Infected Implants Research Articles

Chitosan -based nanoniosome for potential wound healing applications: Synergy of controlled drug release and antibacterial activity

This study aims to develop a niosomal platform which can delivery drugs such as tetracycline hydrochloride (TCH) to treat bacterial infections in wounds. To this end, chitosan (CS) was used to obtain a controlled drug release and at the same time antibacterial activity. By design of experiments the niosome encapsulated TCH (TCH-Nio) were optimized for their particle size and encapsulation efficiency, followed by analysis of the release profile of TCH and stability of TCH-Nio and TCH-Nio@CS. The antibacterial activity and cytotoxicity of the fabricated nanoparticles were investigated as well. The release rate of TCH from TCH-Nio@CS in all conditions is less than TCH-Nio. In addition, higher temperature increases the release rate of drug from these formulations. The size, polydispersity index, and encapsulation efficacy of TCH-Nio and TCH-Nio@CS were more stable in 4 °C compared to 25 °C. TCH, TCH-Nio, and TCH-Nio@CS had MIC values of 7.82, 3.91, and 1.95 μg/mL for Escherichia coli, 3.91, 1.95, and 0.98 μg/mL for Pseudomonas aeruginosa, and 1.96, 0.98, and 0.49 μg/mL for Staphylococcus aureus, respectively. Coating of chitosan on niosome encapsulated TCH (TCH-Nio@CS) led to a reduced burst release of TCH from niosome (TCH-Nio), and enabled 2-fold higher antibacterial and anti-biofilm activity against the tested bacterial pathogens E. coli, P. aeruginosa and S. aureus, compared to the uncoated TCH-Nio, and 4-folder higher than the TCH solution, suggesting the synergetic effect of niosome encapsulation and chitosan coating. Moreover, the formulated niosomes displayed no in vitro toxicity toward the human foreskin fibroblast cells (HFF). Both TCH-Nio and TCH-Nio@CS were found to down-regulate the expression of certain biofilm genes, i.e., csgA, ndvB, and icaA in the tested bacteria, which might partially explain the improved antibacterial activity compared to TCH. The obtained results demonstrated that TCH-Nio@CS is capable of controlled drug release, leading to high antibacterial efficacy. The established platform of TCH-Nio@CS enlighten a clinic potential toward the treatment of bacterial infections in skin wounds, dental implants and urinary catheter.

Advances in Research on Titanium and Titanium Alloys with Antibacterial Functionality for Medical Use—A Review

Materials based on titanium and its alloys are widely used in the medical and dental fields because of their excellent physical properties such as hardness, ductility and elastic modulus, etc. However, because commonly used titanium alloy internal plants do not have antibacterial properties, when these implants are implanted into the human body, there is a certain risk of infection. Such infections are extremely painful for the patient and problematic for the attending physician. In the past, infections of implants were usually treated with systemic antibiotics in combination with thorough debridement or implant replacement. However, these are passive treatments and typically cause huge physical and economic burdens on the patient. Therefore, attempts towards the development of implants with antibacterial functionality have been increasing, with the combination of titanium alloys with antibiotics, antibacterialmetals, and antibacterial peptides being the main research direction. Therefore, this paper will discuss the latest research progress in the preparation of titanium alloys with antibacterial strategies such as combining antibiotics or antimicrobial peptides, adding antimicrobial metals, and the antibacterial properties and biocompatibility of proposed systems are summarised and discussed herein. This review should serve as a reference for further research on antibacterial titanium alloy implants.

Biocompatible cationic polypeptoids with antibacterial selectivity depending on hydrophobic carbon chain length.

The overuse of antibiotics has triggered a new infection crisis and natural antimicrobial peptides (AMPs) have been extensively studied as an alternative to fight microorganisms. Polypeptoids, or polypeptide-biomimetics, offer similar properties to polypeptides and a highly tunable structure that has been synthesized by various methods such as ring opening polymerization (ROP) using N-carboxyanhydride monomers. Simultaneous high antibacterial activity and biocompatibility of a structure by efficient synthesis is desired in the application of those materials. Herein, a series of cationic polypeptoids (PNBs) with variable side chain lengths was obtained by introducing positive charges to the main chain in one step and preserving the backbone structure, namely polypeptoids (PNBM, PNBE, PNBB) with different end groups (methyl (M), ethyl (E), butyl (B)). To address the issue of infection in interventional biomedical implants, we report cost-effective modified polyurethane (PU) films (PU-PNBM, PU-PNBE, PU-PNBB) as physical-biological synergistic antibacterial surfaces that overcome problems such as steric hindrance and the solubility of the materials. Antibacterial selectivity was achieved by regulating the different side chain lengths. When methyl and ethyl were used as hydrophobic side chains, they can only selectively kill Gram-positive Staphylococcus aureus. PNBB, the most hydrophobic and with a butyl side chain can kill both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and inhibit the growth of bacterial biofilms. Effective in both solution and modified substrate, its biocompatibility is not compromised while the antibacterial properties are substantially improved. Furthermore, PU-PNBB films demonstrated their potential in vivo antimicrobial efficiency in a model of S. aureus infection established on mouse skin. The synthesis route and the surface modification strategies are convenient, providing a solution to the problem of poor biocompatibility in antimicrobial surface applications and a strategy for the use of peptide polymers for targeted therapy after specific infections in the biomedical field.

Recent advances in the treatment of biofilms induced surgical site infections.

Recent advances in the treatment of biofilms induced surgical site infections.

Antibacterial Properties of TiO<sub>2</sub> Layers Formed by Au-Sputtering and Thermal Oxidation of Titanium under Visible Light

To prevent infection in dental implants using photocatalytic activity under visible-light irradiation, the fabrication of Au-added TiO2 layers on Ti substrates and their antibacterial properties were studied. Pure Au and Ti–(60, 40) mol%Au alloy films with thicknesses of 10–47 nm were sputtered onto Ti, followed by thermal oxidation in air at 873 K for 1.8 ks to form TiO2 layers. The antibacterial properties against Escherichia coli, cytotoxicity, and bonding strength to Ti substrates were evaluated. The highest antibacterial activity under visible-light irradiation was obtained when the sputtered film was pure Au and its thickness was 38 nm. Compared with as-polished commercially pure Ti, the number of viable mouse osteoblast-like cells and human gingival fibroblasts on Au-added TiO2 layers increased after placement in the dark but decreased after visible-light irradiation. The best antibacterial property-bonding strength balance was achieved when the Ti–40 mol%Au sputtered film with a thickness of 42 nm was formed on Ti. To the best of our knowledge, this study is the first to report the formation of TiO2 layers with antibacterial activity under visible-light irradiation by combining Au-sputtering and thermal oxidation of Ti.

The Effect of Slime Factor in the Treatment of Spinal Implant Infections.

To investigate the effect of the biofilm-forming ability of the bacteria on treatment in rats by using biofilm-forming and nonbiofilm- forming strains of Staphylococcus aureus (S. aureus). Forty rats were divided into four equal groups as Group 1A, 1B, 2A, and 2B. All rats underwent single distance lumbar laminectomy, and titanium implants were introduced. Group 1 rats were inoculated with Slime factor (-) S. aureus, while Group 2 rats were inoculated with biofilm Slime factor (+) S. aureus. None of the rats were given antibiotics. One week later, the surgical field was reopened and microbiological samples were taken. The implants of rats in Groups 1A and 2A were left in place, while the implants of rats in Groups 1B and 2B were removed. There was no statistically significant difference between the groups inoculated with slime factor (+) S. aureus; although, Groups 1A and 2A showed statistically significant difference. Statistical analysis with respect to bacterial count also showed a statistically significant difference between Groups 1A and 2A. There was a statistically significant difference between Group 1B and 2B. The results obtained in the present study reveal that in case of implant-dependent infection, the first sample taken can be checked for slime factor, and if there is infection with slime factor-negative bacterium, treatment without removing the implant may be recommended. S. aureus was used in the study because it is the most common cause of implant-related infection at surgical sites. Further studies using different bacterial species are needed to reach a definitive conclusion.

Strontium-doped bioactive glass/PDA functionalized polyetheretherketone with immunomodulatory property for enhancing photothermal clearance of Staphylococcus aureus

The infection of implants following orthopedic surgery is a “catastrophic” surgical complication, particularly when biofilms form, protecting bacteria from antibiotics as well as the patient’s immune system. To address the current difficulties in treating biofilm infections, we fabricate a functional strontium doped bioactive glass nanoparticles (Sr-BGNs)-instructed orthopedic implant composed of PEEK, Sr-BGNs and polydopamine (PDA). In addition to destroying the permeability and integrity of MRSA biofilm, PDA also endowed PEEK substrate with effective antibacterial ability when exposing to near-infrared (NIR) irradiation. The NIR mediated photothermal disruption of biofilms contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of methicillin-resistant Staphylococcus aureus strains (MRSA) biofilm in vitro and in vivo. Notably, the engineered implants exhibit satisfactory cytocompatibility. In addition, Sr ions released from Sr-BGNs inhibited the expression of inflammatory genes, thereby providing a superior environment for tissue repair after infection clearance. The synergistic effect of photothermal effect and immunomodulatory property might have promising applications for preventing perioperative infection and tissue repair after infection.

Strontium doped electrospinning fiber membrane with antibacterial and osteogenic properties prepared by pulse electrochemical method

• Composite fibers were prepared by electrostatic spinning and pulse electrochemical deposition. • PPy controls the slow release of Sr 2+ and Cu 2+ for a long time. • Good physiological stability and long-term antibacterial effect. • Fiber has good osteogenic and angiogenic properties. The osteogenic differentiation and new bone formation are commonly delayed by bacterial infection of orthopedic implants, which is urgent to be resolved quickly in the clinic. The current paper prepared a strontium-doped electrospinning fiber membrane with antibacterial and osteogenic properties by pulse electrochemical method. Polylactic acid/hydroxyapatite (PLLA/HA) composite fiber substrate was fabricated by electrospinning technology, and strontium doped SrHA/Cu/Polypyrrole (PPy) composite coating was constructed with pulse electrodeposition method on its surface. The strontium doping technique, degradation of Sr 2+ and Cu 2+ , cellular compatibility, and the antibacterial activity of the fiber membrane were examined. The results revealed that the deposition of phosphorus and calcium on composite fiber was the highest, indicating good biological activity. The release of Sr 2+ and Cu 2+ was stable and gradual due to the modulation of PPy. The composite fiber presented excellent antibacterial performance and the antibacterial rate was close to 100% against Staphylococcus aureus and Escherichia coli. Furthermore, it is conducive to the adhesion, spread, and proliferation of vascular endothelial cells and osteoblasts, namely outstanding osteogenesis and angiogenesis abilities. In conclusion, the multifunctional PLLA/HA@SrHA/Cu/PPy composite fiber membrane with good antibacterial and osteogenic activity by electrospinning technology and pulsed electrochemical deposition method provides an effective strategy for the poor bone healing of infected bone defects. Strontium doped antibacterial osteogenic PLLA/HA@SrHA/Cu/PPy composite fiber was constructed by electrostatic spinning and pulsed electrochemical deposition technology, which showed good antibacterial properties and had the ability to promote bone induction and angiogenesis.

Silver antibacterial surface adjusted by hierarchical structure on 3D printed porous titanium alloy

Bacterial infection of porous implants at an early stage of healing is one of the causes of bone implant failure since the porous structure will increase the adhesion of bacteria. In general, antimicrobial agents can be added to the surface of the implant to kill bacteria. However, the regulation of surface topography on the release of antimicrobial agents from porous implants is still unclear. In this work, a strategy combining a hierarchical microgroove structure constructed by a femtosecond laser and silver adhered by polydopamine (PDA) is developed on a porous titanium alloy. This study finds that the surface parameters of the hierarchical structure control the total amount and rate of silver release, and PDA improves the total amount of absorbed silver. The synergistic effect of PDA and the hierarchical structure realizes the adjustability of silver adsorption and release. In vitro tests show that the modified surface has better antibacterial properties than the original surface, and it allows the cells on the surface to display a certain orientation. This surface strategy has great potential for morphologically regulated ion release and can be applied to bone regeneration.

Salvage Reconstruction of Oncologic Humeral Defects with Free Fibula Flap after Failure with Prosthesis-based Reconstruction

PURPOSE: Advancements in orthoplastic reconstructive surgery have enabled surgeons to perform limb salvage surgery successfully after long bone tumor extirpation of upper extremities. A variety of reconstructive options (allograft, prosthetics, allograft-prosthetic combination, non-vascularized autografts) exist for surgical rehabilitation of such cases. Even though reconstruction by prosthesis is most commonly used in this setting, the associated risks of mechanical failure, aseptic loosening, and infection, can potentially lead to failure and amputation. Furthermore, revision procedures of the primary surgery after implant failure are complicated by unfavorable local tissue properties like massive bone loss, unreliable local tissue, and osteopenic process of the host bone. Therefore, prosthetic reconstruction is usually undesirable; whereas vascularized bone flaps have proven to be an excellent alternative to restore the biomechanical framework of the limb. Herein, we present the free fibula flap (FFF) used to reconstruct oncological humeral defects previously treated with prosthetic based reconstruction which failed. METHOD: We conducted a retrospective review of patients who underwent salvage of the humeral reconstructions in which the prosthesis failed, during 2009 and 2019. We included patients with previous reconstruction of humeral defects only with prosthetic material and no tissue transfer. All cases were reconstructed with the FFF. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate functional outcomes. RESULTS: The mean age was 24 ± 5.54 years. Six male patients (85.7%) and one female were included (14.3%). None of the patients had comorbidities. Four patients had primitive neuro-ectodermal tumors (57.1%) while three had osteogenic sarcomas (42.9%). All patients had the radial nerve preserved during onco-resection. The average gap between implant surgery and salvage with FFFs was 77.5 ± 49.024 months. The indications for salvage with the FFF were infection of implants (42.9%) and aseptic loosening (57.1%). The defects were located proximally in seven patients (85.7%) and mid-shaft in one patient (14.3%). Seven patients had adjuvant chemotherapy (85.7%), while two had neoadjuvant radiotherapy (28.6%). The defect length after debridement and implant removal was 13 ± 5.62 cm. The fibula head was incorporated in 57.1% of the flaps (n=4). For flap fixation dynamic compression plates was used in one patient (14.3%); number 20 cerclage wiring, prolene mesh, and ethibond was used in another patient (14.3%); K wires were used in four patients (57.1%); and ethibond in 1 patient (14.3%). Only one flap had a double venous anastomosis. Two patients underwent re-exploration of the anastomosis (57.1%), the only flap harvested with a skin paddle required debridement of the cutaneous component (14.3%), and one patient had wound dehiscence (14.3%). Six flaps survived (85.7%). Bone union was achieved at 17 ± 1.25 weeks on average. The average MSTS score was 74.9%. The average follow up was 59.57 ± 43.48 months. CONCLUSION: The FFF is a resourceful alternative for the management of a failed prosthesis after oncologic resection of the proximal and mid-humerus, especially with previously infected prosthetic material. Due to its anatomical shape and the vascularized nature of tissue, the FFF provides a long bone segment for humeral reconstruction.

Infection rate of penile prosthesis implants in men with spinal cord injury: a meta-analysis of available evidence.

The risk of penile prosthesis implants (PPIs) infection in men with spinal cord injury (SCI), empirically theorized to be high, is widely variable among the studies. We performed a meta-analysis to define the pooled PPI infection rate and its possible risk factors in men with SCI. A thorough search of PubMed, Scopus and Web of Science was performed. The eighteen included studies provided information on 1079 implantation procedures, determining a pooled PPI infection rate of 8.0% (95% CI: 5.0-11.0%), with significant heterogeneity (I² = 67.0%). Trim-and-fill adjustment for publication bias had a small effect on the pooled estimate (adjusted odds ratio: 6.3%, 95% CI: 2.5-10.0%) with a substantial reduction in heterogeneity (I2 = 32.4%). The PPI infection rate was higher for inflatable PPIs than for malleable PPIs (16.4% vs 8.9%, p = 0.027). No differences were found between the different levels of SCI. In conclusion, the risk of PPI infection in SCI would be higher than that reported in the general population. However, the results were produced from dated and low/moderate quality studies that may not fully reflect the outcomes of modern PPIs and implantation protocols. There is an urgent need to gather more information on this topic through studies relevant to contemporary practice.

Designing a novel bio-compatible hydroxyapatite (HA)/hydroxyquinoline (8-HQ)-inbuilt polyvinylalcohol (PVA) composite coatings on Mg AZ31 implants via electrospinning and immersion protocols: Smart anti-corrosion and anti-bacterial properties reinforcements

To overcome the magnesium’s high corrosion rate issue, triple polyvinylalcohol (PVA) coatings containing hydroxyapatite (HA) and 8-hydroxyquinoline (8-HQ) were prepared by two different methods of electrospinning and immersion. The formation of HA and Mg(8-HQ)2 layers during exposure to a corrosive medium was indicated by X-ray diffraction (XRD) and fluorescent images, respectively. Results showed that the electrospinning coating containing HA and 8-HQ, revealed a significant anti-corrosion performance (Rct = 7891, and 12,680 ohm cm2 in NaCl 3.5 wt.%, and simulated body fluid (SBF), respectively) compared to the same composition immersion samples (Rct = 3231, and 3727 ohm cm2). The increment in anti-corrosion performance is caused by the release of HA and 8-HQ from the nanofibers. The problem of bacterial infections in magnesium implants has been improved (reduction in bacterial-growth percentage = 90% in coating prepared by electrospinning method) by cleverly designing the triple coating containing 8-HQ as an anti-bacterial compound.

Ultrathin Nanostructured Films of Hyaluronic Acid and Functionalized β-Cyclodextrin Polymer Suppress Bacterial Infection and Capsular Formation of Medical Silicone Implants.

A type of ultrathin films has been developed for suppressing capsule formation induced by medical silicone implants and hence reducing the inflammation response to such formation and the differentiation to myofibroblasts. The films were each fabricated from hyaluronic acid (HA) and modified β-cyclodextrin (Mod-β-CyD) polymer which was synthesized with a cyclodextrin with partially substituted quaternary amine. Ultrathin films comprising HA and Mod-β-CyD or poly(allylamine hydrochloride) (PAH) were fabricated by using a layer-by-layer dipping method. The electrostatic interactions produced from the functional groups of Mod-β-CyD and HA influenced the surface morphology, wettability, and bio-functional activity of the film. Notably, medical silicone implants coated with PAH/HA and Mod-β-CyD multilayers under a low pH condition exhibited excellent biocompatibility and antibiofilm and anti-inflammation properties. Implantation of these nanoscale film-coated silicones showed a reduced capsular thickness as well as reduced TGFβ-SMAD signaling, myofibroblast differentiation, biofilm formation, and inflammatory response levels. We expect our novel coating system to be considered a strong candidate for use in various medical implant applications in order to decrease implant-induced capsule formation.

P390 A lateral flow assay for the immunodiagnosis of human cat-transmitted Sporotrichosis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesSporotrichosis is a neglected endemic implantation (subcutaneous) mycosis caused by different species of Sporothrix spp. Since the 1990s, cat-transmitted sporotrichosis (CTS) by Sporothrix brasiliensis has emerged as an important zoonosis in Brazil, being a public health issue. The disease continues to spread in the country and in neighboring countries. Therefore, the aim of the study is the validation of a fast and accurate test by Lateral Flow Assay (LFA) for serodiagnosis of CTS using human sera.MethodsThe anti-Sporothrix LFA was developed and provided by IMMY (Oklahoma, USA), and obtained via ConA purification of culture filtrate, composed by a 50:50 mix of S. schenkii (ATCC 58251), and S. brasiliensis (ATCC-MYA 4824). The control line was a goat anti-human IgG/IgM. The gold conjugate was a blend of proteins G and L. The strip uses a conjugate pad, nitrocellulose membrane, and an absorbent pad. A prospective cross-sectional study was performed with 300 human sera specimens divided into three groups: Group 1 (n = 100)—patients with a proven or probable diagnosis of CTS based on Guide to Health Surveillance from Ministry of Health Brazil; Group 2 (n = 100)—patients with other mycoses (implantation, systemic or opportunistic infections) confirmed in the laboratory by direct examination and/or culture and/or serological tests; Group 3 (n = 100)—asymptomatic volunteers (Fig. 1). Specimens were collected between November 2018 and March 2021 at the Mycology Laboratory of the Clinical Hospital Complex of the Federal University of Paraná, Curitiba, Brazil. The sera were diluted 1:441 with specimen diluent, 100 μL of the dilution dispensed into a flat bottom well, inserted strip, and incubated at room temperature (15-25°C) for 30 min. A visual read of the strips was done, this read was performed by two operators, within 10 min after the time of incubation. This study was approved by the Research Ethics Committee under registration CAAE 12379819.4.0000.0096. Data analysis was performed using MedCalc software.ResultsUsing the IMMY's anti-Sporothrix detection antibody LFA, we observed a global sensitivity of 83% [95% confidence interval (CI) 74%-90%], a specificity of 82% (95% CI 76%-87%), positive predictive value of 69% (95% CI 62%-75%), negative predictive value of 90% (95% CI 85%-93%), and an accuracy of 82% (77%-86%). The results by clinical form and cross-reactivity analysis can be seen in Table 1.ConclusionThese findings suggest that IMMY's anti-Sporothrix detection antibody LFA prototype is promising, can be a useful diagnostic tool for the diagnosis of CTS in human specimens, and can be used for the qualitative detection of serum antibodies against Sporothrix spp. Like other rapid tests, this LFA is faster and simpler to perform in comparison with other conventional laboratory assays for the diagnosis of sporotrichosis. This test can improve the evidence level of diagnosis of probable disease. Rapid detection of CTS reduces the morbimortality of the disease, and consequently the time of therapy. It could have an impact on the control of the outbreak.

Bacitracin for Injection Recall: Impact on Immediate Breast Implant Surgical Outcomes.

Background Triple-antibiotic irrigation of breast implant pockets is a mainstay of infection prophylaxis in breast reconstruction and augmentation. The recall of bacitracin for injection due to risk of anaphylaxis and nephrotoxicity in January 2020, a staple component of the irrigation solution, has raised concern for worsened postoperative sequelae. This study aimed to investigate pre- and post-recall implant-based breast surgery to analyze the impact of bacitracin in irrigation solutions on infection rates. Methods All implant-based breast reconstruction or augmentation surgeries from January 2019 to February 2021 were retrospectively reviewed. In a regression discontinuity study design, patients were divided into pre- and post-recall groups. Patient demographics, surgical details, and outcomes including infection rates were collected. Differences in complication rates were compared between groups and with surgical and patient factors. Results 254 implants in 143 patients met inclusion criteria for this study, with 172 implants placed before recall and 82 placed after recall. Patients in each cohort did not differ in age, BMI, smoking status, or history of breast radiation or capsular contracture (p > 0.05). All breast pockets were irrigated with antibiotic solution, most commonly bacitracin, cefazolin, gentamycin, and povidone-iodine before recall (116,67.4%) and cefazolin, gentamycin, and povidone-iodine after recall (59,72.0%). There was no difference in incidence of infection (6.4% vs. 8.5%, p=0.551) or cellulitis (3.5% vs. 3.7%, p=0.959) before and after recall. Implant infection was associated with smoking history (p < 0.001) and increased surgical time (p=0.003). Conclusions Despite the recent recall of bacitracin from inclusion in breast pocket irrigation solutions, our study demonstrated no detrimental impact on immediate complication rates. This shift in irrigation protocols calls for additional investigations into optimizing antibiotic combinations in solution, as bacitracin is no longer a viable option, to improve surgical outcomes and long-term benefits.

Controlled Release Mechanism of Vancomycin from Double-Layer Poly-L-Lactic Acid-Coated Implants for Prevention of Bacterial Infection.

Implantation failure due to bacterial infection incurs significant medical expenditure annually, and treatment tends to be complicated. This study proposes a method to prevent bacterial infection in implants using an antibiotic delivery system consisting of vancomycin loaded into poly-L-lactic acid (PLLA) matrices. A thin layer of this antibiotic-containing polymer was formed on stainless steel surfaces using a simple dip-coating method. SEM images of the polymeric layer revealed a honeycomb structure of the PLLA network with the entrapment of vancomycin molecules inside. In the in vitro release study, a rapid burst release was observed, followed by a sustained release of vancomycin for approximately 3 days. To extend the release time, a drug-free topcoat of PLLA was introduced to provide a diffusion resistance layer. As expected, the formulation with the drug-free topcoat exhibited a significant extension of the release time to approximately three weeks. Furthermore, the bonding strength between the double-layer polymer and the stainless steel substrate, which was an important property reflecting the quality of the coating, significantly increased compared to that of the single layer to the level that met the requirement for medical coating applications. The release profile of vancomycin from the double-layer PLLA film was best fitted with the Korsmeyer–Peppas model, indicating a combination of Fickian diffusion-controlled release and a polymer relaxation mechanism. More importantly, the double-layer vancomycin-PLLA coating exhibited antibacterial activity against S. aureus, as confirmed by the agar diffusion assay, the bacterial survival assay, and the inhibition of bacterial surface colonization without being toxic to normal cells (L929). Our results showed that the proposed antibiotic delivery system using the double-layer PLLA coating is a promising solution to prevent bacterial infection that may occur after orthopedic implantation.

6. Utility of next generation sequencing and isothermal microcalorimetry for identification of bacteria in presumed aseptic thoracolumbar revision spine surgery

<h3>BACKGROUND CONTEXT</h3> Recent studies have been able to detect the subclinical presence of bacteria in 10%-40% of patients undergoing revision spinal instrumentation procedures, suggesting that clinically silent bacteria may be responsible for presumed aseptic revisions. <h3>PURPOSE</h3> The purpose of this study is to determine the rate of bacterial presence in revision thoracolumbar spinal instrumentation surgery due to implant failure. In patients without clinical signs or symptoms of infection, we will utilize next generation sequencing (NGS) technology as well as cultures and isothermal microcalorimetry (IMC) to determine the rate of subclinical infection. <h3>STUDY DESIGN/SETTING</h3> A prospective pilot case-series at a single academic institution between September 2020 and September 2021. <h3>PATIENT SAMPLE</h3> Patients undergoing consecutive thoracolumbar revision spine surgery resulting from implant failure. <h3>OUTCOME MEASURES</h3> The main outcome measure was bacterial presence. Routine patient and clinical information including age, sex, body mass index, preoperative indication, and additional clinical/operative information were also identified. Lab values included ESR, CRP and procalcitonin. COVID tests results were documented. <h3>METHODS</h3> Patients undergoing thoracolumbar revision spine surgery due to implant failure by a single surgeon at a single institution were prospectively identified. Tissue and blood samples were taken intraoperatively and transported to a lab for analysis using IMC and NGS. <h3>RESULTS</h3> In the pilot study, 22 consecutive patients were included based on prespecified criteria. The average (SD) age of the patients was 65 (14) with 25% female sex. There were 82 total tissue samples obtained (mean 3.7 samples per patient), with a concordance of 93% between cultures and IMC, 85% between cultures and NGS, and 88% between IMC and NGS. The prevalence of occult surgical site infection was detected in 4/22 (18%) cases by NGS, 2/22 (9%) cases by IMC, and 0/22 (0%) by standard cultures. Two out of two (100%) infections detected by IMC and 2/4 (50%) of the NGS infections had grossly loose/broken pedicle screws without clear etiology for breaking, suggesting these are potentially real subclinical infection cases. There was one additional loosening of screws case without pathogen identification by any platform. However, no patients have undergone subsequent surgery for concern for infection to date. For that reason, considering loose/broken screw cases as true subclinical infections IMC had 67% sensitivity, 100% specificity, 100% PPV, and 95% NPV, while NGS was 67%, 90%, 50%, 94% respectively, and cultures were 0%, 100%, 0%, 87% respectively. Pathogens identified include Fusarium equiseti (fungi), Acinetobacter spp., Brevundimonas spp., Lecythophora spp. (fungi), Enterobacter cloacae, Escherichia coli, Enterococcus faecalis, and Staphylococcus haemolyticus. <h3>CONCLUSIONS</h3> The detection of infection in spinal implants is challenging. The use of IMC and NGS identified two occult cases of infection, while NGS also falsely identified two additional cases of infection in our pilot case series of thoracolumbar revision spine surgery, while one possible subclinical infection had no pathogens identified on any platform. Research using IMC and NGS to detect subclinical infection in revision spine surgery requires further investigation but indicates subclinical infection may be an explanation for some instances of revision surgery, particularly those involving loose or broken pedicle screws. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways

Strategies to manipulate immune cell co-inhibitory or co-activating signals have revolutionized immunotherapy. However, certain immunologically cold diseases, such as bacterial biofilm infections of medical implants are hard to target due to the complexity of the immune co-stimulatory pathways involved. Here we show that two-dimensional manganese chalcogenophosphates MnPSe3 (MPS) nanosheets modified with polyvinylpyrrolidone (PVP) are capable of triggering a strong anti-bacterial biofilm humoral immunity in a mouse model of surgical implant infection via modulating antigen presentation and costimulatory molecule expression in the infectious microenvironment (IME). Mechanistically, the PVP-modified MPS (MPS-PVP) damages the structure of the biofilm which results in antigen exposure by generating reactive oxidative species, while changing the balance of immune-inhibitory (IL4I1 and CD206) and co-activator signals (CD40, CD80 and CD69). This leads to amplified APC priming and antigen presentation, resulting in biofilm-specific humoral immune and memory responses. In our work, we demonstrate that pre-surgical neoadjuvant immunotherapy utilizing MPS-PVP successfully mitigates residual and recurrent infections following removal of the infected implants. This study thus offers an alternative to replace antibiotics against hard-to-treat biofilm infections.

Use of Antibacterial Envelopes for Prevention of Infection in Intrathecal Pump Implantation

Intrathecal pumps for targeted delivery of baclofen for spasticity or morphine/hydromorphone for chronic pain are attractive treatment options for a variety of conditions, with increasing utilization. Placement of these devices carries a historic infection rate as high as 12%. Treatment of pump-related infection includes removal of the system, potentially leading to dangerous medication withdrawal. TYRX antibacterial envelopes (Medtronic Inc., Minneapolis, MN), which are absorbable mesh envelopes that elute minocycline and rifampin, have been used in implantable cardiac devices with substantial risk reduction for infection.

Secondary amine pendent β-peptide polymers realizing antimicrobial surfaces to prevent bacterial infection of implants

Antimicrobial coatings covalently grafted on the implant surfaces are considered to be one of the powerful weapons to prevent implant-associated infections. β-Peptide polymers and host defense peptide mimicking polymers are considered promising candidates to fight against drug-resistant bacteria. Here, we compared the antimicrobial activity of Au surface modified by these β-peptide polymers containing primary, secondary, and tertiary amino groups in the side chains. Copolymer P3 containing secondary amino groups was found to have high antibacterial activity. P3-modified thermoplastic polyurethane (TPU) can serve as a promising antimicrobial material for practical application, because of its effective prevention of TPU-related infection and the promotion of host cell growth in the subcutaneous implant infection model.