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.

Bio-Inspired Micro- and Nano-Scale Surface Features Produced by Femtosecond Laser-Texturing Enhance TiZr-Implant Osseointegration.

Surface design plays a critical role in determining the integration of dental implants with bone tissue. Femtosecond laser-texturing has emerged as a breakthrough technology offering excellent uniformity and reproducibility in implant surface features. However, when compared to state-of-the-art sandblasted and acid-etched surfaces, laser-textured surface designs typically underperform in terms of osseointegration. This study investigated the capacity of a bio-inspired femtosecond laser-textured surface design to enhance osseointegration compared to state-of-the-art sandblasted & acid-etched surfaces. Laser-texturing facilitates the production of an organized trabeculae-like microarchitecture with superimposed nano-scale laser-induced periodic surface structures on both 2D and 3D samples of titanium-zirconium-alloy. Following a boiling treatment to modify the surface chemistry, improving wettability to a contact angle of 10°, laser-textured surfaces enhance fibrin network formation when in contact with human whole blood, comparable to state-of-the-art surfaces. In vitro experiments demonstrate that laser-textured surfaces significantly outperform state-of-the-art surfaces with a 2.5-fold higher level of mineralization by bone progenitor cells after 28 days of culture. Furthermore, in vivo evaluations reveal superior biomechanical integration of laser-textured surfaces after 28 days of implantation. Notably, during abiological pull-out tests, laser-textured surfaces exhibit comparable performance, suggesting that the observed enhanced osseointegration is primarily driven by the biological response to the surface. This article is protected by copyright. All rights reserved.

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.

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.

Assessing the osseointegration potential of a strontium releasing nanostructured titanium oxide surface: A biomechanical study in the rabbit tibia plateau model.

OBJECTIVES: To investigate the impact of a Ti-Sr-O technology, applied to either a turned surface or an SLA surface, on the mechanical robustness of osseointegration, benchmarked against the SLActive surface. MATERIAL AND METHODS: Ti discs (6.25-mm-diameter and 2-mm-thick) with three different surfaces were inserted on the proximal-anterior part of the tibial plateau of adult Swedish loop rabbits: (I) turned surface modified with Ti-Sr-O (turned + Ti-Sr-O), (II) SLA surface modified with Ti-Sr-O (SLA + Ti-Sr-O), and (III) SLActive surface (SLActive). Following a healing period of 2 weeks and 4 weeks, the pull-out (PO) force needed to detach the discs from the bone was assessed, as a surrogate of osseointegration. RESULTS: The SLActive surface exhibited statistically significant higher median PO forces, compared with the SLA + Ti-Sr-O surfaces at both 2- and 4 weeks post-op (p > .05). In this study, no single turned + Ti-Sr-O surface disk was integrated. CONCLUSIONS: The tested Ti-Sr-O technology failed to enhance osseointegration; however, this finding may be related to the inappropriateness of the rabbit tibia plateau model for assessing third-generation implant surface technologies, due to the limited diffusion and clearance at the disk-bone interface.

Two- and three-piece implants to boost data generation in preclinical in vivo research-A short technical report.

The purpose of this technical report is to present two novel experimental implant designs to boost data generation in preclinical in vivo research. Specifically, the report describes the rationale and the components of (1) a two-piece experimental implant suitable for a small animal platform (e.g., the rabbit femur/tibial epiphysis model), consisting of a threaded apical- and a coronal cylindrical piece, which is intended for collecting two types of biomechanical data, and (2) a three-piece experimental implant suitable for a large animal platform (e.g., the mini-pig mandible model), consisting of an apical "wound chamber", which allows the collection of histological/histomorphometrical data, and a middle threaded and coronal cylindrical piece, which also allow the collection of two types of biomechanical data. The increased volume of information generated from a single experiment in a small animal platform, using the proposed two-piece implant design, may assist in a more qualified decision-making process, on whether it is relevant to proceed to further assessment using a large animal platform. Furthermore, the increased volume of information generated in a single animal experiment either in a small or large animal platform, using the proposed two- and three-piece implants, respectively, likely decreases the number of animals otherwise needed for collecting the same information with standard one-piece implants and, thus, contributes to the reduction/refinement elements of the 3R principle.

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.

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.

Assessing minipig compact jawbone quality at the microscale.

Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs' jawbones, which is crucial for implant studies and a direct comparison to human tissue. In the present work, we demonstrate a multimodal framework to assess the jawbone quantity and quality for a minipig animal model that could be further extended to humans. Three minipig genotypes, commonly used in dental research, were examined: Yucatan, Göttingen, and Sinclair. Three animals per genotype were tested. Cortical bone samples were extracted from the premolar region of the mandible, opposite to the teeth growth. Global morphological, compositional, and mechanical properties were assessed using micro-computed tomography (micro-CT) together with Raman spectroscopy and nanoindentation measurements, averaged over the sample area. Local mineral-mechanical relationships were investigated with the site-matched Raman spectroscopy and micropillar compression tests. For this, a novel femtosecond laser ablation protocol was developed, allowing high-throughput micropillar fabrication and testing without exposure to high vacuum. At the global averaged sample level, bone relative mineralization demonstrated a significant difference between the genotypes, which was not observed from the complementary micro-CT measurements. Moreover, bone hardness measured by nanoindentation showed a positive trend with the relative mineralization. For all genotypes, significant differences between the relative mineralization and elastic properties were more pronounced within the osteonal regions of cortical bone. Site-matched micropillar compression and Raman spectroscopy highlighted the differences between the genotypes' yield stress and mineral to matrix ratios. The methods used at the global level (averaged over sample area) could be potentially correlated to the medical tools used to assess jawbone toughness and morphology in clinics. On the other hand, the local analysis methods can be applied to quantify compressive bone mechanical properties and their relationship to bone mineralization.

Characterization of a cotton-wool like composite bone graft material.

Bone graft materials are applied in patients to augment bone defects and enable the insertion of an implant in its ideal position. However, the currently available augmentation materials do not meet the requirements of being completely resorbed and replaced by new bone within 3 to 6 months. A novel electrospun cotton-wool like material (Bonewool®, Zurich Biomaterials LLC, Zurich, Switzerland) consisting of biodegradable poly(lactic-co-glycolic) acid (PLGA) fibers with incorporated amorphous ß-tricalcium phosphate (ß-TCP) nanoparticles has been compared to a frequently used bovine derived hydroxyapatite (Bio-Oss®, Geistlich Pharma, Wolhusen, Switzerland) in vitro. The material composition was determined and the degradation behavior (calcium release and pH in different solutions) as well as bioactivity has been measured. Degradation behavior of PLGA/ß-TCP was generally more progressive than for Bio-Oss®, indicating that this material is potentially completely resorbable. Graphical abstract.

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.

Greater Osseointegration Potential with Nanostructured Surfaces on TiZr: Accelerated vs. Real-Time Ageing.

Surface chemistry and nanotopography of dental implants can have a substantial impact on osseointegration. The aim of this investigation was to evaluate the effects of surface chemistry and nanotopography on the osseointegration of titanium-zirconium (TiZr; Roxolid®) discs, using a biomechanical pull-out model in rabbits. Two discs each were placed in both the right and left tibiae of 16 rabbits. Five groups of sandblasted acid etched (SLA) discs were tested: (1) hydrophobic without nanostructures (dry/micro) (n = 13); (2) hydrophobic with nanostructures, accelerated aged (dry/nano/AA) (n = 12); (3) hydrophilic without nanostructures (wet/micro) (n = 13); (4) hydrophilic with nanostructures, accelerated aged (wet/nano/AA; SLActive®) (n = 13); (5) hydrophilic with nanostructures, real-time aged (wet/nano/RTA). The animals were sacrificed after four weeks and the biomechanical pull-out force required to remove the discs was evaluated. Adjusted mean pull-out force was greatest for group wet/nano/RTA (64.5 ± 17.7 N) and lowest for group dry/micro (33.8 ± 10.7 N). Multivariate mixed model analysis showed that the pull-out force was significantly greater for all other disc types compared to the dry/micro group. Surface chemistry and topography both had a significant effect on pull-out force (p < 0.0001 for both), but the effect of the interaction between chemistry and topography was not significant (p = 0.1056). The introduction of nanostructures on the TiZr surface significantly increases osseointegration. The introduction of hydrophilicity to the TiZr implant surface significantly increases the capacity for osseointegration, irrespective of the presence or absence of nanotopography.

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.

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.

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.