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.

Osteoinduction and osteoimmunology: Emerging concepts.

The recognition and importance of immune cells during bone regeneration, including around bone biomaterials, has led to the development of an entire field termed "osteoimmunology," which focuses on the connection and interplay between the skeletal system and immune cells. Most studies have focused on the "osteogenic" capacity of various types of bone biomaterials, and much less focus has been placed on immune cells despite being the first cell type in contact with implantable devices. Thus, the amount of literature generated to date on this topic makes it challenging to extract needed information. This review article serves as a guide highlighting advancements made in the field of osteoimmunology emphasizing the role of the osteoimmunomodulatory properties of biomaterials and their impact on osteoinduction. First, the various immune cell types involved in bone biomaterial integration are discussed, including the prominent role of osteal macrophages (OsteoMacs) during bone regeneration. Thereafter, key biomaterial properties, including topography, wettability, surface charge, and adsorption of cytokines, growth factors, ions, and other bioactive molecules, are discussed in terms of their impact on immune responses. These findings highlight and recognize the importance of the immune system and osteoimmunology, leading to a shift in the traditional models used to understand and evaluate biomaterials for bone regeneration.

Spontaneous regeneration of keratinized tissue at implants and teeth.

AIM: To investigate the spontaneous regeneration of the implanto-mucosal and dento-gingival unit after complete removal of keratinized tissue (KT). MATERIALS AND METHODS: One hemi-mandible per dog (n = 4) was allocated to receive three dental implants (test sites, premolar region), whereas three premolars on the contralateral side were controls. After osseointegration, the entire KT (buccal + lingual) was surgically excised on all test and control sites, leaving the bone exposed. Clinical measurements were performed before excision (T0 ) and after 12 weeks (T1 ). Following healing, the animals were euthanized, and the specimens were histologically processed. Descriptive statistical analyses were performed. RESULTS: Clinical measurements revealed that at T1 , on all teeth, a band of KT was spontaneously regenerated (mean width: 2.60 ± 0.66 mm), whereas on implants, KT was detected only occasionally at mesial or distal but not at buccal sites (mean total: 0.35 ± 0.53 mm; p < .0001). Histologically, spontaneous regeneration of the dento-gingival unit was evident, displaying masticatory mucosa. At the implant sites, on the other hand, the implanto-mucosal unit was characterized by a non-keratinized epithelium and elastic fibres, indicating the characteristics encountered in alveolar mucosa. CONCLUSION: After excision of KT at implant sites, the spontaneous regeneration of the soft tissue is characterized by a non-keratinized epithelium typical for alveolar mucosa, while at tooth sites the spontaneous regeneration was characterized by soft tissue resembling gingiva.

Sequential osseointegration of a novel implant system based on 3D printing in comparison with conventional titanium implants.

OBJECTIVES: To evaluate the sequential osseointegration of a novel titanium implant system based on a 3D printing technology in comparison with conventional titanium implants. MATERIAL AND METHODS: Two novel titanium implants based on 3D printing were tested in the mandible of eight Beagle dogs. As a control, two different commercially available titanium implants were used. The implants were staged to accommodate healing periods of 2 and 6 weeks. The primary outcome variable was bone-to-implant contact (BIC) in non-decalcified tissue sections and micro-CT analysis. RESULTS: Histomorphometrically, the proportions of tissues adjacent to the implant surfaces were similar for all implants, whereas the BIC percentage of new mineralized bone was greater for the control implants after both 2 and 6 weeks (p < .05). Micro-CT analysis revealed increasing osseous volume and BIC from 2 to 6 weeks. In contrast to the histomorphometry, the BIC evaluation with the micro-CT data revealed a significantly higher BIC for the two test implants compared with controls (p < .001). The analysis of the total implant surface area disclosed a value that was approximately double as high for the test compared to the control implants. CONCLUSIONS: The novel titanium implant system based on 3D printing yielded values for osseointegration that were adequate and satisfactory. The higher percentage of new mineralized bone in the control implants is explained by the fact of a completely different three-dimensional surface area.

Clinical and histologic evaluation of heterotopic mucosa transpositioning at teeth and dental implants.

AIM: To investigate the healing after heterotopic mucosa transpositioning at dental implants and teeth. MATERIALS AND METHODS: One hemimandible per dog (n = 4) was allocated to receive 3 implants (test), whereby 3 premolars on the contralateral side served as controls. After osseointegration, a Z-plasty was performed on the buccal aspect of the test and control sites to heterotopically move the zone of keratinized tissue (KT) into a region with non-keratinized tissue (nKT) and vice versa. Clinical measurements were performed before (T0) and at 12 weeks following heterotopic transposition (T1). Thereafter, specimens were processed for histological analysis. RESULTS: Clinical measurements revealed that at T1, a band of KT was reestablished at teeth (mean: 2.944 ± 1.866 mm), whereas at implants, the transpositioned nKT resulted in a mucosa without any signs of keratinization (mean: 0 mm; p < .0001). At implant sites, the probing attachment level loss was more pronounced compared to tooth sites (-1.667 ± 1.195 mm and -1.028 ± 0.878 mm, respectively; p = .0076). Histologically, the transpositioned nKT, was accompanied by the formation of KT at the tooth but not at implant sites. The supracrestal soft tissues were statistically significantly higher at tooth compared to implant sites (2.978 ± 0.483 mm and 2.497 ± 0.455 mm, p = .0083). The transpositioned KT remained mostly unaltered in its morphological characteristics. CONCLUSIONS: The findings of this study indicate that: (a) transpositioned KT may retain its morphological characteristics; and (b) transpositioned nKM was accompanied by the formation of KT at the tooth but not at implant sites.

Histological evaluation following treatment of recession-type defects with coronally advanced flap and a novel human recombinant amelogenin.

OBJECTIVES: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing / regeneration in recession-type defects. MATERIALS AND METHODS: A total of 17 gingival recession-type defects were surgically created in the maxilla of three minipigs. The defects were randomly treated with a coronally advanced flap (CAF) and either rAmelX (test), or a CAF and placebo (control). At three months following reconstructive surgery, the animals were euthanized, and the healing outcomes histologically evaluated. RESULTS: The test group yielded statistically significantly (p = 0.047) greater formation of cementum with inserting collagen fibers compared with the control group (i.e., 4.38 mm ± 0.36 mm vs. 3.48 mm ± 1.13 mm). Bone formation measured 2.15 mm ± 0.8 mm in the test group and 2.24 mm ± 1.23 mm in the control group, respectively, without a statistically significant difference (p = 0.94). CONCLUSIONS: The present data have provided for the first-time evidence for the potential of rAmelX to promote regeneration of periodontal ligament and root cementum in recession-type defects, thus warranting further preclinical and clinical testing. CLINICAL RELEVANCE: The present results set the basis for the potential clinical application of rAmelX in reconstructive periodontal surgery.

The effect of connective tissue graft or a collagen matrix on epithelial differentiation around teeth and implants: a preclinical study in minipigs.

OBJECTIVES: This study aimed to histologically evaluate the healing at 8 weeks after coronally advanced flap (CAF) with either a superficial (SCTG) or deep palatal connective tissue graft (DCTG), or a collagen matrix (CM) to cover recession defects at teeth and implants. MATERIAL AND METHODS: One mandibular side of 6 miniature pigs received each 3 titanium implants 12 weeks after extraction. Eight weeks later, recession defects were created around implants and contralateral premolars and 4 weeks later randomly subjected to CAF + SCTG, CAF + DCTG, or CAF + CM. After 8 weeks, block biopsies were histologically analyzed. RESULTS: For the primary outcome, i.e., keratinization of the epithelium, all teeth and implants exhibited a keratinized epithelium with no histological differences among them also not in terms of statistically significant differences in length (SCTG 0.86 ± 0.92 mm, DCTG 1.13 ± 0.62 mm, and Cm, 1.44 ± 0.76 mm). Pocket formation was histologically seen at all teeth, around most implants with SCTG and DCTG, however not in the CM implant group. The connective tissue grafts showed hardly signs of degradation, whereas the CM was partly degraded and integrated in connective tissue. The mean gain in gingival height was similar in all experimental groups (SCTG 3.89 ± 0.80 mm, DCTG 4.01 ± 1.40 mm, CM 4.21 ± 0.64 mm). Statistically significant differences were found in the height of the junctional epithelium between the control teeth and the connective tissue groups (p = 0.009 and 0.044). CONCLUSIONS: In this animal model, the use of either a superficial or deep connective tissue graft or a collagen membrane did not seem to have any impact on the epithelial keratinization around both teeth and implants. All procedures (CAF + SCTG/DCTG/CM) resulted in a long JE that was even longer at implants. CLINICAL RELEVANCE: Deep/superficial palatal connective tissue graft yielded similar keratinization around teeth/implants. Given the absence of pocket formation and inflammatory processes at implants when using a CM, CAF + CM might bear potential clinical benefits.

Evidence of re-osseointegration after electrolytic cleaning and regenerative therapy of peri-implantitis in humans: a case report with four implants.

OBJECTIVE: To evaluate re-osseointegration after electrolytic cleaning and regenerative therapy of dental implants with peri-implantitis in humans. MATERIAL AND METHODS: Four dental implants that developed peri-implantitis underwent electrolytic cleaning followed by regenerative therapy with guided bone regeneration. All four implants developed recurrent peri-implantitis and were therefore explanted 6 to 13 months later. Radiographic bone level, probing depth, and bleeding on probing were determined at the time of surgery, 6 months later, and before implant retrieval. The peri-implant tissues were histologically and histomorphometrically analyzed. RESULTS: All four implants demonstrated radiographic and histological bone gain, reduced probing depth, and bleeding on probing. Radiographic bone gain was 5.8 mm mesially and 4.8 mm distally for implant #1, 3.3 mm and 2.3 mm for implant #2, 3.1 mm and 0.5 mm for implant #3, and 3.5 mm and 2.8 mm for implant #4. The histometric mean and maximum vertical bone gain for implant #1 to #4 was 1.65 mm and 2.54 mm, 3.04 mm and 3.47 mm, 0.43 mm and 1.27 mm, and 4.16 mm and 5.22 mm, respectively. The percentage of re-osseointegration for implant #1 to #4 was 21.0%, 36.9%, 5.7%, and 39.0%, respectively. In one implant, the newly formed bone was deposited directly onto calculus on the implant surface. CONCLUSIONS: We found that (1) re-osseointegration is possible on a formerly contaminated implant surface and (2) the electrolytic cleaning process seems to be effective enough at sites with calculus residues. CLINICAL RELEVANCE: Since re-osseointegration can be achieved by electrolytic cleaning, this decontamination technique may be considered as a future treatment concept.

Cross-linked hyaluronic acid slows down collagen membrane resorption in diabetic rats through reducing the number of macrophages.

OBJECTIVES: We previously showed that accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated here its effect on the number of macrophages and endothelial cells (ECs) within the CM as a possible mechanism for inhibition of CM resorption. MATERIALS AND METHODS: Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS, and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and transglutaminase II, respectively. RESULTS: Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and fourfold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p < 0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. CONCLUSIONS: Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals. CLINICAL RELEVANCE: The combination of CLHA and CM may represent a valuable approach when guided tissue regeneration or guided bone regeneration procedures are performed in diabetic patients.

Horizontal bone grafting using equine-derived cancellous bone blocks is associated with severe complications: A prospective clinical and histological pilot study.

AIMS: The aim of this prospective, clinical study was to evaluate the clinical performance and histological outcome of a new equine hydroxyapatite collagenated bone block (eHAC) for horizontal bone grafting prior to implant placement. MATERIALS AND METHODS: Five patients (two male/three female) with a mean age of 51.6 years (range 22-66 years) and a reduced horizontal bone width of the alveolar ridge (mean 3.5 mm) underwent horizontal bone grafting using eHAC at 10 grafting sites. Reentry was performed 6.9 months after the horizontal grafting procedure. Clinical follow-up (mean 28.9 month) considered width gain of the alveolar ridge, soft tissue healing, and complications. To evaluate graft incorporation, four additional patients underwent histological assessment of equine blocks adjacent to autologous blocks 3 and 6 months after grafting. RESULTS: The study was terminated after graft failure was observed in four of five patients. Mean horizontal bone width had increased by 3.6 ± 1.22 mm. Three out of nine implants placed had to be removed due to graft failure. Histological evaluation revealed large amounts of soft connective tissue within the grafts (mean 67.3 ± 9.5%). The proportion of new bone formation 3 months after the lateral grafting procedure revealed an average of 8.6%, compared to 11.4% after 6 to 7 months. CONCLUSION: Lateral ridge grafting using eHAC achieved measurable horizontal width gain but revealed high rates of severe complications. CLINICAL IMPLICATIONS: Within the limitations of this study, eHAC bone blocks cannot be recommended for horizontal bone grafting.

Crestal bone response to loaded zirconia and titanium implants: a radiographic and histometric analysis in canines.

OBJECTIVES: To evaluate the crestal bone response to a two-piece zirconia implant compared with a control titanium implant using periapical radiographs (PAs) and histometry. MATERIALS AND METHODS: Thirty zirconia and 30 titanium implants were placed in healed posterior mandibles of five canines. Full-ceramic single-tooth restorations were cemented after 6 weeks of healing. Three observers measured the distance between the implant shoulder and the crestal bone (DIB) at placement, loading, and harvesting after 4 or 16 weeks in function. The influence of implant material and loading time on DIB as well as the inter-observer agreement were analyzed. Additionally, histometric distance between implant shoulder and most coronal bone-to-implant contact (IS-cBIC) was compared with DIB. RESULTS: Mean DIB values increased between 4 and 16 weeks of loading for both zirconia (from 1.66 to 2.25 mm; P < 0.0001) and titanium (from 1.81 to 1.95 mm; P = 0.06). Zirconia yielded mean IS-cBIC values of 2.18 mm and 2.48 mm (P < 0.001) and titanium 2.23 mm and 2.34 mm (P = 0.27) after 4 and 16 weeks, respectively. The raters reached an excellent intraclass correlation coefficient. PAs underestimated the bone loss on average by 0.39 mm. CONCLUSIONS: Zirconia implants showed a greater increase of DIB during early healing and function than titanium. CLINICAL RELEVANCE: Crestal peri-implant tissue dimensions may show more pronounced changes around two-piece zirconia implants during early healing. PAs may underestimate peri-implant bone loss.

Hyaluronic acid slows down collagen membrane degradation in uncontrolled diabetic rats.

AIM: To examine the in vitro biokinetics of hyaluronic acid (HA) from a collagen membrane (CM) and to evaluate the in vivo effect of immersion of the CM in HA solution on its degradation in streptozotocin (STZ)-induced diabetes conditions in a rat calvaria subcutaneous model. BACKGROUND: CM degradation is accelerated in uncontrolled diabetic rats. Immersion of CM in HA has been suggested to decrease their resorption rate without interfering with their tissue integration and structural degradation. However, it is unknown to what extent CM degradation may be influenced by its immersion in HA solution under a condition mimicking a medically compromised situation with an increased inflammatory level such as diabetes. MATERIALS AND METHODS: CMs were soaked in cross-linked HA. Protein adsorption and the HA release were quantified by ELISA. Diabetes was induced in sixteen rats, while 16 healthy rats served as control. CM was prepared and labeled prior to implantation with Biotin. Seventeen CM were immersed in HA and 17 CM in PBS. In each animal, one test or one control disk was implanted. In order to compare the collagen content, two similar non-implanted CM were used as baseline. Fourteen days after surgery, thirty-two animals were sacrificed. The entire calvaria including the skin above, was chemically fixed, decalcified, and embedded in paraffin. Five-µm-thick sections were analyzed histologically and histomorphometrically using H&E and avidin-peroxidase staining. RESULTS: The in vitro results demonstrated that the CM adsorbed roughly 80% of the total HA content. After 10 days, 36.3% of the initial HA remained on the CM. The in vivo results demonstrated that diabetes significantly reduced the thickness of the CM, while HA had a significant effect on keeping the membrane thickness. HA increased the residual collagen content in the diabetic group (P < 0.0001) but no such effect was observed in the healthy group. CONCLUSION: Immersion of CM in HA prior to the implantation delays membrane degradation in uncontrolled diabetic compared with normoglycemic rats.

Self-regenerative capacity of intra-oral bone defects.

OBJECTIVE: To provide an overview on the self-regenerative capacity of various types of intra-oral bone defects. MATERIALS AND METHODS: This paper has narratively reviewed the most important aspects of bone biology and the healing outcomes related to the self-regenerative capacity (i.e. without the placement of any biomaterial) of bone defects that occur following tooth extraction, autogenous graft harvesting, periapical lesions, cystic lesions of the jaws, third molar extraction and experimentally created ridge defects. RESULTS: In animals (i.e. dogs and monkeys), the greatest changes in horizontal and vertical dimension occur during the first 6 months following tooth extraction. In humans, bone remodelling may take from several months to years and exhibits marked inter-individual variability. Following tooth extraction at compromised sites (e.g. presence of severe bone loss at the time-point of extraction), the healing may occur slower and a substantial volume reduction can be expected than following tooth extraction at non-compromised sites. In the mandibular symphysis and ramus, the bone defects resulting following bone block harvesting are gradually healing to a large extent, but complete healing appears not to occur due to poorer space provision and wound stability capacities. Defects after peri-apical surgery display a substantial self-regenerative capacity and heal at a great extent without the use of any adjunct measures. The vast majority of jawbone defects after cystectomy heal at a great extent and without apparent influence in the shape of the jaw, without the need of adjunct measures. After surgical removal of mandibular third molars, bone fill can be observed over a period of at least 12 months, with the most substantial change (e.g. the greatest bone fill) occurring during the first 3 months after surgery. However, complete fill of these residual bone defects does not always occur. CONCLUSIONS: Intra-oral bone defects possess a high self-regenerative capacity. Factors such as extent of bone loss, presence of bony walls, closed healing environment, space provision and mechanical wound stability substantially influence healing/regeneration.

Excessive occlusal load on chemically modified and moderately rough titanium implants restored with cantilever reconstructions. An experimental study in dogs.

OBJECTIVE: To evaluate the outcomes of excessively loaded implants. MATERIAL AND METHODS: In five dogs, all mandibular premolars were extracted. After 3 months, six implants (three SLA® and three SLActive®) were placed (S). After 4 weeks, implants were restored: one single crown with stable occlusal contacts (SC), one crown and a cantilever unit with excessive occlusal contacts (OL), and a non-loaded implant (NL). Bleeding-on-probing (BoP), attachment level (AL), mucosal margin (GM) were assessed. Resonance frequency analysis (RFA) was assessed weekly. Standardized X-rays were taken at S, 4 and 24 weeks. RESULTS: Similar findings were observed for SLA® and SLActive® implants regarding PlI, GI, GM, AL, and BL. No significant differences were detected between baseline and 24-weeks or between treatment modalities for all clinical parameters (p > .05). Six months after loading, RFA values were significantly greater than at implant placement. No significant differences between treatment modalities were found. Linear radiographic measurements yielded similar results between SLA® and SLActive® implants. SLA® OL implants yielded a statistically significant gain on peri-implant bone density over all other groups (p = .012). Radiographic results were confirmed by descriptive histology. Technically, loosened occlusal screws occurred in 13.3% (SC = 3.3%; OL = 10%), while abutment fractures totalized 23.3% (SC = 6.6%; OL = 16.6%). CONCLUSIONS: Excessive occlusal load applied to implants (SLA® or SLActive®) restored with cantilevers did not cause loss of osseointegration or significant changes in their clinical, radiographic, or histologic outcomes. Early excessive occlusal load on SLA® implants promoted a gain in peri-implant bone density. Excessively loaded implants showed more technical complications.

Soft tissue response to dental implant closure caps made of either polyetheretherketone (PEEK) or titanium.

OBJECTIVE: Polyetheretherketone (PEEK) is a popular synthetic thermoplastic polymer for medical applications, but its clinical use suffers from several limitations. Therefore, the aim was to compare the soft tissue response to dental implant closure caps made of PEEK or titanium as evaluated by the occurrence of multinucleated giant cells (MNGCs). MATERIAL AND METHODS: Forty-two implants were placed in the maxilla of seven miniature pigs. While commercially pure titanium (Ti) implants had a Ti closure cap, ceramic implants made of either zirconia (Zr) or alumina-toughened zirconia (Zr + Al) received a PEEK closure cap. Histomorphometry was performed to evaluate the number of small and large MNGCs being in contact with the PEEK or the Ti in different compartments of the implant systems. RESULTS: No histological signs of inflammation were noticed, and MNGCs were observed on both PEEK and Ti closure caps and on all three implant types. Significantly higher numbers of MNGCs were found on closure caps made of PEEK than on closure caps made of Ti on the external closure cap surface facing both soft (p = 0.0008 for PEEK on Zr and p = 0.0016 for PEEK on Zr + Al) and hard tissues (p = 0.016 for PEEK on Zr and p = 0.003 for PEEK on Zr + Al) as well as in the internal closure cap surface (p = 0.014 for PEEK on Zr and p = 0.0088 for PEEK on Zr + Al). No statistically significant differences in the number of MNGCs were observed on the three implant types. CONCLUSIONS: Significantly more MNGCs were in contact with PEEK than with Ti closure caps.

Macrophage behavior and interplay with gingival fibroblasts cultured on six commercially available titanium, zirconium, and titanium-zirconium dental implants.

OBJECTIVES: The host-material interface has been a crucial relationship dictating the successful integration of biomaterials, including dental implants. The aim of the present study was to first investigate how macrophages behaved on various dental implant surfaces and thereafter to investigate their effect on soft tissue cells. MATERIALS AND METHODS: Macrophage adhesion, proliferation, and polarization towards either an M1 or M2 phenotype were investigated on six implant surfaces fabricated from pure titanium (Ti), pure zirconium (ZLA), and a titanium-zirconium (Ti-Zi) alloy of various surface topographies/chemistries. Thereafter, conditioned media (CM) collected from macrophages seeded on these various implant surfaces was cultured with murine gingival fibroblasts and investigated for their ability to promote collagen synthesis. RESULTS: Macrophages attached and proliferated in similar levels on all implant surfaces; however, the modSLA hydrophilic surfaces tended to decrease the pro-inflammatory response by lowering the gene expression of TNF-alpha, IL-1, and IL-6 and promoting tissue resolution through the expression of an M2-macrophage cytokine IL-10. Thereafter, CM from macrophages were seeded with gingival fibroblasts on each implant surface. In general, CM from macrophages significantly promoted gingival fibroblast cell attachment on all implant surfaces at either 4 or 8 h and, most notably, significantly promoted fibronectin and TGF-beta gene expression on both Ti and Ti-Zi hydrophilic surfaces. CONCLUSIONS AND CLINICAL RELEVANCE: The present study found that implant surface topography and chemistry substantially impacted macrophage behavior. Most notably, modifications via hydrophilicity to both the pure Ti and Ti-Zi were shown to favor the secretion of macrophage pro-resolution markers and favored subsequent gingival fibroblast cell behavior when cultured with CM, whereas surface composition (Ti vs ZLA vs Ti-Zi) had little effect on macrophage polarization or gingival fibroblast behavior. This finding suggests that surface hydrophilicity would improve the soft tissue integration of dental implants, irrespective of material composition.

The periodontal pocket: pathogenesis, histopathology and consequences.

The conversion of junctional epithelium to pocket epithelium is regarded as a hallmark in the development of periodontitis. Knowledge of factors contributing to the initiation and progression of pocket formation is important and may result in the development of better preventive measures and improve healing outcomes after therapeutic interventions. The periodontal pocket is a pathologically deepened gingival sulcus. In healthy periodontal conditions, the defense mechanisms are generally sufficient to control the constant microbiological challenge through a normally functioning junctional epithelium and the concentrated powerful mass of inflammatory and immune cells and macromolecules transmigrating through this epithelium. In contrast, destruction of the structural integrity of the junctional epithelium, which includes disruption of cell-to-cell contacts and detachment from the tooth surface, consequently leading to pocket formation, disequilibrates this delicate defense system. Deepening of the pocket apically, and also horizontal expansion of the biofilm on the tooth root, puts this system to a grueling test. There is no more this powerful concentration of defense cells and macromolecules that are discharged at the sulcus bottom and that face a relatively small biofilm surface in the gingival sulcus. In a pocket situation, the defense cells and the macromolecules are directly discharged into the periodontal pocket and the majority of epithelial cells directly face the biofilm. The thinning of the epithelium and its ulceration increase the chance for invasion of microorganisms and their products into the soft connective tissue and this aggravates the situation. Depending on the severity and duration of disease, a vicious circle may develop in the pocket environment, which is difficult or impossible to break without therapeutic intervention.

Bone response to functionally loaded, two-piece zirconia implants: A preclinical histometric study.

OBJECTIVE: To evaluate the bone response to a two-piece zirconia implant in comparison with a control titanium implant in the canine mandible 4 and 16 weeks after restoration. MATERIAL AND METHODS: Zirconia and titanium implants were alternately placed bilaterally in healed mandibular molar and premolar sites of five canines. Full-ceramic single-tooth restorations were cemented after 6 weeks of transmucosal healing, allowing for full functional loading of the implants. Histologic and histometric analyses were performed on orofacial and mesiodistal undecalcified sections of the specimens obtained upon sacrifice after 4 and 16 weeks of functional loading. Bone-to-implant contact (BIC), multinucleated giant cells-to-implant contact (MIC), crestal bone level, and peri-implant bone density were histometrically assessed. RESULTS: All 60 implants and 60 restorations were still in function after 4 and 16 weeks of loading in both test and control groups. No implant loss, no implant or abutment fracture, and no chipping of the restorations could be detected. Histometric analysis showed no statistically significant differences between zirconia and titanium implants in BIC, crestal bone level, and peri-implant bone density at both time points. Between 4 and 16 weeks, the crestal bone level around zirconia implants showed a small but statistically significant increase in its distance from the implant shoulder. MIC was very low on both implant types and both time points and decreased statistically significantly overtime. CONCLUSION: The present two-piece zirconia implant showed a similar bone integration compared to the titanium implant with similar surface morphology after 4 and 16 weeks of loading.

The role of macrophage polarization on fibroblast behavior-an in vitro investigation on titanium surfaces.

OBJECTIVES: This study investigated the effect of smooth and rough titanium surface topographies on macrophage polarization and their influence on gingival fibroblast behavior cultured on titanium surfaces. MATERIALS AND METHODS: RAW 264.7 macrophages were seeded on smooth (pickled titanium (PT)) and rough Sand-blasted with Large grit particles followed by Acid-etching (SLA) titanium surfaces and first investigated for macrophage polarization towards tissue-inflammatory M1 macrophages or wound-healing M2 macrophages. Thereafter, culture media collected from macrophages on both surfaces were cultured with gingival fibroblasts seeded on their respective topographies. All experiments were performed in triplicate with three independent experiments. RESULTS: Macrophages seeded on SLA surfaces polarized towards tissue-inflammatory M1 macrophages at early time points. Immunofluorescent staining and RT-PCR analysis demonstrated higher levels of iNOS and gene expression of IL-1ß, IL-6, and TNF-alpha on SLA surfaces at 3 days when compared to both tissue culture plastic (TCP) and PT surfaces (p < 0.001). Very little differences were found between smooth PT surfaces and TCP. Interestingly, proliferation assay (CCK-8) suggested that conditioned media (CM) from macrophages seeded on SLA surfaces drastically inhibited gingival fibroblast proliferation at 3 and 5 days (p < 0.001). Meanwhile, CM from macrophages cultured on SLA surfaces also significantly reduced collagen 1 synthesis on SLA surfaces at 14 days as assessed by immunofluorescent staining (p < 0.001). CONCLUSION: The results from this study demonstrate that the polarization of macrophages towards a pro-inflammatory (M1) phenotype on SLA surfaces may have a negative impact on gingival fibroblast behavior on titanium surfaces. Future strategies to better modulate macrophage polarization should be investigated to support a favorable immune response and encourage tissue integration. CLINICAL RELEVANCE: As SLA surfaces have a potential to shift macrophages towards tissue-inflammatory M1 macrophages, this might be a negative impact for soft tissue healing. Therefore, SLA surfaces should be kept within the bone, as when in contact with soft tissue, they are prone to support a lack of soft tissue integration leading to inflammation.

Osseointegration of titanium, titanium alloy and zirconia dental implants: current knowledge and open questions.

Bone healing around dental implants follows the pattern and sequence of intramembraneous osteogenesis with formation of woven bone first of all followed later by formation of parallel-fibered and lamellar bone. Bone apposition onto the implant surface starts earlier in trabecular bone than in compact bone. While the first new bone may be found on the implant surface around 1 week after installation, bone remodeling starts at between 6 and 12 weeks and continues throughout life. Bone remodeling also involves the bone-implant interface, thus transiently exposing portions of the implant surface. Surface modifications creating micro-rough implant surfaces accelerate the osseointegration process of titanium implants, as demonstrated in numerous animal experiments. Sandblasting followed by acid-etching may currently be regarded as the gold standard technique to create micro-rough surfaces. Chemical surface modifications, resulting in higher hydrophilicity, further increase the speed of osseointegration of titanium and titanium-zirconium implants in both animals and humans. Surface modifications of zirconia and alumina-toughened zirconia implants also have an influence on the speed of osseointegration, and some implant types reach high bone-to-implant contact values in animals. Although often discussed independently of each other, surface characteristics, such as topography and chemistry, are virtually inseparable. Contemporary, well-documented implant systems with micro-rough implant surfaces, placed by properly trained and experienced clinicians, demonstrate high long-term survival rates. Nevertheless, implant failures do occur. A low percentage of implants are diagnosed with peri-implantitis after 10 years in function. In addition, a low number of implants seem to be lost for primarily reasons other than biofilm-induced infection. Patient factors, such as medications interfering with the immune system and bone cells, may be an element contributing to continuous bone loss and should therefore be monitored and studied in greater detail.