Percutaneous Titanium Implants Research Articles

Titanium Surfaces Modified with Graphene Oxide/Gelatin Composite Coatings for Enhanced Antibacterial Properties and Biological Activities

Titanium alloys have been widely used in orthopedic implants due to their excellent physicochemical properties and good biocompatibility. However, in practice, titanium implants may fail to integrate or develop an implant-centered infection. Because of its excellent mechanical properties, bone integrability, biocompatibility, antibacterial properties, and so on, graphene oxide is increasingly being used in the preparation of composite biomaterials. The percutaneous titanium implants are used as the research object in this project. To solve the integration of implant and tissue, a graphene oxide/gelatin (GO/gel) composite coating was used to optimize the implant surface. Bacterial and cell experiments were used to investigate the antimicrobial activity, biocompatibility, and regulation of macrophage polarization of GO/gel-modified titanium. According to our findings, GO/gel-modified titanium has a good bacteriostatic effect against Staphylococcus aureus. On the modified surface, L929 cells proliferated well and showed no cytotoxicity. Simultaneously, the GO/gel-modified titanium surface could inhibit macrophage adhesion and spread in the early stage of culture and showed a more obvious inflammatory decline in the late stage of culture. These findings implied that GO/gel-modified titanium is advantageous for resistant bacteria and tissue remolding.

How surface coatings on titanium implants affect keratinized tissue: A systematic review.

Apart from osseointegration, the stability and long‐term survival of percutaneous titanium implants is also strongly dependent on a qualitative soft‐tissue integration in the transcutaneous region. A firm connective tissue seal is needed to minimize soft‐tissue dehiscence and epithelial downgrowth. It is well‐known that the implant surface plays a key role in controlling the biological response of the surrounding keratinized tissue and several coating systems have been suggested to enhance the soft‐tissue cell interactions. Although some promising results have been obtained in vitro, their clinical significance can be debated. Therefore, the purpose of this systematic review is to gain more insight into the effect of such coatings on the interface formed with keratinized soft‐tissue in vivo. A comprehensive search was undertaken in March 2021. Relevant electronic databases were consulted to identify appropriate studies using a set of search strings. In total, 12 out of 4971 publications were included in this review. The reported coating systems were assigned to several subgroups according to their characteristics: metallic, ceramic and composite. Notwithstanding the differences in study characteristics (animal model, implantation period, reported outcomes), it was noticed that several coatings improve the soft‐tissue integration as compared to pristine titanium. Porous titanium coatings having only limited pore sizes (<250 μm) do not support dermal fibroblast tissue attachment. Yet, larger pores (>700 μm) allow extensive vascularized soft‐tissue infiltration, thereby supporting cell attachment. Nanostructured ceramic coatings are found to reduce the inflammatory response in favor of the formation of cell adhesive structures, that is, hemidesmosomes. Biomolecule coatings seem of particular interest to stimulate the soft‐tissue behavior provided that a durable fixation to the implant surface can be ensured. In this respect, fibroblast growth factor‐2 entrapped in a biomimetic apatite coating instigates a close to natural soft‐tissue attachment with epidermal collagen fibers attaching almost perpendicular to the implant surface. However, several studies had limitations with respect to coating characterization and detailed soft‐tissue analysis, small sample size and short implantation periods. To date, robust and long‐term in vivo studies are still lacking. Further investigation is required before a clear consensus on the optimal coating system allowing enhancing the soft‐tissue seal around percutaneous titanium implants can be reached.

Enzymatically-degradable hydrogel coatings on titanium for bacterial infection inhibition and enhanced soft tissue compatibility via a self-adaptive strategy

Ideal percutaneous titanium implants request both antibacterial ability and soft tissue compatibility. ZnO structure constructed on titanium has been widely proved to be helpful to combat pathogen contamination, but the biosafety of ZnO is always questioned. How to maintain the remarkable antibacterial ability of ZnO and efficiently reduce the corresponding toxicity is still challenging. Herein, a hybrid hydrogel coating was constructed on the fabricated ZnO structure of titanium, and the coating was proved to be enzymatically-degradable when bacteria exist. Then the antibacterial activity of ZnO was presented. When under the normal condition (no bacteria), the hydrogel coating was stable and tightly adhered to titanium. The toxicity of ZnO was reduced, and the viability of fibroblasts was largely improved. More importantly, the hydrogel coating provided a good buffer zone for cell ingrowth and soft tissue integration. The curbed Zn ion release was also proved to be useful to regulate fibroblast responses such as the expression of CTGF and COL-I. These results were also validated by in vivo studies. Therefore, this study proposed a valid self-adaptive strategy for ZnO improvement. Under different conditions, the sample could present different functions, and both the antibacterial ability and soft tissue compatibility were finely preserved.

The IPS-scale: A new soft tissue assessment scale for percutaneous and transcutaneous implants for bone conduction devices.

Percutaneous titanium implants for bone conduction devices (BCDs) have offered, since 1977, a solution for patients with hearing loss not treatable by conventional hearing aids, such as patients with chronic ear infections or microtia and/or ear canal atresia. Percutaneous implants imply a continuous breach in the mechanical defensive barrier of the skin. To compensate for this breach, immunological mechanisms in the subcutaneous tissue surrounding the implant become more active. This article is protected by copyright. All rights reserved.

A decomposable silica-based antibacterial coating for percutaneous titanium implant.

Although percutaneous titanium implants have become one of the best choices as retainers in the facial defects, peri-implantitis still occurs at a significant rate. This unwanted complication occurs due to adhesion of bacteria and subsequent biofilm formation. To solve this problem, we have developed a novel antibiotic nanodelivery system based on self-decomposable silica nanoparticles. In this study, silica-gentamycin (SG) nanoparticles were successfully fabricated using an innovative one-pot solution. The nanoparticles were incorporated within a gelatin matrix and cross-linked on microarc-oxidized titanium. To characterize the SG nanoparticles, their particle size, zeta potential, surface morphology, in vitro drug release, and decomposition process were sequentially evaluated. The antibacterial properties against the gram-positive Staphylococcus aureus, including bacterial viability, antibacterial rate, and bacteria morphology, were analyzed using SG-loaded titanium specimens. Any possible influence of released gentamycin on the viability of human fibroblasts, which are the main component of soft tissues, was investigated. SG nanoparticles from the antibacterial titanium coating continuously released gentamycin and inhibited S. aureus growth. In vitro investigation showed that the obtained nanodelivery system has good biocompatibility. Therefore, this design can be further investigated as a method to prevent infection around percutaneous implants.

The clinical, radiological, microbiological, and molecular profile of the skin-penetration site of transfemoral amputees treated with bone-anchored prostheses.

The breach of the skin barrier is a critical issue associated with the treatment of individuals with transfemoral amputation (TFA) using osseointegrated, percutaneous titanium implants. Thirty TFA patients scheduled for abutment exchange or removal were consecutively enrolled. The aims were to determine the macroscopic skin signs, the presence of bacteria and the gene expression in abutment‐adherent cells and to conduct correlative and comparative analyses between the different parameters. Redness and a granulation ring were present in 47% of the patients. Bacteria were detected in 27/30 patients, commonly in the bone canal. Staphylococcus aureus, coagulase‐negative staphylococci, streptococci, and Enterococcus faecalis were the most common. A positive correlation was found between TNF‐α expression and the detection of S. aureus. Staphylococcus aureus together with other bacterial species revealed a positive relationship with MMP‐8 expression. A negative correlation was demonstrated between the length of the residual femur bone and the detection of a granulation ring and E. faecalis. A positive correlation was revealed between fixture loosening and pain and the radiological detection of endosteal bone resorption. Fixture loosening was also correlated with the reduced expression of interleukin‐10 and osteocalcin. It is concluded that several relationships exist between clinical, radiological, microbiological, and molecular assessments of the percutaneous area of TFAs. Further long term studies on larger patient cohorts are required to determine the precise cause‐effect relationships and unravel the role of host‐bacteria interactions in the skin, bone canal and on the abutment for the longevity of percutaneous implants as treatment of TFA. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 578–589, 2017.

A ten-year review of soft tissue reactions around percutaneous titanium implants for auricular prosthesis.

Soft tissue reactions around abutments are the most common complications of percutaneous osseointegrated implants. The main objective of this study was to review our series of osseointegrated implants, evaluate the degree of adverse skin reactions around the auricular abutments, and compare with skin reactions in the pediatric bone-anchored hearing aid (BAHA) population. The reason for comparing these two groups was the difference in abutment shape and position in skin with different characteristics. A retrospective case analysis of 131 patient notes. We retrospectively studied 131 pediatric and adult patients who underwent an osseointegrated auricular prosthesis over a 10-year period (1997-2007). There were 95 adults and 36 children who had been implanted and fitted with an auricular prosthesis during the 10-year study period. All patients were followed up postoperatively for a 2-year minimum up to a 14-year maximum follow-up. Thirteen (13/36, 36%) children and seven adults (7/95, 7%) had a skin reaction around the ear prosthesis. The literature review has supported our study results and has shown that children have higher skin reactions in both BAHA and auricular prostheses than adults. Adverse skin reactions in the pediatric auricular group were significantly lower that the pediatric BAHA group. 4

Assessment of More Than 1,000 Implanted Percutaneous Bone Conduction Devices

This study assesses soft tissue reactions and implant stability of 1,132 percutaneous titanium implants (970 patients) for bone conduction devices (BCDs). In addition, it examines BCD usage and comparisons between different patient groups. Retrospective survey. Mean follow-up time of 4.6 years. Tertiary care referral center. The surveyed cohort was divided into 3 different age groups (children, adults, and the elderly). In addition, 4 groups with variable loading times (i.e., the time between placement of the implant and loading the BCD sound processor) were identified as well as a subgroup of patients with mental retardation. Soft tissue reactions around the percutaneous implants as classified by the Holgers grading system, implant failure, and revision surgery rates. In 95.5% of the 7,415 observations of 1,132 implants, there were no adverse soft tissue reactions. Implant loss was 8.3%. Significantly more soft tissue reactions and implant failures were observed in children compared with adults and the elderly (p < 0.05). Implant survival was lower in patients with mental retardation compared with patients without mental retardation (p = 0.001). The loading time did not influence the occurrence of soft tissue reactions and implant survival rates. Children and patients with mental retardation are the most vulnerable to soft tissue reactions and implant losses. Additional and more frequent care needs to be given during outpatient consultations. Because loading as early as 3 to 5 weeks did not negatively affect skin reactions or implant survival, full BCD installation can occur earlier without risk.

Feasibility of detecting trabecular bone around percutaneous titanium implants in rabbits by in vivo microfocus computed tomography

The goal of this study was to examine the feasibility of in vivo imaging of trabecular bone around titanium implants by means of microfocus computed tomography (micro-CT) and the use of rabbits for this purpose. Ten male rabbits type Hollander, received a titanium implant (1.7 mm diameter and 10 mm length) in the trabecular bone of the left tibia. Seven weeks later a micro-CT scan was taken. Four rabbits were used to monitor potential harmful effects from X-ray absorption until 4 weeks after scanning. A second group of six rabbits was used for testing the hypothesis that a good correlation exists between in vivo micro-CT images and histological images of trabecular bone around titanium implants. The six rabbits were scanned and sacrificed immediately. The tibias were extracted and submitted to standard histological procedures. This resulted in a total of 12 histological sections and their corresponding 12 micro-CT images. Bone area measurements were performed at the left and right side of the implant in three regions: 0-500, 500-1000 and 1000-1500 microm distance from the implant interface. Intra-class correlations (ICC) were calculated between both techniques. The four rabbits did not show any sign of radiodermatitis 4 weeks after scanning. In the micro-CT images of the group of six rabbits, trabeculae are visible, but not well defined, due to the presence of noise in the image. The ICC for the right implant side were 0.44 for zone 0-500 microm, 0.48 for zone 500-1000 microm and 0.40 for zone 1000-1500 microm. The ICC for the left implant side could not be calculated. A low agreement was found between the bone measurements from histology and in vivo micro-CT images. The use of the in vivo micro-CT for trabecular bone imaging around metallic implants should be restricted to track tendencies in follow-up studies.

Positive effect of early loading on implant stability in the bi‐cortical guinea‐pig model

Loading, early after implant placement, has gained rapid interest in dentistry. Primary implant stability, as e.g. defined by resonance frequency instrumentation, has been isolated as a predicator when immediate and early implant loading is applied. The aim of this study was to investigate the effect of early (after 7 days) mechanical loading on the establishment of osseointegration by means of resonance frequency analysis (RFA). Percutaneous titanium implants were installed in both tibiae of 10 guinea-pigs. One week after implant installation, one implant (test) was loaded daily for 6 weeks, while the contra-lateral served as the unloaded one (control). A sinusoidally varying bending moment was applied at a frequency of 3 Hz and a force amplitude of 5 N, for 1800 cycli. Resonance frequency was measured at implant installation and from then on weekly using the RFA-device (Osstell). Contrary to control implants, that showed a decrease in stability 1 week after installation, reaching a minimum at 3 weeks (-200 Hz), test implants showed a progressive increase in stability over time. After 6 weeks, the mean resonance frequency of test and control implants reached the same values. As confirmed by recent literature, early loading does not have to endanger the establishment of osseointegration of titanium implants. On the contrary, controlled loading is beneficial to maintain the implant stability during the early critical healing period as determined by RFA-measurements.

Craniofacial titanium implants and chronic pain: histologic findings.

To determine whether histologic features or histomorphometric outcomes of retrieved craniofacial percutaneous titanium implants could be found that could be related to chronic pain at the implant site in the temporal bone. Histologic investigation and histomorphometric measurements of seven retrieved titanium implants with surrounding bone tissue. Tertiairy referral center. Four patients who had previously received percutaneous titanium implants for auricular prostheses (1 patient) and a bone anchored hearing aid (three patients) had chronic pain at the implant site despite conservative treatment. The implants were retrieved, sectioned, and ground for qualitative light microscopic inspection and quantitative measurement of the bone-to-metal contact and bone area. Qualitative inspection of the sections of the implants demonstrated soft tissue zones at the interface, especially under the flange. Inflammatory cells were seen in the interface in all seven implants. In the implants with good bone-to-metal contact, the percentage of bone-to-metal contact rose with time. In the two implants with poor bone-to-metal contact, the soft tissue zones were more extensive, and slightly more skin reactions were observed than in the other implants while still in situ. A clear explanation for the chronic pain is not at hand. The only common histologic findings were the inflammatory cells present in the interface, but with varying density, and the presence of soft tissue zones. A variety of bone-to-metal was found among the retrieved implants.

Immunohistochemical Study Of Clinical Skin-Penetrating Titanium Implants For Orthopaedic Prostheses Compared With Implants In The Craniofacial Area

The technique of using osseointegrated bone-anchored percutaneous titanium implants in the rehabilitation of patients with amputated limbs has recently been introduced at the Brånemark Osseointegration Centre in Göteborg. The new method is based on an implantation technique that is well-established for anchorage of bone-conductive hearing aids and craniofacial prostheses. The soft tissues around skin-penetrating titanium implants used to anchor orthopaedic prostheses were evaluated histochemically using quantitative analyses. The implants had been in clinical use for between 6 to 24 months. The number of inflammatory cells was higher in the area close to the interface than in the area distant from the skin-penetrating site, and higher than in the corresponding controls. The current data was also compared with corresponding data from tissue around skin-penetrating craniofacial implants. The number of inflammatory cells was lower in the orthopaedic samples than in the craniofacial specimens. We conclude that skin-penetration of orthopaedic implants is as safe as when titanium implants are used for craniofacial rehabilitation, which is a clinically well-established procedure.

Cell surface characteristics of microbiological isolates from human percutaneous titanium implants in the head and neck.

Percutaneous implants are commonly associated with several problems, and different failure modes have been described. Infections constitute one serious complication which may lead to the removal of the implant. In contrast to infections around polymer implants, infections around skin-penetrating titanium implants anchored in the temporal bone are often cured by local treatment. Coagulase-negative staphylococci are the most common etiological agents in infections related to polymers whereas Staphylococcus aureus is considered as the main pathogen in infections around metallic implants. Microbial adhesion is a prerequisite for an infection. In the present study, the cell surface of microbes isolated from the skin around skin-penetrating titanium implants, with and without signs of infection, was characterized with respect to expression of cell surface hydrophobicity and to binding of immobilized fibronectin, vitronectin and collagen type 1 which could mediate adhesion. Expression of protein binding was similar in strains isolated from the two groups. No strain expressed a hydrophobic cell surface as determined by two-phase separation, and we conclude that the microenvironment around a titanium implant promotes expression of a hydrophilic rather than a hydrophobic cell surface which in turn makes many infections around a titanium implant curable by local treatment.

Sensitivity to bone-conducted sound: excitation of the mastoid vs the teeth.

The sensitivity of nine subjects to bone-conducted sound was measured at three positions: osseointegrated percutaneous titanium implants in the temporal bone, the skin-covered mastoid and the teeth. Voltage levels supplied to a bone-anchored hearing aid (BAHA) transducer and to an Oticon bone-transducer were measured and the thresholds obtained at the three positions were compared. Using the mechanical impedance of the teeth, the parameters of a first order model for the vibration transmission through the teeth was calculated. Also, the equivalent force thresholds were calculated from the voltage threshold levels. The sensitivity to bone-conducted sound, for both voltage and force thresholds, conformed fairly well at the three positions for frequencies below 1 kHz; however, above 1 kHz, bone-conducted sound applied at the titanium implant becomes more sensitive than at the two other positions investigated. It was concluded that the teeth can be used for the application of bone-conducted sound, in particular for pre-operative assessment of a BAHA and to facilitate service and quality control of such a hearing device.

Immunohistochemical study of the soft tissue around long-term skinpenetrating titanium implants

Bone-anchored percutaneous titanium implants have become a well-established clinical procedure with a low incidence of adverse reactions. However, passage through the skin leads to a breach in the barrier to exogenous pathogens. In the present study, monoclonal antibodies were used to investigate the distribution of lymphocyte subpopulations in the soft tissue around such implants. Eight biopsies from patients with clinically irritated skin, five from non-irritated and eight from skin without skinpenetrating implants were analysed. The number of immune cells was increased in the group of patients with skin penetration compared with patients without skin penetration. In the group with clinical irritation there was an increased level of B-lymphocytes compared with those without irritation. The data suggest that there is an immunological compensation for the mechanical loss in barrier function at these implants and that an antibody-mediated response is present at clinical signs of irritation.

Electron microscopic observations on the soft tissue around clinical long-term percutaneous titanium implants

Percutaneous implants of titanium ad modum Brånemark have been in clinical use in the head and neck since 1977. The incidence of adverse reactions is low. In a previous study we have demonstrated the presence of inflammatory cells in the subcutaneous connective tissue surrounding the implants and this increased exposure to exogenous antigens was suggested to be compensated by a barrier of inflammatory cells in the soft tissue. To get further information on the nature of the tissue-implant contact, in the present study we have examined the structure of the tissue close to the percutaneous implant using transmission electron microscopy. We could not see evidence for an attachment of the epithelium to the implant, nor between the connective tissue and the implant. Retrieved implants were also analysed and we did not find any organized tissue remaining on the implants.

Experience with Percutaneous Titanium Implants in the Head and Neck: A Clinical and Histological Study

Percutaneous implants have been associated with numerous problems. However, by using skin-penetrating, bone-anchored titanium implants, developed by Professor Brånemark at the Department of Anatomy, University of Göteborg, good long-term results have been observed. These implants have been in clinical use for anchorage of bone-conducting hearing aids and facial prostheses since 1977 and 1979, respectively. The total number of implants is approximately 700. Less than 4% of the observations have shown significant irritation. Biopsies from 33 patients were collected for histological studies. In the irritated skin there was an increased number of inflammatory cells, mainly polymorphonuclear cells, B-cells, and plasma cells but not T-cells. This suggests a response directed against exogenous agents rather than an allergic reaction against the implant per se.

Percutaneous healing of clinical tympanic membrane implants.

Percutaneous healing is plagued by materials compatibility problems, epidermal reactions, and mechanical factors. To our knowledge, no studies have evaluated the effects of one of these factors while controlling the others. The tympanic membrane is an implant site where mechanical factors are minimized. Titanium has been shown to be a very histocompatible material, although no reports of the histology of percutaneous titanium implants exist. This study reports on aspects of the epidermal and connective tissue healing around titanium tympanic membrane implants that were explanted from human subjects. The lack of inflammation and the direct adherence of the tissues substantiate the materials compatibility and the absence of mechanical factors. Tissue healing patterns appear to reach an equilibrium which is suitable for the long-term existence of the percutaneous device. This implant location provides a suitable model for studying the tissue reactions to various percutaneous materials.