Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma. Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316

Periprosthetic joint infections (PJIs) and osteosynthesis-associated infections (OSIs) present significant challenges in trauma and orthopaedic surgery, substantially impacting patient morbidity, mortality, and economic burden. This concern is heightened in patients with pre-existing comorbidities, such as diabetes mellitus, which are not always modifiable at presentation. A novel intraoperative strategy to prevent these infections is the use of Defensive Antibacterial Coating (DAC), a bio-absorbable antibiotic-containing hydrogel applied to implant surfaces at implantation, acting as a physical barrier to prevent infection. The purpose of this study is to assess the use of a commercially available hydrogel (DAC), highlighting its characteristics that make it suitable for managing PJIs and OSIs in orthopaedics and traumatology. Twenty-five patients who underwent complex orthopaedic procedures with intraoperative application of DAC between March 2022 and April 2023 at a single hospital site were included. Post-operative assessment encompassed clinical, laboratory, and radiographic examinations. In this study, 25 patients were included, with a mean age of 70 ± 14.77 years and an average ASA grade of 2.46 ± 0.78. The cohort presented an average Charleston Comorbidity score of 5.45 ± 2.24. The procedures included 8 periprosthetic fractures, 8 foot and ankle surgeries, 5 upper limb surgeries, and 4 elective hip and knee surgeries. Follow-up assessments at 6 weeks and 6 months revealed no evidence of PJI or OSI in any patients, nor were any treatments for PJI or OSI required during the interim period. DAC demonstrated efficacy in preventing infections in high-risk patients undergoing complex orthopaedic procedures. Our findings warrant further investigation into the use of DAC in complex hosts with randomized control trials

Introduction: Since the establishment of osteosynthesis as the treatment of choice for bone fractures, the issues relating to complications and their prophylaxis have become a major topic of scientific discussion and research in the field of traumatology. Infection of the bone and soft tissue represents one major complication that arises after the implantation of osteosynthetic material at the fracture site. The treatment of these infections is often time-consuming and involves repeated, extensive surgical interventions. The aim of this study was to acquire information about the effect of an antibacterial and biodegradable poly-L-lactide (PLLA) coated titanium plate osteosynthesis on local infection resistance. Material and Methods: We compared infection rates in white New Zealand rabbits after titanium plate osteosynthesis of the tibia with or without antibacterial coating after local percutaneous bacterial inoculations at different concentrations (2x10. 5. –2xlO. 8. ):. group I (n=12):uncoated titanium plate,. group II (n=12): PLLA coated titanium plate,. group III (n=12): titanium plate coated with PLLA + 3% Rifampicin and 7% Fusidic acid, group IV (n= 12): titanium plate coated with PLLA + 2% Octenidin und 8% Irgasan. The plate, the contaminated soft tissues and the underlying bone were removed under sterile conditions after 28 days and quantitatively evaluated for bacterial growth. A stepwise experimental design with an “up-and-down” dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the differences between the infection rates of both groups was performed using the two-sided Fisher exact test (p< 0.05). Results: The overall infection rate was 50%. For group I and II the infection rate was both 83% (10 of 12 animals). In group III and IV with antibacterial coating the infection rate was both 17% (2 of 12 animals). The ID50 in the antibacterial coated groups III and IV was recorded as lxl10. 8. CFU, whereas the ID50 values in the groups I and II without antibacterial coating were a hundred times lower at lxl10. 6. CFU, respectively. The difference between the groups with and without antibacterial coating was statistically significant (p=0.033). Conclusions: Using an antibacterial biodegradable PLLA coating on titanium plates, a significant reduction of infection rate in a canine infection model could be demonstrated. For the first time we were able to show, under standardized and reproducable conditions, that an antiseptic coating leads to the same reduction in infection rate as an antibiotic coating. Taking the problem of antibiotic-induced bacterial resistance into consideration, we thus regard the antiseptic coating, which shows the same level of effectiveness, as advantageous

Background. External fixation is a method of osteosynthesis currently required in traumatology and orthopaedic surgery. Pin tract infection is a common problem in clinical practice. Infection occurs after a bacterial colonisation of the pin due to its contact with skin and local environment. To prevent such local contamination, one way to handle this issue is to create a specific coating using method which could be applied in the medical field. In this work we develop a surface coating for external fixator pins based on photocatalytic TiOα properties, producing a bactericidal effect with sufficient mechanical strength to be compatible with surgical use. Method. The morphology and structure of the sol-gel coating layers were characterised using, respectively, scanning electron microscopy and X-ray diffraction. Resistance properties of the coating were investigated by mechanical testing. Photo-degradation of acid orange 7 in aqueous solution was used as a probe, to assess the photo-catalytic activity of titanium dioxide layers under UV irradiation. The bactericidal effect induced by the process was evaluated against 2 strains: a Staphylococcus aureus and a multiresistant Staphylococcus epidermidis. Results. The coated pins showed good mechanical strength and efficient antibacterial effect after 1 hour of UV irradiation. Conclusion. Our study allowed to develop an antibacterial coating for stainless steel commonly used in surgical practice. The process using photoactive TiO2 exposed to UV irradiation is actually well known and applied in many disinfection fields, and exhibited efficiency against the two main bactericidal strains involved in pin tract infections. Mechanical tests confirmed the coating's ability to resist to important stresses. Moreover, this kind of coating created by sol-gel dip-coating techniques is not expensive and quite easy to do. As a consequence, we can hope that this new option would treat preventively pin tract infection, even if there is an important optimisation task to be done in order to amplify bactericidal properties. Level of evidence. II

Infection remains among the first reasons for failure of joint prosthesis. Currently, the golden standard for treating prosthetic joint infections (PJIs) is two-stage revision. However, two-stage procedures have been reported to be associated with higher costs and possible higher morbidity and mortality, compared to one-stage. Furthermore, recent studies showed the ability of a fast-resorbable, antibacterial-loaded hydrogel coating to reduce surgical site infections after joint replacement, by preventing bacterial colonization of implants. Aim of this study was then to compare the infection recurrence rate after a one-stage, cemenless exchange, performed with an antibacterial coated implant versus a standardized two-stage revision procedure. In this two-center prospective study, 22 patients, candidate to revision surgery for PJI, were enrolled to undergo a one-stage revision surgery with cementless implants, coated intra-operatively with a fast-resorbable, antibiotic-loaded hyaluronan and poly-D,L-lactide based hydrogel coating (“Defensive Antibacterial Coating”, DAC, Novagenit, Italy). DAC was reconstructed according to manufacturer indications and loaded with Vancomycin or Vancomycin + Meropenem, according to cultural examinations, and directly spread onto the implant before insertion. This prospective cohort was compared with a retrospective series of 22 consecutive patients, matched for age, sex, host type, site of surgery, that underwent a two stage procedure, using a preformed, antibiotic-loaded spacer (Tecres, Italy) and a cementless implant. The second surgery, for definitive implant placing, was performed only after CRP normalization and no clinical sign of infection. Clinical, laboratory and radiographic evaluation were performed at 3, 6 and 12 months, and every 6 months thereafter. Infection recurrence was defined by the presence of a sinus tract communicating with the joint, or at least two among the following criteria: clinical signs of infections; elevated CRP and ESR; elevated synovial fluid WBC count; elevated synovial fluid leukocyte esterase; a positive cultural examination from synovial fluid; radiographic signs of stem loosening. The two groups did not differ significantly for age, sex, host type and site of surgery (18 knees and 4 hips, respectively). The DAC hydrogel was loaded intra-operatively, according to cultural examination, with vancomycin (14 patients) or vancomycin and meropenem (8 cases). At a mean follow-up of 20.2 ± 6.3 months, 2 patients (9.1%) in the DAC group showed an infection recurrence, compared to 3 patients (13.6%) in the two-stage group. No adverse events associated with the use of DAC or radiographic loosening of the stem were observed at the latest follow-up months. This is the first report on one-stage cementless revision surgery for PJI, performed with a fast-resorbable antibacterial hydrogel coating. Our data, although in a limited series of patients and at a relatively short follow-up, show similar infection recurrence rate after one-stage exchange with cementless, coated implants, compared to two-stage revision. These findings warrant further studies in the possible applications of antibacterial coating technologies to treat implant-related infections

Summary Statement. An Implant Disposable Antibacterial Coating (i-DAC®) is described, consisting of a fully resorbable, biocompatible hydrogel, able to release antibacterial and antibiofilm agents. Direct application of the hydrogel on implants prevented infection occurrence in an in vitro model of peri-prosthetic infection. Introduction. Biofilm-related infections are among the main reasons for failure of joint prosthesis with high associated social and economical costs. Bacterial adhesion and subsequent biofilm formation have been shown to develop early after biomaterials implant into the human body, when a “race to the surface” takes place between the host's cells and the colonizing bacteria eventually present at the surgical site. Providing an antibacterial/antibiofilm coating of the implant may then play a strategic role in preventing biofilm related infections. Here we report the results of a series of in vitro and in vivo studies, partially performed under the European 7th Framework Programme (Implant Disposable Antibiotic Coating, IDAC, collaborative research project # 277988), concerning a fully resorbable, biocompatible antibacterial hydrogel coating (DAC®, Novagenit, Italy). The patented hydrogel, a co-polimer comprising of hyaluronic acid and a polylactic acid, has been designed to be mixed with various antibacterial agents and applied directly on the implant at the time of surgery, being fully resorbed within few days. Patients & Methods. The tested hydrogel (DAC®, Novagenit, Italy) is a derivative of a low molecular weight hyaluronan, grafted with poly-D, L-lactic acid and provided in powder form. At the point of care, the powder is hydrated with the antibiotic or antibiofilm solution, thus generating the final compound to be applied onto the implant surface. In vitro studies were conducted using DAC® coating on different biomaterials, including titanium, chrome-cobalt and polyethylene discs. The release of different antibacterial agents, including vancomycin, ciprofloxacin, meropenem, gentamycin, amikacin, tobramycin, clindamycin, doxycyclin, linezolid, NAsalycilate and N-acetylcisteine, adequately mixed with the hydrogel, has been tested by means of gas chromatography and microbiological methods. In vivo studies were then performed on 35 rabbits divided in 7 groups. Animals were implanted with an intramedullary titanium rod in their femur, with a known inoculum of methicillin-resistant Staph. aureus and vancomycin-loaded DAC® at different concentrations (2% and 5%) and compared with controls. Results. Regardless of the tested material, in vitro studies showed the ability of the hydrogel to be loaded and to sustain the release of the following antibacterial/antibiofilm compounds for up to 96 hours: vancomycin, ciprofloxacin, meropenem, gentamycin, amikacin, tobramycin, clindamycin, doxycyclin, linezolid, NAsalycilate, N-acetylcisteine. In vivo studies showed a bacterial load reduction ranging from 94% to 99.9% using vancomycin-loaded DAC®, compared to controls. Discussion/Conclusion. DAC®, a fast-resorbable antibacterial coating, showed the ability to be loaded with various antibacterial compounds and the ability to provide a highly significant reduction of bacterial colonization of implanted biomaterials in an animal model, opening a new pathway to local prevention and treatment of biofilm-/implant-related infections

Previous studies showed that a fast-resorbable antibacterial hydrogel coating (DAC®, Novagenit Srl, Mezzolombardo, TN, Italy) composed of covalently linked hyaluronan and poly-D, L-lactide, is able to reduce early post-surgical infection both after joint replacement and osteosynthesis. Aim of the present report is to investigate medium-term safety and efficacy of the coating in patients undergoing primary and revision cementless total hip replacement (THR). We designed a two-phases study. In both phases, DAC was prepared according to manufacturer's instructions. In brief, the syringe prefilled with 300 mg of sterile DAC powder was mixed, at the time of surgery, with a solution of 5 mL of sterile water and with the tailored antibiotics, at a concentration ranging from 25 mg/mL to 50 mg/mL. The resulting antibacterial hydrogel was then spread on the outer surface of the prosthesis just before implantation. In the first phase, safety was assessed. Forty-six patients (13 primary and 33 revision THR) were treated with DAC between 2013 and 2015 and evaluated at a 2.8 ± 0.7 years follow up (FU). Antibiotics used for DAC reconstruction were Vancomycin in 33 cases, Vancomycin + Meropenem in 10, Vancomycin + Rifampicin, Teicoplanin or Ceftazidime in 1 case, respectively. Patients were evaluated at 3, 6, 12 months and yearly after with a clinical and radiographic FU. No evidence of infection and no failure/loosening of the prosthesis were observed. No adverse events were reported. The second phase was designed to evaluate efficacy of DAC in preventing infection recurrences after a two stage revision for infected THR. Twenty-seven patients, treated with DAC coating, were compared with a control group of 32, treated in the same time period, without the coating. Demographics, host type and and identified bacteria were similar in the two groups (18.6% of MRSA in DAC group vs 18.5% MRSA in no-DAC group). Patients were evaluated clinically and radiographically at 3, 6, 12 months and yearly thereafter. At a minimum 2 years FU (mean 2.7), we observed 1 dislocation in each group and 2 cases of loosening in the no-DAC group. 4 cases (11%) of recurrence of infection in the no-DAC group (1 MRSA and 3 St. Epidermidis) and no infection recurrences in the DAC group. Due to the small cohort of patients this difference is not statistically significant (Fisher's exact test, p=0.18). This is, to our knowledge, the longest observation concerning the safety and efficacy of the DAC antibacterial coating, applied to hip replacement. The results are in line with those previously reported and point out the absence of side effects of the antibacterial coating in this application and the tendency to reduce re-infection in second stage. This finding needs to be confirmed by a larger dataset

This study aimed to verify the hypothesis that an antibiotic loaded hydrogel, defensive antimicrobial coating (DAC), reduces overall complication and infection rates when used for high-risk primary and revision total hip arthroplasty (THA).

This was a retrospective study matched cohort study of 238 patients, treated with cementless implants with and without DAC. A sub-group analysis of patients undergoing 2nd stage revision THA for prosthetic joint infection (PJI) was also conducted. Re-infection rates within 2 years, complications necessitating surgical intervention and radiographic analysis for aseptic loosening was assessed.

The mean age was 68.3±11.5 years, with 39 (32.8%) Macpherson class A, 64 (53.8%) class B and 16 (13.4%) class C patients. 4 (3.4%) patients in the DAC group developed complications including 1 PJI and 1 delayed wound healing, while 13 (10.9%) patients in the control group developed complications including 5 PJIs and 3 delayed wound healing (p=0.032). PJI rates (p=0.136) and delayed wound healing rates (p=0.337) were not statistically significant. For 2nd stage revision THA for PJI there were 86 patients in the DAC group and 45 in the control group. 1 (1.2%) patient in the DAC group developed complications with no recurrences of infection or delayed wound healing, while 10 (22.2%) patients in the control group developed complications including 4 recurrent PJI and 1 delayed wound healing (p=0.003). Recurrent PJI rates were statistically significant (p=0.005) while delayed wound healing rates were not (p=0.165). Patients treated with DAC also had lower rates of aseptic loosening (0% vs 6.7%; p=0.015).

Antibiotic impregnated hydrogel coatings on cementless implants showed decreased complication rates after complex primary or revision THA. In 2nd stage revision THA for PJI, it was associated with reduced risk of re-infection and aseptic loosening.

Bacterial infection related to orthopaedic implants is a significant complication today. One of the ways to reduce the incidence of implant-associated infections is assumed to give antibacterial activity to surface of implant itself. We focused attention on Ag, because it has a broad antibacterial spectrum, strong antimicrobial activity and low toxicity. In the previous works, sputtering, electrochemically deposition and sol-gel coating of Ag-containing hydroxyapatite (HA) have been reported. However, since practical technique of HA coating widely used for medical and dental implants has been the “thermal spraying” technique over the last two decades, we aimed at developing the novel thermal spraying technology for Ag-HA coating with antibacterial activity. In this study, physical and chemical properties, in vitro antibacterial activity, inhibition activity of bacterial attachment, HA-forming ability, cytotoxicity and release of Ag ions of the thermal-sprayed Ag-HA coating were evaluated. HA powder containing 3wt % of silver oxide (Ag2O) was sprayed on surface of titanium disks by the thermal spraying method using acetylene torch. SEM images showed a typical structure of the thermal-sprayed coating and the X-ray diffraction (XRD) pattern of the coating showed an amorphous structure. Ag residue in the coating was determined by the elementary analysis. The coating showed strong antibacterial activity and inhabitation activity of bacterial attachment to the methicillin-resistant Staphylococcus aureus (MRSA) in fetal bovine serum (FBS). On the other hand, the coating showed fast HA-forming ability in simulated body fluid (SBF) and no cytotoxicity related to Ag contained in the coating. Therefore, it is expected that the thermal-sprayed Ag-HA coating provides antibacterial and bone-bonding ability on the surface of the implant itself. In addition, though the HA coating is generally liable to adhere bacteria, the thermal-sprayed Ag-HA coating overcomes this problem. Pre-evaluation of release of Ag ions from the Ag-containing ceramic powders indicated that the releasing behavior of Ag ions in SBFs is dependent on the existing form of Ag in the Ag-containing material. It is assumed that most of Ag components in the Ag-HA coating are not retained as metallic Ag but as Ag2O in the amorphous layer. Time-course release tests of Ag ions from the coating in FBS showed a large release rate of Ag ions until 24 h after the immersion. It is expected that the Ag-HA coating could show strong antibacterial activity at the early post-operative stage. In the repeated release testing, the amount of released Ag ions was about 6500 ppb for the first release test, after which it gradually decreased. However, a significant release amount of Ag ions was observed even after the sixth repeat test. Therefore, it was assumed that the thermal-sprayed Ag-HA coating has a slow-release property of Ag ions in FBS

Aim. In the current study we aim to characterize the use of cationic host defense peptides (HDPs) as alternative antibacterial agents to include into novel antibacterial coatings for orthopedic implants. Staphyloccous aureus represent one the most challenging cause of infections to treat by traditional antibacterial therapies. Thanks to their lack of microbial resistance described so far, HDPs represent an attractive therapeutic alternative to antibiotics. Furthermore, HDPs have been showed to control infections via a dual function: direct antimicrobial activity and regulation of immune response. However, HDPs functions characterization and comparison is controversial, as changing test conditions or cell type used might yield different effects from the same peptide. Therefore, before moving towards the development of HDP-based coatings, we need to characterize and compare the immunomodulatory and antibacterial functions under the same conditions in vitro of 3 well-known cathelicidins: human LL-37, chicken CATH-2, and bovine-derived IDR-1018. Method. S. aureus, strain SH1000, was incubated with different concentrations of each HDP and bacterial growth was monitored overnight. Primary human monocytes were isolated from buffy coats using Ficoll-Paque density and CD14 microbeads, and differentiated for 7 days to macrophages. After 24h incubation in presence of LPS and HDPs, macrophages cytokines production was measured by ELISA. Macrophages cultured for 24h in presence of HDPs were infected with serum-opsonized S. aureus. 30 min and 24h after infection, bacterial phagocytosis and intracellular killing by macrophages were measured by flow cytometry and colony forming units (CFU) count respectively. Results. All HDPs efficiently inhibit macrophages LPS-mediated activation, as observed by a reduced production of TNF-α and IL-10. Despite a comparable anti-inflammatory action, only CATH-2 shows direct antibacterial properties at concentrations 10-times lower than those needed to stimulate immune cells. Although stimulation with HDPs fails to improve macrophages ability to kill intracellular S. aureus, IDR-1018 decreases the proportion of cells phagocytosing bacteria. Conclusions. In addition to a strong anti-inflammatory effect provided by all HDPs tested, CATH-2 has direct antibacterial effects while IDR-1018 reduces the proportion of macrophages infected by S. aureus. Use of these HDPs in combination with each other or with other conventional antibacterial agents could lead the way to the design of novel antibacterial coatings for orthopedic implants

Aim. To develop a new system for antibacterial coating of joint prosthesis and osteosynthesis material. The new coating system was designed to release gentamicin immediately after insertion to eradicate surgical contamination. Method. Steel implants (2×15mm) were coated with a solid nanocomposite xerogel made from silica and the dendritic polymer, hyperbranched polyethyleneimine. The xerogel was anchored inside a porous surface made by pre-coating with titanium microspheres. Finally, gentamicin was encapsulated in the xerogel, i.e. no chemical binding. A total of 50 µg gentamicin was captured into each implant. The efficacy of the new coating was evaluated in a porcine model of implant associated osteomyelitis. In total, 30 female pigs were randomized into 3 study groups (n=10). Group A; plain implants + saline, Group B; plain implants + 10. 4. CFU of Staphylococcus aureus, and Group C; coated implants + 10. 4. CFU of S. aureus. Implant + inoculum was placed into a pre-drilled implant cavity of the right tibia and the pig was euthanized 5 days afterwards. Postmortem microbiology and pathology were performed. Two additional pigs were used in a pharmacokinetic study where microdialysis (MD) catheters were placed alongside coated implants. Extracellular fluid was sampled regularly for 24 hours from the MD catheters and analyzed for gentamicin content. Results. Within Groups A and C, all implants were found sterile by sonication and bacteria could not be identified within the surrounding bone tissue. In contrast, all Group B animals had S. aureus positive implant and tissue microbiology. Macroscopic and microscopic pathological examinations confirmed that Group A and C animals were complete identic, i.e. no pus around implants and only minor peri-implant inflammation related to insertion of implants per se. All Group B animals had pus around their implants and a massive peri-implant inflammatory response dominated by neutrophil granulocytes. Maximum gentamicin release (35 µg /mL) was measured in the first obtained MD sample, i.e. after 30 min, and the concentration stayed above the MIC level for the used S. aureus strain for 8 hours. Conclusions. The new xerogel coating prevented development of osteomyelitis. Prevention was due to a fast gentamicin release immediately following insertion and antimicrobial active concentrations were detectable several hours after implantation. This means that the critical time point of most relevant surgical procedures potentially could be protected by the novel coating. The new coating will be investigated on larger scale implants and full-size prosthesis in the future

Infections are among the main complications connected to implantation of biomedical devices, having high incidence rate and severe outcome. Since their treatment is challenging, prevention must be preferred. For this reason, solutions capable of exerting suitable efficacy while not causing toxicity and/or development of resistant bacterial strains are needed. To address infection, inorganic antibacterial coatings, and in particular silver coatings, have been extensively studied and used in the clinical practice, but some drawbacks have been evidenced, such as scarce adhesion to the substrate, delamination, or scarce control over silver release. Here, antibacterial nanostructured silver-based thin films are proposed, obtained by a novel plasma-assisted technique, Ionized Jet Deposition (IJD). Coatings are obtained by deposition of metallic silver targets. Films thickness is selected based on previous results aimed at measuring extent and duration of silver release and at evaluating toxicity to host cells (fibroblasts). Here, composition (grazing incidence XRD) and morphology (SEM) of the obtained coatings are characterized for deposition onto different substrates, both metallic and polymeric. For heat sensitive substrates, possible alterations caused by coatings deposition in terms of morphology (SEM) and composition (FT-IR) is assessed. Then, a proof-of-concept study of the capability of these films to inhibit microbial biofilm formation is performed by using two different supports i.e., the Calgary Biofilm Device and the microplates. To the best of the Authors knowledge, this is the first study describing the application of specific anti-biofilm analyses to nanostructured coatings. In particular, anti-biofilm activities are tested against the following pathogenic strains: Escherichia (E.) coli NCTC12923, Staphylococcus (S.) aureus ATCC29213 and S. aureus 86. Among these, the strain 86 is not only pathogen but it also possesses several antibiotic resistance genes, allowing the evaluation of the utilization of nanostructured coatings as an alternative anti-microbial system to face the global threat of antibiotic resistance. Results indicate that films deposited from silver targets are composed of nanosized aggregates of metallic silver, indicating a perfect transfer of composition from the deposition target to the coatings. Results obtained here indicate that the films have significant antibacterial and antibiofilm activity. In addition, they prove that the system can be successfully applied for evaluation of coatings antibacterial efficacy for biomedical applications

Implant-related infections pose a severe economical and societal burden, hence solutions capable of exerting suitable efficacy while not causing toxicity and/or development of resistant bacterial strains are needed. Thus, inorganic antibacterial coatings, and in particular silver coatings, have been extensively studied and used in the clinical practice. However, some drawbacks such as scarce adhesion to the substrate, delamination, or scarce control over silver release have been evidenced. Here, antibacterial nanostructured silver thin films have been developed by a novel plasma-assisted technique. The technique allows deposition on several substrates, including heat sensitive materials and objects of complex shape. Thanks to nanostructured surface, a tuned release can be achieved, preventing citoxicity. Composition (grazing incidence XRD, XPS) and morphology (SEM, AFM, ASTM) of the obtained coatings were characterized, then, their efficacy was validated in vitro against relevant bacterial strains (gram+ S. Aureus and gram– E. Coli). Live/dead kit and confocal microscopy were used to evaluate antibacterial efficacy. Super resolution imaging in the Structured Illumination Microscopy (SIM) setup was used to investigate damage to the bacterial wall. Results indicate that the coatings are composed of nanosized aggregates of metallic silver, indicating a perfect transfer of composition from the deposition target to the coating. Because of the sub-micrometric thickness, they do not alter the micro- and macro- morphology and surface finishing of the implants, developed by the manufacturers to ensure optimal integration in the host bone. Finally, remarkable efficacy was found against both gram+ and gram- bacteria, indicating that the developed coatings are promising for antibacterial applications

Aim. Infection remains among the first reasons of failure of joint prosthesis. According to various preclinical reports, antibacterial coatings of implants may prevent bacterial adhesion and biofilm formation. Aim of this study is to present the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating. *. , in patients undergoing hip or knee prosthesis. Method. In this multi-center, randomized, prospective, study, a total of 380 patients, scheduled to undergo primary or revision total hip or knee joint replacement, using a cementless or a hybrid implant, were randomly assigned, in six European orthopedic centers, to receive the antibiotic-loaded DAC coating or to a control group, without coating. Pre- and post-operative assessment of clinical scores, wound healing, laboratory tests and x-ray were performed at fixed time intervals. Results. Overall 373 patients were available at a minimum follow-up of 6 months (maximum 24 months). On average, wound healing, laboratory tests and radiographic findings did not show any significant difference between the two-groups. Eleven early surgical site infections (6%) were observed in the control group, compared to one (0.6%) in the treated group (p=0.003). No local or systemic side effects related to DAC hydrogel coating were observed and no detectable interference with implant osteointegration was noted. Conclusions. The use of a fast-resorbable, antibiotic-loaded hydrogel implant coating provides a reduced rate of early surgical site infections after hip or knee joint replacement using cementless or hybrid implants, without any detectable adverse event or side effects

Infection is among the first reasons for failure of orthopedic implants. Various antibacterial coatings for implanted biomaterials are under study, but only few technologies are currently available in the clinical setting. Previous studies showed the in vitro and in vivo efficacy and safety of a fast resorbable (<96 h) hyaluronic and polylactic acid based hydrogel, loaded with antibiotic or antibiofilm agents (DAC®, Novagenit Srl, Mezzolombardo, TN). Aim of this study is to report the results of the largest clinical trial in trauma and orthopedic patients. In this prospective, controlled, study, a total of 184 patients (86 treated with internal osteosinthesis for closed fractures and 98 undergoing cementless total hip or knee joint prosthesis) were randomly assigned in three European orthopaedic centers to receive antibiotic-loaded DAC coating or to a control group, without coating. Pre- and post-operative assessment of laboratory tests, wound healing (ASEPSIS score), clinical score (SF-12 score) and x-rays were performed at fixed time intervals. Statistical analysis was performed with Fisher exact test or Student's t test. Significance level was set at p<0.05. The study was approved by the local Ethical Committee and all patients provided a written informed consent. On average, wound healing, clinical scores, laboratory tests and radiographic findings did not show any significant difference between the two-groups at a mean 12 months follow-up (min: 6, max: 18 months). Four surgical site infections and two delayed union were observed in the control group compared to none in the treated group. No local or systemic side effects, that could be related to DAC hydrogel coating, were noted and no detectable interference with bone healing or osteointegration could be found. This is the largest study, with the longest follow-up, reporting on clinical results after the use of a fast-resosrbable anti-bacterial hydrogel coating for orthopaedic and trauma implants. Our results show the safety of the tested coating in different indications; although not statistically significant, the data also show a trend towards surgical site infection reduction, as previously demonstrated in the animal models

Background: Bacteria form a biofilm on the surface of orthopaedic devices, causing persistent and infection. Little is known about biofilms formation on bone grafts and bone substitutes. We analyzed various representative materials regarding their propensity for biofilm formation caused by Staphylococcus aureus. Methods: As bone graft beta-tricalciumphosphate (b-TCP, CyclOsTM) and as bone substitute a tantalum metal mesh (trabecular metalTM) and PMMA (Pala-cosTM) were investigated. As test organism S. aureus (strain ATCC 29213) was used. Test materials were incubated with bacterial solution of 105 colony-forming units (cfu)/ml at 37°C for 24 h without shaking. After 24 h, the test materials were removed and washed 3 times in normal saline, followed by sonication in 50 ml Ringer solution at 40 kHz for 5 minutes. The resulting sonication fluid was plated in aliquots of 0.1 ml onto aerobe blood agar with 5% sheep blood and incubated at 37°C with 5% CO2 for 24 h. Then, bacterial counts were enumerated and expressed as cfu/ml. All experiments were performed in triplicate to calculate the mean ± standard deviation. The Wilcoxon test was used for statistical calculations. Results: The three investigated materials show a differing specific surface with b-TCB> trabecular metal> PMMA per mm2. S. aureus formed biofilm on all test materials as confirmed by quantitative culture after washing and sonication. The bacterial counts in sonication fluid (in cfu/ml) were higher in b-TCP (5.1 x 106 ± 0.6 x 106) and trabecular metal (3.7 x 106 ± 0.6 x 106) than in PMMA (3.9 x 104 ± 1.8 x 104), p< 0.05. Conclusion: Our results demonstrate that about 100-times more bacteria adhere on b-TCP and trabecular metal than on PMMA, reflecting the larger surface of b-TCP and trabecuar metal compared to the one of PMMA. This in-vitro data indicates that bone grafts are susceptible to infection. Further studies are needed to evaluate efficient approaches to prevent and treat infections associated with bone grafts and substitutes, including modification of the surface or antibacterial coating

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Aims

Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation.

Aims

The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement.

At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating.

These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.