Orthopedic Devices Research Articles

Management of AO-type C thoracolumbar fractures during COVID-19 pandemic using distractor device: a novel technique

Study design Prospective cohort study. Introduction Management of the severe thoracolumbar (TL) spine fracture–dislocation injuries have been further complicated by the COVID-19 pandemic. The need to optimize resources and minimize the personnel in the operating room (OR) led us to develop a novel technique to reduce TL fracture–dislocations (AO type-C) using an orthopedic distractor device (ODD). Methods This prospective study was conducted at a tertiary care spine center with a study duration from March 2020 to May 2020 coinciding with the nationwide lockdown and travel restrictions imposed in view of the COVID-19 crisis. Only patients with AO type C fracture–dislocation managed using the ODD operated by a single surgeon were included in the study. Results Of 12 cases, the most commonly affected level was D12-L1. Nine patients were American Spinal Injury Association Impairment Scale (AIS) A at presentation, two patients were AIS B, and one AIS C. The mean operative time was 125 min and mean blood loss was 454 ml. Eight patients remained AIS A, one patient improved from AIS B to C. Two patients became independent walkers, one remained AIS B. The post-operative VAS score improved to a mean value of 2.33. The improvement in kyphosis was 26.24° immediate postoperatively and maintained at 25.9°, percentage height loss reduced to 2.75% immediate postoperatively and maintained at 3.16% at 3 months follow-up. Conclusions Management of TL fracture–dislocations in COVID times of health care resource scarcity can be challenging. Single surgeon with ODD is a useful technique for achieving good results in these injuries.

Efficacy of a plasma-deposited, vancomycin/chitosan antibiotic coating for orthopaedic devices in a bacterially challenged rabbit model

This study investigated the efficacy of co-deposited vancomycin/chitosan coatings prepared using a plasma process on metallic implants in a bacterially challenged rabbit model. A BioDepTM plasma coating process was used to deposit thin layers of chitosan with vancomycin onto titanium alloy surfaces. Coated implants were examined using standard microscopy, profilometry and elution studies. Nitrided titanium alloy Ti-6Al-4V (Ti alloy) dynamic compression plates (DCP) (n=45) were implanted onto rabbit femurs and then challenged with a bacterial inoculum prior to closure. Three treatment groups were compared: an unmodified Ti alloy DCP that was considered the control, a DCP with the antibacterial coating of chitosan with vancomycin, and a DCP first blasted with alumina grit followed by a coating of chitosan with vancomycin. Bone, surrounding soft tissue, and implants were harvested after 28 days for bacterial quantification. The thin coating of chitosan and vancomycin was clearly detected on the implant surfaces after the plasma coating process. This coating eluted antimicrobial agents and prevented bacterial adhesion, regardless of surface roughness, and prevented biofilm formation compared to the control Ti alloy DCP. The blasting of the Ti alloy implant surface with alumina grit resulted in both roughening and partial implantation of the alumina particles, but did not alter the short-term antimicrobial effects of the chitosan/vancomycin coating. This study suggests that the plasma process is capable of depositing an antimicrobial agent directly onto the surface of metallic implants and that this vancomycin/chitosan coating may prove to be a useful pathway to prevent short-term biofilm formation.

Orthopaedic device manufacturers’ perspective on MDR compliance

Orthopaedic device manufacturers’ perspective on MDR compliance

In Silico Clinical Trials in the Orthopedic Device Industry: From Fantasy to Reality?

The orthopedic device industry relies heavily on clinical evaluation to confirm the safety, performance, and clinical benefits of its implants. Limited sample size often prevents these studies from capturing the full spectrum of patient variability and real-life implant use. The device industry is accustomed to simulating benchtop tests with numerical methods and recent developments now enable virtual “in silico clinical trials” (ISCT). In this article, we describe how the advancement of computer modeling has naturally led to ISCT; outline the potential benefits of ISCT to patients, healthcare systems, manufacturers, and regulators; and identify how hurdles associated with ISCT may be overcome. In particular, we highlight a process for defining the relevant patient risks to address with ISCT, the utility of a versatile software pipeline, the necessity to ensure model credibility, and the goal of limiting regulatory uncertainty. By complementing—not replacing—traditional clinical trials with computational evidence, ISCT provides a viable technical and regulatory strategy for characterizing the full spectrum of patients, clinical conditions, and configurations that are embodied in contemporary orthopedic implant systems.

Evaluation of Interventions Addressing Timely Access to Surgical Care in Low-Income and Low-Middle-Income Countries as Outlined by the LANCET Commission 2030 Global Surgery Goals: A Systematic Review.

In 2015, the Lancet Commission on Global Surgery published six global surgery goals, one of which was to provide 80% of the world's population with timely access to the Bellwether Surgical procedures. Little is known about the prevalence or efficacy of subsequent interventions implemented in under-resourced countries to increase timely access to Bellwether surgical procedures. A systematic review of articles and grey literature published in MEDLINE, Embase, Cochrane, CINAHL, and Web of Science databases was conducted. Two independent reviewers evaluated 1923 captured abstracts using explicit inclusion and exclusion criteria. Following a thematic analysis, two reviewers conducted data extraction on the eleven manuscripts included in the final review. The studied innovations, sparse in number, centred on improved educational resources, the development of orthopaedic devices, and models for assessing surgical access disparity. Eight papers were centred around timely access to caesarean sections, three around open fracture reduction, and three around laparotomy; all focused on adult populations. Five papers addressed innovations in West Africa, two in East Africa, two in South Asia, and one in Southeast Asia. Common outcome metrics were not used to assess improvements to timely surgical access. Few published interventions have been implemented since the publication of the 2015 Lancet Commission on Global Surgery goals that have or will longitudinally increase the availability of timely surgical access in Low and Middle-Income Countries (LMIC). Tangible outcome measures in existing literature are lacking. An up-scaling and wider adoption of successful strategies is necessary and possible.

User-friendliness of a dedicated orthopedic device for knee joint distraction: Experiences from clinical practice

<h3>Introduction</h3> Knee joint distraction (KJD) is a surgical technique for treatment of severe knee osteoarthritis at a relatively young age. In the absence of devices intended for KJD, this procedure has only been performed with devices with another intended use. In collaboration with patients, clinicians and medical device experts, a dedicated distraction (DD) device intended for KJD was developed. <h3>Objectives</h3> To compare user-friendliness between the new DD device and a previously used concept distraction (CD) device. <h3>Methods</h3> Patients were treated with either of the devices (<i>n</i> = 22 versus <i>n</i> = 22). The intervention duration and treatment complications were registered. After treatment, patients filled out a questionnaire about user-friendliness of the device during treatment, containing questions on difficulties performing activities regarding clothing, sleeping, pin care, daily activities, mobility, and complications. Results were compared between the 2 groups. <h3>Results</h3> Intervention duration was on average 56 versus 44 minutes (<i>P</i> < .001) for CD and DD device, respectively. Pin tract infections were the most prevalent complication (73% of CD patients vs 55% of DD patients; <i>P</i> = .210). 34 patients filled out the questionnaire (16 CD device vs 18 DD device). User-friendliness was better for the DD device for 6/25 questions (all <i>P</i> < .05) and not different between devices for remaining questions (all <i>P</i> > .1). <h3>Conclusions</h3> The DD device intended for KJD reduces surgery time and improves user-friendliness compared to the CD device. As such, the DD device contributes to implementation of KJD treatment in regular care.

Enhanced biomechanical performance of additively manufactured Ti-6Al-4V bone plates

As the global trauma fixation devices market expands rapidly, it is imperative to improve the production of fixation devices through enhanced design accuracy and fit for best performance and maximum patient comfort. Selective laser melting (SLM) is one of the mature additive manufacturing methods, which provides a viable route for the rapid production of such devices. In this work, the ability of SLM to produce near-net-shape parts, as desired for medical implants, was utilized for the fabrication of bone plates from Ti-6Al-4V alloy powder. Martensitic microstructure obtained after the printing of alloy resulted in poor ductility, limiting its application in the field of orthopedics. A specially designed repeated cyclic heating and cooling close to but below the β-transus was used to transform from acicular to a bimodal microstructure without the need for plastic deformation prior to heat treatment for improving the ductility. Bone plates subjected to this heat treatment were mechanically tested by means of tensile and 3-point bend tests and demonstrated large improvement in ductility, and the values were comparable to those similar plates prepared from wrought alloy. Other important properties required for implants were assessed, such as corrosion resistance in simulated body fluid and cytocompatibility in vitro using MC3T3-E1 cells. These results for the bone plate after heat treatment were excellent and similar to those of the additively manufactured and wrought plates. Taken together, the performance of the additively manufactured bone plates after subjecting to heat treatment was similar to those of bone plate manufactured using wrought alloy. These results have important implications for the fabrication of patient-specific metallic orthopedic devices using SLM without compromising their biomechanical performance by subjecting them to a tailored heat treatment.

Further Improvement of Customized Vibration Generator for Machine–Human Feedbacks with the Help of Resonant Networks

Modern industrial, household and other equipment include sophisticated power mechanisms and complicated control solutions and require tighter human–machine–human interaction, forming the structures known as cyber–physical–human systems. Their significant parts are human–machine command links and machine–human feedbacks. Such systems are found in medicine, for example, in orthopedics, where they are important for operation and functional abilities of orthopedic devices—smart wheelchairs, verticalizers, prosthesis, rehabilitation units, etc. The mentioned feedbacks may be implemented based on the haptic perceptions that require vibration actuators. In orthopedics, such actuators can also be used for diagnostic purposes. This research brings forward the idea of the use of resonant operation of the driver of vibration actuator. The corresponding driver has been built and experimentally tested. It has been found that (1) the point of maximal current is actually defined by the resonant frequency, (2) change of the capacitance allows shifting of the point of maximal current output and (3) damping factors make the above-described effect less obvious. Further development of the proposed idea requires a comprehensive comparison of four-quadrant and two-quadrant schemes in this application and development of a real-time programmable capacitor pack consisting of several binary weighted capacitors and a commutating circuit, which is installable to these schemes.

Development and heat treatment of β-phase titanium alloy for orthopedic application

In the current study, the latest class of titanium alloy β-phase (Ti-Nb-Ta-Zr) using orthopaedic device vacuum arc melting methods. The alloy is repeatedly melted to strengthen its homogeneity. To ensure homogeneity, the ß-phase Ti-Nb-Ta-Zr alloy was replenished 4 times using the electric arch. The analysis of the β-phase as-developed titanium alloy's microstructure, elemental and phase composition was examined. Vickers Micro-hardness tester and a universal testing machine have calculated the micro-hardness and tensile strength of the formed β-phase titanium alloy (UTM, BIS). The metastatic β-Phase alloy with a coarse kernel range of ~ 250 μm was found in the micro-structure study. The crystallographic analysis revealed that the metastable 'β' stage in the matrix was β-TNTZ alloy. The mechanical properties include the 590 MPa train strength (UTS) with an elongation of 13.47 percent, and are smaller than those in Ti-6Al-4 V alloy and SS-316L with a 55 MPa young modulus near the cortical bone (approximately 10-30GPa). The surface properties were improved after heat treatment. The mechanical properties of β-Ti alloy relative to other titanium alloys for biomedical application.

Regulation of orthopaedic devices: Future implications for research and innovation.

The conception-to-market development of orthopaedic devices occurs across the total product life cycle including device design and preclinical testing, clinical investigations to support marketing applications, and monitoring of device performance after market introduction. This process involves industry, regulatory agencies, health care providers, engineers, scientists, and patients. The Food and Drug Administration (FDA) is responsible for regulating medical devices in the United States, and uses a 3-tier classification system based on the level of control necessary to provide reasonable assurance of safety and effectiveness. Classification directs the required regulatory pathway and premarket submission type. Variations in global regulations, particularly between the United States, European Economic Area (EEA), and the United Kingdom (UK), may impact industry response to orthopaedic device development. Changing device innovation and reimbursement models have led to the consolidation of market share among larger companies. Although larger companies are better able to cope with more rigorous regulatory requirements, this leads to decreased competition and increased upward price pressure. To assist with the complex regulatory processes, the FDA offers pre-submission assistance as an opportunity for early collaboration and discussion about the medical device or device-led combination product submissions. Orthopaedic organizations, such as the Orthopaedic Trauma Association (OTA), may assist in postmarket device surveillance through the coordinated development and maintenance of clinical data registries. Such registries can longitudinally follow patients with a specific orthopaedic pathology or device usage, and monitor outcomes towards improvements in next-generation device development. As technology evolves, the nexus of regulation, industry, and patient outcome monitoring will continue to support safe and effective device innovation.

Implant-associated osteomyelitis: Development, characterisation, and application of a porcine model.

Implant-associated osteomyelitis: Development, characterisation, and application of a porcine model.

Orthotics of Patient with Poliomyelitis and Power Lifting

A special category of Paralympian athletes can be attributed to people with disorders of the musculoskeletal system. In turn, among them a small group of athletes who had undergone the disease poliomyelitis, which are paralytic deformities of the spine and lower extremities. A clinical case is the result of orthotic fitting after surgery of a woman, of 30 years, who had childhood poliomyelitis, with severe consequences in the form of scoliosis of the spine 3 degrees and paralytic deformities of the feet. The patient traveled in a wheelchair or using crutches. It was manufactured orthopedic devices and spine orthosis. After the orthotics the patient was able to move independently and successfully engage in powerlifting.

Osteointegration, antimicrobial and antibiofilm activity of orthopaedic titanium surfaces coated with silver and strontium-doped hydroxyapatite using a novel blasting process.

Poor integration of orthopaedic devices with the host tissue owing to aseptic loosening and device-associated infections are two of the leading causes of implant failure, which represents a significant problem for both patients and the healthcare system. Novel strategies have focused on silver to combat antimicrobial infections as an alternative to drug therapeutics. In this study, we investigated the impact of increasing the % substitution (12% wt) of silver and strontium in hydroxyapatite (HA) coatings to enhance antimicrobial properties and stimulate osteoblasts, respectively. Additionally, we prepared a binary substituted coating containing both silver and strontium (AgSrA) at 12% wt as a comparison. All coatings were deposited using a novel blasting process, CoBlast, onto biomedical grade titanium (V). Surface physicochemical properties, cytocompatibility and antimicrobial functionality were determined. The anticolonising properties of the coatings were screened using Staphylococcus aureus ATCC 1448, and thereafter, the AgA coating was evaluated using clinically relevant strains. Strontium-doped surfaces demonstrated enhanced osteoblast viability; however, a lower inhibition of biofilm formation was observed compared with the other surfaces. A co-substituted AgSrA surface did not show enhanced osteoblast or anticolonising properties compared with the SrA and AgA surfaces, respectively. Due to its superior anticolonising performance in preliminary studies, AgA was chosen for further studies. The AgAcoated surfacesdemonstrated good antibacterial activity (eluted and immobilised ion) against methicillin-resistant S. aureus followed by methicillin-sensitive Staphylococcus aureus clinical isolates; however, the AgA surface displayed poor impact against Staphylococcus epidermidis. In conclusion, herein, we demonstrate that HA can be substituted with a range of ions to augment the properties of HA coatings on orthopaedic devices, which offer promising potential to combat orthopaedic device-associated infections and enhance device performance.

Bloodstream infections in older population: epidemiology, outcome, and impact of multidrug resistance

Bloodstream infections (BSIs) among older patients are frequent with high rate of mortality. Infections with multidrug-resistant organisms (MDRO) are associated with higher mortality than with susceptible microorganisms. We aimed to evaluate the prevalence of MDRO infection during BSI in older population and the factors associated with unfavorable outcome. This study is a retrospective cohort of all BSI episodes occurring among older patients (> 65yo), from April 1, 2010, to December 31, 2016, in a French university hospital for geriatric medicine. A total of 255 BSI episodes were analyzed. Mean age was 86.3±6.5 years, and sex ratio (M/F) was 0.96. Main comorbidities were orthopedic device (26.7%), active neoplasia (24.3%), and diabetes mellitus (18.4%). Main primary sites of infection were urinary tract infections (56.9%), respiratory tract infections (10.6%), intra-abdominal infections (7.1%), and skin and soft tissue infections (4.7%). Main bacteria identified were Escherichia coli (45.1%), Staphylococcus aureus (14.1%), enterococci (10.7%), coagulase-negative staphylococci (CoNS) (5.5%), and streptococci (5.1%). MDROs were involved in 17.2% of BSI (gram-negative bacilli: 9.0%; CoNS: 4.3%; and methicillin-resistant S. aureus (MRSA): 3.9%). The main factor associated with MDRO BSI was colonization with MDRO (OR=6.29; 95%CI=2.9-14.32). Total mortality was 18.4% and significantly higher in case of initial severity (OR=3.83; 95%CI=1.75-8.38), healthcare-associated infection (OR=5.29; 95%CI=1.11-25.30), and MRSA BSI (OR=9.16; 95%CI=1.67-50.16). BSI due to MDRO is frequent in older population and is strongly associated with carriage of MDRO. Healthcare-associated BSI, severe episodes, and BSI due to MRSA are associated with unfavorable outcome. In these cases, a broad-spectrum antibiotic should be promptly initiated.

Systematic Review of the Long-Term Effects of Presurgical Orthopedic Devices on Patient Outcomes.

Objective:To perform a systematic review of the literature to identify the long-term effects of presurgical orthopedic (PSO) device use on patient outcomes.Design:A comprehensive literature review of Embase and Ovid databases was performed to identify all English-language publications related to unilateral cleft lip and palate, presurgical devices, and patient outcomes. Studies were excluded if they did not report patient outcomes beyond 2 years of age, did not describe the use of a PSO device, were case reports (n < 10), or were purely descriptive studies.Main Outcome Measures:Reported patient outcomes following the use of PSO devices.Results:Following a review of all articles by 2 independent reviews, 30 articles were selected for inclusion. Overall, there was no reported consensus as to the long-term effects of PSO devices. Furthermore, this study identified that only 10% of published research controlled for confounding factors that could influence the reported results. Confounding factors that were identified included different operating surgeon, different surgical protocols, and different rates of revision surgeries.Conclusions:Overall, this systematic review identified 2 important conclusions. Firstly, there is no consensus in the literature about the long-term effects of PSO devices on long-term patient outcomes. Secondly, research in this domain is limited by confounding factors that influence the applicability of the reported results.

The Usage of Smart Materials for Development of Rehabilitation Orthopedic Device for Plantar Fasciitis Treatment

This article demonstrates the initial research results, related to the construction of rehabilitation orthopedic device for plantar fasciitis treatment. The results include the calculations of the pressure distribution, considering the human weight and individual gait peculiarities. Three calculation methods are considered: “theoretical” calculation, using the anatomical proportions of load distribution in human foot, empirical calculation, using weights coefficients and human weight distributions, and experimental calculation, using specific medical equipment. the Moreover, this article covers the usage of specific smart materials which can be implemented in the insole construction process. Each smart material has particular properties, considered in the functionality of the insole during the construction.

Diabetes as a Risk Factor for Orthopedic Implant Surface Performance: A Retrieval and In Vitro Study

Orthopedic devices are often associated with increased risk for diabetic patients due to impaired wound healing capabilities. Adverse biological responses for immunocompromised patients at the implant-tissue interface can lead to significant bone resorption that may increase failure rates. The goal of this study was to characterize the surface of implants removed from diabetic patients to determine underlying mechanisms of diabetes-induced impaired osseointegration. Thirty-nine retrieved titanium and stainless-steel orthopedic devices were obtained from diabetic and non-diabetic patients, and compared to non-implanted controls. Optical Microscopy, Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, and X-ray Photoelectron Spectroscopy revealed changes in morphology, chemical composition, oxidation state, and oxide thickness of the retrieval specimens, respectively. Additionally, titanium disks were immersed for 28 days in simulated in vitro diabetic conditions followed by Inductively Coupled Plasma-Optical Emission Spectroscopy to quantify metal dissolution. Electrochemical testing was performed on specimens from retrievals and in vitro study. Aside from biological deposits, retrievals demonstrated surface discoloration, pit-like formations and oxide thinning when compared to non-implanted controls, suggesting exposure to unfavorable acidic conditions. Cyclic load bearing areas on fracture-fixation screws and plates depicted cracking and delamination. The corrosion behavior was not significantly different between diabetic and non-diabetic conditions of immersed disks or implant type. However, simulated diabetic conditions elevated aluminum release. This elucidates orthopedic implant failures that potentially arise from diabetic environments at the implant-tissue interface. Design of new implant surfaces should consider specific strategies to induce constructive healing responses in immunocompromised patients while also mitigating corrosion in acidic diabetic environments.

Improving follow-up of incomplete lower extremity venous duplex ultrasound examinations performed for deep and superficial vein thromboses

ObjectiveA lower extremity venous duplex ultrasound (LEVDUS) examination is the standard diagnostic test to evaluate patients for lower extremity deep vein thrombosis (DVT). However, some studies will be incomplete for a variety of reasons, including patient-related factors such as pain, edema, a large leg circumference, or the presence of overlying bandages or orthopedic devices. We previously reported that the frequency of obtaining a follow-up examination after an incomplete and negative (I/N) LEVDUS examination was low but that the rates of DVT found on the follow-up studies of initially I/N LEVDUS studies were similar to the rates of DVT found with initially complete LEVDUS examinations. Therefore, we recommended process improvements to increase follow-up LEVDUS studies after an I/N LEVDUS examination. In the present study, we have described the results of appending a recommendation to obtain a follow-up LEVDUS study to preliminary and final reports of I/N LEVDUS. MethodsStarting in January 2019 through December 2019, a recommendation to obtain a repeat LEVDUS examination after an I/N study was appended to the preliminary and final reports of all I/N LEVDUS examination of patients who did not, otherwise, have an indication for anticoagulation (group 2). The patients were identified on an ongoing basis through the study period and entered into an Excel database (Microsoft Corp, Redmond, Wash). Group 2 was compared with a previously reported historic control cohort of patients identified from January 2017 to December 2017 (group 1). We compared groups 1 and 2 with respect to the frequency of the repeat studies performed within 4 weeks after an I/N LEVDUS examination and the DVT rates found from the follow-up LEVDUS examinations after an I/N LEVDUS study. ResultsOf the patients in groups 1 and 2, 187 and 229 had had I/N LEVDUS examinations, with 28% and 40.2% of group 1 and 2 studies having follow-up LEVDUS examinations (P < .01). Previously unidentified lower extremity thrombi were discovered in 21% of the group 2 follow-up examinations. Also, the rate of new thrombi detected was not different between groups 2 and 1 (historic controls; DVT, 14.3% vs 18.5% [P = .25]; SVT, 6.3% vs 3.3% [P = .15]). A definitive finding of either positive or negative for DVT and SVT with a complete examination in 50% of the group 2 patients with follow-up examinations. ConclusionsA recommendation to obtain a follow-up examination appended to the preliminary and final I/N LEVDUS reports was associated with an increased rate of follow-up examinations, which revealed many previously undetected DVTs and SVTs or had allowed for definitive exclusion of DVT.

The yield of sonication fluid culture for presumed aseptic loosening of orthopedic devices: a meta-analysis

Sonication fluid culture is routinely conducted in patients with suspected orthopedic devicerelated infection (ORI). However, its value in the assessment of orthopedic devices that have explanted because of presumed aseptic loosening is still debatable. A meta-analysis was conducted to estimate the yield of sonication fluid culture in detecting the presence of microorganisms in orthopedic devices with presumed aseptic loosening, and to summarize the clinical characteristics and outcomes of these patients. A meta-analysis was performed of peer-reviewed publications detailing the characteristics of patients whose orthopedic devices were explanted for presumed aseptic loosening and who underwent subsequent sonication fluid culture. Diagnostic data were extracted and pooled to estimate the yield of sonication fluid culture for detecting the presence of microorganisms with 95% confidence intervals (CI). Eight studies involving 421 patients were included in the meta-analysis analysis. The pooled results showed that sonication fluid culture had a yield of approximately 30% (95% CI: 20-41%) for identifying the presence of microorganisms in presumed aseptic loosening of orthopedic devices; this yield was higher than that of intraoperative tissue culture (22%, 95% CI: 8-41%) and aspirated fluid culture (13%, 95% CI: 7-21%). Sonication and vortexing for ≤5 min had a detection rate of 49% (95% CI: 43-55%), which exceeded that of >5 min. Coagulase-negative Streptococcus accounted for 74% (95% CI: 51-92%) of the isolated microorganisms. However, patients with positive microbiological results of sonication fluid culture and those with negative results showed similar outcomes after revision surgery. Colonization of low-virulent microorganisms may exist in a considerable number of patients with clinically presumed aseptic loosening of orthopedic devices. When this occurs, sonication (1-5 min at 40 kHz) of fluid culture could act as a sensitive diagnostic tool. However, the question of whether sonication fluid culture should be integrated into the routine treatment of loosened orthopedic devices requires further investigation.

A Hyaluronic Acid Hydrogel Loaded with Gentamicin and Vancomycin Successfully Eradicates Chronic Methicillin-Resistant Staphylococcus aureus Orthopedic Infection in a Sheep Model.

Implantable orthopedic devices have had an enormously positive impact on human health; however, despite best practice, patients are prone to developing orthopedic device-related infections (ODRI) that have high treatment failure rates. One barrier to the development of improved treatment options is the lack of an animal model that may serve as a robust preclinical assessment of efficacy. We present a clinically relevant large animal model of chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI that persists despite current clinical practice in medical and surgical treatment at rates equivalent to clinical observations. Furthermore, we showed that an injectable, thermoresponsive, hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment in this model, eliminating bacteria from all animals. These results confirm that local antibiotic delivery with an injectable hydrogel can dramatically increase treatment success rates beyond current clinical practice, with efficacy proven in a robust animal model.