The mesenteric entry site as a potential weak point in gastrointestinal anastomoses - findings from an ex-vivo biomechanical analysis.

PURPOSE: Gastrointestinal disorders frequently necessitate surgery involving intestinal resection and anastomosis formation, potentially leading to severe complications like anastomotic leakage (AL) which is associated with increased morbidity, mortality, and adverse oncologic outcomes. While extensive research has explored the biology of anastomotic healing, there is limited understanding of the biomechanical properties of gastrointestinal anastomoses, which was aimed to be unraveled in this study. METHODS: An ex-vivo model was developed for the biomechanical analysis of 32 handsewn porcine end-to-end anastomoses, using interrupted and continuous suture techniques subjected to different flow models. While multiple cameras captured different angles of the anastomosis, comprehensive data recording of pressure, time, and temperature was performed simultaneously. Special focus was laid on monitoring time, location and pressure of anastomotic leakage (LP) and bursting pressures (BP) depending on suture techniques and flow models. RESULTS: Significant differences in LP, BP, and time intervals were observed based on the flow model but not on the suture techniques applied. Interestingly, anastomoses at the insertion site of the mesentery exhibited significantly higher rates of leakage and bursting compared to other sections of the anastomosis. CONCLUSION: The developed ex-vivo model facilitated comparable, reproducible, and user-independent biomechanical analyses. Assessing biomechanical properties of anastomoses offers an advantage in identifying technical weak points to refine surgical techniques, potentially reducing complications like AL. The results indicate that mesenteric insertion serves as a potential weak spot for AL, warranting further investigations and refinements in surgical techniques to optimize outcomes in this critical area of anastomotic procedures.

One-Step Cascade Synthesis of ortho-bay-Imidazolo-Extended Perylene Biscarboximides (OBISIM) and Their Application as Broad-Spectrum Fluorescent Dyes.

A one-step synthesis of perylene dyes with lateral extension by condensed imidazoles in a cascade reaction of sodium amide and benzonitrile is described in which multiple extensions can be controlled by the reaction conditions. The extensions lead to bathochromic shifts in absorption and fluorescence while maintaining high fluorescence quantum yields. The condensed imidazole units cause additional absorption bands in the hypsochromic visible region, resulting in broad-band absorbers. Multiple extensions of the aromatic system enable the NIR spectral approach of the spectra. Energy transfer (fluorescence resonance energy transfer, FRET) of dyads with perylene biscarboximides is very efficient and achieves quantum yields close to unity regardless of the lengths and orientation of the spacer. Applications as broad-band-absorbing fluorescent dyes, such as in solar collectors, are discussed.

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

IMPORTANCE: The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

Differentiation of Spontaneous Bacterial Peritonitis from Secondary Peritonitis in Patients with Liver Cirrhosis: Retrospective Multicentre Study.

Ascitic fluid infection is a serious complication of liver cirrhosis. The distinction between the more common spontaneous bacterial peritonitis (SBP) and the less common secondary peritonitis in patients with liver cirrhosis is crucial due to the varying treatment approaches. This retrospective multicentre study was conducted in three German hospitals and analysed 532 SBP episodes and 37 secondary peritonitis episodes. Overall, >30 clinical, microbiological, and laboratory parameters were evaluated to identify key differentiation criteria. Microbiological characteristics in ascites followed by severity of illness and clinicopathological parameters in ascites were the most important predictors identified by a random forest model to distinguish between SBP and secondary peritonitis. To establish a point-score model, a least absolute shrinkage and selection operator (LASSO) regression model selected the ten most promising discriminatory features. By aiming at a sensitivity of 95% either to rule out or rule in SBP episodes, two cut-off scores were defined, dividing patients with infected ascites into a low-risk (score ≥ 45) and high-risk group (score < 25) for secondary peritonitis. Overall, the discrimination of secondary peritonitis from SBP remains challenging. Our univariable analyses, random forest model, and LASSO point score may help clinicians with the crucial differentiation between SBP and secondary peritonitis.

A Novel Machine Learning-Based Point-Score Model as a Non-Invasive Decision-Making Tool for Identifying Infected Ascites in Patients with Hydropic Decompensated Liver Cirrhosis: A Retrospective Multicentre Study.

This study is aimed at assessing the distinctive features of patients with infected ascites and liver cirrhosis and developing a scoring system to allow for the accurate identification of patients not requiring abdominocentesis to rule out infected ascites. A total of 700 episodes of patients with decompensated liver cirrhosis undergoing abdominocentesis between 2006 and 2020 were included. Overall, 34 clinical, drug, and laboratory features were evaluated using machine learning to identify key differentiation criteria and integrate them into a point-score model. In total, 11 discriminatory features were selected using a Lasso regression model to establish a point-score model. Considering pre-test probabilities for infected ascites of 10%, 15%, and 25%, the negative and positive predictive values of the point-score model for infected ascites were 98.1%, 97.0%, 94.6% and 14.9%, 21.8%, and 34.5%, respectively. Besides the main model, a simplified model was generated, containing only features that are fast to collect, which revealed similar predictive values. Our point-score model appears to be a promising non-invasive approach to rule out infected ascites in clinical routine with high negative predictive values in patients with hydropic decompensated liver cirrhosis, but further external validation in a prospective study is needed.

Coating of Intestinal Anastomoses for Prevention of Postoperative Leakage: A Systematic Review and Meta-Analysis.

Background: For several decades, scientific efforts have been taken to develop strategies and medical aids for the reduction of anastomotic complications after intestinal surgery. Still, anastomotic leakage (AL) represents a frequently occurring postoperative complication with serious consequences on health, quality of life, and economic aspects. Approaches using collagen and/or fibrin-based sealants to cover intestinal anastomoses have shown promising effects toward leak reduction; however, they have not reached routine use yet. To assess the effects of covering intestinal anastomoses with collagen and/or fibrin-based sealants on postoperative leakage, a systematic review and meta-analysis were conducted. Method: PubMed, Web of Science, Cochrane Library, and Scopus (01/01/1964 to 17/01/2022) were searched to identify studies investigating the effects of coating any intestinal anastomoses with collagen and/or fibrin-based sealants on postoperative AL, reoperation rates, Clavien-Dindo major complication, mortality, and hospitalization length. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Overall, 15 studies (five randomized controlled trials, three nonrandomized intervention studies, six observational cohort studies) examining 1,387 patients in the intervention group and 2,243 in the control group were included. Using fixed-effects meta-analysis (I 2 < 50%), patients with coated intestinal anastomoses presented significantly lower AL rates (OR = 0.37; 95% CI 0.27-0.52; p < 0.00001), reoperation rates (OR, 0.21; 95% CI, 0.10-0.47; p = 0.0001), and Clavien-Dindo major complication rates (OR, 0.54; 95% CI, 0.35-0.84; p = 0.006) in comparison to controls, with results remaining stable in sensitivity and subgroup analyses (stratified by study design, age group, intervention used, location of anastomoses, and indication for surgery). The length of hospitalization was significantly shorter in the intervention group (weighted mean difference (WMD), -1.96; 95% CI, -3.21, -0.71; p = 0.002) using random-effects meta-analysis (I 2 ≥ 50%), especially for patients with surgery of upper gastrointestinal malignancy (WMD, -4.94; 95% CI, -7.98, -1.90; p = 0.001). Conclusion: The application of collagen-based laminar biomaterials or fibrin sealants on intestinal anastomoses can significantly reduce postoperative rates of AL and its sequelae. Coating of intestinal anastomoses could be a step toward effective and sustainable leak prevention. To assess the validity and robustness of these findings, further clinical studies need to be conducted.

Treatment of vascular graft infections: gentamicin-coated ePTFE grafts reveals strong antibacterial properties in vitro.

Vascular graft infections (VGI) are severe complications in prosthetic vascular surgery with an incidence ranging from 1 to 6%. In these cases, synthetic grafts are commonly used in combination with antimicrobial agents. Expanded polytetrafluoroethylene (ePTFE) is in clinical use as a synthetic graft material and shows promising results by influencing bacterial adhesion. However, the literature on antibiotic-bound ePTFE grafts is scarce. Gentamicin is a frequently used antibiotic for local treatment of surgical site infections, but has not been evaluated as antimicrobial agent on ePTFE grafts. In this study, we examine the antimicrobial efficacy and biocompatibility of novel types of gentamicin-coated ePTFE grafts in vitro. ePTFE grafts coated with gentamicin salt formulations with covalently-bound palmitate were evaluated in two drug concentrations (GP1.75% and GP3.5%). To investigate effects from types of formulations, also suspensions of gentamicin in palmitate as well as polylactide were used at comparable levels (GS + PA and GS + R203). Antibacterial efficacies were estimated by employing a zone of inhibition, growth inhibition and bacterial adhesion assay against Staphylococcus aureus (SA). Cytotoxicity was determined with murine fibroblasts according to the ISO standard 10993-5. Gentamicin-coated ePTFE grafts show low bacterial adherence and strong antibacterial properties in vitro against SA. Bactericidal inhibition lasted until day 11. Highest biocompatibility was achieved using gentamicin palmitate GP1.75% coated ePTFE grafts. ePTFE grafts with gentamicin-coating are effective in vitro against SA growth and adherence. Most promising results regarding antimicrobial properties and biocompatibility were shown with chemically bounded gentamicin palmitate GP1.75% coatings. Graphical abstract.

Patient-specific effects of soluble factors from Staphylococcus aureus and Staphylococcus epidermidis biofilms on osteogenic differentiation of primary human osteoblasts.

Due to the frequency of biofilm-forming Staphylococcus aureus and Staphylococcus epidermidis in orthopedics, it is crucial to understand the interaction between the soluble factors produced by prokaryotes and their effects on eukaryotes. Our knowledge concerning the effect of soluble biofilm factors (SBF) and their virulence potential on osteogenic differentiation is limited to few studies, particularly when there is no direct contact between prokaryotic and eukaryotic cells. SBF were produced by incubating biofilm from S. aureus and S. epidermidis in osteogenic media. Osteoblasts of seven donors were included in this study. Our results demonstrate that the detrimental effects of these pathogens do not require direct contact between prokaryotic and eukaryotic cells. SBF produced by S. aureus and S. epidermidis affect the metabolic activity of osteoblasts. However, the effect of SBF derived from S. aureus seems to be more pronounced compared to that of S. epidermidis. The influence of SBF of S. aureus and S. epidermidis on gene expression of COL1A1, ALPL, BGLAP, SPP1, RUNX2 is bacteria-, patient-, concentration-, and incubation time dependent. Mineralization was monitored by staining the calcium and phosphate deposition and revealed that the SBF of S. epidermidis markedly inhibits calcium deposition; however, S. aureus shows a less inhibitory effect. Therefore, these new findings support the hypotheses that soluble biofilm factors affect the osteogenic processes substantially, particularly when there is no direct interaction between bacteria and osteoblast.

Emergency room as primary point of access in the German healthcare system : Objective evaluation and interview of motivation for ER entrance of 235 ER patients in a German hospital.

BACKGROUND: The importance of emergency rooms (ERs) as everyday healthcare suppliers is growing. Due to increasing patient flows, hospitals are forced to raise physicians' and caregivers' headcount continuously to meet the new demand of patients seeing the ER as primary point of contact in non-emergency situations. Patients from various cultural and educational backgrounds approach the ER for different reasons. Detailed understanding of these reasons and their roots is key to be able to offer guidance for patients as well as planning and staffing of hospitals in the future. AIM: This study examines motivation for the entrance to the medical system via the ER in Germany via an anonymized patient survey. Evaluation in regard to socioeconomic and medical reasons is taken into account. MATERIALS AND METHODS: Over the course of 210 h in the ER, a total of 235 patients were interviewed in the surgical emergency room of Klinikum rechts der Isar in the year 2016. Focus was set on standard cases to allow for facilitated comparability. Heavily injured patients were excluded from the study. RESULTS: The main reasons for patients entering the ER were immediate help (45.9%) and treatment by a specialist (35.4%). Furthermore, the location/good accessibility (47.9%) and prior positive experience with the emergency room (20.7%) were decisive reasons for choosing the hospital over the outpatient sector. Analysis of demands of patients in relation to their migration background and their religious confession showed no significant difference between groups. CONCLUSION: Younger patients tend to more often access the ER instead of an outpatient clinic or doctor in private practice. As a survey suits the less urgent patients, our research describes this population in detail. The need for better information of patients regarding treatment options becomes apparent. The study's outcomes aim to teach physicians as well as operators how to influence resource management in the healthcare system by meaningful information of patients. Further research may evaluate long-term results of information measures.

Peri-Prosthetic Joint Infection of the Knee Causes High Levels of Psychosocial Distress: A Prospective Cohort Study.

Background: Peri-prosthetic joint infection (PJI) is a major complication of knee arthroplasty that can cause long-term disability. In addition to its physical impact, there is a clear psychological burden that has not been measured yet. We hypothesized that the psychosocial burden of PJI can be assessed quantitatively using standardized questionnaires and may be correlated with treatment stage. Methods: Thirty-one patients were enrolled in this longitudinal prospective cohort study from August 2015 to November 2016. Participants had clinically established knee PJI after primary total knee replacement in osteoarthritis according to the Musculoskeletal Infection Society criteria and underwent a standardized two-stage protocol. After explantation of the prosthesis and implantation of a polymethylmethacrylate knee spacer, patients were treated with organism-specific intravenous antibiotics for two weeks, followed by oral antibiotics for four weeks; and then reimplantation was performed in all cases. Psychometrically validated standardized questionnaires were used to measure psychosocial stress via self-assessment at four time points: (1) Before explantation of the prosthesis; (2) after explantation; (3) after the antibiotic treatment before reimplantation; and (4) three months after reimplantation (follow-up). The Patient Health Questionnaire (PHQ)-4, Short Form (SF)-12 (including PSK and KSK), Questions about Life Satisfaction (FLZM) and Fear of Progression (PA-F-KF) (titles and abbreviations in German) scores were interpreted according to cut-off values for depression, fear of progression, anxiety, and quality of life. Results: Eighteen patients (58.1%) showed a PHQ-4 score above the cut-off value for depression at least once, with the highest score before reimplantation (time point 3). On the SF-12, the mean subtest mental scale (PSK) score was 42.6 (± 14.5), and the mean subtest physical scale (KSK) score was 26.9 (± 7.5) over the four time points, which was significantly lower than that of the general German population (PSK 53.1, KSK 44.0; p < 0.05). The SF-12 scores did not change significantly over time. On the FLZ, health was least satisfactory, followed by recreational activities and work. On the PA-F-KF, patients had the greatest fear of being dependent on outside help, drastic medical interventions, and infection progression. The mean PA-F-KF value was 31.24 (± 9.60; values ≥34 are regarded as critical). Conclusion: Peri-prosthetic joint infection is a measurable, relevant psychosocial stressor for patients. Their quality of life and fear of the disease progressing are comparable to those of oncology patients. Routine screening should be conducted to identify affected patients early for appropriate treatment, improving long-term outcomes. Orthopaedic surgeons who treat patients with PJI should initiate by psychologists as well in order to maintain the patient's long-term quality of life.

Smart antimicrobial efficacy employing pH-sensitive ZnO-doped diamond-like carbon coatings.

One of the main challenges in endoprosthesis surgeries are implant-associated infections and aseptic-loosenings, caused by wear debris. To combat these problems, the requirements to surfaces of endoprostheses are wear-resistance, low cytotoxicity and antimicrobial efficacy. We here present antimicrobial coatings with a smart, adaptive release of metal ions in case of infection, based on ZnO-nanoparticles embedded in diamond-like carbon (DLC). The Zn2+ ion release of these coatings in aqueous environments reacts and adapts smartly on inflammations accompanied by acidosis. Moreover, we show that this increased ion release comes along with an increased toxicity to fibroblastic cells (L929) and bacteria (Staphylococcus aureus subsp. aureus, resistant to methicillin and oxacillin. (ATCC 43300, MRSA) and Staphylococcus epidermidis (ATCC 35984, S. epidermidis). Interestingly, the antimicrobial effect and the cytotoxicity of the coatings increase with a reduction of the pH value from 7.4 to 6.4, but not further to pH 5.4.

Prognostic Factors and Outcomes for Patients With Myxofibrosarcoma: A 13-Year Retrospective Evaluation.

BACKGROUND: Soft-tissue sarcomas are rare entities that are divided into approximately 50 histological subtypes. Myxofibrosarcoma (MFS) represents approximately 20% of all soft-tissue sarcomas, especially in elderly patients in their sixth to eighth decades of life. The treatment for soft-tissue sarcomas varies from primary surgical resection to neoadjuvant or adjuvant radiotherapy or cytotoxic chemotherapy. The aim of this study was to evaluate the prognostic factors affecting survival of patients with MFS, taking into account gender, tumour grade, state of the resection margin, local recurrence, use of radiotherapy, presence of metastases and blood levels of haemoglobin and C-reactive protein in a retrospective, single-centre analysis with a minimum follow-up period of 60 months (range=60-156 months). PATIENTS AND METHODS: The study included 34 patients (male/female=20/14). Tumour localization, tumour grade, tumour margins, local recurrence, the use of radiotherapy, the presence of metastasis, and the blood levels of haemoglobin and C-reactive protein preoperatively and during follow-up were evaluated. RESULTS: MFS constituted the most common high-grade sarcoma (G2/G3, 79.4%) in our cohort and was generally located in a lower limb (73.6%). Negative margins (R0) were detected in 67.6% of patients after surgical resection, and local recurrence occurred in 23.5% of all patients after a mean disease-free period of 19.4 months. Both parameters exerted no significant influence on survival. Radiotherapy was performed in a neoadjuvant or an adjuvant setting in 50% of patients (eight neoadjuvant, nine adjuvant). Metastasis occurred after a mean of 20.4 months in 38.2% of the patients. Higher C-reactive protein levels showed a trend towards being associated with worse survival, but the association was not significant (p=0.084); haemoglobin level had no influence on the survival rate (p=0.426). Tumour grade and metastasis were significant prognostic factors of survival (log-rank test p=0.041 and p=0.00007). Ten patients (29.4%) died due to MFS during our follow-up period. CONCLUSION: The tumour grade and metastasis of MFS are independently associated with disease-specific survival, whereas negative surgical margins, local recurrence and blood levels of C-reactive protein and haemoglobin were not significant prognostic factors. The understanding of the molecular biological patterns that result in the metastasis of these tumours will help develop better treatment plans in the future.

Novel antimicrobial coatings based on polylactide for plastic biliary stents to prevent post-endoscopic retrograde cholangiography cholangitis.

BACKGROUND: Cholangitis is a common complication after endoscopic retrograde cholangiography (ERC). OBJECTIVES: To evaluate antimicrobial coatings for biliary plastic stents in relation to efficacy against biliary pathogens, drug release and toxicity. METHODS: Biliary plastic stents were prepared by coating using a polylactide drug carrier. Stent coatings contained 4% (w/w) drug content of Resomer-octenidine (RO), Resomer-octenidine and citrate (ROC), Resomer-triclosan (RT) or Resomer-gentamicin (RG). Drug-release kinetics, antimicrobial efficacies of coated biliary stents against biliary pathogens and biocompatibilities were tested. Antimicrobial efficacy measurements included MIC testing, zone of inhibition (ZOI) assays and log reduction in bacterial suspensions. RESULTS: Continuous drug release was observed in all antimicrobial stent coatings for at least 168 h with an initial peak within the first 24 h. RT-, ROC- and RG-coated stents resulted in the following log reductions in suspensions: Escherichia coli (-0.3, -7.4 and -6.6, respectively); Enterococcus faecalis (-0.05, -6.3 and -3.9, respectively); and Candida albicans (-0.04, -1.5 and -0.2, respectively). ROC had the highest log reduction in suspension and the most favourable time course of ZOI (≥2 mm, over 72 h) against all tested pathogens. Although RT coatings showed the lowest MICs, they had the lowest ZOIs after 24 h. Concerning RO, acceptable biocompatibility could only be reached by adding a citrate component. RG showed the largest ZOI after 24 h against E. coli (19.3 mm) and E. faecalis (5.1 mm), whereas the ZOI was lower against C. albicans (1.3 mm) compared with ROC (3.7 mm). CONCLUSIONS: ROC corresponds most closely to the requirements of an ideal antimicrobial stent coating to prevent post-ERC cholangitis, showing the highest log reduction in pathogen counts, the most favourable time course of ZOI and high biocompatibility.

Influence of Absorbable Calcium Sulfate-Based Bone Substitute Materials on Human Haemostasis-In Vitro Biological Behavior of Antibiotic Loaded Implants.

Calcium sulfate (CS) formulations are frequently implanted as antibiotically impregnated bone substitutes in orthopedic and trauma surgery to prevent or treat bone infections. Calcium ions have been discussed as candidates to accelerate blood coagulation. The goal of this study is to evaluate substance-specific influences of CS formulations on blood coagulation. Specific ELISAs were conducted to determine markers of activated blood coagulation after incubation of human blood with CS beads. Additionally, wettability with freshly drawn human blood was measured. Three different types of CS bone substitute beads were compared (CS dihydrate with tripalmitin, containing Gentamicin (Herafill®-G: Group A) or Vancomycin (CaSO4-V: Group B); and a CS hemihydrate with Tobramycin (Osteoset®: Group C)). Examinations were performed by ELISA assays for F1+2, FXIIa and C3a. Our results prove that none of the CS preparations accelerated single specific assays for activated coagulation markers. This allows the conclusion that neither Herafill®-G (CaSO4-G) nor CaSO4-V alter haemostasis negatively. Blood samples incubated with Osteoset® display an elevated F1+2-activity. The addition of tripalmitin in Herafill®-G shifts the original into a significantly hydrophobic formulation. This was additionally proven by contact angle examination of the three substances with freshly drawn human blood, showing that acceleration of plasmatic coagulation is hindered by lipids and induced by surface effects caused by presence of rapidly soluble calcium ions in the Osteoset® preparation.

Correction: Viable adhered Staphylococcus aureus highly reduced on novel antimicrobial sutures using chlorhexidine and octenidine to avoid surgical site infection (SSI).

[This corrects the article DOI: 10.1371/journal.pone.0190912.].

Viable adhered Staphylococcus aureus highly reduced on novel antimicrobial sutures using chlorhexidine and octenidine to avoid surgical site infection (SSI).

BACKGROUND: Surgical sutures can promote migration of bacteria and thus start infections. Antiseptic coating of sutures may inhibit proliferation of adhered bacteria and avoid such complications. OBJECTIVES: This study investigated the inhibition of viable adhering bacteria on novel antimicrobially coated surgical sutures using chlorhexidine or octenidine, a critical factor for proliferation at the onset of local infections. The medical need, a rapid eradication of bacteria in wounds, can be fulfilled by a high antimicrobial efficacy during the first days after wound closure. METHODS: As a pretesting on antibacterial efficacy against relevant bacterial pathogens a zone of inhibition assay was conducted with middle ranged concentrated suture coatings (22 µg/cm). For further investigation of adhering bacteria in detail the most clinically relevant Staphylococcus aureus (ATCC®49230™) was used. Absorbable braided sutures were coated with chlorhexidine-laurate, chlorhexidine-palmitate, octenidine-laurate, and octenidine-palmitate. Each coating type resulted in 11, 22, or 33 µg/cm drug content on sutures. Scanning electron microscopy (SEM) was performed once to inspect the coating quality and twice to investigate if bacteria have colonized on sutures. Adhesion experiments were assessed by exposing coated sutures to S. aureus suspensions for 3 h at 37°C. Subsequently, sutures were sonicated and the number of viable bacteria released from the suture surface was determined. Furthermore, the number of viable planktonic bacteria was measured in suspensions containing antimicrobial sutures. Commercially available sutures without drugs (Vicryl®, PGA Resorba®, and Gunze PGA), as well as triclosan-containing Vicryl® Plus were used as control groups. RESULTS: Zone of inhibition assay documented a multispecies efficacy of novel coated sutures against tested bacterial strains, comparable to most relevant S. aureus over 48 hours. SEM pictures demonstrated uniform layers on coated sutures with higher roughness for palmitate coatings and sustaining integrity of coated sutures. Adherent S. aureus were found via SEM on all types of investigated sutures. The novel antimicrobial sutures showed significantly less viable adhered S. aureus bacteria (up to 6.1 log) compared to Vicryl® Plus (0.5 log). Within 11 µg/cm drug-containing sutures, octenidine-palmitate (OL11) showed the highest number of viable adhered S. aureus (0.5 log), similar to Vicryl® Plus. Chlorhexidine-laurate (CL11) showed the lowest number of S. aureus on sutures (1.7 log), a 1.2 log greater reduction. In addition, planktonic S. aureus in suspensions were highly inhibited by CL11 (0.9 log) represents a 0.6 log greater reduction compared to Vicryl® Plus (0.3 log). CONCLUSIONS: Novel antimicrobial sutures can potentially limit surgical site infections caused by multiple pathogenic bacterial species. Therefore, a potential inhibition of multispecies biofilm formation is assumed. In detail tested with S. aureus, the chlorhexidine-laurate coating (CL11) best meets the medical requirements for a fast bacterial eradication. This suture coating shows the lowest survival rate of adhering as well as planktonic bacteria, a high drug release during the first-clinically most relevant- 48 hours, as well as biocompatibility. Thus, CL11 coatings should be recommended for prophylactic antimicrobial sutures as an optimal surgical supplement to reduce wound infections. However, animal and clinical investigations are important to prove safety and efficacy for future applications.

Evaluation of calcium dihydroxide- and silver-coated implants in the rat tibia.

BACKGROUND: Silver ions (Ag+) have strong antibacterial effects, and silver-coated materials are in widespread clinical use. However, the application of silver-coated medical devices is not without concerns: its use with direct bone contact is not established, and systemic toxic side effects of released Ag+ have been described. Therefore, alternative bactericidal coatings with a more localized way of acting - e.g., calcium dihydroxide, Ca(OH)2 (CH) - would be advantageous. METHODS: A new rat model of the animal's tibial metaphysis was developed. In the left proximal tibiae of 36 male Wistar rats, titanium screws were implanted. The screws were coated with hydroxyapatite (HA; 12 animals: group I), low-dosed HA silver (HA-Ag; 12 animals: group II) and CH (12 animals: group III). After 6 weeks, all rats were sacrificed. The implants were evaluated for morphological changes on their surfaces, by light microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy; for osteointegration, by measurement of resistance to removal; and for bacterial colonization, by quantitative culture analysis. Additionally, the tibial bone was investigated histologically for signs of osteomyelitis and sonicated to detect bacterial loads. RESULTS: (i) No microbiological or histological signs of infection could be determined on any of the screws or the surrounding bone. (ii) The bone-implant interface analysis revealed extensive bone formation and direct bone-implant contact on all HA, HA-Ag and HA-CH coated screws. (iii) HA and HA-Ag were partially, and CH was fully, degraded on the screw coating, allowing host bone to osteointegrate.

A new model of implant-related osteomyelitis in the metaphysis of rat tibiae.

BACKGROUND: Animal models serve as an important tool to understand peri-implant infection. Most of the models use high bacterial loads (>10(4) colony forming units, CFU) to provide high infection rates. Therefore these animals evolve rather similarly, making comparison between groups and statistical analysis possible. On the other hand, to mimic clinical constellation of surgery-related infections the use of low amounts of bacteria would be more advantageous. METHODS: We developed a metaphyseal rat model of peri-implant bone infection with low amount of bacterial loads (10(2) and 10(3) CFU of Staphylococcus aureus) and investigated osseointegration of the implants coated with hydroxyapatite (HA) and low-dosed HA-silver (HA-Ag). Non-infected implants served as controls. After 6 weeks rats were sacrificed and implants evaluated for osseointegration and infection. RESULTS: Infection of implanted devices was reliably induced, independently whether 10(2) or 10(3) CFU of S. aureus were inoculated and HA or HA-Ag coated implants were used. No systemic infection was present in any of the animals at the time of sacrifice, and no animal developed acute infection requiring premature sacrifice. All CFU counts of the implant and the bone at sacrifice were significantly higher than the inoculated load (p < .05). All sterilely inserted implants showed excellent osseointegration and no infection. CONCLUSIONS: Our present study of a rat tibia model reliably induced osteomyelitis in the metaphysis with low-doses of bacteria. The addition of low-dosed Ag to the implant coating was not able to reduce the infection rates. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with low amounts of bacteria to better mimic clinical constellations. No other promoters of infection besides insertion of the screw implant were used in this model.

Silver nanoparticle-enriched diamond-like carbon implant modification as a mammalian cell compatible surface with antimicrobial properties.

The implant-bone interface is the scene of competition between microorganisms and distinct types of tissue cells. In the past, various strategies have been followed to support bony integration and to prevent bacterial implant-associated infections. In the present study we investigated the biological properties of diamond-like carbon (DLC) surfaces containing silver nanoparticles. DLC is a promising material for the modification of medical implants providing high mechanical and chemical stability and a high degree of biocompatibility. DLC surface modifications with varying silver concentrations were generated on medical-grade titanium discs, using plasma immersion ion implantation-induced densification of silver nanoparticle-containing polyvinylpyrrolidone polymer solutions. Immersion of implants in aqueous liquids resulted in a rapid silver release reducing the growth of surface-bound and planktonic Staphylococcus aureus and Staphylococcus epidermidis. Due to the fast and transient release of silver ions from the modified implants, the surfaces became biocompatible, ensuring growth of mammalian cells. Human endothelial cells retained their cellular differentiation as indicated by the intracellular formation of Weibel-Palade bodies and a high responsiveness towards histamine. Our findings indicate that the integration of silver nanoparticles into DLC prevents bacterial colonization due to a fast initial release of silver ions, facilitating the growth of silver susceptible mammalian cells subsequently.