Antibiotic cement coating in orthopedic surgery: a systematic review of reported clinical techniques

Background Antibiotic-containing cement and bone graft substitute-coated orthopedic implants provide the advantages of simultaneous local antibiotic delivery and internal stable fixation, aiding in both infection eradication and osseous healing. Standardized protocols pertaining to implant coating techniques in various clinical and particularly intraoperative settings are scarce, and available literature is limited. This systematic review aims to provide a summary of the available current literature reporting on custom-made coating techniques of orthopedic implants, indications, outcomes, and associated complications in clinical use. Methods A systematic search of the literature in PubMed, Medline, Embase, and Cochrane Library databases was performed in accordance with PRISMA guidelines. Articles reporting specifically on custom-made coating techniques of orthopedic implants in a clinical setting were eligible. Results A total of 41 articles with a cumulative total number of 607 cases were included. Indications for treatment mostly involved intramedullary infections after previous plate osteosynthesis or nailing. A variety of implants ranging from intramedullary nails, plates, wires, and rods served as metal cores for coating. Polymethylmethacrylate (PMMA) bone cement was most commonly used, with vancomycin as the most frequently added antibiotic additive. Chest tubes and silicone tubes were most often used to mold. Common complications are cement debonding and breakage of the metallic implant. Conclusion Adequate coating techniques can reduce the burden of treatment and be associated with favorable outcomes. Lack of general consensus and heterogeneity in the reported literature indicate that the perfect all-in-one implant coating method is yet to be found. Further efforts to improve implant coating techniques are warranted. Level of evidence III.

Antibacterial and Anti-Inflammatory Coating Materials for Orthopedic Implants: A Review

Orthopedic implant failure is the most common complication of orthopedic surgery, causing serious trauma and resulting in a tremendous economic burden for patients. There are many reasons for implant failure, among which peri-implant infection (or implant-related infection) and aseptic loosening are the most important. At present, orthopedic doctors have many methods to treat these complications, such as revision surgery, which have shown good results. However, if peri-implant infection can be prevented, this will bring about significant social benefits. Many studies have focused on adding antibacterial substances to the implant coating, and with a deeper understanding of the mechanism of implant failure, adding such substances by different modification methods has become a research hot spot. This review aims to summarize the antibacterial and anti-inflammatory substances that can be used as coating materials in orthopedic implants and to provide a reference for the prevention and treatment of implant failure caused by implant-related infection and excessive inflammation.

Infections @ Trauma/Orthopedic Implants: Recent Advances on Materials, Methods, and Microbes—A Mini-Review

Implants and materials are indispensable in trauma and orthopedic surgery. The continuous improvements of implant design have resulted in an optimized mechanical function that supports tissue healing and restoration of function. One of the still unsolved problems with using implants and materials is infection. Trauma and material implantation change the local inflammatory situation and enable bacterial survival and material colonization. The main pathogen in orthopedic infections is Staphylococcus aureus. The research efforts to optimize antimicrobial surfaces and to develop new anti-infective strategies are enormous. This mini-review focuses on the publications from 2021 with the keywords S. aureus AND (surface modification OR drug delivery) AND (orthopedics OR trauma) AND (implants OR nails OR devices). The PubMed search yielded 16 original publications and two reviews. The original papers reported the development and testing of anti-infective surfaces and materials: five studies described an implant surface modification, three developed an implant coating for local antibiotic release, the combination of both is reported in three papers, while five publications are on antibacterial materials but not metallic implants. One review is a systematic review on the prevention of stainless-steel implant-associated infections, the other addressed the possibilities of mixed oxide nanotubes. The complexity of the approaches differs and six of them showed efficacy in animal studies.

Stability and Biocompatibility Tests of Alginate as Cochlear Implant Coating Material

Inner ear trauma caused by cochlear implantation is a severe clinical problem. It was shown that an electrode alginate coating can reduce the insertion forces in vitro. The grade of the alginate viscosity can be adjusted by using different metal ions for cross-linking the salts of the alginic acid. The aim was to investigate the stability and inner ear biocompatibility of alginate using different in vitro established cross-linkers. Alginate beads were cross-linked in either calcium chloride (CaCl2) or barium chloride (BaCl2) solution. The beads were cultivated in artificial perilymph and stability and swelling were observed for 13 months. Ototoxicity was tested on cochlear whole mount explants from neonatal rats. Neomycin served as positive control to induce hair cell damage and explants without any addition served as negative control. The beads and explants were co-cultured for 48 hours and the hair cell survival was analysed microscopically. Neomycin treatment induced an extensive inner and outer hair cell loss. Neither CaCl2 nor BaCl2 cross-linked alginate beads caused any damage to the hair cells. Even though the same volume of alginate and cross-linkers were used, in CaCl2 cross-linked beads were initially almost double the size of in BaCl2 cross-linked beads. None of the cross-linked alginate beads had a significant volume change within 3 months being cultured in artificial perilymph. After 3 months the CaCl2 cross-linked beads swelled massively and dissolved within one week whereas BaCl2 cross-linked alginate beads remained unchanged until month 13 after culture start. Alginate beads gelled with both cross-linkers are biocompatible with the inner ear sensory epithelium. Both cross-linkers ensure a stable gelation of alginate but a swelling followed by degradation of the in CaCl2 cross-linked beads occurred after 3 months. For coatings, which need to be long term stable, BaCl2 should be chosen whereas CaCl2 may be more suitable for applications where limited stability is needed and the swelling is not affecting the surrounding tissue. Therefore, BaCl2 cross-linking of alginate may be the best choice for cochlear implant coating.

Nintedanib suppresses expression of extracellular matrix proteins in TGF-β1-stimulated primary human fibroblasts of the Tenon

The development of strategies for fibrosis prevention is a perpetual cutting the edge challenge, especially in ophthalmologic fistulating surgery. Stenosis of liquid draining implants but also fibrotic activation of implant-associated tissues are major clinical examples for fibrosis induced implant failure. Implant coating or incorporation of antifibrotic agents offer a promising approach to minimise failure rates. Nintendanib is a drug that has been successfully used for the treatment of ideopathic pulmonary fibrosis since 2015. In this study, we evaluated the suitability of Nintedanib for ophthalmic therapeutic treatment. Therefore, the antifibrotic potential of the active substance was tested with a fibrotic cell culture model on primary fibroblasts of the Tenon (hTF) in vitro. The concentration of 10μM Nintedanib demonstrated a marginal effect on cell viability but coincidently diminished cell proliferation remarkably. Both, immunocytochemical and Western blot analyses revealed a significant inhibitory effect of Nintedanib on the TGF-β1 induced expression of the extracellular matrix (ECM) components fibronectin and collagen. Moreover it supressed the expression and formation of stress fibres of the fibrotic marker protein alpha smooth muscle actin (α-SMA).

Antibiotic-loaded nonwovens as protection against implant-associated infection

Implant-associated infections still must be considered as a major risk factor and represent a significant threat to the well-being of patients. The detection of such complications is often late, making therapy at this stage difficult. However, the common route of systemic antibiotic prophylaxis can be associated with numerous side effects on the patient or even lead to resistant strains of bacteria. In this context, local antibiotic drug load is a promising way to protect implants against pathogen adhesion and biofilm formation. This work addresses the incorporation of the antibiotic Doxycycline into a biodegradable nonwoven matrix as potential implant coating. While the nonwoven matrix itself displayed already inhibitory effects on Staphylococcus aureus (S. aureus) biofilm formation in vitro, this effect was even more pronounced by the incorporation of Doxycycline. Antibiotic loaded nonwovens display the possibility for local inhibition of biofilm formation. In the shape of an implant coating, this may further help to avoid implantassociated infections. Nevertheless, as pathogens vary in shape and type, further adjustments have to be performed to improve wide-ranging protective effects

Comparing the Incidence of Disruption in Daily Activities and Quality of Life Score Associated With Oral Health in Patients With Implant Candidates Before and After Treatment

Background: Changes in oral health like tooth loss can have a profound effect on the patients’ quality of life. The condition of relative or complete toothlessness exerts negative effects on chewing, speech, and appearance of the individual. The high capability of dental implants in restoring the beauty and oral function of the patients has led to their widespread usage. This study aimed to compare the quality of life of the toothless patients before and after treatment with implant. Methods: In the present study, 50 patients afflicted with complete or relative toothlessness were examined. Before completing the questionnaires, all participants were asked to complete and sign the consent form of the questionnaire from Oral Impacts on Daily Performance) OIDP). The questionnaires were completed before receiving the implant coating, and a month after the delivery of the patients’ prosthesis. Finally, the data were analyzed using SPSS statistical software, ANOVA, Mann-Whitney, and McNemar. Results: In this study, 50 patients with the mean age of 46.84±11.87 years were investigated. As for the gender and marital status of the participants, 50% (25 patients) were male and 84% (42 ones) were married. According to the data obtained from the OIDP questionnaire, the most significant changes were detected in eating, smiling, laughing and showing teeth without discomfort and speaking clearly, respectively. Moreover, a significant difference was found between the total score of oral effect on daily activities and some levels included in disruption questionnaire on daily activities such as eating, speaking clearly, going out, sleeping, relaxation, smiling, enjoying communication with others, job-related activities, as well as emotional conditions (Irritability); however, no significant difference was found between cases of cleaning teeth and light physical activity. Conclusions: According to the data from OIDP questionnaire and the study results, implant had favorable effects on the quality of life of the patients. However, long-term studies and follow-ups are necessary to determine other possible favorable effects of implant treatment.

In Vitro Corrosion of SiC-Coated Anodized Ti Nano-Tubular Surfaces

Peri-implantitis leads to implant failure and decreases long-term survival and success rates of implant-supported prostheses. The pathogenesis of this disease is complex but implant corrosion is believed to be one of the many factors which contributes to progression of this disease. A nanostructured titanium dioxide layer was introduced using anodization to improve the functionality of dental implants. In the present study, we evaluated the corrosion performance of silicon carbide (SiC) on anodized titanium dioxide nanotubes (ATO) using plasma-enhanced chemical vapor deposition (PECVD). This was investigated through a potentiodynamic polarization test and bacterial incubation for 30 days. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze surface morphologies of non-coated and SiC-coated nanotubes. Energy dispersive X-ray (EDX) was used to analyze the surface composition. In conclusion, SiC-coated ATO exhibited improved corrosion resistance and holds promise as an implant coating material.

Therapeutic assessment of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in reducing periprosthetic joint infection

Despite many preventive measures, including prophylactic antibiotics, periprosthetic joint infection (PJI) remains a devastating complication following arthroplasty, leading to pain, suffering, morbidity and substantial economic burden. Humans have a powerful innate immune system that can effectively control infections, if alerted quickly. Unfortunately, pathogens use many mechanisms to dampen innate immune responses. The study hypothesis was that immunomodulators that can jumpstart and direct innate immune responses (particularly neutrophils) at the surgical site of implant placement would boost immune responses and reduce PJI, even in the absence of antibiotics. To test this hypothesis, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (a potent chemoattractant for phagocytic leukocytes including neutrophils) was used in a mouse model of PJI with Staphylococcus aureus (S. aureus). Mice receiving intramedullary femoral implants were divided into three groups: i) implant alone; ii) implant + S. aureus; iii) implant + fMLP + S. aureus. fMLP treatment reduced S. aureus infection levels by ~ 2-Log orders at day 3. Moreover, fMLP therapy reduced infection-induced peri-implant periosteal reaction, focal cortical loss and areas of inflammatory infiltrate in mice distal femora at day 10. Finally, fMLP treatment reduced pain behaviour and increased weight-bearing at the implant leg in infected mice at day 10. Data indicated that fMLP therapy is a promising novel approach for reducing PJI, if administered locally at surgical sites. Future work will be toward further enhancement and optimisation of an fMLP-based therapeutic approach through combination with antibiotics and/or implant coating with fMLP.

Review on Surface Treatment for Implant Infection via Gentamicin and Antibiotic Releasing Coatings

Surface treatment of metallic implants plays a crucial role in orthopedics and orthodontics. Metallic implants produce side-effects such as physical, chemical/electro-chemical irritations, oligodynamic/catalytic and carcinogenic effects. These effects cause bacterial infections and account for huge medical expenses. Treatment for these infections comprises repeated radical debridement, replacement of the implant device and intravenous or oral injection antibiotics. Infection is due to the presence of bacteria in the patient or the surrounding environment. The antibiotic-based medication prevents prophylaxis against bacterial colonization, which is an emphatic method that may otherwise be catastrophic to a patient. Therefore, preventive measures are essential. A coating process was developed with its drug infusion and effect opposing biofilms. Modification in the medical implant surface reduces the adhesion of bacterial and biofilms, the reason behind bacterial attachment. Other polymer-based and nanoparticle-based carriers are used to resolve implant infections. Therefore, using an implant coating is a better approach to prevent infection due to biofilm.