed, self-cutting progressive tissue-level implants (TLX) in a minipig model. MATERIALS AND METHODS: TLX implants (n = 56) were immediately placed following the extraction of the mandibular first and second premolars, bilaterally, in a total of n = 14 minipigs. In each animal, the implant sites were allocated to the following four groups: (1) unloaded with simultaneous grafting using a bovine bone mineral; (2) unloaded without grafting; (3) loaded with simultaneous grafting; and (4) loaded without grafting. Histomorphometric assessments at 4 and 12 weeks (n = 7 animals each) included primary (i.e., bone-to-implant contact [BIC]) and secondary outcome measures (e.g., first BIC [fBIC], junctional epithelium length [JE], connective tissue contact length [CTC], biological width [BW = JE + CTC]). RESULTS: At 4 weeks, mean BIC values ranged from 74.5 ± 11.6% in Group 2 to 83.8 ± 13.3% in Group 1, and, at 12 weeks, from 75.5% ± 7.9% in Group 2 to 79.9 ± 8.6% in Group 1. Multivariate linear mixed regression did not reveal any associations between BIC and implant loading or grafting at 4 and 12 weeks. At 12 weeks, significantly higher fBIC values were noted in Group 2 when compared with Group 1. All groups showed comparable JE, CTC, and BW values. CONCLUSIONS: Implant loading and grafting had no major effects on osseointegration and peri-implant soft tissue healing at TLX implants.

Determining primary stability for adhesively stabilized dental implants.

OBJECTIVES: To examine factors influencing the primary stability of dental implants when stabilized in over-sized osteotomies using a calcium phosphate-based adhesive cement was the objective. METHODS: Using implant removal torque measurements as a surrogate for primary stability, we examined the influence of implant design features (diameter, surface area, and thread design), along with cement gap size and curing time, on the resulting primary implant stability. RESULTS: Removal torque values scaled with implant surface area and increasing implant diameters. Cement gap size did not alter the median removal torque values; however, larger gaps were associated with an increased spread of the measured values. Among the removal torque values measured, all were found to be above 32 Ncm which is an insertion torque threshold value commonly recommended for immediate loading protocols. CONCLUSION: The adhesive cement show potential for offering primary implant stability for different dental implant designs. In this study, the primary parameters influencing the measured removal torque values were the implant surface area and diameter. As the liquid cement prevents the use of insertion torque, considering the relationship between insertion and removal torque, removal torque can be considered a reliable surrogate for primary implant stability for bench and pre-clinical settings. CLINICAL RELEVANCE: At present, the primary stability of dental implants is linked to the quality of the host bone, the drill protocol, and the specific implant design. The adhesive cement might find applications in future clinical settings for enhancing primary stability of implants under circumstances where this cannot be achieved conventionally.

Immediate loading of a fully tapered implant with deep apical threads placed in healed alveolar ridges vs. immediate extraction sockets.

OBJECTIVES: Immediate implant placement and loading is a practice that continues to gain traction in implant dentistry because it reduces treatment time and improves satisfaction. Novel implant designs that facilitate increased primary stability, while not compromising osseointegration and long-term survival are important to offer immediate solutions for missing teeth. Here, we hypothesize that fully tapered implants can obtain successful osseointegration with high survival rates after immediate loading in fresh extraction sockets and healed sites. MATERIALS AND METHODS: A total of 13 swine with 73 implants were evaluated. Fully tapered or apically tapered implants were placed in extraction sockets and healed sites. Insertion torque and resonance frequency analysis were determined at placement and euthanasia. Animals were evaluated at: placement, and 1-week and 12-weeks after placement. Bone to Implant Contact (BIC), Bone Area/Total Area (BA/TA), and first BIC (fBIC) analyses were conducted. RESULTS: The fully tapered implant achieved similar primary stability with lower insertion torque at placement. Apically and fully tapered implants had comparable BIC (50.1% vs 59.4%) and ISQ (82.5 vs 80.3) values by 12 weeks in healed sites. In extraction sockets, BIC and ISQ for the apically tapered implant was 35.8% and 73.2 and 37.8% and 79.2 for the fully tapered implants, respectively. CONCLUSIONS: In this short-term study, immediately loaded fully tapered implants obtained high survival with similar osseointegration ability as apically tapered implants when placed in healed sites and fresh extraction sockets. Fully tapered implants show promise for use in immediate loading and immediate placement.

Development of a new preclinical model to study early implant loss: a validation study in the beagle dog.

OBJECTIVES: To develop a new preclinical model to study early implant loss, where local infection conditions would impair the implant osseointegration. MATERIALS AND METHODS: Forty-eight smooth, 2.9-mm diameter experimental implants were placed in the mandible of 8 beagle dogs (3 in each side). In half of the animals (test group, n = 24 implants), the implants received ligatures around the implant-abutment connection. In the other half, no ligatures were placed (control group, n = 24 implants). Four weeks later, implants were extracted in a flapless approach and standard 3.3-mm diameter SLActive implants were placed into the same osteotomy site without any further drilling. Eight weeks after the second implantation, animals were sacrificed and analyzed in terms of implant survival. RESULTS: After 8 weeks of healing, 4 implants were lost in the control group and 14 in the test group. This corresponded to a 17.4% of early implant loss in the control group and 58.3% in the test. Most of the early failures occurred within the first 5 weeks of healing. CONCLUSIONS: Implants placed in a pre-contaminated site present higher early loss than those placed in a non-contaminated site. This study represents a valid and robust preclinical model to study mechanisms and reduction of early implant loss as new technologies become available. CLINICAL RELEVANCE: Scientific rationale for the study: There is lack of animal models to study early implant loss. Thus, a proposal of a new model is presented. With the validation of this model, new technologies can be implemented to prevent early implant loss.

Thermal exposure of implant osteotomies and its impact on osseointegration-A preclinical in vivo study.

OBJECTIVES: Thermal and mechanical stresses during osteotomy preparation can impair implant osseointegration. This study investigated implant osseointegration following the measurement of temperature exposure during osteotomy drilling, varying drill design, sequence, and drill wear. MATERIALS AND METHODS: 36 tapered implants were placed in a mandibular minipig model after guided drilling of implant osteotomies using 4 different groups: (1) control drills with a conservative, sequential drilling sequence, (2) control drills using a shortened drill sequence (PF), (3) novel test drill displaying an optimized drill design and surface treatment, PF, and (4) aged test drill, PF. Intraosseous temperatures during drilling were measured using a temperature probe. BIC, fBIC, and tissue reactions were histomorphometrically derived after 2 and 8 weeks of healing. RESULTS: Compared to control drills (1) or (2), test drills (3) resulted in significantly lower maximum temperatures ((35.4 (CI 30.2-40.5)°C vs. (46.5 (CI 41.0-52.0)°C, p = .0021)) and shorter drill times ((4.5 (CI 1.6-7.3)sec vs. 10.3 (7.3-13.4)sec). Lower osteotomy temperature values and shorter drill times corroborated with significantly higher BIC after 2 and 8 weeks healing for the test (3) compared to control groups (2) (2 weeks: (44.9 (CI 34.1-55. 7)% vs. (31.3 (CI 20.5-42.2)%, p = <.0001 and 8 weeks: (73.7 ( CI 64.2-83.2)% vs. (66.2 (CI 57.0-75.4)%, p = <.0455). CONCLUSION: The improved osseointegration of implants placed after osteotomy preparation with novel test drills using a shortened drill sequence compared to standard drills and conventional drill protocols might be attributed to more favorable thermal profiles and less mechanical stress exerted on the bone surrounding the implant osteotomy.

Evaluation of air polishing with a sterile powder and mechanical debridement during regenerative surgical periimplantitis treatment: a study in dogs.

OBJECTIVES: To evaluate the effectiveness of mechanical debridement and/or air polishing on the healing of ligature-induced buccal periimplantitis dehiscence defects in dogs. MATERIAL AND METHODS: Forty-eight implants were placed in the mandibles of twelve beagle dogs, and periimplantitis was induced for 2 months using ligatures. The resulting buccal dehiscence-type defects were surgically cleaned and augmented (xenogenic filler and resorbable membrane) according to one of the following treatments: (1) Cleaning with carbon curette (debridement - D) and guided bone regeneration (GBR/G): DG, (2) air polishing cleaning (A) and GBR: AG, (3) a combination of D/A/G: DAG, and (4) D/A without GBR: DA. After 2 months, histomorphometric and inflammatory evaluations were conducted. RESULTS: The median bone gain after therapy ranged between 1.2 mm (DG) and 2.7 mm (AG). Relative bone gain was between 39% (DG) and 59% (AG). The lowest inflammation scores were obtained in DA without GBR (5.84), whereas significantly higher values between 8.2 and 9.4 were found in the groups with augmentation. At lingual sites without defects, scores ranged from 4.1 to 5.9. According to ISO, differences above 2.9 were considered representative for irritative properties. CONCLUSIONS: All treatments resulted in partial regeneration of the defects. No treatment group showed a significantly (p < 0.05) better outcome. However, pretreatment with air polishing showed a tendency for less inflammation. Noteworthy, inflammation assessment showed an overall irritative potential after GBR in the evaluated early healing phase. CLINICAL RELEVANCE: Periimplantitis treatment still represents a big issue in daily practice and requires additional preclinical research in order to improve treatment concepts.

Osseointegration of a novel injection molded 2-piece ceramic dental implant: a study in minipigs.

OBJECTIVES: This study compared the osseointegrative potential of a novel injection molded zirconia dental implant (Neodent Zi ceramic implant, test) and a commercially available titanium implant (Neodent Alvim implant, control) in terms of histomorphometrically derived bone-to-implant contact (BIC), first bone-to-implant contact (fBIC), and the ratio of bone area to total area (BATA) around the implant. MATERIALS AND METHODS: A total of 36 implants, 18 per individual test device, were implanted in a split-mouth arrangement in either side of the edentulous and fully healed mandible of 6 minipigs. Histomorphometric analysis of BIC, fBIC, and BATA were performed 8 weeks post implantation and subjected to statistical non-inferiority testing. Surface characteristics of both implant types were compared in terms of contact angle, surface topography, and elemental composition. RESULTS: BIC, fBIC, and coronal BATA values of test and control implants were statistically comparable and non-inferior. BIC values of 77.8 ± 6.9% vs. 80.7 ± 6.9% (p = 0.095) were measured for the test and control groups. fBIC lingual values were - 238 ± 328 µm compared with - 414 ± 511 µm (p = 0.121) while buccal values were - 429 ± 648 µm and - 588 ± 550 µm (p = 0.230) for the test and control devices, respectively. BATA in the apical segment was significantly higher in the test group compared with the control group (67.2 ± 11.8% vs. 59.1 ± 11.4%) (p = 0.0103). Surface topographies of both implant types were comparable. Surface chemical analysis indicated the presence of carbonaceous adsorbates which correlated with a comparable and predominantly hydrophobic character of the implants. CONCLUSION: The results demonstrate that the investigated zirconia implants, when compared with a commercially available titanium implant, show equivalent and non-inferior bone integration, bone formation, and alveolar bone level maintenance. This qualifies the investigated zirconia implant as a potential candidate for clinical development. CLINICAL RELEVANCE: This study investigated the osseointegration of a novel zirconia 2-piece dental implant prototype intended for clinical development. With the aim of translating this prototype into clinical development preclinical models, procedures and materials within this study have been selected as close to clinical practice and human physiological conditions as possible.

A novel fully tapered, self-cutting tissue-level implant: non-inferiority study in minipigs.

OBJECTIVES: To assess the osseointegration and crestal bone level maintenance of a novel fully tapered self-cutting tissue-level implant for immediate placement (test) compared to a clinically established tissue-level implant (control) in moderate bone quality. MATERIALS AND METHODS: Test and control implants were compared in 3 groups, i.e., small-, medium-, and large-diameter implants in an edentulous mandibular minipig model with moderate bone quality after 12 weeks of healing. Histometrically derived bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC) were subjected to statistical non-inferiority testing. Maximum insertion torque values in artificial bone were assessed for comparison. RESULTS: BIC values for the tests and control implants for all 3 diameters were comparable and non-inferior: small diameter (61.30 ± 10.63% vs. 54.46 ± 18.31%) (p=0.99), medium diameter (60.91 ± 14.42 vs. 54.68 ± 9.16) (p=0.55), and large diameter (45.60 ± 14.67 vs. 52.52 ± 14.76) (p=0.31). fBIC values for test implants were higher and non-inferior compared to control implants in all three groups. Test implants further showed distinctly higher maximum insertion torque values compared to control implants. CONCLUSION: The investigated novel tissue-level implant is able to achieve high levels of primary and secondary implant stability under simultaneous preservation of crestal bone levels. This qualifies the studied implant as an attractive candidate for immediate placement in bone of limited quality. CLINICAL RELEVANCE: This pilot pre-clinical study investigated a novel tissue-level implant for immediate placement. With the aim of translating the studied prototype into clinical application pre-clinical models, procedures and controls have been chosen with the aim of reflecting its future clinical indication and use.

Peri-implant bone preservation of a novel, self-cutting, and fully tapered implant in the healed crestal ridge of minipigs: submerged vs. transgingival healing.

OBJECTIVES: The aim of this study was to assess the influence of transgingival compared with submerged healing on peri-implant bone maintenance around a novel, fully tapered implant in a healed crestal ridge in minipigs. MATERIALS AND METHODS: In each of 12 minipigs, two implants (Straumann® BLX, Roxolid® SLActive®, Ø 3.75 × 8 mm) were placed. Implants were either left for submerged or for transgingival healing for 12 weeks. Measurements performed were bone-to-implant contact (BIC), first bone-to-implant contact (fBIC), bone area to total area (BATA), perpendicular bone crest to implant shoulder (pCIS), bone height change from placement, and bone overgrowth (for submerged implants). RESULTS: No significant differences were found between transgingival and submerged healing in any of the measured parameters, except for BATA on the buccal aspect in which significantly more bone formation was found for the transgingival healing group. For both groups, there was a gain in crestal bone height during the 12-week healing period. CONCLUSIONS: Loaded compared with unloaded implants displayed comparable levels of osseointegration and equivalent marginal bone levels. This qualifies the implant placement protocol with respect to the osteotomy dimensions and subcrestal placement protocol for immediate loading. CLINICAL RELEVANCE: The here presented results related to osseointegration and crestal bone maintenance after submerged or transgingival healing have demonstrated a high level of consistency in the used in vivo translational model. The obtained results support the translation of the novel implant type in conjunction with the developed surgical workflow and placement protocol into further clinical investigation and use.

Maxillary Sinus Floor Elevation Surgery With BioOss Mixed With Enamel Matrix Derivative: A Human Randomized Controlled Clinical and Histologic Study.

Xenograft bone substitutes are commonly used to increase bone volume and height in the deficient posterior maxilla. The addition of enamel matrix derivate (Emdogain) could increase the efficiency of the bone healing process. The aim of this prospective randomized, controlled split-mouth design study was to compare the percentage of newly formed bone in sinus floor augmentation with deproteinized bovine bone mineral with or without the addition of enamel matrix derivative after 6 months of healing. Sixteen bilateral sinus floor augmentation procedures were performed. Deproteinized bovine bone mineral combined with enamel matrix derivative (test) and deproteinized bovine bone mineral alone (control) groups were randomly allocated within each patient. Six months after augmentation and concurrent to implant placement, bone biopsies were taken for histomorphometric analysis. Additionally, implant survival and peri-implant bone levels were radiographically assessed at baseline and 24 months after functional loading. Histomorphometric analysis revealed a significantly higher amount of newly formed bone in the test group compared with the control group (22.6% and 15.5%, respectively; P = .033). No significant differences in the amount of remaining graft or connective tissue was found. Enamel matrix derivative added to deproteinized bovine bone mineral particles significantly increased new bone formation in sinus lift procedures in edentulous or partially edentulous patients with deficient bilateral posterior alveolar ridges requiring augmentation for implant placement.

Surface modification of ultrafine-grained titanium: Influence on mechanical properties, cytocompatibility, and osseointegration potential.

OBJECTIVE: The main objective of this study was to demonstrate that dental implants made from ultrafine-grain titanium (UFG-Ti) can be created that replicate state of the art surfaces of standard coarse-grain titanium (Ti), showing excellent cytocompatibility and osseointegration potential while also providing improved mechanical properties. MATERIAL AND METHODS: UFG-Ti was prepared by continuous equal channel angular processing (ECAP), and surfaces were treated by sandblasting and acid etching. Mechanical properties (tensile and fatigue strength), wettability, and roughness parameters were evaluated. Human trabecular bone-derived osteoblast precursor cells (HBCs) were cultured on all samples to examine cytocompatibility and mineralization after 4 and 28 days, respectively. Biomechanical pull-out measurements were performed in a rabbit in vivo model 4 weeks after implantation. RESULTS: Both yield and tensile strength as well as fatigue endurance were higher for UFG-Ti compared to Ti by 40%, 45%, and 34%, respectively. Fatigue endurance was slightly reduced following surface treatment. Existing surface treatment protocols could be applied to UFG-Ti and resulted in similar roughness and wettability as for standard Ti. Cell attachment and spreading were comparable on all samples, but mineralization was higher for the surfaces with hydrophilic treatment with no significant difference between UFG-Ti and Ti. Pull-out tests revealed that osseointegration of surface-treated UFG-Ti was found to be similar to that of surface-treated Ti. CONCLUSION: It could be demonstrated that existing surface treatments for Ti can be translated to UFG-Ti and, furthermore, that dental implants made from surface-treated UFG-Ti exhibit superior mechanical properties while maintaining cytocompatibility and osseointegration potential.

Effect of Obesity or Metabolic Syndrome and Diabetes on Osseointegration of Dental Implants in a Miniature Swine Model: A Pilot Study.

PURPOSE: The increasing prevalence of obesity or metabolic syndrome (O/MS) and type 2 diabetes mellitus (DM) remains a global health concern. Clinically relevant and practical translational models mimicking human characteristics of these conditions are lacking. This study aimed to demonstrate proof of concept of the induction of stable O/MS and type 2 DM in a Göttingen minipig model and validate both of these disease-adjusted Göttingen minipig models as impaired healing models for the testing of dental implants. MATERIALS AND METHODS: Nine minipigs were split into 3 groups-control (normal diet), obese (cafeteria diet), and diabetic (cafeteria diet plus low-dosage streptozotocin)-followed by placement of dental implants. Inflammatory markers including tumor necrosis factor α, C-reactive protein, and cortisol were recorded for each study group. Removal torque was measured, and histomorphometric analysis (bone-to-implant contact and bone area fraction occupancy) was performed. RESULTS: O/MS pigs showed, on average, a 2-fold increase in plasma C-reactive protein (P < .05) and cortisol (P < .09) concentrations compared with controls; DM pigs showed, on average approximately, a 40-fold increase in plasma tumor necrosis factor α levels (P < .05) and a 2-fold increase in cortisol concentrations (P < .05) compared with controls. The impact of O/MS and DM on implants was determined. The torque to interface failure was highest in the control group (200 N-cm) and significantly lower in the O/MS (90 N-cm) and DM (60 N-cm) groups (P < .01). Bone formation around implants was significantly greater in the control group than in the O/MS and DM groups (P < .02). CONCLUSIONS: Both O/MS and DM minipigs express a human-like disease phenotype, and both presented bone-healing impairment around dental implants. Our finding of no significant difference between type 2 DM and O/MS in bone formation around implants provides evidence that further investigation of the impact of O/MS is warranted.

Osteogain® loaded onto an absorbable collagen sponge induces attachment and osteoblast differentiation of ST2 cells in vitro.

OBJECTIVES: Dimensional changes of the alveolar bone following tooth extraction are a major challenge in daily dental practice. To limit bone loss, a variety of biomaterials including bone grafts, barrier membranes, and growth factors have been utilized either alone or in combination therapies to increase the speed and quality of new bone formation. The aim of the present in vitro study was to investigate the regenerative potential of Osteogain®, a new liquid carrier system of enamel matrix derivative (EMD) in combination with an absorbable collagen sponge (ACS) specifically designed for extraction socket healing. MATERIALS AND METHODS: The potential of ACS was first investigated using ELISA to quantify total amelogenin adsorption and release from 0 to 10 days. Thereafter, the cellular effects of ST2 pre-osteoblasts were investigated for cellular attachment at 8 h and cell proliferation at 1, 3, and 5 days as well as osteoblast differentiation by real-time PCR and alizarin red staining for cells seeded on (1) tissue culture plastic, (2) ACS alone, and (3) ACS + Osteogain®. RESULTS: ACS efficiently loaded nearly 100% of the amelogenin proteins found in Osteogain® which were gradually released up to a 10-day period. Osteogain® also significantly induced a 1.5-fold increase in cell attachment and resulted in a 2-6-fold increase in mRNA levels of osteoblast differentiation markers including runt-related transcription factor 2 (Runx2), collagen1a2, alkaline phosphatase, and bone sialoprotein as well as induced alizarin red staining when combined with ACS. CONCLUSIONS: In summary, these findings suggest that Osteogain® is capable of inducing osteoblast attachment and differentiation when combined with ACS. Future animal studies and randomized human clinical trials are necessary to further support these findings. CLINICAL RELEVANCE: The use of Osteogain® in combination with ACS may provide a valuable means to limit dimensional changes following tooth extraction.

Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts.

The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in cultured OB. Expanded cells continued to express differentiated OB markers independently of AA supplementation and demonstrated no changes in their capacity to osteogenically differentiate. Transcriptomic analyses revealed that apoptotic, cell cycle-proliferation, and catabolic pathways were the main pathways affected in the presence of AA during OB expansion. Supplementation with AA can thus help to expand subchondral bone OB in vitro while maintaining their special cellular characteristics. The clearance of such senescent OB could be envisioned as a potential therapeutic target for the treatment of OA.

TGF-ß-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms.

Cellular transformation into myofibroblasts is a central physiological process enabling tissue repair. Its deregulation promotes fibrosis and carcinogenesis. TGF-ß is the main inducer of the contractile gene program that drives myofibroblast differentiation from various precursor cell types. Crucial regulators of this transcriptional program are serum response factor (SRF) and its cofactor MKL1 (also known as MRTF-A). However, the exact mechanism of the crosstalk between TGF-ß signaling and MKL1 remains unclear. Here, we report the discovery of a novel MKL1 variant/isoform, MKL1_S, transcribed from an alternative promoter and uncover a novel translation start for the published human isoform, MKL1_L. Using a human adipose-derived mesenchymal stem cell differentiation model, we show that TGF-ß specifically upregulates MKL1_S during the initial phase of myofibroblast differentiation. We identified a functional N-terminal motif in MKL1_S that allows specific induction of a group of genes including the extracellular matrix (ECM) modifiers MMP16 and SPOCK3/testican-3. We propose that TGF-ß-mediated induction of MKL1_S initiates progression to later stages of differentiation towards a stationary myofibroblast.

Histological assessment of hard and soft tissues surrounding a novel ceramic implant: a pilot study in the minipig.

OBJECTIVE: The aim of this study was to investigate clinical and soft/hard tissues histomorphological outcomes of a ceramic implant comparatively to a titanium implant in a minipig model. MATERIAL AND METHODS: Eighteen soft tissue level implants (9 Ceramic with ZLA(®) surface as test, and 9 titanium SLActive(®) as control, Institut Straumann, Basel, Switzerland) were randomly placed into the mandible of 6 minipigs (n = 6). Two months later, animals were sacrificed and block biopsies were obtained to assess histomorphological outcomes. Unadjusted paired comparisons, of both groups were performed using the Wilcoxon signed rank test. The Dunnett-Hsu test was used to adjust for multiple comparisons. RESULTS: All implants showed excellent integration into bone and soft tissue. The fBIC (distance implant shoulder to most coronal implant contact) and BIC% (percentage bone-to-implant contact) were for both groups; test: 3.95 mm and 85.4%; control 3.97 mm and 84.3% respectively. No difference in peri-implant mucosa height was found, however, the sulcular epithelium was significantly shorter for the ZrO2 (mean: 0.76, 95%CI: 0.46-1.06) than for the Ti (mean: 1.40, 95%CI: 1.10-1.70) (p = 0.0090). CONCLUSIONS: Within the limits of this pilot study, no difference was found between the ceramic implant with ZLA(®) surface and a titanium implant in terms of bone tissue integration. Furthermore, the epithelial attachment favoured this ceramic implant over titanium.