Orthopedic Infections Research Articles

<i>Mycobacterium abscessus</i> as a causative agent of periprosthetic infection

Introduction Mycobacterium abscessus species belongs to the group of non-tuberculosis mycobacteria responsible for chronic infections in people with weakened immunity. M. abscessus exist in various ecological niches and are able to colonize artificial surfaces, including medical and surgical instruments/ devices. Due tothe low incidence of M. abscessus as a causative agent of orthopedic infection, a rare clinical case of periprosthetic infection caused by M.abscessus would interest practitioners.The aim is to present a clinical case of periprosthetic infection caused by M. abscessus.Materials and methods From the medical records and discharge documents, it was known that female patient X. underwent total hip replacement at her residence hospital. Signs of acute infection of the postoperative wound appeared in the early postoperative period.Results Three months later, the patient was hospitalized in a specialized institution with a diagnosis of chronic deep periprosthetic infection. During the examination, the mycobacterial etiology of the process was established. During two hospitalizations, the patient underwent 4 consecutive revision surgeries (including muscle plastic surgery and installation of an antimicrobial spacer) and massive parenteral antibiotic therapy for 8 months, including at the outpatient stage, using at least 3 antibacterial agents. After 4 years, the patient does not complain of the infectious process. Postoperative scar is 45 cm. The residual shortening of the right lower limb of 3 cm was compensated by orthopedic shoes.Discussion Treatment of infection caused by M. abscessus is challenging due to the natural resistance of the pathogen to a wide range of antibacterial drugs. The literature describes separate cases of orthopedic infections caused by this pathogen. All authors agree that the key to successful treatment is a combination of radical surgical debridement and antibacterial therapy using at least three antimicrobial drugs.Conclusion A rare clinical case of periprosthetic infection caused by Mycobacterium abscessus after primary hip replacement is presented. This infectious agent is a rare pathogen, for which there is no proven therapeutic algorithm. Long-term aggressive antibiotic therapy in combination with stage-by-stage surgical treatment was successful.

Longitudinal intravital imaging of the bone marrowfor analysis of the race for the surface in a murine osteomyelitis model.

Critical knowledge gaps of orthopedic infections pertain to bacterial colonization. The established dogma termed the Race for the Surface posits that contaminating bacteria compete with host cells for the implant post-op, which remains unproven without real-time in vivo evidence. Thus, we modified the murine longitudinal intravital imaging of the bone marrow (LIMB) system to allow real-time quantification of green fluorescent protein(GFP+) host cells and enhanced cyan fluorescent protein(ECFP+) or red fluorescent protein(RFP+) methicillin-resistant Staphylococcus aureus (MRSA) proximal to a transfemoral implant. Following inoculation with ~105 CFU, an L-shaped metal implant was press-fit through the lateral cortex at a 90° angle ~0.150 mm below a gradient refractive index (GRIN) lens. We empirically derived a volume of interest (VOI) = 0.0161 ± 0.000675 mm3 during each imaging session by aggregating the Z-stacks between the first (superior) and last (inferior) in-focus LIMB slice. LIMB postimplantation revealed very limited bacteria detection at 1 h, but by 3 h,56.8% of the implant surface was covered by ECFP+ bacteria, and the rest were covered by GFP+ host cells. 3D volumetric rendering of the GFP+ and ECFP+ or RFP+ voxels demonstrated exponential MRSA growth between 3 and 6 hin the Z-plane, which was validated with cross-sectional ex vivo bacterial burden analyses demonstrating significant growth by ~2 × 104 CFU/hon the implant from 2 to 12 hpost-op (p < 0.05; r2 > 0.98). Collectively, these results show the competition at the surface is completed by 3 hin this model and demonstrate the potential of LIMB to elucidate mechanisms of bacterial colonization, the host immune response, and the efficacy of antimicrobials.

Efficacy of ceftaroline and rifampin, alone or combined, in a rat model of methicillin-resistant Staphylococcus epidermidis osteomyelitis without implant.

The in vivo efficacy of ceftaroline and rifampin alone or in combination was investigated in an experimental rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteomyelitis. After a 3-day treatment, the mean tibial bacterial load was significantly reduced in animals receiving rifampin alone or combined with ceftaroline (1.89 and 1.68 log10 CFU/g, respectively, P < 0.0001), whereas ceftaroline alone did not show any significant reduction at this early stage. After a 7-day treatment, the mean tibial bacterial load was reduced for ceftaroline alone compared to control animals (3.6 log10 CFU/g versus 4.4 log10 CFU/g, respectively, P < 0.05) and reached the limit of detection in almost all animals receiving rifampin alone or combined with ceftaroline (P < 0.0001). Finally, after a 14-day treatment the efficacy of ceftaroline alone was enhanced (P < 0.0001), and no MRSE was recovered from the tibias of animals receiving rifampin alone or combined with ceftaroline. No emergence of rifampin resistance was observed, regardless of the treatment group (monotherapy or combined therapy) or the timepoint of interest. Ceftaroline administered with rifampin could represent a valuable therapeutic option in the management of MRSE osteomyelitis. IMPORTANCE Methicillin-resistant Staphylococcus epidermidis (MRSE) contributes to a high percentage of orthopedic infections, and their treatment represents a huge challenge. The present study aimed to evaluate the efficacy of ceftaroline alone or combined with rifampin in a rat MRSE osteomyelitis model and the bone penetration of ceftaroline. A ceftaroline monotherapy showed a significant bacterial reduction in infected bones after a 7-day period of treatment. The combination ceftaroline plus rifampin leveraged rifampin's bactericidal activity, shortening the duration of positive culture in infected animals. These results suggest that ceftaroline and rifampin combination therapy could represent a valuable therapeutic option for human MRSE osteomyelitis and deserves further preclinical and clinical evaluation.

Functional Outcomes of Knee Arthrodesis for Infected Total Knee Arthroplasty.

As the occurrence of total knee arthroplasties (TKAs) is forecasted to continue rising, so too will the frequency of prosthetic joint infections (PJIs) and revision TKAs. Multiple revisions can result in an unreconstructible knee. In such instances, the knee may be salvaged through arthrodesis. We evaluated whether height, BMI, and age impacted patient-reported outcome measures (PROMs) in patients who underwent knee arthrodesis after revision TKA due to PJI. We conducted a retrospective review of patients undergoing arthrodesis for an infected TKA at a dedicated orthopedic infection service from 2014 to 2022. Patient demographics and PROMs from 36-Item Short Form Survey (SF-36) and Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaires were collected. Correlation analysis was performed to determine if any association between height, BMI, and age was present with the various PROMsand sub-scores. Forty-four patients (19 males, 25 females) were included, with a mean follow-up of 48 months. Increases in height (>166 cm), BMI (>30), and age (>62 years) had a statistically significant negative impact on three SF-36 components: health changes (P = 0.016), physical functioning ability (P = 0.0096), and general health components (P = 0.0075). Our results suggest that a knee arthrodesis is an acceptable option in patients with a persistent knee PJI with good functional PROMs and ambulatory status. Patients with shorter height, lower BMI, and younger age showed overall better outcomes. Knee arthrodesis can be an alternative option for amputationin patients with an infected TKA and provide good functional outcomes in selected patients.

Controversies in the microbiological diagnosis and treatment of bone and joint infections

Recently, bone and joint infections such as fracture-related infection (FRI) and prosthetic joint infections (PJI) have been defined for clinical and research purposes. National and international guidelines are being produced to guide clinicians towards what is considered best practice. However, much of what we do regarding the microbiological diagnosis and management of orthopaedic infection is based on expert opinion, rather than evidence-based medicine. This is largely because, prior to the publication of the clinical definitions of orthopaedic infection, studies included a heterogeneous population making comparisons between them difficult. More recently the publication of large clinical trials in the antimicrobial management of orthopaedic infection has demonstrated that such clinical research is possible, and can both challenge the existing dogma in this field and lead to universal changes in clinical practice. There is robust evidence for microbiological sampling techniques and their interpretation in diagnosis of orthopaedic infection, as well as the choice of empiric broad-spectrum antibiotics and the non-inferiority of oral versus intravenous systemic antibiotics. For other elements of the diagnosis and management of orthopaedic infection this is not the case. For example, there are limited or no data to support recommendations regarding time off antibiotics prior to microbiological sampling, systemic antibiotic duration, when to do a joint aspirate in PJI revisions or the timing of definitive joint implantation in the two-stage management of PJI. In summary, this review highlights what is currently considered best practice within the field of orthopaedic infection and discusses both the evidence behind it and where there is controversy or where further research is warranted.

Soft-tissue reconstruction in bone and joint infection

Bone and joint infection are commonly associated with disruption of the soft tissue envelope around the skeleton. Respect and consideration must be given to the soft tissue when treating orthopaedic infection as this can be the most challenging part of reconstruction during effective eradication of infection. Failure to plan for soft tissue problems will increase the risk of treatment failure. We describe the role of plastic surgeons and modern approaches to timely and effective joint working to deliver patient-centric care. Reconstructive options for soft tissues are described and the rationale behind our clinical approach.

Prevalence and drug resistance of Escherichia coli among patients with orthopaedic surgical site infections in China: A systematic review and meta-analysis

To summarize current prevalence and drug resistance rate of Escherichia coli (E. coli) among orthopaedic surgical site infections (SSIs) in China from English and Chinese language sources. Online databases were searched to collect related researches. A meta-analysis was performed to analyse prevalence and 95 % confidence interval (CI) of E. coli among patients with orthopedic surgical site infections. Meta-regression analysis was used to investigate the difference in the prevalence and antimicrobial resistance of E. coli among different subgroups. A total of 52 studies were enrolled into our meta-analysis, with a total of 31,285 strains isolated. The overall E. coli prevalence was 13.4 % (95 % CI 11.6–15.5). Study design (R2 = 8.98) and sample size (R2 = 10.95) might be potential sources of heterogeneity and there were no significant differences in risk of bias (R2 = 0.28), study time (R2 < 0.01), region (R2 = 2.46) and hospital level (R2 = 1.42). E. coli resistance were reported in 43 of the 52 papers. Antimicrobial resistance of E. coli to Ampicillin [87.9 % (95 % CI 83.7–91.1)] before 2015 was higher than that after 2015 [80.3 % (95 % CI 75.0–84.7)] (R2 = 30.93, P = 0.033). While, resistance rate to Cefepime and Amikacin was significantly higher before 2015 (R2 = 17.25 and 6.54, P = 0.043 and 0.048), i.e., 46.4 % (36.3–56.9), 19.9 % (13.8–27.7) and 29.1 % (19.4–41.2), 8.6 % (4.4–16.2) in 2015 and after. It is necessary to carry out long-term monitoring to understand the actual prevalence and antimicrobial resistance of E. coli to develop appropriate health care mechanisms.

Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model.

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

Colon Injuries and Infectious Complications in Concurrent Gunshot-Related Fractures

IntroductionConcurrent colonic injury among patients with gunshot-related fractures presents a potential risk for infectious complications. We hypothesized that colon injuries are associated with more infectious orthopedic complications among gunshot victims with concurrent fractures. Materials and methodsWe reviewed trauma patients arriving at our level 1 trauma center from January 1, 2019 to May 31, 2022 who suffered any gunshot-related fracture and also underwent an exploratory laparotomy. Of these patients, those with colon injuries were compared to those without colon injuries. Baseline characteristics, including antibiotic regimens, were collected in addition to outcomes of length of stay, intensive care unit admission, ventilator requirement, and development of infectious orthopedic complications. ResultsOverall, 56 of the 107 included patients had colon injuries. Age, sex, race/ethnicity, and Injury Severity Score were similar between groups. Of patients with colonic injuries, 16.1% received early, repeat dosing of broad-spectrum antibiotics, while only 3.9% of patients without colonic injuries received this antibiotic dosing (P = 0.04). Interestingly, only patients with colon injuries developed infectious orthopedic complications and none of the patients without colon injuries developed such complications (10.7% versus 0.0%, P = 0.03). All patients with orthopedic infections had infected pelvic fractures. Length of stay was 3 d longer in the colon injury group (P = 0.04). There was no difference in intensive care unit admission, ventilator requirement, or death. ConclusionsConcurrent colon injuries among patients with gunshot-related fractures are associated with higher risk of infectious orthopedic complications, likely from direct spread of fecal contaminant. Early, broad-spectrum antibiotics may be associated with reduced infectious orthopedic complications.

Analysis of Negative Pressure Sealing Drainage Technology for the Treatment of Orthopedic Trauma Infection

To explore the effective treatment of orthopedic trauma infection, the cases selected were 35 patients with orthopedic trauma infection. The study period was from January 2020 to December 2022. They were divided into the study group (n = 18) and the control group (n = 17) through the double-blind randomization of the medical record numbered envelopes. The patients in the control group were treated with conventional debridement and dressing change, and the patients in the study group were treated with negative pressure sealing drainage technology. The frequency of dressing changes, visual analogue scale (VAS) score, wound healing time, hospitalization time, and good wound healing rate were compared between the two groups. The number of dressing changes, VAS score, wound healing time, and hospitalization time in the study group were lower than those in the control group (P &lt; 0.05), and the rate of good wound healing in the study group was higher than that in the control group (P &lt; 0.05). Negative pressure sealing drainage technology for orthopedic trauma infection patients can decrease the number of dressing changes, reduce pain, accelerate the time for wound healing, shorten hospitalization time, and improve wound healing effect, which has the value of popularization and application.

Biocomposites containing poly(lactic acid) and chitosan for 3D printing – Assessment of mechanical, antibacterial and in vitro biodegradability properties

New bone repair materials are needed for treatment of trauma- and disease-related skeletal defects as they still represent a major challenge in clinical practice. Additionally, new strategies are required to combat orthopedic device-related infections (ODRI), given the rising incidence of total joint replacement and fracture fixation surgeries in increasingly elderly populations. Recently, the convergence of additive manufacturing (AM) and bone tissue engineering (BTE) has facilitated the development of bone healthcare to achieve personalized three-dimensional (3D) scaffolds. This study focused on the development of a 3D printable bone repair material, based on the biopolymers poly(lactic acid) (PLA) and chitosan. Two different types of PLA and chitosan differing in their molecular weight (MW) were explored. The novel feature of this research was the successful 3D printing using biocomposite filaments composed of PLA and 10 wt% chitosan, with clear chitosan entrapment within the PLA matrix confirmed by Scanning Electron Microscopy (SEM) images. Tensile testing of injection molded samples indicated an increase in stiffness, compared to pure PLA scaffolds, suggesting potential for improved load-bearing characteristics in bone scaffolds. However, the potential benefit of chitosan on the biocomposite stiffness could not be reproduced in compression testing of 3D printed cylinders. The antibacterial assays confirmed antibacterial activity of chitosan when dissolved in acetic acid. The study also verified the biodegradability of the scaffolds, with a process producing an acidic environment that could potentially be neutralized by chitosan. In conclusion, the study indicated the feasibility of the proposed PLA/chitosan biocomposite for 3D printing, demonstrating adequate mechanical strength, antibacterial properties and biodegradability, which could serve as a new material for bone repair.

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections.

Vancomycin is frequently used for prolonged courses in treating osteoarticular infections despite a high rate of adverse drug events (ADE). The objective of this study was to evaluate the safety and effectiveness of transitioning to oral therapy compared to continuing parenteral vancomycin in patients with orthopedic infections. We conducted a single-center, retrospective cohort study of patients with orthopedic infections discharged on parenteral vancomycin with a planned duration of at least four weeks. We compared rates of ADE while on vancomycin to rates of ADE after switching to an oral regimen. As a secondary analysis, we compared unplanned hospital readmission within 60 days and treatment failure at one year between patients who were transitioned to oral antibiotics within four weeks of vancomycin initiation and those that were not. Two hundred twenty-eight patients met inclusion criteria. Vancomycin was associated with significantly greater toxicity compared to oral regimens. Fifty-one patients had an adverse event while on vancomycin (5.87 ADE per 1000 patient-days) while 9 patients had an adverse event on oral therapy (1.49 ADE per 1000 patient-days) (Rate difference 4.39 per 1000 patient days, 95% CI: 2.52 to 6.26 events per 1000 patient-days). In proportional hazards analysis, transition to an oral antibiotic regimen was independently associated with a lower rate of ADE (aHR 0.12, 95% CI: 0.02-0.86). Forty-one patients (18%) were transitioned to oral therapy within four weeks; these patients did not have an increased rate of unplanned readmission (12.2% vs 17.1%) or treatment failure (17.1% vs 21.9%). Patients transitioned to oral therapy within 4 weeks of discharge had significantly fewer adverse events and similar incidences of one-year treatment failure compared to patients maintained on parenteral vancomycin. Substituting oral antibiotics for parenteral vancomycin is a potential strategy to minimize vancomycin toxicity during the treatment of orthopedic infections.

Silver nanoparticle technology in orthopaedic infections.

The irrational and prolonged use of antibiotics in orthopaedic infections poses a major threat to the development of antimicrobial resistance. To combat antimicrobial resistance, researchers have implemented various novel and innovative modalities to curb infections. Nanotechnology involves doping ions/metals onto the scaffolds to reach the target site to eradicate the infective foci. In this connotation, we reviewed silver nanoparticle technology in terms of mechanism of action, clinical applications, toxicity, and regulatory guidelines to treat orthopaedic infections.

Developing an antibiogram for empiric antibiotic prescribing for adult non-spinal orthopaedic infections in a developing world setting

PurposeEmpiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy.MethodsA retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens.ResultsA total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin–tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations.ConclusionAntibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.

Killing of a Multispecies Biofilm Using Gram-Negative and Gram-Positive Targeted Antibiotic Released from High Purity Calcium Sulfate Beads.

Multispecies biofilm orthopedic infections are more challenging to treat than mono-species infections. In this in-vitro study, we aimed to determine if a multispecies biofilm, consisting of Gram positive and negative species with different antibiotic susceptibilities could be treated more effectively using high purity antibiotic-loaded calcium sulfate beads (HP-ALCSB) containing vancomycin (VAN) and tobramycin (TOB) in combination than alone. Three sets of species pairs from bioluminescent strains of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) and clinical isolates, Enterococcus faecalis (EF) and Enterobacter cloacae were screened for compatibility. PA + EF developed intermixed biofilms with similar cell concentrations and so were grown on 316L stainless steel coupons for 72 h or as 24 h agar lawn biofilms and then treated with HP-ALCSBs with single or combination antibiotics and assessed by viable count or bioluminescence and light imaging to distinguish each species. Replica plating was used to assess viability. The VAN + TOB bead significantly reduced the PA + EF biofilm CFU and reduced the concentration of surviving antibiotic tolerant variants by 50% compared to single antibiotics. The combination of Gram-negative and positive targeted antibiotics released from HP-ALCSBs may be more effective in treating multispecies biofilms than monotherapy alone.

In vitro activity of exebacase against methicillin-resistant Staphylococcus aureus biofilms on orthopedic Kirschner wires

Orthopedic foreign body-associated infection can be difficult to treat due to the formation of biofilms protecting microorganisms from both antimicrobials and the immune system. Exebacase is an antistaphylococcal lysin (cell wall hydrolase) under consideration for local treatment for biofilm-based infections caused by methicillin-resistant Staphylococcus aureus (MRSA). To determine the activity of exebacase, we formed MRSA biofilms on orthopedic Kirschner wires and exposed them to varying concentrations (0.098, 0.98, 9.8 mg/ml) of exebacase and/or daptomycin over 24 h. The biofilm consisted of 5.49 log10 colony forming units (cfu)/K-wire prior to treatment and remained steady throughout the experiment. Exebacase showed significant biofilm reduction at all timepoints (up to 5.78 log10 cfu/K-wire; P < 0.0495) compared to the controls at all concentrations and all time points with bactericidal activity (> 3 log10 cfu/K-wire reduction) observed for up to 12 h for the 0.098 and 0.98 mg/ml concentrations and at 24 h for 9.8 mg/ml. Daptomycin showed significant biofilm reduction, although non-bactericidal, at all time points for 0.98 and 9.8 mg/ml and at 4 and 8 h with 0.098 mg/ml (P < 0.0495). This study supports further evaluation of local administration of exebacase as a potential treatment for orthopedic implant infections.

Trends in microbiological epidemiology of orthopedic infections: a large retrospective study from 2008 to 2021

BackgroundThis study assessed the distribution characteristics of pathogens isolated from cases of orthopedic infections and focused on the antimicrobial susceptibility of the main pathogens.MethodsThis retrospective study involved patients with orthopedic infection in a tertiary medical center located in Shanghai, China, from 2008 to 2021.Pathogen information and the basic information of patients were identified from clinical microbiology laboratory data and the institutional medical record system.ResultsIn total, the pathogen information of 2821 patients were enrolled in the study. S. aureus (37.71%) was the main causative pathogen responsible for orthopedic infection. Gender, pathogens distribution and polymicrobial infection rates were significantly different (P < 0.05) among patients with different orthopedic infection diseases.The trends in the distribution of pathogens in the total cohort, implant-related infection group (Group A), non-implant-related infection group (Group B), and the sub-group of cases with arthroplasty showed significant linear changes over time. And the polymicrobial infection rates of the total cohort (from 17.17% to 11.00%), Group B(from 24.35% to 14.47%), and the sub-group of cases with internal fixation (from 10.58% to 4.87%) decreased significantly. The antimicrobial susceptibility showed changing trends with time for some main pathogens, especially for S.aureus and Enterobacter spp.ConclusionsOur research indicated that the pathogen distribution and antimicrobial susceptibility in orthopedic infections changed over time. And the distribution of pathogens varied significantly among different types of orthopedic infectious diseases. These findings may serve as a reference for prophylaxis and empirical treatment strategies of orthopedic infection.

Tuning of Silver Content on the Antibacterial and Biological Properties of Poly(ɛ-caprolactone)/Biphasic Calcium Phosphate 3D-Scaffolds for Bone Tissue Engineering.

There is a growing interest in tissue engineering, in which biomaterials play a pivotal role in promoting bone regeneration. Furthermore, smart functionalization can provide biomaterials with the additional role of preventing orthopedic infections. Due to the growing microbial resistance to antimicrobials used to treat those infections, metal ions, such as silver, thanks to their known wide range of bactericidal properties, are believed to be promising additives in developing antibacterial biomaterials. In this work, novel poly(ε-caprolactone) (PCL)-based 3D scaffolds have been designed and developed, where the polymer matrix was modified with both silver (Ag), to supply antibacterial behavior, and calcium phosphates (biphasic calcium phosphate, BCP) particles to impart bioactive/bioresorbable properties. The microstructural analysis showed that constructs were characterized by square-shaped macropores, in line with the morphology and size of the templating salts used as pore formers. Degradation tests demonstrated the important role of calcium phosphates in improving PCL hydrophilicity, leading to a higher degradation degree for BCP/PCL composites compared to the neat polymer after 18 days of soaking. The appearance of an inhibition halo around the silver-functionalized PCL scaffolds for assayed microorganisms and a significant (p < 0.05) decrease in both adherent and planktonic bacteria demonstrate the Ag+ release from the 3D constructs. Furthermore, the PCL scaffolds enriched with the lowest silver percentages did not hamper the viability and proliferation of Saos-2 cells. A synergic combination of antimicrobial, osteoproliferative and biodegradable features provided to 3D scaffolds the required potential for bone tissue engineering, beside anti-microbial properties for reduction in prosthetic joints infections.

In vitro cytocompatibility of antibacterial silver and copper-doped bioactive glasses

Fighting the formation of bacterial biofilm and simultaneously providing a bioactive environment for bone regeneration during the treatment of orthopedic infections is one of the greatest challenges in surgery. Moreover, the major global threat of rapidly increasing antimicrobial resistance calls for non-antibiotic alternatives. Bioactive glasses doped with antibacterial metal ions silver (Ag), or copper (Cu), offer a potential solution. However, an added challenge is the cytocompatibility of these antimicrobial biomaterials, which could be compromised due to the possible cytotoxic effect of the dopants.This work evaluates the cytocompatibility of two bioactive glasses, SBA2 and SBA3, either doped with Ag- (Ag-SBA2) or Cu-ions (Cu-SBA3) via ion-exchange process. The viability, proliferation, and morphology of human adipose stem cells (hASCs) were evaluated using different culture conditions: i) direct culture on glass discs, with and without pre-incubation, and ii) in medium containing glass dissolution byproducts. The release kinetics of the doped ions was evaluated in α-MEM and during cell culture. Moreover, the effect of protein adsorption on the cell response was studied by introducing a layer of fibronectin on the glass discs before direct culture with hASCs.Ag-SBA2 and Cu-SBA3 both initially inhibited the hASC viability in direct cell culture. However, cells remain viable with healthy morphology when cultured directly on pre-treated discs, or indirectly with the glass dissolution byproducts. This suggests that the cytotoxicity effect seems to arise from the contact toxicity between the cells and the material surface. Fibronectin adsorption significantly improved the cytocompatibility of Ag-SBA2, while Cu-SBA3 requires further optimization. To conclude, Ag-SBA2, through its contact toxicity, has the potential for treating early infection, without compromising long-term cytocompatibility and bioactivity. However, further optimization of the Cu-SBA3 glass is needed due to its cytotoxicity towards hASCs.

New developments in combating infection from biofilm forming bacteria of orthopedic implants

Orthopedic device related infections (ODRI’s) represent a difficult to treat situation owing to their biofilm based nature. Biofilm infections once established are difficult to eradicate even with an aggressive treatment regimen due to their recalcitrance towards antibiotics and immune attack. The definitive treatment to eradicate the infections once a biofilm has established is surgical excision of the implant and thorough local debridement, but this carries a significant socioeconomic cost, the outcomes for the patient are often poor, and there is a significant risk of recurrence. The aim of the study was to provide a comprehensive insight into the newer anti-biofilm interventions (non-antibiotic approaches) and a better understanding of their mechanism of action essential for improved management of orthopedic implant infections.