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Abstract Background A strong seal of soft-tissue around dental implants is essential to block pathogens from entering the peri-implant interface and prevent infections. Therefore, the integration of soft-tissue poses a challenge in implant-prosthetic procedures, prompting a focus on the interface between peri-implant soft-tissues and the transmucosal component. The aim of this study was to analyse the effects of sandblasted roughness levels on in vitro soft-tissue healing around dental implant abutments. In parallel, proteomic techniques were applied to study the interaction of these surfaces with human serum proteins to evaluate their potential to promote soft-tissue regeneration. Results Grade-5 machined titanium discs (MC) underwent sandblasting with alumina particles of two sizes (4 and 8 μm), resulting in two different surface types: MC04 and MC08. Surface morphology and roughness were characterised employing scanning electron microscopy and optical profilometry. Cell adhesion and collagen synthesis, as well as immune responses, were assessed using human gingival fibroblasts (hGF) and macrophages (THP-1), respectively. The profiles of protein adsorption to the surfaces were characterised using proteomics; samples were incubated with human serum, and the adsorbed proteins analysed employing nLC–MS/MS. hGFs exposed to MC04 showed decreased cell area compared to MC, while no differences were found for MC08. hGF collagen synthesis increased after 7 days for MC08. THP-1 macrophages cultured on MC04 and MC08 showed a reduced TNF-α and increased IL-4 secretion. Thus, the sandblasted topography led a reduction in the immune/inflammatory response. One hundred seventy-six distinct proteins adsorbed on the surfaces were identified. Differentially adsorbed proteins were associated with immune response, blood coagulation, angiogenesis, fibrinolysis and tissue regeneration. Conclusions Increased roughness through MC08 treatment resulted in increased collagen synthesis in hGF and resulted in a reduction in the surface immune response in human macrophages. These results correlate with the changes in protein adsorption on the surfaces observed through proteomics.

The reconstruction of orbital fracture sequelae is a major challenge due to concerns regarding surgical approach and implant stability. Few anatomical sites of such minute size have presented with as much variation in treatment as the orbital floor fractures and related sequelae. Our patient developed sequelae of an orbital fracture over the last 3 years, presenting with dystopia, ophthalmoplegia, and diplopia in the supra- and lateroversion and aesthetic impairment. The variety of implant materials for reconstruction after orbital fractures is extensive, and the decision as to which material to use continues to be debated. The continuing development of computer-aided diagnosis and management and the construction of stereolithographic models offer comparable reproduction of anatomical detail. This technology is described in relation to the planning of trauma surgery and sequelae and the planning of ablative surgery for malignant neoplasms of the head and neck. The use of specific 3D printed titanium implants for bone defects was first reported in cranial reconstruction in 2012, and several studies have reported their use in orbital fractures. The advantages of this implant were increased stiffness, preventing shape loss during placement, a precise fit, and decreased surgical time. However, in the existing literature, the one-piece implant done in this way was a precise fit; therefore, it is possible that navigation between intraoperative anatomical landmarks is lost. However, in cases where reconstruction is difficult, such as extensive orbital wall fractures and large orbital sequelae, the 3D printed implant has been helpful in decreasing surgical time and can be accessed by a limited surgical approach with a precise fit. Our clinical case involved a 37-year-old male patient who experienced severe physical aggression in 2020, amid the COVID-19 pandemic. At the time, due to the overwhelming healthcare demands and resource constraints imposed by the pandemic, immediate surgical intervention for the correction of the fracture was not feasible. As a result of this delay, the patient developed sequelae of the orbital fracture over the last 3 years.

IntroductionWhile titanium and its alloys exhibit excellent biocompatibility and corrosion resistance, their polished surfaces can hinder fast and effective osseointegration and other biological processes, such as angiogenesis, due to their inert and hydrophobic properties. Despite being commonly used for orthopedic implants, research focuses on developing surface treatments to improve osseointegration, promoting cell adhesion and proliferation, as well as increasing protein adsorption capacity. This study explores a chemical treatment intended for titanium-based implants that enhances tissue integration without compromising the mechanical properties of the Ti6Al4V substrate. However, recognizing that inflammation contributes to nearly half of early implant failures, we assessed the impact of this treatment on T-cell viability, cytokine production, and phenotype.MethodsTi6Al4V with extra low interstitial (ELI) content discs were treated with hydrofluoric acid followed by a controlled oxidation step in hydrogen peroxide that creates a complex surface topography with micro- and nano-texture and modifies the chemistry of the surface oxide layer. The acid etched surface contains an abundance of hydroxyl groups, crucial for promoting bone growth and apatite precipitation, while also enabling further functionalization with biomolecules.ResultsWhile cell viability remained high in both groups, untreated discs triggered an increase in Th2 cells and a decrease of the Th17 subset. Furthermore, peripheral blood mononuclear cells exposed to untreated discs displayed a rise in various pro-inflammatory and anti-inflammatory cytokines compared to the control and treated groups. Conversely, the treated discs showed a similar profile to the control, both in terms of immune cell subset frequencies and cytokine secretion.DiscussionThe dysregulation of the cytokine profile upon contact with untreated Ti6Al4V-ELI discs, namely upregulation of IL-2 could be responsible for the decrease in Th17 frequency, and thus might contribute to implant-associated bacterial infection. Interestingly, the chemical treatment restores the immune response to levels comparable to the control condition, suggesting the treatment’s potential to mitigate inflammation by enhancing biocompatibility.

There are numerous variables governing the formation of new bone around a dental implant. Of those variables, the implant surface is an important factor influencing the quality of osseointergration. Numerous techniques and materials have been used to alter the surface of an implant to enhance osseointergration and improve the survival and success rate. One such modification is utilizing graphene to modify the surface of an implant. This paper summarizes data collected form articles published in online databases in the past 10 years about the various means of modifying the implant surfaces and provides an in-depth review of the impact of graphene incorporation in dental implants.The document comprised of different sections and emphasized on the use of graphene as an implant surface coating material. The role of graphene on flexural strength, hardness and corrosion resistance have been discussed under mechanical properties whereas the potential of this combination on the osteogenesis, osseointergration and soft tissue seal is covered under biological properties. Lastly, how this combination acts as a drug delivery carrier and renders antimicrobial property has been addressed under pharmacological properties.This review has highlighted the various applications of graphene in the field of implant dentistry. It has outlined the various implant surface modifying methods and thrown light on the various affect this combination has on the mechanical, biological and pharmacological properties. Considering the various research done on the material, it can be concluded that graphene does have a bright future in implant dentistry and continued research in this area will provide fruitful benefits.

Background. Modifying the dental implant’s surface texture enhances its biological response to the bone and implant‒tissue interface, resulting in the successful support of forces. This study assessed the impact of sandblasting, sandblasting plus acid etching, Er,Cr:YSGG laser, and propolis implant surface treatments and occlusal load on the osseointegration of titanium dental implants in dogs. Methods. Seventy-two titanium dental implants with a diameter of 4 mm and a length of 10 mm were divided into four groups according to implant surface modifications (n=18 for each group): group A: sandblasting plus acid etching, group B: sandblasting with Al2 O3 , group C: Er,Cr:YSGG laser, group D: propolis coating. Twenty-four local breed male dogs were used. Premolar teeth (P1, P2, and P3) were extracted on the left side of the mandible, and after 12 weeks of bone healing, implants were unilaterally installed. The osseointegration at three study times from implant installation (14, 90, and 180 days) was evaluated. The dog jaws were scanned using an intraoral scanner for the virtual design of screw-retained three-unit crowns after 90 days of osseointegration. Final radiographs were taken before the animals were sacrificed at 14, 90, and 180 days, and the histological analysis was performed. Results. Radiographic analysis showed new bone formation (NBF) along and in contact with the implant surface of the treated groups. The histological analysis after 14 days in groups A and B revealed a uniform and ongoing pattern of bone growth and many osteoblasts with few osteocytes within lacunae in new bone trabeculae. Group C showed an increase in the number of osteoblasts lining thin bone trabeculae. Group D showed a generative power concerning bone. At 90 days, there was increased bone ingrowth, and the new bone matured in all the treated implant groups. At 180 days, dense mature bone apposition was in direct contact with delayed-loaded implant surfaces. Conclusion. A radiographic examination revealed that surface modification significantly impacted osseointegration, with a strong bond between the implant surface and the surrounding bone. The histological sections at the 14-day interval revealed obvious bone remodeling activity, especially in sandblasting plus acid etching and sandblasting-modified implant surface groups. At the 90-day interval, bone ingrowth had increased, and the new bone became mature, especially in sandblasting and propolis surface modification groups. After 180 days of the delayed-loaded implant osseointegration, differences were observed between different implant-treated groups with a remarkable remodeling of the bone, especially in the propolis coating group.

Introduction: Smart multifunctional surfaces targeting intricate biological events or versatile therapeutic strategies are imminent to achieve long-term transmucosal implant success.Methods: This study used dopamine (DA), graphene oxide (GO), and type IV collagen (COL-IV) to construct multilayer nanofilms (DGCn) based on their universal adhesive and biomimetic properties to design a versatile and bioactive titanium implant. The characterization of DGCn on different titanium surfaces was performed, and its loading capacity, release profile, in situ gene delivery, and in vitro biological properties were preliminarily evaluated.Results: Our results demonstrate that hydrogenated TiO2 nanotubes (H) provide a better platform for the DGCn coating than machined Ti and air-TiO2 nanotubes. The H-DGC10 displayed the most stable surface with excellent loading capacity, sustained-release profile, and in situ gene transfection efficiency; this could be due to the high specific surface area of H and GO, as well as the functional groups in H, DA, and GO. Moreover, the H-DGC10 exhibited good biocompatibility for human oral epithelial cells and promoted the expression of integrin β4 and laminin 332, both being hemidesmosome-related proteins.Discussion: Our findings suggest that H-DGCn can be designed as a smart multifunctional interface for titanium implants to achieve long-term transmucosal implant success and aid in versatile therapeutic strategies.

Titanium and titanium alloys are the prevailing dental implant materials owing to their favorable mechanical properties and biocompatibility, but how roughness dictates the biological response is still a matter of debate. In this study, laser texturing was used to generate eight paradigmatic roughened surfaces, with the aim of studying the early biological response elicited on MC3T3-E1 pre-osteoblasts. Prior to cell tests, the samples underwent SEM analysis, optical profilometry, protein adsorption assay, and optical contact angle measurement with water and diiodomethane to determine surface free energy. While all the specimens proved to be biocompatible, supporting similar cell viability at 1, 2, and 3 days, surface roughness could impact significantly on cell adhesion. Factorial analysis and linear regression showed, in a robust and unprecedented way, that an isotropic distribution of deep and closely spaced valleys provides the best condition for cell adhesion, to which both protein adsorption and surface free energy were highly correlated. Overall, here the authors provide, for the first time, a thorough investigation of the relationship between roughness parameters and osteoblast adhesion that may be applied to design and produce new tailored interfaces for implant materials.

Introduction: Laser micromachining of titanium and its alloys can create micro-grooves with sizes similar to cell diameter of about 10 μm. Its coating with arginine-glycine-aspartic acid (RGD) may enhance cellular spreading and adhesion. This study aimed to evaluate the effect of laser micro-grooving and laser micro-grooving combined with RGD coating on the strength of the dental implants/bone interface using destructive mechanical pullout testing in experimental animals. Materials and methods: In this study, the test groups consisted of 1.5-mm diameter, 5-mm long laser-grooved and laser-grooved/RGD coated titanium alloy (Ti–6Al–4 V) rods, and the control group included plain titanium alloy (Ti–6Al–4 V) rods. These rods were implanted in the mandibles of New Zealand white rabbits for 2, 4, and 6 weeks. After sacrifice, the test and control specimens were retrieved for mechanical pullout testing. The DMA 7-e was used to pull the titanium rods out of the bone, the probe position was plotted versus time graph to monitor the test progression, and the static modulus versus time graph was viewed; such graphs was then transformed into tables. The results were analyzed using the Mann-Whitney test. Results: The laser-grooved/RGD coated rods had significantly higher pull-out strength than the laser-grooved and control rods. Additionally, the laser-grooved rods had significantly higher pull-out strength than control rods. Conclusion: Two novel surface treatments were used: laser micro-grooving and tri peptide RGD coating, both of which had different effects on the dental implant interface. Laser grooving improved peri-implant bone healing, whereas RGD coating facilitated earlier bone–implant adhesion and better mineralization.

In this work, we show the in vitro anticancer potential of surgical wires, obtained from zinc (ZnMg0.004) or magnesium (MgCa0.7) alloys by spatial technology comprising casting, extrusion, and final drawing processes. We also present the selective anticancer effects of applied soluble multilayer nanocoatings of zinc and magnesium onto titanium surfaces using the pulse laser deposition method. In the latter, the titanium samples were produced via 3D printing using the selective laser melting method and coated with various combinations of zinc and magnesium layers. For cytotoxicity studies, human dental pulp-derived stem cells (hDPSCs) and human osteosarcoma SaOS-2 cell line were used as representatives of healthy and cancer cells. Cells were examined against the 0.3–3.0 cm2/mL material extract ratios obtained from experimental and steel surgical wires, the latter being the current clinical industry standard. The MgCa0.7 alloy wires were approx. 1.5 times more toxic to cancer cells at all examined extract ratios vs. the extracts from steel surgical wires that exhibited comparable toxicity towards healthy and cancer cells. The ZnMg0.004 alloy wires displayed increased toxicity towards cancer cells with decreasing extract ratios. This was also reflected in the increased anticancer effectiveness, calculated based on the viability ratio of healthy cells to cancer cells, from 1.1 to 4.0 times. Healthy cell viability remained at 80–100%, whereas cancer cell survival fluctuated at 20–75%, depending on the extract ratio. Furthermore, the culture of normal or cancer cells on the surface of Zn/Mg-coated titanium allowed us to select combinations of specific coating layers that yielded a comparable anticancer effectiveness to that observed with the experimental wires that ranged between 2 and 3. Overall, this work not only demonstrates the substantial anticancer properties of the studied wires but also indicates that similar anticancer effects can be replicated with appropriate nanocoatings on titanium samples. We believe that this work lays the groundwork for the future potential development of the category of new implants endowed with anticancer properties.

The failure of a titanium implant is often attributed to inflammatory reactions following implantation. This study focuses on the synthesis of a polyethylene glycol (PEG) layer on porous titanium dioxide (TiO2) coatings using plasma electrolytic oxidation (PEO). This PEG layer serves as a foundation for a drug-eluting platform designed to respond to pH stimuli during inflammation. Betamethasone (BET), a widely used anti-inflammatory drug, was loaded onto the pH-responsive functional PEG layers. The application of the PEG-BET layer onto TiO2 coatings through the vacuum dip coating method resulted in a pH-sensitive sustained release of BET over a 30-day period. Notably, the release rates were 81% at pH 5.0 and 55% at pH 7.2. Electrochemical corrosion tests conducted in both normal and acidic inflammatory solutions demonstrated that duplex composite coatings offer superior protection compared to simple oxide coatings. In a pH 5.0 solution, corrosion current density measurements revealed values of 1.75 μA cm−2 (PEO/PEG-BET), 8.87 μA cm−2 (PEO), and 49.17 μA cm−2 (bare titanium). These results highlight the effectiveness of the PEO/PEG-BET layer in sealing pores within PEO coatings, subsequently reducing the infiltration of corrosive ions in inflammatory environments.

Titanium has been widely used in orthopedics and dental implants due to its excellent biocompatibility and mechanical properties. However, the surface of titanium is biologically inert and lacks biological activity, resulting in poor integration between titanium-based implants and surrounding natural bone tissue, which is a common challenge in its clinical application. Surface modification is currently an effective means to improve the biocompatibility and bioactivity of titanium implants. The natural tissues of the human body are assembled from nanomodules, so from a biomimetic perspective, nanostructures should have better biological activity. TiO2 nanotubes have unique physical and chemical properties due to their elastic modulus, large specific surface area, and regular hollow structure similar to those of bone tissue. This study used anodic oxidation technology to prepare TiO2 nanotubes on the surface of titanium. The surface properties of the nanotubes were evaluated using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), atomic force microscopy profilometry, contact angle measurements, etc. The corrosion resistance was tested using an electrochemical workstation. The results indicate that anodic oxidation can be used to successfully prepare titanium dioxide nanotube arrays on the surface of titanium. The nanotubes not only exhibit a good structure but also improve the surface hydrophilicity and corrosion resistance of titanium, thereby demonstrating potential for clinical application.

AbstractIn head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM). The hOBs were exposed to ionizing γ-irradiation in single doses of 2, 6 or 10 Gy. Twenty-one days post-irradiation, cell nuclei and collagen production were quantified. Cytotoxicity and indicators of differentiation were measured and compared to unirradiated controls. Radiation with backscatter from titanium significantly reduced the number of hOBs but increased the alkaline phosphatase activity in both types of medium when adjusted to the relative cell number on day 21. Irradiated hOBs on the TiF-surface produced similar amounts of collagen as unirradiated controls when cultured in DM. The majority of osteogenic biomarkers significantly increased on day 21 when the hOBs had been exposed to 10 Gy, while the opposite or no effect was observed after lower doses. High doses reinforced with backscatter from titanium resulted in smaller but seemingly more differentiated subpopulations of osteoblasts.

Background/Objective: Platelet derived extracellular vesicles (pEV) are promising therapeutical tools for bone healing applications. In fact, several in vitro studies have already demonstrated the efficacy of Extracellular Vesicles (EV) in promoting bone regeneration and repair in various orthopedic models. Therefore, to evaluate the translational potential in this field, an in vivo study was performed. Methods: Here, we used hyaluronic acid (HA) gels formulated with pEVs, as a way to directly apply pEVs and retain them at the bone defect. In this study, pEVs were isolated from Platelet Lysate (PL) through size exclusion chromatography and used to formulate 2% HA gels. Then, the gels were locally applied on the tibia cortical bone defect of New Zeland White rabbits before the surgical implantation of coin-shaped titanium implants. After eight weeks, the bone healing process was analyzed through biomechanical, micro-CT, histological and biochemical analysis. Results: Although no biomechanical differences were observed between pEV formulated gels and non-formulated gels, biochemical markers of the wound fluid at the interface presented a decrease in Lactate dehydrogenase (LDH) activity and alkaline phosphatase (ALP) activity for pEV HA treated implants. Moreover, histological analyses showed that none of the treatments induced an irritative effect and, a decrease in the fibrotic response surrounding the implant for pEV HA treated implants was described. Conclusion: In conclusion, pEVs improve titanium implants biocompatibility at the bone–implant interface, decreasing the necrotic effects of the surgery and diminishing the fibrotic layer associated to the implant encapsulation that can lead to implant failure.

Titanium implants undergo an aging process through surface hydrocarbon deposition, resulting in decreased wettability and bioactivity. Plasma treatment was shown to significantly reduce surface hydrocarbons, thus improving implant hydrophilicity and enhancing the osseointegration process. This study investigates the effect of plasma surface treatment on bone-to-implant contact (BIC) of implants presenting a nanostructured calcium-incorporated surface (XPEED®). Following a Randomized Controlled Trial (RCT) design, patients undergoing implant surgery in the posterior maxilla received additional plasma-treated (n = 7) or -untreated (n = 5) 3.5 × 8 mm implants that were retrieved after a 4-week healing period for histological examination. Histomorphometric analysis showed that plasma-treated implants exhibited a 38.7% BIC rate compared to 22.4% of untreated implants (p = 0.002), indicating enhanced osseointegration potential. Histological images also revealed increased bone formation and active osteoblastic activity around plasma-treated implants when compared to untreated specimens. The findings suggest that plasma treatment improves surface hydrophilicity and biological response, facilitating early bone formation around titanium implants. This study underscores the importance of surface modifications in optimizing implant integration and supports the use of plasma treatment to enhance osseointegration, thereby improving clinical outcomes in implant dentistry and offering benefits for immediate and early loading protocols, particularly in soft bone conditions.

Abstract Post‐surgery microbial infections are still one of the main reasons for implant failure, which results in very high physical and psychological pain for the patient and an increased cost for the healthcare system. A polymer nanocomposite antibacterial coating on titanium implants represents a valuable alternative to the more expensive and energy‐consuming technological solutions nowadays used. In this regard, a sprayable thermoset nanocomposite composed of silanized‐terminals polyethylene glycol (PEG)/ZnO nanoparticle is herein proposed. Initially, PEG's terminals' solvent‐free silanization and curing are studied by Fourier Transform Infrared and µRaman spectroscopies. Scanning Electron Microscope investigations and scratch tests have shown that the spraying procedure optimization and the oxidation treatment of the titanium substrate lead to a homogeneous coverage and improved adhesion of the coatings. The antibacterial activity is tested against not only both S. aureus and P. aeruginosa bacterial American Type Culture Collection strains, but also using very aggressive antibiotic‐resistant clinical strains. Interestingly, antibacterial activity, evaluated by time‐killing tests, is observed for all tested bacterial strains. Live/dead tests further confirm that 5 wt% of ZnO allows obtaining a bacteriostatic activity within 24 h, whereas a complete growth inhibition (bactericidal activity) of both tested strains is observed for coatings with 20 wt% of ZnO nanoparticles.

Abstract Owing to their mechanical resilience and non‐toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF‐coated Ti implants and highlights their potential utility for modulating the bio‐implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF‐coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.

Abstract Background Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient’s body and expected to find a method to treat implant with BMSC-exos in vivo directly. Methods A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface. Results Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy. Conclusion This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.

Bone fractures can lead to disability and a prolonged rehabilitation period. In some patients, the risk of complications can increase if the healing process is not efficacious or if the metallic implants are loose. Photobiomodulation is a physiotherapeutic method of treatment that can stimulate the cell proliferation and reduce the simpthomatology. We evaluated the effect of LASER therapy on the osseointegration of smooth titanium implants in 12 female rats that suffered fractures on both tibiae. The LASER therapy was performed second day after surgery on half of the rats on both tibia for 7 sessions, every 48 hours. Both tibia were removed in the control and experimental group at 2,4 and 6 weeks after finalizing the last photobiomodulation session. The methods of assesment were micro-CT scans, histology and mechanical tests. The mechanical tests show better bone/implant stability in favor of the experimental group at all 3 times of tissue prelevation. Histological fidings show more bone lamellas in the experimental group after 2 weeks, but no significant differences afterward. The micro-CT imaging show no significant differences between the 2 groups. LASER therapy could prove as an important tool in orthopedic patients and can potentially reduce the rehabilitation time.

Objective To compare the efficiency and biocompatibility of four different silanes on immobilizing c(RGDfK) peptide on titanium surface. Methods After alkali-heat treatment (group OH), the titanium surface was treated with 3-aminopropyltriethoxysilane (APTES) (group OHAP), 3-chloropropyltriethoxysilane (CPTES) (group OHCP) (3-mercaptopropyltrimethoxysilane (MPTS) (group OHMPT) and 3-isobutyryloxy propyltrimethoxysilane(γ- MPS) (group OHMPS) to immobilize the c(RGDfK) cyclic peptide and constructa titanium-silane-c(RGDfK) coating. The NT group was the blank control group. The surface morphology and wettability of the coatings were detected using scanning electron microscopy and contact angle measurement. The elemental composition of the titanium surface was analyzed using X-ray photoelectron spectroscopy. After fluorescent staining with 4’,6-diamino-2-phenylindole (DAPI) and phalloidin, the adhesion of mouse preosteoblast MC3T3-E1 cells on the surface of the materials was observed using laser confocal microscopy. Cell counting kit-8 (CCK-8) and alkaline phosphatase (ALP) activity assays were used to evaluate the proliferation and osteogenic differentiation of MC3T3-E1 cells on the surface of the materials, respectively. Results Scanning electron microscope observation showed a spongy-like 3-dimensional network formed on the titanium surface after alkali-heat treatment with silane-c(RGDfK) coating adhesion. The wettability of each group was greatly improved compared to the untreated titanium surface. The element ratios of Si/Ti and amide-N/Ti in the OHMPS group were the highest. The OHAP group exhibited the best cell adhesion effect. The cell proliferation and ALP activity of the OHAP, OHMPT, and OHMPS groups were significantly higher than the control group (P

Aims: To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. Methods: 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. Results: iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). Conclusion: iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260–269.

Abstract Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.

Hydrophilicity/hydrophobicity—or wettability—is a key surface characterization metric for titanium used in dental and orthopedic implants. However, the effects of hydrophilicity/hydrophobicity on biological capability remain uncertain, and the relationships between surface wettability and other surface parameters, such as topography and chemistry, are poorly understood. The objective of this study was to identify determinants of surface wettability of titanium and establish the reliability and validity of the assessment. Wettability was evaluated as the contact angle of ddH2O. The age of titanium specimens significantly affected the contact angle, with acid-etched, microrough titanium surfaces becoming superhydrophilic immediately after surface processing, hydrophobic after 7 days, and hydrorepellent after 90 days. Similar age-related loss of hydrophilicity was also confirmed on sandblasted supra-micron rough surfaces so, regardless of surface topography, titanium surfaces eventually become hydrophobic or hydrorepellent with time. On age-standardized titanium, surface roughness increased the contact angle and hydrophobicity. UV treatment of titanium regenerated the superhydrophilicity regardless of age or surface roughness, with rougher surfaces becoming more superhydrophilic than machined surfaces after UV treatment. Conditioning titanium surfaces by autoclaving increased the hydrophobicity of already-hydrophobic surfaces, whereas conditioning with 70% alcohol and hydrating with water or saline attenuated pre-existing hydrophobicity. Conversely, when titanium surfaces were superhydrophilic like UV-treated ones, autoclaving and alcohol cleaning turned the surfaces hydrorepellent and hydrophobic, respectively. UV treatment recovered hydrophilicity without exception. In conclusion, surface roughness accentuates existing wettability and can either increase or decrease the contact angle. Titanium must be age-standardized when evaluating surface wettability. Surface conditioning techniques significantly but unpredictably affect existing wettability. These implied that titanium wettability is significantly influenced by the hydrocarbon pellicle and other contaminants inevitably accumulated. UV treatment may be an effective strategy to standardize wettability by making all titanium surfaces superhydrophilic, thereby allowing the characterization of individual surface topography and chemistry parameters in future studies.

Abstract Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed. Graphical Abstract

Electrochemically anodized titanium-based implants with controlled titania nanotopography enables enhanced bioactivity. However, anodization optimizations have been restricted to polished flat Ti foils, while clinical implants are often micro-rough with curved geometry. To enable anodization optimization of Ti implants, we performed short-time anodizations (10 s–600 s) on implant relevant micro-rough Ti wires (D: 0.8 mm) and rods (D: 5 mm) to understand the nanostructure self-ordering. We also studied the influence of electrolyte aging (repeated use of an electrolyte to tune its chemical balance) on implant anodization. Results revealed a higher electric field around Ti in aged electrolytes promotes the vertical elongation of nanotubes/pores. In comparison, fresh electrolytes established a lower electric field that limited the tube/pore elongation and caused cracks on the anodic film after an extended anodization time. We report an efficient implant nano-engineering protocol (PBR value of 2.7–3.0) for Ti rods (mimicking dental implants/abutments) via tailored anodization parameters. Further, reduced anodization voltage is proposed for anodizing Ti wires (mimicking orthopaedic fracture pins) to minimize excessive TiO2 dissolution. The current study evaluated nanostructure self-ordering on clinically relevant curved/micro-rough Ti, towards an improved understanding of implant nano-engineering.

In nature, many natural porous tissues of animals or plants follow heterogeneous structures pattern. Including turtle back pattern, leaf veins, wood porous fiber and porous cancellous bone are classic heterogeneous structures. In order to better design bionic microenvironment porous bone implants, herein, a bionic porous structure based on Voronoi-Thiessen diagram to create heterogeneous topology microenvironment promoting bone regeneration were proposed. Porous structures with tunable heterogeneity were built and achieved by selective laser melting (SLM). The topology analysis revealed the introduce of heterogeneity brought wide pore size distribution and irregular topology. The mechanical and hydrodynamics properties were predesigned and simulated by finite element analysis (FEA). The heterogeneity hardly influenced the overall strength, stiffness and permeability but the irregular stress and fluid shear rate distribution in FEA results indicated fluctuating local stiffness and permeability. In vitro and in vivo experimental results indicated that Quasi-homogeneous structure had irregular topology mimicking that of the natural bone structure and semi-heterogenous structure shown better osteogenesis. It is found that the scaffold heterogeneous microenvironment factors play important roles for bone regeneration, and which is crucial for the development of new orthopedic implants.

Osteoporosis is a major challenge to oral implants, and this study focused on improving the osseointegration ability of titanium (Ti) implants in osteoporosis environment via surface modification, including doping of strontium ion and preparation of nanoscale surface feature. Our previous studies have shown that strontium (Sr) ions can enhance osteogenic activity. Therefore, we aimed to comprehensively evaluate the effect of hydrothermal treatment of Sr-doped titanium implant coating on bone-binding properties in the microenvironment of osteoporosis in this study. We fabricated Sr-doped nanocoating (AHT-Sr) onto the surface of titanium implants via hydrothermal reaction. The rough Sr-doping had good biological functions and could apparently promote osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells (OVX-BMSCs). Most importantly, AHT-Sr significantly promoted bone integration in the osteoporosis environment. This study provides an effective approach to implant surface modification for better osseointegration in an osteoporotic environment.

Despite the high biocompatibility of titanium and its alloys, the need to remove titanium implants is increasingly being debated due to the potential for adverse effects associated with long-term retention. Therefore, new solutions are being sought to enhance the biocompatibility of titanium implants. One of them is to increase the thickness of the passive layer of the implant made of titanium dioxide. We were the first to evaluate the effect of hard-anodized (type II) Ti-6Al-4V alloy discs on the cytotoxicity, mitochondrial function, and redox balance of fibroblasts mitochondria compared to standard-anodized (type III) and non-anodized discs. The study used fibroblasts obtained from human gingival tissue. The test discs were applied to the bottom of 12-well plates. Cells were cultured for 24 h and 7, 14, and 21 days and mitochondria were isolated. We demonstrated the occurrence of oxidative stress in the mitochondria of fibroblasts of all tested groups, regardless of the presence and type of anodization. Type II anodization prevented changes in complex II activity (vs. control). The lowest degree of citrate synthase inhibition occurred in mitochondria exposed to titanium discs with type II anodization. In the last phase of culture, the presence of type II anodization reduced the degree of cytochrome c oxidase inhibition compared to the other tests groups and the control group, and prevented apoptosis. Throughout the experiment, the release of titanium, aluminium, and vanadium ions from titanium discs with a hard-anodized passive layer was higher than from the other titanium discs, but decreased with time. The obtained results proved the existence of dysfunction and redox imbalance in the mitochondria of fibroblasts exposed to hard-anodized titanium discs, suggesting the need to search for new materials perhaps biodegradable in tissues of the human body.

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.

Artificial prostheses for joint replacement are indispensable in orthopedic surgery. Unfortunately, the implanted surface is attractive to not only host cells but also bacteria. To enable better osteointegration, a mechanically stable porous structure was created on a titanium surface using laser treatment and metallic silver particles were embedded in a hydrophilic titanium oxide layer on top. The laser structuring resulted in unique amphora-shaped pores. Due to their hydrophilic surface conditions and capillary forces, the pores can be loaded preoperative with the antibiotic of choice/need, such as gentamicin. Cytotoxicity and differentiation assays with primary human osteoblast-like cells revealed no negative effect of the surface modification with or without gentamicin loading. An in vivo biocompatibility study showed significantly enhanced osteointegration as measured by push-out testing and histomorphometry 56 days after the implantation of the K-wires into rat femora. Using a S. aureus infection model, the porous, silver-coated K-wires slightly reduced the signs of bone destruction, while the wires were still colonized after 28 days. Loading the amphora-shaped pores with gentamicin significantly reduced the histopathological signs of bone destruction and no bacteria were detected on the wires. Taken together, this novel surface modification can be applied to new or established orthopedic implants. It enables preoperative loading with the antibiotic of choice/need without further equipment or post-coating, and supports osteointegration without a negative effect of the released dug, such as gentamicin.

Aim: The aim of this study was to investigate the combined effect of the lateral-compression of host-bone (undersized-osteotomy-preparation) and axial-compression of host-bone (not drilling the full length of the implant) on the primary-implant-stability and the host-bone-architecture. Materials and Methods: In this experimental-study, 44 dental implants (diameter-4.2 mm; length-10 mm; Dyna®) were installed in the femoral-condyles of four cadaver-goats using four different surgical approaches (11 implant/surgical approach; n = 11). Approach-1: Standard preparation according to the manufacturer's guidelines. The bone-cavity was prepared up to 10 mm in depth and 4 mm in diameter. Approach-2: Preparation up to 8 mm in depth and 4 mm in diameter. Approach-3: Preparation up to 10 mm in depth. Approach-4: The bone-cavity was prepared up to 8 mm in depth and 3.6 mm in diameter. Insertion torque (n = 11), removal torque (n = 7) and % bone-implant contact (n = 4) measurements were recorded. Bone architecture was assessed by micro-computer tomography and histological analysis (n = 4). Results: For approaches 2, 3, and 4 (P

Titanium-based dental implants have been highly optimized to enhance osseointegration, but little attention has been given to the soft tissue-implant interface, despite being a major contributor to long term implant stability. This is strongly linked to a lack of model systems that enable the reliable evaluation of soft tissue-implant interactions. Current in vitro platforms to assess these interactions are very simplistic, thus suffering from limited biological relevance and sensitivity to varying implant surface properties. The aim of this study was to investigate how blood-implant interactions affect downstream responses of different soft tissue cells to implants in vitro, thus taking into account not only the early events of blood coagulation upon implantation, but also the multicellular nature of soft tissue. For this, three surfaces (smooth and hydrophobic; rough and hydrophobic; rough and hydrophilic with nanostructures), which reflect a wide range of implant surface properties, were used to study blood-material interactions as well as cell-material interactions in the presence and absence of blood. Rough surfaces stimulated denser fibrin network formation compared to smooth surfaces and hydrophilicity accelerated the rate of blood coagulation compared to hydrophobic surfaces. In the absence of blood, smooth surfaces supported enhanced attachment of human gingival fibroblasts and keratinocytes, but limited changes in gene expression and cytokine production were observed between surfaces. In the presence of blood, rough surfaces supported enhanced fibroblast attachment and stimulated a stronger anti-inflammatory response from macrophage-like cells than smooth surfaces, but only smooth surfaces were capable of supporting long-term keratinocyte attachment and formation of a layer of epithelial cells. These findings indicate that surface properties not only govern blood-implant interactions, but that this can in turn also significantly modulate subsequent soft tissue cell-implant interactions.

Abstract Background Calcium (Ca) is a well-known element in bone metabolism and blood coagulation. Here, we investigate the link between the protein adsorption pattern and the in vivo responses of surfaces modified with calcium ions (Ca-ion) as compared to standard titanium implant surfaces (control). We used LC–MS/MS to identify the proteins adhered to the surfaces after incubation with human serum and performed bilateral surgeries in the medial section of the femoral condyles of 18 New Zealand white rabbits to test osseointegration at 2 and 8 weeks post-implantation (n=9). Results Ca-ion surfaces adsorbed 181.42 times more FA10 and 3.85 times less FA12 (p

Objective: The present work was aimed to evaluate the effect of valproic acid (VPA)，Parathyroid hormone (1–34) (PTH)+VPA on Ti rods osseointegration in ovariectomized rats and further investigation of the possible mechanism. Methods: The MC3T3-E1 cells were co-cultured with VPA，PTH ​+ ​VPA and induced to osteogenesis, and the cell viability，mineralization ability were observed by MTT and ALP staining，Alizarin Red staining and Western blotting. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group OVX and VPA，PTH ​+ ​VPA, and all the rats received Ti implants and animals belong to group VPA，PTH ​+ ​VPA received valproic acid (300 ​mg/day), valproic acid (300 ​mg/day) plus Parathyroid hormone (1–34) every 3 days (60 ​μg/kg), respectively, treatment until death at 12 weeks. Micro-CT, histology, biomechanical testing, bone metabolism index and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. Results: Results shown that VPA decreased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed combined application of systemic VPA showed harmful effects than OVX group on bone formation in osteopenia rats, with the worse effects on CTX-1, P1NP and microarchitecture as well as biomechanical parameters by down-regulated gene expression of Runx2, OCN, Smad1, BMP-2 and OPG, while up-regulated RANKL. However, after PTH treatment, the above indicators were significantly improved. Conclusions: The present study suggests that systemic use of VPA may bring harm to the stability of titanium implants in osteoporosis, PTH can reverse the negative effect of VPA on the osseointegration of titanium rods in ovariectomized rats. Translational potential of this article: According to our research, when patients with epilepsy have osteoporotic fractures, after joint replacement or internal fixation, continue to use sodium valproate for anti-epileptic therapy, the possibility of postoperative loosening increases, again on the basis of It can be reversed with the anti-osteoporosis drug parathyroid hormone (1-34).

Previously, functional coatings on 3D-printed titanium implants were developed to improve their biointegration by separately incorporating Ga and Ag on the biomaterial surface. Now, a thermochemical treatment modification is proposed to study the effect of their simultaneous incorporation. Different concentrations of AgNO3 and Ga(NO3)3 are evaluated, and the obtained surfaces are completely characterized. Ion release, cytotoxicity, and bioactivity studies complement the characterization. The provided antibacterial effect of the surfaces is analyzed, and cell response is assessed by the study of SaOS-2 cell adhesion, proliferation, and differentiation. The Ti surface doping is confirmed by the formation of Ga-containing Ca titanates and nanoparticles of metallic Ag within the titanate coating. The surfaces generated with all combinations of AgNO3 and Ga(NO3)3 concentrations show bioactivity. The bacterial assay confirms a strong bactericidal impact achieved by the effect of both Ga and Ag present on the surface, especially for Pseudomonas aeruginosa, one of the main pathogens involved in orthopedic implant failures. SaOS-2 cells adhere and proliferate on the Ga/Ag-doped Ti surfaces, and the presence of gallium favors cell differentiation. The dual effect of both metallic agents doping the titanium surface provides bioactivity while protecting the biomaterial from the most frequent pathogens in implantology.

Background context. Dental implants are designed to replace a missing tooth. Implant stability is vital to achieving osseointegration and successful implantation. Although there are many implants available on the market, there is room for improvement. Purpose. We describe a new dental implant with improved primary stability features. Study design. Lab bench test studies. Methods. We evaluated the new implant using static and flexion–compression fatigue tests with compression loads, 35 Ncm tightening torque, displacement control, 0.01 mm/s actuator movement speed, and 9–10 Hz load application frequency, obtaining a cyclic load diagram. We applied variable cyclic loadings of predetermined amplitude and recorded the number of cycles until failure. The test ended with implant failure (breakage or permanent deformation) or reaching five million cycles for each load. Results. Mean stiffness was 1151.13 ± 133.62 SD N/mm, mean elastic limit force 463.94 ± 75.03 SD N, and displacement 0.52 ± 0.04 SD mm, at failure force 663.21 ± 54.23 SD N and displacement 1.56 ± 0.18 SD mm, fatigue load limit 132.6 ± 10.4 N, and maximum bending moment 729.3 ± 69.43 mm/N. Conclusions. The implant fatigue limit is satisfactory for incisor and canine teeth and between the values for premolars and molars for healthy patients. The system exceeds five million cycles when subjected to a 132.60 N load, ensuring long-lasting life against loads below the fatigue limit.

Over the past couple of decades, additive manufacturing and the use of root-analogue-printed titanium dental implants have been developed. Not all powder particles are sintered into the final product during the additive manufacturing process. Reuse of the remaining powder could reduce the overall implant manufacturing cost. However, Ti-6Al-4V powder particles are affected by heat, mechanical factors, and oxidization during the powder bed fusion manufacturing process. Degradation of the powder may harm the final surface composition and decrease the biocompatibility and survival of the implant. The uncertainty of the recycled powder properties prevents implant fabrication facilities from reusing the powder. This study investigates the chemical composition of controlled, clean, and recycled titanium alloy powder and root-analogue implants (RAI) manufactured from these powders at three different depths. The change in titanium’s quantity, oxidization state, and chemical composition in powder and RAI implants have been demonstrated and analyzed. While not identical, the surface chemical composition of the recycled powder implant and the implant manufactured from unused powder are similar. The results also indicate the presence of TiO2 on all surfaces. Many studies confirmed that titanium dioxide on the implant’s surface correlates with better osteointegration, reduced bacterial infection, and increased corrosion resistance. Considering economic and environmental aspects, surface chemical composition comparison of clean and reused powder is crucial for the future manufacturing of cost-effective and biocompatible implants.

Treatment of implant-associated infection is becoming more challenging, especially when bacterial biofilms form on the surface of the implants. Developing multi-mechanism antibacterial methods to combat bacterial biofilm infections by the synergistic effects are superior to those based on single modality due to avoiding the adverse effects arising from the latter. In this work, TiO2 nanorod arrays in combination with irradiation with 808 near-infrared (NIR) light are proven to eradicate single specie biofilms by combining photothermal therapy, photodynamic therapy, and physical killing of bacteria. The TiO2 nanorod arrays possess efficient photothermal conversion ability and produce a small amount of reactive oxygen species (ROS). Physiologically, the combined actions of hyperthermia, ROS, and puncturing by nanorods give rise to excellent antibacterial properties on titanium requiring irradiation for only 15 min as demonstrated by our experiments conducted in vitro and in vivo. More importantly, bone biofilm infection is successfully treated efficiently by the synergistic antibacterial effects and at the same time, the TiO2 nanorod arrays improve the new bone formation around implants. In this protocol, besides the biocompatible TiO2 nanorod arrays, an extra photosensitizer is not needed and no other ions would be released. Our findings reveal a rapid bacteria-killing method based on the multiple synergetic antibacterial modalities with high biosafety that can be implemented in vivo and obviate the need for a second operation. The concept and antibacterial system described here have large clinical potential in orthopedic and dental applications.

Abstract Background To explore the effects of topographical modification of titanium substrates at submicron level by oxalic acid treatment on bone quality and quantity around dental implants in rabbit tibiae. Methods A total of 60 blasted CP-grade IV titanium dental implants were used. Twenty-eight control implant surfaces were treated with a mixture of HCl/H2SO4, whereas 28 other test implant surfaces were treated with oxalic acid following HCl/H2SO4 treatment. Two randomly selected sets of control or test implants were placed in randomly selected proximal tibiae of 14 female Japanese white rabbits. Euthanasia was performed 4 and 8 weeks post-implant placement. Bone to implant contact (BIC), bone area fraction (BAF), ratios of mature and immature bone to total bone, and the amount and types of collagen fibers were evaluated quantitatively. Two control and two test implants were used to analyze surface characteristics. Results Treatment by oxalic acid significantly decreased Sa and increased Ra of test implant surfaces. BIC in test implants was increased without alteration of BAF and collagen contents at 4 and 8 weeks after implant placement when compared with control implants. The ratios of immature and mature bone to total bone differed significantly between groups at 4 weeks post-implantation. Treatment by oxalic acid increased type I collagen and decreased type III collagen in bone matrices around test implants when compared with control implants at 8 weeks after implant placement. The effects of topographical changes of implant surfaces induced by oxalic acid on BAF, mature bone, collagen contents, and type I collagen were significantly promoted with decreased immature bone formation and type III collagen in the later 4 weeks post-implantation. Conclusions Treatment of implant surfaces with oxalic acid rapidly increases osseointegration from the early stages after implantation. Moreover, submicron topographical changes of dental implants induced by oxalic acid improve bone quality based on bone maturation and increased production of type I collagen surrounding dental implants in the late stage after implant placement.

In the design of multifunctional orthopedic biomaterials, enhanced biological activities, reinforced mechanical property, improved hydrophilicity and osteo-compatibility are the essential criteria. For achieving these goals, here a bioactive multifunctional Ti6Al4V implant with nanowire structured surface topography is designed and fabricated using 3D printing technique. Selective laser melting (SLM) is applied to fabricate scaffold materials with diamond cellular structures to meet the requirements of load-bearing function of bone tissue. With the alkali treatment of sodium hydroxide, osteogenic layer of Na2Ti6O13 is generated on the porous Ti6Al4V, on which apatite is easily deposited and immobilized. Clusters of Na2Ti6O13 exhibits excellent hydrophilicity and surface roughness with precise control of alkali treatment time. Additionally, the compressive strength of the modified porous Ti6Al4V (121.2 MPa-84.5 MPa) decreases due to the corrosion of sodium hydroxide, while it can satisfy the basic mechanical requirement of cortical bone. The results prove that the surface-modified 3D printed porous Ti6Al4V possesses balanced mechanical strength and osteogenic function, promising for potential application in complex multifunctional bone defects.

Abstract Background The biofunctionalization of titanium implants for high osteogenic ability is a promising approach for the development of advanced implants to promote osseointegration, especially in compromised bone conditions. In this study, polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach with a chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolytes on microarc-oxidized (MAO) Ti surfaces via silane-glutaraldehyde coupling. Methods Dynamic contact angle and scanning electron microscopy measurements were conducted to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. The in vitro transfection efficiency and the cytotoxicity were investigated after seeding mesenchymal stem cells (MSCs) on the CS-antimiR-138/HA PEM-functionalized microporous Ti surface. The in vitro osteogenic differentiation of the MSCs and the in vivo osseointegration were also evaluated. Results The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles were distributed evenly across the MAO surface. The miRNA loading increased with increasing bilayer number. More importantly, a sustained miRNA release was obtained over a timeframe of approximately 2 weeks. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced the osteogenic differentiation of MSCs in terms of enhanced alkaline phosphatase, collagen production and extracellular matrix mineralization. Substantially enhanced in vivo osseointegration was observed in the rat model. Conclusions The findings demonstrated that the novel CS-antimiR-138/HA PEM-functionalized microporous Ti implant exhibited sustained release of CS-antimiR-138, and notably enhanced the in vitro osteogenic differentiation of MSCs and in vivo osseointegration. This novel miRNA-functionalized Ti implant may be used in the clinical setting to allow for more effective and robust osseointegration.

Peri-implantitis is a pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant connective tissue and progressive loss of supporting bone. In the treatment of peri-implantitis, a laser surgical technique is used. Lasers are a safe and gentle alternative to traditional dental tools. They allow oral surgeons and dentists to accomplish more complex tasks, reduce blood loss, decrease post-operative discomfort, reduce the chance of wound infection, achieve better wound healing and perform some procedures in close methods without access flap. The aim of the work was to determine the impact of laser surface treatment of titanium dental implants on its electrochemical behavior in artificial saliva at 37°C. The study used an Er,Cr:YSGG laser and diode lasers 810 nm and 980 nm for debridement of titanium implant surface. In the research, the thread on the surface of implant was scanned with the diode laser beam of energy 1, 1.25, 1.5 and 2 W, cw and Er, Cr YSGG: 1,5 and 2W, pulse 30Hz.

Abstract Titanium is commonly and successfully used in dental and orthopedic implants. However, patients still have to face the risk of implant failure due to various reasons, such as implant loosening or infection. The risk of implant loosening can be countered by optimizing the osteointegration capacity of implant materials. Implant surface modifications for structuring, roughening and biological activation in favor for osteogenic differentiation have been vastly studied. A key factor for a successful stable long‐term integration is the initial cellular response to the implant material. Hence, cell–material interactions, which are dependent on the surface parameters, need to be considered in the implant design. Therefore, this review starts with an introduction to the basics of cell–material interactions as well as common surface modification techniques. Afterwards, recent research on the impact of osteogenic processes in vitro and vivo provoked by various surface modifications is reviewed and discussed, in order to give an update on currently applied and developing implant modification techniques for enhancing osteointegration.

(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient’s fracture healing process. (2) Methods: In detail, osteogenic differentiation of several cell types was monitored under continuous or pulsatile electrical stimulation at 0.7 V AC/20 Hz for at least seven days on a titanium implant by electric cell-substrate impedance sensing (ECIS). For control, chemical induction of osteogenic differentiation was induced. (3) Results: The most significant challenge was to discriminate impedance changes caused by proliferation events from those initiated by osteogenic differentiation. This discrimination was achieved by remodeling the impedance parameter Alpha (α), which increases over time for pulsatile electrically stimulated stem cells. Boosted α-values were accompanied by an increased formation of actin stress fibers and a reduced expression of the focal adhesion kinase in the cell periphery; morphological alterations known to occur during osteogenesis. (4) Conclusions: This work provided the basis for developing an effective fracture therapy device, which can induce osteogenesis on the one hand, and would allow us to monitor the induction process on the other hand.

Reduced skeletal loading associated with many conditions, such as neuromuscular injuries, can lead to bone fragility and may threaten the success of implant therapy. Our group has developed a botulinum toxin A (botox) injection model to imitate disease-reduced skeletal loading and reported that botox dramatically impaired the bone formation and osseointegration of titanium implants. Semaphorin 3A (sema3A) is an osteoprotective factor that increases bone formation and inhibits bone resorption, indicating its potential therapeutic role in improving osseointegration in vivo. We first evaluated the sema3A effect on whole bone morphology following botox injections by delivering sema3A via injection. We then evaluated the sema3A effect on the osseointegration of titanium implants with two different surface topographies by delivering sema3A to cortical bone defect sites prepared for implant insertion and above the implants after insertion using a copper-free click hydrogel that polymerizes rapidly in situ. Implants had hydrophobic smooth surfaces (PT) or multiscale biomimetic micro/nano topography (SLAnano). Sema3A rescued the botox-impaired bone formation. Furthermore, biomimetic Ti implants improved the bone-to-implant contact (BIC) and mechanical properties of the integrated bone in the botox-treated rats, which sema3A enhanced. This study demonstrated the value of biomimetic approaches combining multiscale topography and biologics in improving the clinical outcomes of implant therapy.

MOFs (Metal–Organic Frameworks) are so-called coordination polymers with a porous crystalline structure. In this review, the main emphasis was placed on these compounds’ use in modifying titanium implants. The article describes what MOFs are, gives examples of ligands used in the synthesis of MOFs, and describes a subgroup of these materials, i.e., Zeolitic imidazolate frameworks. The article also lists the basic biomedical applications of these compounds. This review shows the significant impact of titanium surface modification with Metal–Organic Frameworks. These modifications make it possible to obtain layers with antibacterial properties, better corrosion resistance, increasing cell proliferation, faster bone growth in vivo, and much more. The presented work shows that the modification of titanium with MOFs is a very promising method of improving their properties. We hope that the prepared review will help research groups from around the world in the preparation of implants modified with Metal–Organic Frameworks with enhanced properties and utility applications.

Titanium and its alloys are dominant material for orthopedic/dental implants due to their stable chemical properties and good biocompatibility. However, aseptic loosening and peri-implant infection remain problems that may lead to implant removal eventually. The ideal orthopedic implant should possess both osteogenic and antibacterial properties and do proper assistance to in situ inflammatory cells for anti-microbe and tissue repair. Recent advances in surface modification have provided various strategies to procure the harmonious relationship between implant and its microenvironment. In this review, we provide an overview of the latest strategies to endow titanium implants with bio-function and anti-infection properties. We state the methods they use to preparing these efficient surfaces and offer further insight into the interaction between these devices and the local biological environment. Finally, we discuss the unmet needs and current challenges in the development of ideal materials for bone implantation.