Stages Of Osseointegration Research Articles

Nonlinear Finite Element Analysis of Bone–Implant Contact in Three Short Dental Implant Models with Varying Osseointegration Percentages

Objectives: Dental implants have become a cornerstone of restorative dentistry, providing a long-lasting method for tooth replacement. The degree of osseointegration has a significant effect on biomechanical stability at the bone–implant contact (BIC), determining the continued efficacy of these implants. However, the exact consequences of changing osseointegration levels on different implant designs, especially in bones with variable densities, are not well known. Methods: This study used 3D finite element analysis (FEA) to look at the biomechanical performance of three short dental implants: BioMet 3iT3, Straumann® Standard Plus Short-Regular Neck (SPS-RN), and Straumann® Standard Plus Short-Wide Neck (SPS-WN). This paper tested the implants at four stages of osseointegration: 25%, 50%, 75%, and 100% in both high-density (bone type III) and low-density (bone type IV) cancellous bone. It also created and examined realistic CAD models under static occlusal loading conditions to assess stress distribution and major strains at the bone–implant contact. Results: The study discovered that as osseointegration increases, von Mises stress and principal strains go down significantly for all implant types. The SPS-WN implant had the lowest strain values, especially for bone with low density. These reductions demonstrate increased mechanical stability as the bone–implant interface becomes more capable of dispersing mechanical stresses, minimizing the potential for localized deformation and bone resorption. Conclusions: The results highlight the importance of achieving optimum osseointegration to reduce mechanical stress and increase the lifespan of dental implants. The SPS-WN type implant performed better in biomechanical tests than the others, especially when bone conditions were not ideal. This makes it a great choice for clinical applications that need long-term implant success.

Zirconia Implants: A Brief Review and Surface Analysis of a Lost Implant

Zirconia implants have emerged as a valuable alternative for clinical scenarios where aesthetic demands are high, as well as in cases of hypersensitivity to titanium or for patients who refuse metallic objects in their bodies due to personal reasons. However, these implants have undergone various changes in geometry, manufacturing techniques, and surface modifications since the introduction of the first zirconia implants. The present study aims to review the current evidence on zirconia implants, considering the changes they have undergone in recent years. Additionally, it aims to analyze the three-dimensional surface characteristics of a failed zirconia implant using scanning electron microscopy and elemental analysis with energy-dispersive X-ray spectrometry (EDX). A zirconia implant lost three weeks after placement was immediately assessed using VP-SEM equipment and chemically analyzed by EDX using a 410-M detector connected to the microscope. Sparse material depositions were found on all parts of the implant, with a notable concentration in the thread grooves. The elements identified in the sample included zirconium, oxygen, carbon, calcium, and phosphorus. This report demonstrates that the surface of zirconia implants can accumulate elements early in the process of bone matrix neoformation, which is consistent with the initial stage of osseointegration.

Evaluation of masticatory performance and patient satisfaction for conventional and 3D-printed implant overdentures: a randomized crossover study

BackgroundThis crossover clinical study aimed to evaluate and compare masticatory performance and patient satisfaction for patients rehabilitated with conventional heat-cured acrylic resin and 3D-printed mandibular implant overdentures retained with bar attachment.Materials and methodsSixteen completely edentulous healthy participants received new conventional dentures. In the mandible, four interforaminal implants were inserted. Following the stage of osseointegration, the bar was constructed in a trapezoidal configuration. Each patient randomly received the following overdentures using a crossover design: (1) conventional heat-cured acrylic resin overdenture and (2) 3D-printed overdenture (developed by scanning of mandibular conventional overdenture). The masticatory performance was assessed by conducting a two-colour mixing ability test at 5, 10, 20, 30, and 50 masticatory cycles. Moreover, the McGill Denture Satisfaction Questionnaire (MDSQ) was employed to assess patient satisfaction. Evaluation was performed after 3 months of using each overdenture. Paired sample t tests were used to compare the masticatory performance and MDSQ scores of patients for both prostheses.ResultsNo significant difference in masticatory performance was reported between the two types of overdentures. Regarding patient satisfaction, only the esthetic aspect was significantly better for conventionally processed overdentures than for printed overdentures. Insignificant differences were observed regarding other MDSQ items between the two overdentures.ConclusionWithin this clinical study, 3D-printed implant overdentures showed promising results in terms of chewing efficiency and patient satisfaction compared to conventionally fabricated implant overdentures.Trial registrationRetrospectively registered at www.clinicaltrials.gov: NCT06148727.(28/11/2023).

Investigation of the impact of planar microelectrodes on macrophage-mediated mesenchymal stem cell osteogenesis.

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.

Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review.

Dental implant surfaces and their unique properties can interact with the surrounding oral tissues through epigenetic cues. The present scoping review provides current perspectives on surface modifications of dental implants, their impact on the osseointegration process, and the interaction between implant surface properties and epigenetics, also in peri-implant diseases. Findings of this review demonstrate the impact of innovative surface treatments on the epigenetic mechanisms of cells, showing promising results in the early stages of osseointegration. Dental implant surfaces with properties of hydrophilicity, nanotexturization, multifunctional coatings, and incorporated drug-release systems have demonstrated favorable outcomes for early bone adhesion, increased antibacterial features, and improved osseointegration. The interaction between modified surface morphologies, different chemical surface energies, and/or release of molecules within the oral tissues has been shown to influence epigenetic mechanisms of the surrounding tissues caused by a physical-chemical interaction. Epigenetic changes around dental implants in the state of health and disease are different. In conclusion, emerging approaches in surface modifications for dental implants functionalized with epigenetics have great potential with a significant impact on modulating bone healing during osseointegration.

Surface-Mediated Modulation of Different Biological Responses on Anatase-Coated Titanium.

Various surface modification strategies are being developed to endow dental titanium implant surfaces with micro- and nano-structures to improve their biocompatibility, and first of all their osseointegration. These modifications have the potential to address clinical concerns by stimulating different biological processes. This study aims to evaluate the biological responses of ananatase-modified blasted/etched titanium (SLA-anatase) surfaces compared to blasted/acid etched (SLA) and machined titanium surfaces. Using unipolar pulsed direct current (DC) sputtering, a nanocrystalline anatase layer was fabricated. In vitro experiments have shown that SLA-anatase discs can effectively promote osteoblast adhesion and proliferation, which are regarded as important features of a successful dental implant with bone contact. Furthermore, anatase surface modification has been shown to partially enhance osteoblast mineralization in vitro, while not significantly affecting bacterial colonization. Consequently, the recently created anatase coating holds significant potential as a promising candidate for future advancements in dental implant surface modification for improving the initial stages of osseointegration.

Analysis of peri-implant bone tissue between hydrophilic and rough implant surfaces in spontaneously hypertensive rats treated with losartan.

to evaluate the morphological and functional characteristics of the peri-implant bone tissue that was formed during the healing process by the placement implants using two different surface treatments: hydrophilic Acqua™ (ACQ) and rough NeoPoros™ (NEO), in spontaneously hypertensive (SHR) and normotensive rats (Wistar) whether or not treated with losartan. In total, 96 male rats (48 Wistar and 48 SHR) were divided into eight subgroups: absolute control rough (COA NEO), absolute control hydrophilic (COA ACQ), losartan control rough (COL NEO), losartan control hydrophilic (COL ACQ), SHR absolute rough (SHR NEO), SHR absolute hydrophilic (SHR ACQ), SHR losartan rough (SHRL NEO), and SHR losartan hydrophilic (SHRL ACQ). The rats medicated with losartan received daily doses of the medication. NeoPoros™ and Acqua™ implants were installed in the tibiae of the rats. After 14 and 42 days of the surgery, the fluorochromes calcein and alizarin were injected in the rats. The animals were euthanized 67 days after treatment. The collected samples were analyzed by immunohistochemistry, biomechanics, microcomputerized tomography, and laser confocal scanning microscopy analysis. The osteocalcin (OC) and vascular endothelium growth factor (VEGF) proteins had moderate expression in the SHRL ACQ subgroup. The same subgroup also had the highest implant removal torque. Regarding microarchitectural characteristics, a greater number of trabeculae was noted in the control animals that were treated with losartan. In the bone mineralization activity, it was observed that the Acqua™ surface triggered higher values of MAR (mineral apposition rate) in the COA, COL, and SHRL groups (p<0.05). the two implant surface types showed similar responses regarding the characteristics of the peri-implant bone tissue, even though the ACQ surface seems to improve the early stages of osseointegration.

Ozone therapy improves early stages of osseointegration in ovariectomized rats.

the aim of this study was to analyze the influence of ozone therapy (OZN) on peri-implant bone repair in critical bones by installing osseointegrated implants in the tibia of ovariectomized rats. ovariectomy was performed on 30 Wistar rats, aged six months (Rattus novergicus), and, after 90 days, osseointegrated implants were installed in each tibial metaphysis. The study groups were divided into the animals that received intraperitoneal ozone at a concentration of 700 mcg/kg - OZ Group (n=15) - and a control group that received an intraperitoneal saline solution and, for this reason, was named the SAL group (n=15). The applications for both groups occurred during the immediate post-operative period on the 2nd, 4th, 6th, 8th, 10th, and 12th day post-surgery. At various stages (14, 42, and 60 days), the animals were euthanized, and tests were performed on their tibiae. These tests include histomorphometric and immunohistochemical analyses, computerized microtomography, sampling in light-cured resin for calcified sections, and confocal microscopy. The obtained data were then analyzed using One-way ANOVA and the Shapiro-Wilk, Kruskal-Wallis, and student t-tests (P<0.05). our findings indicate that the OZ group (3.26±0.20 mm) showed better cellular organization and bone neoformation at 14 days (SAL group, 0.90±1.42 mm) (P=0.001). Immunohistochemistry revealed that osteocalcin labeling was moderate in the OZ group and mild in the SAL group at 14 and 42 days post-surgery. The data from the analysis of calcified tissues (microtomography, histometric, and bone dynamism analysis) at 60 days showed no statistically significant differences between the groups (P=0.32). it was concluded that ozone therapy anticipated the initial phases of the peri-implant bone repair process.

Nanoscaled Titanium Oxide Layer Provokes Quick Osseointegration on 3D-Printed Dental Implants: A Domino Effect Induced by Hydrophilic Surface.

Three-dimensional printing is a revolutionary strategy to fabricate dental implants. Especially, 3D-printed dental implants modified with nanoscaled titanium oxide layer (H-SLM) have impressively shown quick osseointegration, but the accurate mechanism remains elusive. Herein, we unmask a domino effect that the hydrophilic surface of the H-SLM facilitates blood wetting, enhances the blood shear rate, promotes blood clotting, and changes clot features for quick osseointegration. Combining computational fluid dynamic simulation and biological verification, we find a blood shear rate during blood wetting of the hydrophilic H-SLM 1.2-fold higher than that of the raw 3D-printed implant, which activates blood clot formation. Blood clots formed on the hydrophilic H-SLM demonstrate anti-inflammatory and pro-osteogenesis effects, leading to a 1.5-fold higher bone-to-implant contact and a 1.8-fold higher mechanical anchorage at the early stage of osseointegration. This mechanism deepens current knowledge between osseointegration speed and implant surface characteristics, which is instructive in surface nanoscaled modification of multiple 3D-printed intrabony implants.

Evaluation of nanoscale versus hybrid micro/nano surface topographies for endosseous implants

We examined the effect of a nanoscale titanium surface topography (D) versus two hybrid micro/nanoscale topographies (B and OS) on adherent mesenchymal stem cells (MSCs) and bone marrow derived macrophages (BMMs) function in cell culture and in vivo. In the in vitro study, compared to OS and B surfaces, D surface induced earlier and greater cell spreading, and earlier and profound mRNA expression of RUNX2, Osterix and BMP2 in MSCs. D surface induced earlier and higher expression of RUNX2 and BMP2 and lower expression of inflammatory genes in implant adherent cells in vivo. Measurement of osteogenesis at implant surfaces showed greater bone-to-implant contact at D versus OS surfaces after 21 days. We explored the cell population on the D and OS implant surfaces 24 h after placement using single-cell RNA sequencing and identified distinct cell clusters including macrophages, neutrophils and B cells. D surface induced lower expression and earlier reduction of inflammatory genes expression in BMMs in vitro. BMMs on D, B and OS surfaces demonstrated a marked increase of BMP2 expression after 1 and 3 days, and this increase was significantly higher on D surface at day 3. Our data implicates a dynamic process that may be influenced by nanotopography at multiple stages of osseointegration including initial immunomodulation, recruitment of MSCs and later osteoblastic differentiation leading to bone matrix production and mineralization. The results suggest that a nanoscale topography (D) favorably modulates adherent macrophage polarization toward anti-inflammatory and regenerative phenotypes and promotes the osteoinductive phenotype of adherent mesenchymal stem cells. Statement of significanceOur manuscript contains original data developed to define effects of a novel nanotopography on the process of osseointegration at the cell and tissue level. Few studies have compared the effects of a nanoscale surface versus the more typical hybrid micro/nano-scale surfaces used today. We have utilized single-cell RNA sequencing for the first time to identify earliest cell populations on implant surfaces in vivo. We provide data indicating that the nanoscale surface acts upon both osteoprogenitor and immune cell (macrophages) to alter the process of bone formation in a surface-specific manner. This work represents new observations regarding osseointegration and immunomodulation.

Bone-anchored prostheses for lower limb amputation in a French cohort with 1-15years of follow-up: implant survival rates, mechanical complications, and reported outcomes.

To evaluate the implant survival rate, mechanical complications, and reported patient outcomes of bone-anchored prostheses for patients with lower limb amputation in France after 1-15years of follow-up. This retrospective cohort study included patients who underwent surgery at a single center in France between 2007 and 2021. The primary outcomes were the implant survival rate and functional scores assessed by the Questionnaire for Transfemoral Amputees (Q-TFA). Secondary outcomes were adverse events that occurred during follow-up. The cohort consisted of 20 bone-anchored prostheses in 17 patients. The main level of amputation was transfemoral (82%, n = 14). The main reason for amputation was trauma (n = 15). The mean age at amputation was 32 (range 15-54) years, and the mean age at the first stage of osseointegration was 41 (range 21-58) years. The Kaplan-Meier survival curve showed respective survival rates of 90%, 70%, and 60% at 2, 10, and 15years. All Q-TFA scores were significantly improved at last the follow-up. Eleven patients (65%) experienced mechanical complications. In total, 37 infectious events occurred in 13 patients (76%), mainly comprising stage 1 infections (68%, n = 25). Only two cases of septic loosening occurred (12%), leading to implant removal. This is the first French cohort of bone-anchored prostheses and among the series with the longest follow-up periods. The findings indicate that bone-anchored prostheses are safe and reliable for amputee patients who have difficulties with classic prostheses.

Construction of Multifunctional Zinc Ion Sustained-Release Biocoating on the Surface of Carbon Fiber Reinforced Polyetheretherketone with Enhanced Anti-inflammatory Activity, Angiogenesis, and Osteogenesis.

Current treatments of carbon fiber-reinforced polyetheretherketone (CFRPEEK) as orthopedic implants remain unsatisfactory due to the bioinert surface. The multifunctionalization of CFRPEEK, which endows it with regulating the immune inflammatory response, promoting angiogenesis, and accelerating osseointegration, is critical to the intricate bone healing process. Herein, a multifunctional zinc ion sustained-release biocoating, consisting of a carboxylated graphene oxide, zinc ion, and chitosan layer, covalently grafts on the surface of amino CFRPEEK (CP/GC@Zn/CS) to coordinate with the osseointegration process. The release behavior of zinc ions theoretically conforms to the different demands in the three stages of osseointegration, including the burst release of zinc ions in the early stage (7.27 μM, immunomodulation), continuous release in the middle stage (11.02 μM, angiogenesis), and slow release in the late stage (13.82 μM, osseointegration). In vitro assessments indicate that the multifunctional zinc ion sustained-release biocoating can remarkably regulate the immune inflammatory response, decrease the oxidative stress level, and promote angiogenesis and osteogenic differentiation. The rabbit tibial bone defect model further confirms that, compared to the unmodified group, the bone trabecular thickness of the CP/GC@Zn/CS group increases 1.32-fold, and the maximum push-out force improves 2.05-fold. In this study, a multifunctional zinc ion sustained-release biocoating constructed on the surface of CFRPEEK that conforms to the requirements of different osseointegration stages can be an attractive strategy for the clinical application of inert implants.

Employing Indirect Adenosine 2A Receptors (A2AR) to Enhance Osseointegration of Titanium Devices: A Pre-Clinical Study.

The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (A2AR), on the osseointegration of titanium implants in a large, translational pre-clinical model. Sixty tapered, acid-etched titanium implants, treated with four different coatings ((i) Type I Bovine Collagen (control), (ii) 10 μM dipyridamole (DIPY), (iii) 100 μM DIPY, and (iv) 1000 μM DIPY), were inserted in the vertebral bodies of 15 female sheep (weight ~65 kg). Qualitative and quantitative analysis were performed after 3, 6, and 12 weeks in vivo to assess histological features, and percentages of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO). Data was analyzed using a general linear mixed model analysis with time in vivo and coating as fixed factors. Histomorphometric analysis after 3 weeks in vivo revealed higher BIC for DIPY coated implant groups (10 μM (30.42% ± 10.62), 100 μM (36.41% ± 10.62), and 1000 μM (32.46% ± 10.62)) in comparison to the control group (17.99% ± 5.82). Further, significantly higher BAFO was observed for implants augmented with 1000 μM of DIPY (43.84% ± 9.97) compared to the control group (31.89% ± 5.46). At 6 and 12 weeks, no significant differences were observed among groups. Histological analysis evidenced similar osseointegration features and an intramembranous-type healing pattern for all groups. Qualitative observation corroborated the increased presence of woven bone formation in intimate contact with the surface of the implant and within the threads at 3 weeks with increased concentrations of DIPY. Coating the implant surface with dipyridamole yielded a favorable effect with regard to BIC and BAFO at 3 weeks in vivo. These findings suggest a positive effect of DIPY on the early stages of osseointegration.

Analysis of Bone Density and Bone Morphometry by Periapical Radiographs in Dental Implant Osseointegration Process.

This research aimed to analyze the differences in bone density and bone morphometry by periapical implant radiography in the dental implant osseointegration stages. This experimental research uses 12 periapical radiographs of tibial bones from a New Zealand white rabbit (Oryctolagus cuniculus). The analysis was performed on day 3, 14, and 28 of the osseointegration stages with density, trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), and trabecular number (Tb.N.) as parameters. The implant used is a titanium alloy and coated by SA (sunblasted with alumina acid) of 4 mm in diameter and 7 mm in length. The radiographic assessment of the osseointegration process is obtained with the region of interest (ROI) segmentation results. Additionally, each ROI was analyzed for bone density and morphometry using the open-source ImageJ software with the BoneJ plugin. The significant difference was evaluated by analysis of variance (F-test) with p < 0.05 and nonparametric Kruskal-Wallis test with p < 0.05. Analysis of the osseointegration images of dental implants at day 3, 14, and 28 with the periapical X-ray modality shows significant differences (p < 0.05) in the parameters measuring density and trabecular thickness (Tb.Th.). In the variables of trabecular separation (Tb.Sp.) and number (Tb.N.) (p > 0.05), there is no significant difference. Based on the results, density and trabecular thickness (Tb.Th.) showed a significant difference between healing times. However, trabecular separation (Tb.Sp.) and trabecular number (Tb.N.) showed no difference in healing time.

Impact of a Static Magnetic Field on Early Osseointegration: A Pilot Study in Canines.

A static magnetic field generated by neodymium-iron-boron (NdFeB) magnets placed in the inner cavity of dental implants can enhance bone regeneration in rabbits. It is, however, unknown whether static magnetic fields support osseointegration in a canine model. We therefore determined the potential osteogenic effect of implants carrying NdFeB magnets inserted in the tibia of six adult canines in the early stages of osseointegration. Here, we report that after 15 days of healing, magnetic and regular implants showed a high variation with a median new bone-to-implant contact (nBIC) in the cortical (41.3% and 7.3%) and the medullary (28.6% and 44.8%) region, respectively. Consistently, the median new bone volume/tissue volume (nBV/TV) in the cortical (14.9% and 5.4%) and the medullary (22.2% and 22.4%) region were not significantly different. One week of healing only resulted in negligible bone formation. These findings suggest that considering the large variation and the pilot nature of this study, magnetic implants failed to support peri-implant bone formation in a canine model.

Effect of the Magnetic Field Generated by a New NeFeB Cover Screw on Bone Healing around Endosseous Implants: A Case Series Report from Dental Practice

This study aimed to investigate the effect of static magnetic field (SMF) generated by innovative cover screws made of NeFeB on early bone healing around dental implants. The study was carried out on humans in a private dental practice. Eight 3i implants (Biomet, Palm Beach, FL, USA) were placed in the posterior mandible at 3.6 and 3.7. The control implants were closed with a conventional screw (G1), while the test implants were closed with a Supercharged® screw (G2). Both groups were compared for stability at 0, 7, 14, 21, 50, and 90 days using a resonant frequency analyzer with Ostell Mentor (Osstell AB, Gothenburg, Sweden). After 50 days, the Supercharged® cover screw was removed. A significant increase in implant stability quotient (ISQ), corresponding to a lower degree of bone resorption, was observed in G2 throughout the follow-up period (p &lt; 0.05), while an initial ISQ decrease was observed until day 21 in G1. In conclusion, the effect of SMF seems to be in the early stages of osseointegration and increases the stability of dental implants.

Ipriflavone suppresses NLRP3 inflammasome activation in host response to biomaterials and promotes early bone healing.

Emerging studies have shown that immune response to biomaterial implants plays a central role in bone healing. Ipriflavone is clinically used for osteoporosis. However, the mechanism of ipriflavone in immune response to implants in early stages of osseointegration remains unclear. In this study, we aimed to investigate the potential role of ipriflavone in early bone healing process and uncover the underlying mechanism. We carried out histological examination as well as analysis of proinflammatory cytokines and NLRP3 inflammasome activation in a tibial implantation mouse model with intra-peritoneal injection of ipriflavone. In addition, we explored the mechanism of ipriflavone in the regulation of NLRP3 inflammasome activation in macrophages. In vivo, ipriflavone ameliorated host inflammatory response related to NLRP3 inflammasome activation at implantation sites, characterized by reductions of inflammatory cell infiltration and proinflammatory cytokine interleukin-1β levels. Ipriflavone treatment also showed beneficial effects on early osseointegration. Further investigations of the molecular mechanism showed that the suppression of NLRP3 inflammasome acts upstream of NLRP3 oligomerization through abrogating the production of reactive oxygen species. These results revealed an anti-inflammatory role of ipriflavone in NLRP3 inflammasome activation through improving mitochondrial function. This study provides a new strategy for the development of immune-regulated biomaterials and treatment options for NLRP3-related diseases.

Bone Response to Osteopontin-Functionalized Carboxyethylphosphonic Acid-Modified Implants. Experimental Study in a Minipig Model

Currently, dental implants have become a common and reliable treatment for restoring masticatory function in edentulous patients. Their surface topography is of great importance for the adhesion and remodeling of bone cells, both in the initial phases and over time, and different strategies have been proposed to improve the biological performance of conventional sandblasted, large-grit, acid-etched implant surfaces. Corrosion has been identified as one of the causes of implant failure due to contact with oral fluids. Carboxyethylphosphonic acid is a potent anticorrosive that would form stable bonds with titanium oxide, generating an organic layer on which modifications could be made to improve cell adhesion. Osteopontin is considered a molecule capable of improving the osseointegration of titanium. Our study evaluated the osseointegration capacity of titanium implants modified with carboxyethylphosphonic acid and functionalized with osteopontin in a minipig model. A total of 16 implants were inserted in the tibial diaphysis of two minipigs, 8 implants modified with carboxyethylphosphonic acid and functionalized with osteopontin from the experimental group and 8 from the control group with sandblasted, large-grit, acid-etched surface treatment. After 4 weeks, the animals were sacrificed and the samples were analyzed by histomorphometric analysis, assessing bone-implant contact, cortical bone-implant contact, percentage of new bone, peri-implant bone density and interthread bone area interthread. Statistical analysis was performed using SPSS v.18. Statistical significance was found between groups for the percentage of new bone (p = 0.04) and for interthread bone area interthread (p = 0.01). Functionalization of titanium surfaces by osteopontin may be of interest for conditioning bone remodeling in the early stages of osseointegration, although more in vivo studies are needed to determine its real influence in this aspect.

Effects of local single dose administration of parathormone on the early stages of osseointegration: A pre-clinical study.

The present study aimed to evaluate the effect of parathormone (PTH) administered directly to the implant's surface prior to insertion, using a large translational animal model. Sixty titanium implants were divided into four groups: (i) Collagen, control group, where implants were coated with Type-I Bovine-collagen, and three experimental groups, where implants received varying doses of PTH: (ii) 12.5, (iii) 25, and (iv) 50 μg, prior to placement. Fifteen female sheep (~2 years old, weighing ~65 kg) received four implants in an interpolated fashion in C3, C4 or C5 vertebral bodies. After 3-, 6- and 12-weeks, samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). BIC yielded lower values at 6-weeks for 50 μg relative to the control group, with no significant differences, when compared to the 12.5- and 25-μg. No significant differences were detected at 6-weeks between collagen, 12.5- and 25-μg groups. At 3- and 12-weeks, no differences were detected for BIC among PTH groups. With respect to BAFO, no significant differences were observed between the control and experimental groups independent of PTH concentration and time in vivo. Qualitative observations at 3-weeks indicated the presence of a more mature bone near the implant's surface with the application of PTH, however, no significant differences in new bone formation or healing patterns were observed at 6- and 12-weeks. Single local application of different concentrations of PTH on titanium implant's surface did not influence the osseointegration at any time-point evaluation in low-density bone.

ITRAQ-based proteomic analysis reveals potential osteogenesis-promoted role of ATM in strontium-incorporated titanium implant.

The present study aims to reveal the osteogenic roles played by DNA damage response biomarkers through implementing isobaric tags for relative and absolute quantitation (iTRAQ) technique. First, sandblasted large-grit double acid-etched (SLA) titanium implant and strontium-incorporated (SLA-Sr) titanium implant were used for inserting in the tibiae of rats. iTRAQ technique was used to detect protein expression changes and identify differentially expressed proteins (DEPs). In total, 19,343 peptides and 4280 proteins were screened out. Among them, 91 and 138 DEPs were identified in the SLA-Sr group after implantation for 3 and 7 days, respectively. Ataxia-telangiectasia mutated (ATM) protein up-regulated on the 3rd day showed a trend of further up-regulation on the 7th day. Moreover, functional enrichment analyses were also conducted to explore the biological function of DEPs during the initial stage of osseointegration in vivo, which revealed that the biological functions of the DEPs on the 7th day were mainly related to "mismatch repair" and "mitotic G1 DNA damage checkpoint." Analysis of the Reactome signaling pathway showed that ATM was associated with TP53's regulation and activation. Finally, DNA damage repair related genes were selected for validation at mRNA and protein expression levels. Real-time reverse transcription-polymerase chain reaction and immunohistochemistry validation results demonstrated that mRNA expression level of ATM was higher in SLA-Sr group. In conclusion, SLA-Sr titanium implant could initiate DNA damage repair by activating expression levels of ATM. This study was striving to reveal new faces of better osseointegration and shedding light on the biological function and underlying mechanisms of this important procedure.