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The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the “device”/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth's enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant – as a model percutaneous device – placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists. info:eu-repo/semantics/publishedVersion

An ideal intraosseous transcutaneous implant should form a tight seal with soft tissue, besides a requirement of osseointegration at the bone-fixed position. Si substituted hydroxyapatite (Si-HA) nanorods releasing Si ion and simulating nanotopography of natural tissue were designed on Ti to enhance fibroblast response in vitro and biosealing with soft tissue in vivo. Si-HA nanorods were fabricated by alkali-heat treatment followed with hydrothermal treatment. The hydrothermal formation mechanism of Si-HA nanorods was explored. The surface characteristic of Si-HA nanorods was compared with pure HA nanorods. Fibroblast behaviors in vitro and skin response in vivo on different surfaces were also evaluated. The obtained results show that the substitution of Si did not significantly alter the phase component, morphology, roughness and wettability of HA, but additional Si and more Ca were released from Si-HA into medium. Comparing to pure HA nanrods and Ti substrate, Si-HA nanrods enhanced cell behaviors including proliferation, fibrotic phenotype and collagen secretion in vitro, and reduced epithelial down growth in vivo. The enhanced cell response and biosealing should be due to the releasing of Ca, Si and nanotopography of Si-HA nanorods. Si-HA nanorods can be a potential coating to accelerate skin integration for percutaneous implants in clinic., Graphical abstract Due to the ion releasing and nanotopography, Si-HA nanorods enhanced fibroblast response and biosealing of Ti implant.Image 1, Highlights • Si substituted HA nanorods are prepared by alkali and hydrothermal treatment. • Si-HA nanorods enhance adhesion, proliferation and functional expression of fibroblasts. • Ion release and nanotopography of Si-HA nanorods contribute to good biosealing of Ti.

Percutaneous devices suffer from imperfect sealing of the epidermis-implant interphase, the so-called three-phase junction, allowing invading pathogens access to colonize the implant at the tissue interface and potentially cause an infection. In skin, one of the key components of the epidermal barrier is the E-cadherin mediated adherens junctions. We investigated the response of a human keratinocyte cell line (HaCaT) to a titanium substrate functionalized with the extracellular domain of E-cadherin fused to an Fc domain. Polydopamine was used as a binding layer to attach the E-cadherin to the titanium surface in two ways: 1) by attaching protein A to the polydopamine followed by E-cadherin (aligned orientation) or 2) by direct attachment of the E-cadherin to the polydopamine (random orientation). The E-cadherin surface functionalization was stable for up to two months as determined by ELISA. HaCaTs did attach to the surface irrespective of E-cadherin orientation. However, decreased cell proliferation and increased cell size was observed for cells on aligned E-cadherin surfaces as compared to a positive control coated with fibronectin. The adhesion of the HaCaTs to the surface with aligned E-cadherin was more sensitive to cell media Ca 2+ depletion. A confluent layer of HaCaTs was almost immobile on the aligned E-cadherin surface, as compared to a surface coated with fibronectin, whereas cell migration was also observed on randomly oriented E-cadherin. The E-cadherin coated surfaces were non-adhesive for primary human dermal fibroblasts, a cell type not expressing E-cadherin. These results show the potential of using E-cadherin as a functional surface at the three-phase junction of percutaneous implants to ensure epidermal attachment, limit epidermal downgrowth and prevent fibroblast adhesion.

Percutaneous implants are widely used in clinical practice. However, infection is the main clinical problem of percutaneous implants. Titanium dioxide nanotubes are suitable for forming coatings on complex surfaces such as implants. HHC-36, a cationic antimicrobial peptide, has been identified to have a strong broad-spectrum antibacterial effect. In the present study, we use poly D,L-lactic acid (PDLLA) and poly lactic-co-glycolic acid (PLGA) coating to build HHC-36 sustained-release system on the surface of titanium dioxide nanotubes. The titanium specimens were anodized coated with HHC-36-PDLLA/PLGA. The morphology and surface elemental distribution of the specimens were evaluated. Besides, results in the present study demonstrated that with antibacterial peptide HHC-36 sustained-release coating, titanium dioxide nanotubes maintain effective drug release for 15 days in vitro, and show significant antibacterial activity. The proliferation of Staphylococcus aureus can be effectively inhibited by PDLLA/PLGA-HHC-36 coated titanium dioxide nanotube. In addition, PDLLA-HHC-36 and PLGA-HHC-36 coating was demonstrated to be biocompatible and antibacterial in vivo. These findings demonstrated that HHC-36 coated titanium nanotube could improve antibacterial potential of percutaneous implants, and indicated a novel and efficient strategy in preventing bacterial infection of percutaneous implants.

Percutaneous devices are a key technology in clinical practice, used to connect internal organs to external medical devices. Examples include prosthesis, catheters and electrical drivelines. Percutaneous devices breach the skin’s natural barrier and create an entry point for pathogens, making device infections a widespread problem. Modification of the percutaneous implant surface to increase skin integration with the aim to reduce subsequent infection is attracting a great deal of attention. While novel surfaces have been tested in various in vitro models used to study skin integration around percutaneous devices, no skin model has been reported, for the study of bacterial infection around percutaneous devices. Here, we report the establishment of an in vitro human skin equivalent model for driveline infections caused by Staphylococcus aureus, the most common cause of driveline-related infections. Three types of mock drivelines manufactured using melt electrowriting (smooth or porous un-seeded and porous pre-seeded with human fibroblasts) were implanted in human skin constructs and challenged with S. aureus. Our results show a high and stable load of S. aureus in association with the skin surface and no signs of S. aureus-induced tissue damage. Furthermore, our results demonstrate that bacterial migration along the driveline surface occurs in micro-gaps caused by insufficient skin integration between the driveline and the surrounding skin consistent with clinical reports from explanted patient drivelines. Thus, the human skin-driveline infection model presented here provides a clinically-relevant and versatile experimental platform for testing novel device surfaces and infection therapeutics.

The bone-anchored hearing system (BAHS) has evolved to a common treatment option for various types of hearing revalidation. The BAHS consists of an implant in the skull that breeches the skin. Soft tissue reactions are a common complication associated with BAHS and are generally poorly understood. This study aims to investigate the influence of BAHS and associated skin reactions around the implant. A total of 45 patients were prospectively followed from implantation up to at least 1 year. Swabs were obtained at baseline, 12 weeks follow-up and during cases of inflammation (Holgers score >= 2). The microbiota was assessed using IS-proTM, a bacterial profiling method based on the interspace region between the 16S-23S rRNA genes. Detection of operational taxonomic units, the Shannon Diversity Index, sample similarity analyses and Partial Least Squares Discriminant Analysis (PLS-DA) were employed. Staphylococcus epidermidis, Streptococcus pneumoniae/mitis, Propionibacterium acnes, Staphylococcus capitis, Staphylococcus hominis, Bifidobacterium longum, Haemophilus parainfluenzae, Lactobacillus rhamnosus, Bordetella spp., Streptococcus sanguinis, Peptostreptococcus anaerobius, Staphylococcus aureus, Lactococcus lactis, Enterobacter cloacae, and Citrobacter koseri were the most commonly found bacterial species. S. pneumoniae/mitis was significantly more often observed after implantation, whereas P. acnes was significantly less observed after implantation compared with baseline. The relative abundance of S. epidermidis (17%) and S. aureus (19.4%) was the highest for the group of patients with inflammation. The Shannon Diversity Index was significantly increased after implantation compared with pre-surgical swabs for Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia (FAFV), but not for other phyla. When combining all phyla, there was no significant increase in the Shannon Diversity Index. The diversity index was similar post-surgically for patients experiencing inflammation and for patients without inflammation. With a supervised classifier (PLS-DA), patients prone to inflammation could be identified at baseline with an accuracy of 91.7%. In addition, PLS-DA could classify post-surgical abutments as non-inflamed or inflamed with an accuracy of 97.7%. This study shows the potential of using IS-proTM to describe and quantify the microbiota associated with the percutaneous BAHS. Furthermore, the results indicate the possibility of an early identification of patients susceptible to adverse skin reaction following implantation. Both S. aureus and S. epidermidis should be considered as relevant bacteria for BAHS-associated inflammation.

Contains fulltext : 168234.pdf (Publisher’s version ) (Open Access) Bone conduction devices (BCDs) are advocated as an amplification option for patients with congenital conductive unilateral hearing loss (UHL), while other treatment options could also be considered. The current study compared a transcutaneous BCD (Sophono) with a percutaneous BCD (bone-anchored hearing aid, BAHA) in 12 children with congenital conductive UHL. Tolerability, audiometry, and sound localization abilities with both types of BCD were studied retrospectively. The mean follow-up was 3.6 years for the Sophono users (n = 6) and 4.7 years for the BAHA users (n = 6). In each group, two patients had stopped using their BCD. Tolerability was favorable for the Sophono. Aided thresholds with the Sophono were unsatisfactory, as they did not reach under a mean pure tone average of 30 dB HL. Sound localization generally improved with both the Sophono and the BAHA, although localization abilities did not reach the level of normal hearing children. These findings, together with previously reported outcomes, are important to take into account when counseling patients and their caretakers. The selection of a suitable amplification option should always be made deliberately and on individual basis for each patient in this diverse group of children with congenital conductive UHL.

Femoral amputation is a devastating event. Percutaneous, bone anchored prosthetic systems reduce problems associated with socket suspended prostheses, but the design is inherently vulnerable to infection. The aims of this thesis were to determine the risk of implant-associated infection, bacterial biofilm properties and the functional impact using this implant treatment regime. Definition of implant related osteomyelitis was based on clinical signs, radiography and positive tissue cultures. In 3-year prospective study 39 patients were evaluated twice for infectious frequency, clinical presentation, and its relation to bacterial flora at the skin-implant interface (Paper 1). The frequency of implant infection was 5% at inclusion and 18% at follow-up. The most common bacteria in superficial, and deep cultures were Staphylococcus aureus and coagulase-negative staphylococci. Despite frequent colonization by potentially virulent bacteria, limited disability, and only one implant removal was found. Phenotypical and genotypical biofilm formation was determined in 13 (7 staphylococcal, 6 enterococcal) osteomyelitis strains (Paper II). Antimicrobial resistance was tested with a novel combination of the Calgary biofilm MBEC device, and a custom-made susceptibility MIC plate. The majority of the strains produced biofilm with increased antimicrobial resistance, compared to their planktonic counterparts. Slime producing strains tolerated higher antimicrobial concentrations compared to non-producers. All staphylococcal strains carried ica genes. The long-term risk of implant-associated infection, and its relation to patient and method specific factors was determined in a 20-year retrospective analysis of the first 96 femoral implant patients (102 implants) (Paper III). A 10-year cumulative risk of 20% for developing osteomyelitis (16 patients), and a 10-year cumulative risk of 9 % for implant extraction due to osteomyelitis (10 patients) was found. Antibiotic treatment (median 3.5 months) and selective minor debridement, with retained implants, cured 7 out of 18 patients at the 24- month follow-up (Paper IV). Six patients were cured after implant extraction, and 5 had chronic low-grade infections with stable implants, but variable use of the external prosthetic leg. The most common pathogens were S. aureus and E. faecalis. C-reactive protein serum levels were significantly higher in patients with osteomyelitis caused by S. aureus than other pathogens. It is concluded that the finding of an increased risk of osteomyelitis with time using this implant system calls for; i) careful patient selection and information of long term risks, ii) further studies on infection control, iii) consideration of biofilm in treatment, and iv) improved diagnostics, and antibiotic delivery.

Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number, however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant.

In vitro Studies investigating the influence of electric DC current on bacterial detachment have demonstrated that continuous currents of only 25-125 mu A stimulated Staphylococcal strains to detach from surgical stainless steel. However, DC Currents produce more power that has to be dissipated by the skin as compared to alternating currents. Also, an excess of ions on the steel can Cause negative osteogenesis and fixation results. Therefore, it is the aim of this paper to examine whether detachment of Staphylococcus epidermidis from stainless steel Surfaces in a parallel plate flow chamber can also be Stimulated using electric block Currents. Block currents of 15, 60 and 100 mu A with different frequencies (0.1-2Hz) and duty cycles (5-50%) were applied to induce bacterial detachment. Block Currents of 100 mu A cause detachment of about 76% of adhering staphylococci from stainless steel, whereas in addition the remaining bacteria are less viable, as determined by culturing the remaining bacteria on agar plates. Therewith, block current-induced detachment of adhering bacteria from stainless steel appears to be an equally promising method to prevent infection of orthopaedic fixation pins and screws than application of DC Currents. (c) 2005 Elsevier Ltd. All rights reserved.

Peritoneal dialysis (PD) is a well-established modality of renal replacement therapy, which has as a principle for its proper function the guaranteed access to the peritoneal cavity. PD catheter implant technique should be safe, as well as provide minimal inconvenience to the patient, agility for the service, and few complications. At the University Hospital of Santa Maria (HUSM; Santa Maria, RS, Brazil), the catheters were inserted by laparotomy since the 1980s. It is been desired by the Nephrology department an alternative to facilitate the procedure, leading to greater agility and greater autonomy of the service. This study aimed to analyze the results obtained by professionals trained to implant peritoneal catheters with the Seldinger technique, recently implemented, and those obtained with the standard surgical technique. The samples were obtained from medical records of patients with endstage chronic kidney disease at the Nephrology department of HUSM with peritoneal dialysis indication (n=104). The demographic profile of the patients was evaluated, as well as the presence of infection and / or bleeding in the surgical wound, the first infusion and the 30-day functionality of the catheters, and the survival rate one and two years after implant. Data for each peritoneal catheter insertion mode were expressed as frequencies and then compared by chi-square, Fisher exact or Mann Whitey tests, with a 5% significance level. The profile of the two groups had similar characteristics in relation to gender, age, history of diabetes mellitus and arterial hypertension. The functionality of the implant at first infusion was also similar for both groups (83.9%for Seldinger vs. 79% for surgery). When evaluated the functionality in 30 days, the Seldinger technique demonstrated a higher success rate (76.7%) than the surgical technique (43.6%) (P-value=0,002). Regarding the presence of infection and / or bleeding in the outside wound, the percentage was similar for both groups (14.8% for Seldinger vs. 16.9% for surgical). The survival rate of the catheters at 1 and 2 years was also similar for both groups (37% and 14.8% for Seldinger, 23.7% and 20.6% for surgery, respectively). Given these results, it can be concluded that the implant of peritoneal catheters by Seldinger technique is a qualified alternative that allows greater agility to the service since it is an ambulatory procedure, can be performed by nephrologists and involves less patient management; having similar functionality to surgical implant according to the experience reported at HUSM. A diálise peritoneal (DP) é uma modalidade bem estabelecida de terapia renal substitutiva, que tem como princípio para seu bom funcionamento a garantia de acesso à cavidade peritoneal. A técnica de implante do cateter de DP deve ser segura, além de proporcionar o mínimo de inconveniência para o paciente, agilidade para o serviço, e poucas complicações. No Hospital Universitário de Santa Maria (HUSM; Santa Maria, RS, Brasil) os cateteres foram implantados por laparotomia desde a década de 1980. É almejada pelo Serviço de Nefrologia uma alternativa que facilite o procedimento, levando a maior agilidade e autonomia do Serviço. O presente trabalho se propôs a analisar os resultados obtidos, por profissionais treinados para implante de cateter peritoneal com a técnica percutânea de Seldinger, recentemente implantada, e os resultados obtidos com a técnica padrão, a cirúrgica. As amostras foram obtidas de dados dos prontuários de pacientes entre os pacientes com insuficiência renal crônica terminal do Serviço de Nefrologia do HUSM com indicação de diálise peritoneal (n=104). Foi avaliado o perfil demográfico dos pacientes, assim como a presença de infecção e/ou sangramento na ferida operatória, a funcionalidade do cateter na primeira infusão e após30dias, além da taxa de sobrevivência em um e dois anos após o implante. Os dados obtidos em cada modalidade de implante de cateter peritoneal foram expressos em frequências e posteriormente comparados pelos testes Qui-Quadrado, Exato de Fischer ou Mann Whitey, com um nível de significância de 5%. O perfil dos dois grupos apresentou características semelhantes em relação ao gênero, idade, ocorrência de diabetes mellitus e hipertensão arterial. A funcionalidade do implante, na primeira infusão, também foi semelhante para os dois grupos (83,9% para Seldinger, 79% para cirúrgico). Quando avaliada a funcionalidade em 30 dias, a técnica de Seldinger mostrou um percentual de sucesso (76,7%) maior que a técnica cirúrgica (43,6%) (P-valor=0,002). Com relação à presença de infecção e/ou sangramento no orifício de saída, o percentual foi semelhante para os dois grupos (14,8% para Seldinger, 16,9% para cirúrgico). A taxa de sobrevivência dos cateteres em 1 e 2 anos também foi semelhante para os dois grupos (37% e 14,8% para Seldinger, 23,7% e 20,6% para cirúrgico, respectivamente). Diante dos resultados, pode-se concluir que o implante de cateter peritoneal pela técnica percutânea de Seldinger é uma alternativa qualificada que permite maior agilidade ao serviço já que o procedimento é ambulatorial, pode ser realizado por nefrologistas e implica em menor manejo do paciente; apresentando funcionalidade semelhante ao implante cirúrgico conforme a experiência relatada no HUSM.