Early Phase Of Osseointegration Research Articles

Histological and Histomorphometric Comparison of Innovative Dental Implants Laser Obtained: Animal Pilot Study.

Objective: Evaluation of the in vivo bone response of two innovative titanium surfaces ytterbium laser active fiber obtained (L1-L2) compared to a sandblasted and acid etched (SBAE) during early phase of osseointegration. Material and Methods: Three implant groups with the same macroscopic features were obtained (L1-L2-SBAE) to promote specific surface characteristics. Scanning electron microscopy, profilometric evaluation, X-ray spectrometry, and diffraction analysis were performed. For each group, six implants were placed in the tibiae of three Peli Buey sheep, and histologic, histomorphometric analysis, bone to implant contact (BIC), and the Dynamic Osseointegration index (DOI) were performed. Results: During the early phases of osseointegration, the histological and histomorphometric results showed significant differences between L1-L2-SBAE implants. At 15 and 30 days, histological analysis detected a newly bone formation around all specimens with an higher vital bone in L2 compared to L1 and SBAE both in cortical and in poor-quality marrow bone. At same time, histomorphometric analysis showed significantly higher BIC values in L2 (42.1 ± 2.6 and 82.4 ± 2.2) compared to L1 (5.2 ± 3.1 and 56.2 ± 1.3) and SBAE (23.3 ± 3.9 and 77.3 ± 0.4). DOI medium value showed a higher rate in L2 (2.83) compared to SBAE (2.60) and L1 (1.91). Conclusions: With the limitations of this pilot study, it is possible to assess that the titanium surface characteristics, and not the technologies used to obtain the modification, played a crucial role during the osseointegration process. Histological, histomorphometric, BIC, and DOI evaluation showed a significantly higher rate in L2 specimens compared to others, confirming that the implant surface could increase the bone response in cortical or marrow poor quality bone during the initial phases of osseointegration.

Correlation between LncRNA Profiles in the Blood Clot Formed on Nano-Scaled Implant Surfaces and Osseointegration.

Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system; however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation.

Effects of Novel Laser Dental Implant Microtopography on Human Osteoblast Proliferation and Bone Deposition

The aim of this study was to compare how two innovative laser titanium surfaces and sandblasted and acid-etched surfaces influence human osteoblast behavior during osteogenesis and the initial phases of bone deposition. Human osteoblasts from human adipose stem cells were sorted by flow cytometric analysis and induced to differentiate. After 40 days, the osteogenic differentiation was detected by alizarin red staining, and the alkaline phosphatase (ALP) was evaluated with western blot (WB) and real-time reverse transcriptase-polymerase chain reaction (RT-PcR) analysis. After confluence, human osteoblasts were cultured onto two different innovative laser-obtained titanium surfaces (L1 and L2) and compared with one sandblasted and acid-etched (SBAE) surface as the control. At different times, human osteoblast behavior was evaluated with cell proliferation viability assay (MTT), scanning electron microscopy (SEM), energy-dispersive x-rays (EDAX), osteogenic markers with RT-PcR, and WB analysis of matrix extracellular phosphoglycoprotein (MEPE), ALP, and osteocalcin (OCN). After cell sorting, the human osteoblasts from human adipose stem cells showed increasing values of ALP mRNA and protein expression. The osteogenic differentiation was confirmed by quantitative alizarin red staining assay. Profilometric and SEM analysis showed relevant differences between SBAE, L1, and L2 specimens. After 20 days of culture onto titanium samples, SEM evaluation showed a small number of human osteoblasts and isolated sites of bone matrix deposition in SBAE specimens. At the same time, on L1 surfaces, only an osteoblast mono-layer with initial bone deposition was found, while on L2 specimens, there was a thick network with flattened large stellate cells, many cellular interconnections with strong titanium adhesion, and a large complex mineralized structure of crystal bone. After 20 days, for all titanium samples, human osteoblasts culturing EDAX analysis showed the absence of impurities and a higher bone matrix deposition in L2 specimens compared with L1 and SBAE samples. The innovative microtopography and nanotopography laser-induced surface showed high biocompatibility with primary human osteoblast cultures and the absence of impurities. The innovative laser texture was capable of influencing the osteogenic process, confirming the critical role of titanium surface characteristics in the cell adhesion and bone deposition during the early phases of osseointegration. The association of human adipose stem cells and titanium surfaces laser-induced with an innovative procedure could generate promising improvements and developments in orthopedics, maxillofacial, and dental implant surgery.

The use of platelet‐rich fibrin to enhance the outcomes of implant therapy: A systematic review

ObjectiveTo assess the impact of platelet‐rich fibrin (PRF) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and radiographic outcomes of PRF administration for bone regeneration and implant therapy?MethodA systematic literature search comprised three databases: MEDLINE, EMBASE, and Cochrane followed by a hand search of relevant scientific journals. Human studies using PRF for bone regeneration and implant therapy were considered and articles published up to December 31, 2017 were included. Eligible studies were selected based on the inclusion criteria. Randomized controlled trials (RCT) and controlled clinical trials (CCT) were included.ResultsIn total, 5,963 titles were identified with the search terms and by hand search. A total of 12 randomized controlled trials (RCT) met the inclusion criteria and were chosen for data extraction. Included studies focused on alveolar ridge preservation after tooth extraction, osseointegration process, soft tissue management, bone augmentation, bone regeneration after sinus floor elevation and surgical peri‐implantitis treatment. Overall, the risk of bias was moderate or unclear. Nine studies showed superior outcomes for PRF for any of the evaluated variables, such as ridge dimension, bone regeneration, osseointegration process, soft tissue healing. Three studies failed to show any beneficial effects of PRF. No meta‐analysis could be performed due to the heterogeneity of study designs.ConclusionsThere is moderate evidence supporting the clinical benefit of PRF on ridge preservation and in the early phase of osseointegration. It remains unclear whether PRF can reduce pain and improve soft tissue healing. More research support is necessary to comment on the role of PRF to improve other implant therapy outcomes.

Clinical, radiological, and gene expression analyses in smokers and non-smokers, Part 2: RCT on the late healing phase of osseointegration.

The mechanisms behind the impact of smoking on osseointegration are not fully understood. To investigate the initial clinical and molecular course of osseointegration of different implants in smokers and non-smokers in a randomized controlled trial (RCT). Smoking (n = 16) and non-smoking (n = 16) patients received 3 implant types: machined, oxidized, and laser-modified surfaces. Baseline bone biopsies were retrieved from the implant sites. After 60 and 90 days, the pain score, implant stability quotient (ISQ), and peri-implant crevicular fluid (PICF) gene expression were analyzed. Furthermore, radiological and clinical assessments were made at 90 days. At 90 days, no pain was reported, irrespective of smoking habit. A higher ISQ was found in smokers compared with non-smokers. Marginal bone loss (MBL) was greater in smokers than in non-smokers. The comparison of implant surfaces revealed greater MBL exclusively at the machined implants in smokers. At 90 days in smokers, the PICF around machined implants revealed a higher expression of the proinflammatory cytokine, interleukin-6 (IL-6), and a lower expression of the osteogenic gene, osteocalcin (OC), compared with the PICF around modified implants. Furthermore, OC expression was lower at machined implants in smokers compared with machined implants in non-smokers. After adjustment for age and implant location (maxilla/mandible), multivariate regression revealed the following predictors of MBL: smoking, bleeding on probing at 90 days, hypoxia-inducible factor 1 alpha (HIF-1α) expression at baseline and IL-6 expression in PICF at 90 days. During the early phase of osseointegration, non-smokers and smokers present a similar, high implant survival. In contrast, smokers present a greater MBL, particularly at machined implants. HIF-1α baseline expression in the recipient bone and IL-6 expression in PICF cells are important molecular determinants for MBL after 90 days. It is concluded that smoking has an early effect on osseointegration, which is dependent on the implant surface properties and the local host response.

Gene expression in peri-implant crevicular fluid of smokers and nonsmokers. 1. The early phase of osseointegration.

Smoking is a risk factor for dental implants. The mechanisms behind the impact of smoking on osseointegration are not fully understood. To investigate the initial molecular and clinical course of osseointegration of different titanium implants in smokers and nonsmokers. Smoker (n = 16) and nonsmoker (n = 16) patients were included. Each patient received three implant types: machined, oxidized and laser-modified surfaces. After 1, 7, 14, and 28 days, the peri-implant crevicular fluid (PICF) was sampled for gene expression analysis of selected factors involved in early processes of osseointegration. Furthermore, pain-score (VAS), resonance frequency analysis (RFA) and baseline clinical assessments were performed. Early failure of osseointegration, associated with a high and sustained perception of pain, was encountered in 3/32 patients. In general, high pain scores were reported during the first days after implantation, irrespective to smoking habit, which correlated to high levels of pro-inflammatory cytokines during the first days after implantation. Higher ISQ values were found in smokers compared to nonsmokers. In smokers exclusively, ISQ values correlated to harder and less atrophic bone quality and quantity, respectively. Smokers displayed a higher expression of osteocalcin (OC), but later peak and lower expression of bone morphogenetic protein (BMP-2) (at 7 days) compared to nonsmokers. In comparison to machined implants, surface-modified implants were associated with higher expression of alkaline phosphatase (ALP) and cathepsin K (CatK) at 28 days in nonsmokers. During the early phase of osseointegration, postoperative pain is linked to the inflammatory cell response and, may tentatively serve as an indicator of biological complication and implant loss. The present study suggests that smokers have an altered bone composition and (ultra)structure based on the observations that ISQ values are higher and correlate to recipient bone quality and quantity in smokers.

The influence of controlled surface nanotopography on the early biological events of osseointegration

This study provides a first line of evidence that pre-determined nanopatterns on clinically relevant, screw-shaped, titanium implants can be recognized by cells in the complex in vivo environment. Until now, most of the knowledge relating to cell interactions with nanopatterned surfaces has been acquired from in vitro studies involving mostly two-dimensional nanopatterned surfaces of varying chemical composition. We have managed to superimpose pre-determined nanoscale topography on polished and micro-rough, screw-shaped, implants, without changes in the microscale topography or chemistry. This was achieved by colloidal lithography in combination with a thin titanium film coating on top of both nanopatterned and control implants. The early events of osseointegration were evaluated at the bone interface to these implants. The results revealed that nanotopography, as such, elicits downregulatory effects on the early recruitment and activity of inflammatory cells while enhancing osteogenic activity and woven bone formation.

Effect of platelet rich plasma on stability of dental implants: A prospective comparative clinical study

Background: Good implant stability is the prime concern for successful prosthetic rehabilitation. Many methods and different types of implants have been used to achieve primary and secondary stability with varying success rates. The evolution continued with the use of biological materials for early osseointegration. The present study was aimed to compare and evaluate the effect of platelet rich plasma (PRP) on the early osseointegration and secondary stability of dental implants using implant stability values. Materials and Methods: A total of 18 dental implants were randomly placed among 10 patients in the mandibular posterior region using split mouth design. In the control group, implants were placed following standard surgical protocol. In the study group, autologous PRP was used to moisten the implants before placement. Implant stability was observed and compared using Osstel Implant stability meter at 0, 30, 60, and 90 days. All the cases were followed-up over period of 18 months. Statistical analysis was carried using one-way analysis of variance and paired and unpaired t-test. Results: Significant difference in stability values were observed in the study group following 30 days after implant placement. Control group showed no statistically significant difference at all time intervals. Implant stability values were higher in the early phase of osseointegration in the PRP group. However, at the end of the study period, both groups showed similar stability. Conclusion: Good primary implant stability is beneficial for early loading and rehabilitation. PRP can be successfully used as an adjunct for better and early function. It is safe due to its autologous origin, thus eliminating the risk of disease transmission and immunogenic reactions.

Single-Implant Survival: More Than 30 Years of Clinical Experience.

The aim of this study was to report long-term clinical survival of single implants provided with turned and moderately rough surfaces in routine practice. All patients consecutively treated at a specialist center with single-crown implants from 1982 to 2013 were included. For all these patients, data on implant failure and last examination at the clinic were collected, and thereafter cumulative survival rates (CSR) were calculated for patients treated in the maxilla or mandible with turned or moderately rough surfaces, respectively. In total, 2,417 patients (2,665 operations) were treated with 3,211 single implants during the inclusion period (31 years). Of these, 573 (615 operations, 754 implants) were followed up for at least 10 years. Overall proportions of patients followed up for 5 years up to 25 years decreased from 68.2% to 37.0% of treated patients. A higher follow-up compliance was observed for patients treated during the earlier period of inclusion. Patient CSR for 15 and 10 years for maxillary implant placement was 95.8% for turned surfaces and 98.5% for moderately rough surfaces, respectively. Corresponding patient CSR for 10 and 25 years for mandibles was 95.1% and 97.2%, respectively. No implant was reported as a failure after 10 years of follow-up. A significant number of patients can be expected to be lost to follow-up during long-term periods in routine practice. Single-implant treatment is an overall predictable treatment procedure over the long term, with a lower failure rate for implants with a moderately rough surface placed in the maxilla. This difference seems to be established already during the early phase of osseointegration.

Early loading of hydrophilic titanium implants inserted in low-mineralized (D3 and D4) bone: one year results of a prospective clinical trial

IntroductionPure titanium is the material of choice for contemporary dental implants. However, superficial reaction of the moderately rough titanium surface with atmospheric components decreases its hydrophilicity. INICELL® represents a chemical alteration and hydrophilization of a moderately rough i. e. sand-blasted and acid-etched titanium surface. The hydrophilicity leads to a more homogenous adsorption of proteins on the implant surface in-vitro, supporting the activation of a higher number of platelets and the generation of a homogenous, complete fibrin matrix in the early phases of osseointegration. This in turn helps to reduce the healing time and enhances the predictability of osseointegration in compromised bony situations.The objective of this case series trial was therefore to investigate if early loading (after 8 weeks) of hydrophilic INICELL implants is feasible in patients with reduced bone quality.MethodsIn 10 patients, 35 hydrophilic implants were placed in sites revealing bone quality class 3 and 4, and uncovered after 4 weeks. Eight weeks later implants were released for loading if the tactile resistance was ≥35 Ncm. Lower resistances resulted in 12 weeks initial healing period. Insertion torque, ISQ, tactile resistance and vertical bone level were evaluated at implant installation, after 4 weeks (uncovering), 8 or 12 weeks (loading), and 12 weeks and one year after loading.ResultsMean implant insertion torque was 21 Ncm. 31 (88.6%) showed a tactile resistance of >35 Ncm after eight weeks and were released for prosthetic loading. Eight weeks after insertion, one implant (2.9%) had to be removed following a soft tissue complication. One implant had to be removed after 4 weeks due to a technical complication (fractured Osstell-abutment), it was therefore excluded from the analysis.33 of 34 implants (97%) were loaded to occlusion and were in situ/functional one year after implantation. ISQs increased from 43 at baseline to 63 at eight weeks, and 72 at three months after loading. Then, ISQ remained constant until one year after loading.ConclusionsWithin the limitations of this prospective case series, hydrophilic implants may allow for shortening of the initial healing period even in bone with compromised density.

Early bone apposition to hydrophilic and hydrophobic titanium implant surfaces: a histologic and histomorphometric study in minipigs

The first objective of this pilot study was to evaluate the impact of the hydrophilicity on the early phases of osseointegration. The second objective was to compare two hydrophilic implant surfaces with different geometries, surface roughness, and technologies achieving hydrophilicity. Twelve weeks after extraction, all four quadrants of nine minipigs received three dental implants, alternating between hydrophilic microrough surfaces (INICELL and SLActive) and a conventional hydrophobic microrough surface. After 5, 10, and 15 days of submerged healing, ground sections were prepared and subjected to histologic and histomorphometric analysis. The histologic analysis revealed a similar healing pattern among the hydrophilic and hydrophobic implant surfaces, with extensive bone formation occurring between day 5 and day 10. With BIC values of greater than 50% after 10 days, all examined surfaces indicated favorable osseointegration at this very early point in healing. At day 15, the mean new bone-to-implant contact (newBIC) of one hydrophilic surface (INICELL; 55.8 ± 14.4%) was slightly greater than that of the hydrophobic microrough surface (40.6 ± 20.2%). At day 10 and day 15, an overall of 21% of the implants had to be excluded from analysis due to inflammations primarily caused by surgical complications. Substantial bone apposition occurs between day 5 and day 10. The data suggest that the hydrophilic surface can provoke a slight tendency toward increased bone apposition in minipigs after 15 days. A direct comparison of two hydrophilic surfaces with varying geometries is of limited relevance.

Osteoblastic and cytokine gene expression of implant‐adherent cells in humans

Implant surface topography is a key determinant affecting osteoblastic differentiation and cell-cell signaling of implant-adherent cells. To assess the early osteoinductive and cell-cell signaling events in adherent cells, commercially pure titanium implants (2.2×5mm) with nanotopography (HF-treated TiO2 grit-blasted) were compared with micron-scale topography TiO2 grit-blasted (micron-scale, control) implants in vivo. Six implants (n=3/surface) were placed in 10 systemically healthy subjects and removed by reverse threading at 1, 3, and 7days. Gene expression profiles of adherent cells were interrogated using low-density RT-PCR arrays. Osteoinduction was not observed at day 1 on either surface. At 3days, elevated levels of BMP6, osteopontin, and osterix (OSX) were observed in RNA of cells adherent to both micron-scale and nanotopography surfaces. Both surfaces supported osteoinductive gene expression at 7days; however, modest elevations of most mRNAs and significantly higher OSX mRNA levels were measured for cells adhered to nanotopography implants. Further, chemokine and cytokine profiles including CXCL10, CXCL14, IL-9, IL-22, and TOLLIP were upregulated on nanotopographic surfaces as compared with microtopographic surfaces. Implants with superimposed nanoscale topography generate a greater induction of genes linked to osteogenesis and cell-cell signaling during the early phases of osseointegration.

Stability Evaluation of Implants Integrated in Grafted and Nongrafted Maxillary Bone: A Clinical Study from Implant Placement to Abutment Connection

Clinical studies have shown a higher degree of implant failures in grafted bone compared with normal nongrafted maxillary bone. Additionally, a prolonged time for integration of titanium implants in grafted block bone has been shown by means of resonance frequency analysis (RFA). The aim of this prospective study was to compare the stability of implants placed in particulate bone, onlay block bone, interpositional bone, and nongrafted maxillary bone during the early phase of osseointegration using RFA and implant failure. Thirty-five patients with edentulism in the maxilla were included in the study. In all, 260 Astra Tech TiOblast implants (Astra Tech AB, Mölndal, Sweden) were installed. Twenty-five of these patients had severe maxillary atrophy and were treated with iliac bone grafts 5 to 6 months prior to implant placement, 19 with lateral onlay block grafts on one side (group A, 38 implants) and particulate bone for lateral augmentation on the other (group B, 38 implants). These 19 patients also got bilateral sinus floor augmentation with particulate bone (group C, 76 implants). Six patients had an unfavorable sagittal relation between the jaws and underwent a LeFort I operation with interpositional bone blocks grafted to the nasal and sinus floors (group D, 48 implants). The remaining 10 patients could be treated with implants without bone augmentation and served as control (group E, 60 implants). RFA was performed at implant placement and abutment connection 6 months later and an implant stability quotient (ISQ) value was given for each implant. Four implants (1.5%) were found mobile at abutment connection and removed (two in group A and two in group D). RFA showed a slight increase in stability from installation to abutment connection but the differences were not statistically significant in any of the groups (Wilcoxon signed rank test for comparison of paired data). Implants installed in group D had a significantly lower ISQ value at both measurements compared with the other groups (Wilcoxon Rank Sum test for comparisons of independent samples, p = .05). It is concluded that TiO(2)-blasted implants placed in nongrafted and grafted maxillary bone using a two-staged protocol show similar stability during the early phase of osseointegration. Patients reconstructed with interpositional bone graft after a LeFort I osteotomy showed lower implant stability values than nongrafted patients and other grafting techniques.

Effect of nerve growth factor on the early phase of osseointegration around oral implants

To observe the early bone integration of oral implants after injection of exogenous nerve growth factor (NGF) and investigate the effects of NGF on peri-implant osseointegration. Twelve New Zealand white rabbits were used in this study to establish bi-mandible implant model. Then local injection of 1 µg NGF was given on the right side of the mandible as experimental group and normal saline only was injected on the left side as control group once a day for seven days. The rabbits were respectively sacrificed at 2, 4 and 8 weeks after surgery. The implant-bone grinding samples were prepared and stained by toluidine blue for general observation, X-ray, histology and bone histomorphometry analysis. The density of the new bone around implants at 2 and 4 weeks was lower than normal bone. Compared with the control group, the quantity of new bone and bone-implant contact ratio significantly increased in the experimental group. At 8 weeks, the new bone density in both groups was similar to the normal bone. In the experimental group, the haversian system was observed. Bone contact ratio was significantly different between experimental and control group at 2 and 4 weeks, but similar at 8 weeks.[control group at 2 weeks (26.67 ± 3.88)%, 4 weeks (52.59 ± 5.07)% and 8 weeks (97.33 ± 6.75)%, experimental group at 2 weeks (42.24 ± 6.67)%, 4 weeks (72.25 ± 6.30)% and 8 weeks (99.15 ± 4.68)%]. Applying exogenous NGF in the early phase could accelerate the formation and maturation of trabecular bone around the implants and shorten the period of osseointegration. Nerve growth factor could promote osseointegration in the early stage of oral implantation.

The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

Osteogenic agents, such as bone morphogenetic protein-2 (BMP-2), can stimulate the degradation as well as the formation of bone. Hence, they could impair the osteoconductivity of functionalized implant surfaces. We assessed the effects of BMP-2 and its mode of delivery on the osteoconductivity of dental implants with either a naked titanium surface or a calcium-phosphate-coated one. The naked titanium surface bore adsorbed BMP-2, whilst the coated one bore incorporated, adsorbed, or incorporated and adsorbed BMP-2. The implants were inserted into the maxillae of adult miniature pigs. The volume of bone deposited within a defined “osteoconductive” (peri-implant) space, and bone coverage of the implant surface delimiting this space, were estimated morphometrically 1–3 weeks later. After 3 weeks, the volume of bone deposited within the osteoconductive space was highest for coated and uncoated implants bearing no BMP-2, followed by coated implants bearing incorporated BMP-2; it was lowest for coated implants bearing only adsorbed BMP-2. Bone-interface coverage was highest for coated implants bearing no BMP-2, followed by coated implants bearing either incorporated, or incorporated and adsorbed BMP-2; it was lowest for uncoated implants bearing adsorbed BMP-2. Hence, the osteoconductivity of implant surfaces can be significantly modulated by BMP-2 and its mode of delivery.

A lathe swarf collector for use with radioactive materials

The early cell and tissue interactions with nanopatterned titanium implants are insufficiently described in vivo. A limitation has been to transfer a pre-determined, well-controlled nanotopography to 3D titanium implants, without affecting other surface parameters, including surface microtopography and chemistry. This in vivo study aimed to investigate the early cellular and molecular events at the bone interface with screw-shaped titanium implants superimposed with controlled nanotopography. Polished and machined titanium implants were firstly patterned with 75-nm semispherical protrusions. Polished and machined implants without nano-patterns were designated as controls. Thereafter, all nanopatterned and control implants were sputter-coated with a 30 nm titanium layer to unify the surface chemistry. The implants were inserted in rat tibiae and samples were harvested after 12 h, 1 d and 3 d. In one group, the implants were unscrewed and the implant-adherent cells were analyzed using quantitative polymerase chain reaction. In another group, implants with surrounding bone were harvested en bloc for histology and immunohistochemistry. The results showed that nanotopography downregulated the expression of monocyte chemoattractant protein-1 (MCP-1), at 1 d, and triggered the expression of osteocalcin (OC) at 3 d. This was in parallel with a relatively lower number of recruited CD68-positive macrophages in the tissue surrounding the nanopatterned implants. Moreover, a higher proportion of newly formed osteoid and woven bone was found at the nanopatterned implants at 3 d. It is concluded that nanotopography, per se, attenuates the inflammatory process and enhances the osteogenic response during the early phase of osseointegration. This nanotopography-induced effect appeared to be independent of the underlying microscale topography.This study provides a first line of evidence that pre-determined nanopatterns on clinically relevant, screw-shaped, titanium implants can be recognized by cells in the complex in vivo environment. Until now, most of the knowledge relating to cell interactions with nanopatterned surfaces has been acquired from in vitro studies involving mostly two-dimensional nanopatterned surfaces of varying chemical composition. We have managed to superimpose pre-determined nanoscale topography on polished and micro-rough, screw-shaped, implants, without changes in the microscale topography or chemistry. This was achieved by colloidal lithography in combination with a thin titanium film coating on top of both nanopatterned and control implants. The early events of osseointegration were evaluated at the bone interface to these implants. The results revealed that nanotopography, as such, elicits downregulatory effects on the early recruitment and activity of inflammatory cells while enhancing osteogenic activity and woven bone formation.