Investigation and response to an outbreak of Neisseria meningitidis serogroup Y ST-1466 urogenital infections, Australia.

Abstract: In 2023, an increased number of urogenital and anorectal infections with Neisseria meningitis serogroup Y (MenY) were reported in New South Wales (NSW). Whole genome sequencing (WGS) found a common sequence type (ST-1466), with limited sequence diversity. Confirmed outbreak cases were NSW residents with a N. meningitidis isolate matching the cluster sequence type; probable cases were NSW residents with MenY isolated from a urogenital or anorectal site from 1 July 2023 without WGS testing. Of the 41 cases, most were men (n = 27), of whom six reported recent contact with a female sex worker. Five cases were men who have sex with men and two were female sex workers. Laboratory alerts regarding the outbreak were sent to all Australian jurisdictions through the laboratories in the National Neisseria Network. Two additional states identified urogenital MenY ST-1466 infections detected in late 2023. Genomic analysis showed all MenY ST-1466 sequences were interspersed, suggestive of an Australia-wide outbreak. The incidence of these infections remains unknown, due to varied testing and reporting practices both within and across jurisdictions. Isolates causing invasive meningococcal disease (IMD) in Australia are typed, and there has been no MenY ST-1466 IMD recorded in Australia to end of March 2024. Concerns remain regarding the risk of IMD, given the similarity of these sequences with a MenY ST-1466 IMD strain causing a concurrent outbreak in the United States of America.

Acoustic Activation Imaging With Intravenous Perfluoropropane Nanodroplets Results in Selective Bioactivation of the Risk Area.

BACKGROUND: Acoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ). OBJECTIVE: We hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region. METHODS: We administered intravenous PD in 36 rats and 20 pigs at various stages of myocardial scar formation (30 minutes, 1 day, and 7 days post I/R) to determine what effect infarct age had on the AA within the IZ. This was correlated with histology, myeloperoxidase activity, and tissue nitrite activity. RESULTS: The degree of AA within the IZ in rats was not associated with collagen content, neutrophil infiltration, or infarct age. AA within 24 hours of I/R was associated with increased nitric oxide utilization selectively within the IZ (P < .05 compared with remote zone). The spatial extent of AA in pigs correlated with infarct size only when performed before sacrifice at 7 days (r = .74, P < .01). CONCLUSIONS: Acoustic activation of intravenous PD enhances the developing scar zone following I/R, and results in selective tissue nitric oxide utilization.

Investigation of the anti-inflammatory and analgesic activities of promising pyrazole derivative.

The development of new COX-2 inhibitors with analgesic and anti-inflammatory efficacy as well as minimal gastrointestinal, renal and cardiovascular toxicity, is of vital importance to patients suffering from chronic course pain and inflammatory conditions. This study aims at evaluating the therapeutic activity and adverse drug reactions associated with the use of the newly synthesized pyrazole derivative, compound AD732, E-4-[3-(4-methylphenyl)-5-hydroxyliminomethyl-1H-pyrazol-1-yl]benzenesulfonamide, as compared to indomethacin and celecoxib as standard agents. Anti-inflammatory activity was assessed using carrageenan-induced rat paw edema and cotton pellet granuloma tests; formalin-induced hyperalgesia and hot plate tests were done to study analgesic activity. In vitro tests to determine COX-1/COX-2 selectivity and assessment of renal and gastric toxicity upon acute exposure to AD732 were also conducted. Compound AD732 exhibited promising results; higher anti-inflammatory and analgesic effects compared to standard agents, coupled with the absence of ulcerogenic effects and minimal detrimental effects on renal function. Additionally, compound AD732 was a less potent inhibitor of COX-2 in vitro than celecoxib, which may indicate lower potential cardiovascular toxicity. It may be concluded that compound AD732 appears to be a safer and more effective molecule with promising potential for the management of pain and inflammation.

Oral fluoroquinolones for definitive treatment of gram-negative bacteremia in cancer patients.

PURPOSE: Bloodstream infections (BSI) are significant causes of morbidity and mortality in cancer patients. These patients often receive 10 to 14 days of intravenous (IV) antibiotics. The objective of this study was to compare the outcomes of cancer patients transitioned from IV to oral (PO) therapy compared to continuation of IV treatment. METHODS: This was a single-center, retrospective cohort study of hospitalized adult cancer patients with gram-negative bacteremia. Patients transitioned to a PO fluoroquinolone (FQ) within 5 days were allocated to the IV-to-PO group, while the remaining patients comprised the IV group. The primary outcome was the composite of treatment failure, defined as infection-related readmission, infection recurrence, or inpatient mortality. A multivariable logistic regression model was constructed to account for confounding variables. Secondary outcomes assessed included infection-related length of stay (LOS), hospital LOS, and adverse events, such as Clostridioides difficile infection and catheter-related complications. RESULTS: The IV-to-PO group included 78 patients, while the remaining 133 patients were allocated to the IV group. Differences at baseline included more hematologic malignancy, neutropenia, ICU admissions, and higher Pitt bacteremia scores in the IV group. The rate of treatment failure was significantly higher in the IV group (24% vs 9%; p < 0.01), which persisted in the logistic regression (aOR 3.5, 95% CI 1.3-9.1). The IV-to-PO group had decreased infection-related and hospital length of stay, as well as fewer catheter-related complications. CONCLUSIONS: The use of PO FQ may be considered for the definitive treatment of uncomplicated Enterobacterales BSI in cancer patients.

Municipal wastewater effluent affects fish communities: A multi-year study involving two wastewater treatment plants.

Although effluent from municipal wastewater treatment plants (WWTPs) is a major stressor in receiving environments, relatively few studies have addressed how its discharge affects natural fish communities. Here, we assessed fish community composition over three years along a gradient of effluent exposure from two distinct WWTPs within an International Joint Commission Area of Concern on the Great Lakes (Hamilton Harbour, Canada). We found that fish communities changed with distance from both WWTPs, and were highly dissimilar between sites that were closest to and furthest from the wastewater outfall. Despite differences in the size and treatment technology of the WWTPs and receiving habitats downstream, we found that the sites nearest the outfalls had the highest fish abundances and contained a common set of signature fish species (i.e., round goby Neogobius melanostomus, green sunfish Lepomis cyanellus). Non-native and stress tolerant species were also more abundant near one of the studied WWTPs when compared to the reference site, and the number of young-of-the-year fish collected did not vary along the effluent exposure gradients. Overall, we show that fish are attracted to wastewater outfalls raising the possibility that these sites may act as an ecological trap.

Metabolic implications of exposure to wastewater effluent in bluegill sunfish.

Effluent from wastewater treatment plants (WWTP) contains a complex mixture of contaminants and is a major worldwide source of aquatic pollution. We examined the effects of exposure to treated effluent from a municipal WWTP on the metabolic physiology of bluegill sunfish (Lepomis macrochirus). We studied fish that were wild-caught or experimentally caged (28 d) downstream of the WWTP, and compared them to fish that were caught or caged at clean reference sites. Survival was reduced in fish caged at the effluent-contaminated site compared to those caged at the reference site. Resting rates of O2 consumption (MO2) were higher in fish from the contaminated site, reflecting a metabolic cost of wastewater exposure. The increases in routine MO2 did not reduce aerobic scope (difference or quotient of maximal MO2 and resting MO2), suggesting that physiological compensations accompanied the metabolic costs of wastewater exposure. Fish exposed to wastewater also had larger hearts and livers. The activity of mitochondrial enzymes (cytochrome c oxidase, citrate synthase) per liver mass was unaltered across treatments, so the increased mass of this organ increased its cumulative oxidative capacity in the fish. Wastewater exposure also reduced glycogen content per liver mass. The effects of caging itself, based on comparisons between fish that were wild-caught or caged at clean sites, were generally subtle and not statistically significant. We conclude that exposure to wastewater effluent invokes a metabolic cost that leads to compensatory physiological adjustments that partially offset the detrimental metabolic impacts of exposure.

Synthesis, in silico experiments and biological evaluation of 1,3,4-trisubstituted pyrazole derivatives as antimalarial agents.

New 1,3,4-trisubstituted pyrazole derivatives were synthesized and evaluated for their antiplasmodial activity. Compounds 4b, 4c, 7a and 7d were the most potent antiplasmodial agents against P. berghei with percent of suppression ranging from 90 to 100%. They were also screened for their in vitro antimalarial activity against the chloroquine resistant strain P. falciparum, (RKL9). Compound 4c displayed the highest in vitro antimalarial activity; 13-fold higher than standard chloroquine phosphate. Molecular docking of the most active compounds against the wildtype and quadruple mutant pf DHFR-TS structures rationalized the in vitro antimalarial activity. Furthermore, these compounds exhibited reasonable in silico drug-likeness and pharmacokinetic properties. Toxicity studies of the most active compounds revealed that all tested compounds were non-toxic and well-tolerated up to 150 mg/kg via oral route and 75 mg/kg via parentral route. According to RBC hemolysis assay, it was found that compound 7a was the most potent anti-inflammatory and least toxic derivative with IC50 value 71-fold higher than IC50 value related to the antimalarial activity. Moreover, cytotoxicity assessment revealed that compound 4c was the least toxic derivative with IC50 value 70000-fold higher than IC50 value related to the antimalarial activity.

Metabolic Costs of Exposure to Wastewater Effluent Lead to Compensatory Adjustments in Respiratory Physiology in Bluegill Sunfish.

Municipal wastewater effluent is a major source of aquatic pollution and has potential to impact cellular energy metabolism. However, it is poorly understood whether wastewater exposure impacts whole-animal metabolism and whether this can be accommodated with adjustments in respiratory physiology. We caged bluegill sunfish (Lepomis macrochirus) for 21 days at two sites downstream (either 50 or 830 m) from a wastewater treatment plant (WWTP). Survival was reduced in fish caged at both downstream sites compared to an uncontaminated reference site. Standard rates of O2 consumption increased in fish at contaminated sites, reflecting a metabolic cost of wastewater exposure. Several physiological adjustments accompanied this metabolic cost, including an expansion of the gill surface area available for gas exchange (reduced interlamellar cell mass), a decreased blood-O2 affinity (which likely facilitates O2 unloading at respiring tissues), increased respiratory capacities for oxidative phosphorylation in isolated liver mitochondria (supported by increased succinate dehydrogenase, but not citrate synthase, activity), and decreased mitochondrial emission of reactive oxygen species (ROS). We conclude that exposure to wastewater effluent invokes a metabolic cost that leads to compensatory respiratory improvements in O2 uptake, delivery, and utilization.

Hybridization increases mitochondrial production of reactive oxygen species in sunfish.

Mitochondrial dysfunction and oxidative stress have been suggested to be possible mechanisms underlying hybrid breakdown, as a result of mito-nuclear incompatibilities in respiratory complexes of the electron transport system. However, it remains unclear whether hybridization increases the production of reactive oxygen species (ROS) by mitochondria. We used high-resolution respirometry and fluorometry on isolated liver mitochondria to examine mitochondrial physiology and ROS emission in naturally occurring hybrids of pumpkinseed (Lepomis gibbosus) and bluegill (L. macrochirus). ROS emission was greater in hybrids than in both parent species when respiration was supported by complex I (but not complex II) substrates, and was associated with increases in lipid peroxidation. However, respiratory capacities for oxidative phosphorylation, phosphorylation efficiency, and O2  kinetics in hybrids were intermediate between those in parental species. Flux control ratios of capacities for electron transport (measured in uncoupled mitochondria) relative to oxidative phosphorylation suggested that the limiting influence of the phosphorylation system is reduced in hybrids. This likely helped offset impairments in electron transport capacity and complex III activity, but contributed to augmenting ROS production. Therefore, hybridization can increase mitochondrial ROS production, in support of previous suggestions that mitochondrial dysfunction can induce oxidative stress and thus contribute to hybrid breakdown.

In situ exposure to wastewater effluent reduces survival but has little effect on the behaviour or physiology of an invasive Great Lakes fish.

Treated effluents from wastewater treatment plants (WWTP) are a significant source of anthropogenic contaminants, such as pharmaceuticals, in the aquatic environment. Although our understanding of how wastewater effluent impacts fish reproduction is growing, we know very little about how effluent affects non-reproductive physiology and behaviours associated with fitness (such as aggression and activity). To better understand how fish cope with chronic exposure to wastewater effluent in the wild, we caged round goby (Neogobius melanostomus) for three weeks at different distances from a wastewater outflow. We evaluated the effects of this exposure on fish survival, behaviour, metabolism, and respiratory traits. Fish caged inside the WWTP and close to the outfall experienced higher mortality than fish from the reference site. Interestingly, those fish that survived the exposure performed similarly to fish caged at the reference site in tests of aggressive behaviour, startle-responses, and dispersal. Moreover, the fish near WWTP outflow displayed similar resting metabolism (O2 consumption rates), hypoxia tolerance, haemoglobin concentration, haematocrit, and blood-oxygen binding affinities as the fish from the more distant reference site. We discuss our findings in relation to exposure site water quality, concentrations of pharmaceutical and personal care product pollutants, and our test species tolerance.

Mitochondrial physiology and reactive oxygen species production are altered by hypoxia acclimation in killifish (Fundulus heteroclitus).

Many fish encounter hypoxia in their native environment, but the role of mitochondrial physiology in hypoxia acclimation and hypoxia tolerance is poorly understood. We investigated the effects of hypoxia acclimation on mitochondrial respiration, O2kinetics, emission of reactive oxygen species (ROS), and antioxidant capacity in the estuarine killifish ( ITALIC! Fundulus heteroclitus). Killifish were acclimated to normoxia, constant hypoxia (5 kPa O2) or intermittent diel cycles of nocturnal hypoxia (12 h:12 h normoxia:hypoxia) for 28-33 days and mitochondria were isolated from liver. Neither pattern of hypoxia acclimation affected the respiratory capacities for oxidative phosphorylation or electron transport, leak respiration, coupling control or phosphorylation efficiency. Hypoxia acclimation also had no effect on mitochondrial O2kinetics, but ITALIC! P50(the O2tension at which hypoxia inhibits respiration by 50%) was lower in the leak state than during maximal respiration, and killifish mitochondria endured anoxia-reoxygenation without any impact on mitochondrial respiration. However, both patterns of hypoxia acclimation reduced the rate of ROS emission from mitochondria when compared at a common O2tension. Hypoxia acclimation also increased the levels of protein carbonyls and the activities of superoxide dismutase and catalase in liver tissue (the latter only occurred in constant hypoxia). Our results suggest that hypoxia acclimation is associated with changes in mitochondrial physiology that decrease ROS production and may help improve hypoxia tolerance.

Optimal tube length for the submerged printing of ovarian cancer cells.

Ovarian cancer is the fifth most common cancer affecting US women, killing more women each year than all other gynecologic cancers combined. Treatment of ovarian cancer is challenging with an overall 5-year survival rates of only 28-46% based on the metastatic state of the disease. While overall survival has improved with modern chemotherapy, poor outcomes have persisted. One of the greatest challenges in cancer therapeutic research remains that late-stage drug development trials for drug candidates have high attrition rates, up to 70% in Phase II and 59% in Phase III trials. The development of in vitro, high-throughput, cell based assays could provide a tool to overcome the challenges associated with high attrition rates by allowing for controlled cell deposition with a defined, controlled phenotype. Submerged, three-dimensional (3D) microfluidic printing technology is uniquely capable of controlling cell deposition without sacrificing the viability of cells for cell-based assays. Here, we investigate the phenotypic effects of tube length during printing on the cells. We observe that the length of the tube has minimal effects on the viability and density of A2780 ovarian cancer cells different cell lines. This study details foundational information for developing a high-throughput cell-based assays (CBA) for screening effective cancer drug candidates.

Comparison of submerged and unsubmerged printing of ovarian cancer cells.

A high-throughput cell based assay would greatly aid in the development and screening of ovarian cancer drug candidates. Previously, a three-dimensional microfluidic printer that is not only capable of controlling the location of cell deposition, but also of maintaining a liquid, nutrient rich environment to preserve cellular phenotype has been developed (Wasatch Microfluidics). In this study, we investigated the impact (i.e., viability, density, and phenotype) of depositing cells on a surface submerged in cell culture media. It was determined that submersion of the microfluidic print head in cell media did not alter the cell density, viability, or phenotype.. This article describes an in depth study detailing the impact of one of the fundamental components of a 3D microfluidic cell printer designed to mimic the in vivo cell environment. Development of such a tool holds promise as a high-throughput drug-screening platform for new cancer therapeutics.

Polymer-controlled extended combination release of silver and chlorhexidine from a bone void filler.

Although rates of total joint prosthetic infections remain relatively constant at 1-3%, an increasing number of orthopedic procedures and a corresponding rise in the absolute number of infectious complications mandate distinctly new solutions. In order to combat the implant infection threat, an antibiotic-releasing bone void filler (BVF), commercial tradename, ElutiBone™, has been developed using a combination of commercially available ceramic-based BVF plus clinically familiar biocompatible polymers, and a variety of select, dispersed antibiotics. While several traditional antibiotics have been successfully released for an extended duration, a more versatile strategy, releasing multiple antibiotics simultaneously, may be possible. In this study, the antiseptic chlorhexidine and a variety of bacteriostatic silver compounds were incorporated to provide synergistic antimicrobial activity upon release in combination formulations from ElutiBone matrices. Silver chloride was the most effective bacteriostatic tested (p=0.05), showing a measurable zone of inhibition at spiked concentrations as low as 31µg/ml. Subsequently, silver chloride was used in combination with the antiseptic chlorhexidine to test for enhanced antimicrobial bioactivity against S. aureus. Measurable synergy between the two compounds confirmed the suitability of ElutiBone™ to locally deliver this multidrug antimicrobial cocktail. A myriad of other drug interactions could and should be tested in this novel system in order to expand the utility and combat the increasing prevalence of polymicrobial infections.

Targeted deletion of p53 in the proximal tubule prevents ischemic renal injury.

The contribution of p53 to kidney dysfunction, inflammation, and tubular cell death, hallmark features of ischemic renal injury (IRI), remains undefined. Here, we studied the role of proximal tubule cell (PTC)-specific p53 activation on the short- and long-term consequences of renal ischemia/reperfusion injury in mice. After IRI, mice with PTC-specific deletion of p53 (p53 knockout [KO]) had diminished whole-kidney expression levels of p53 and its target genes, improved renal function, which was shown by decreased plasma levels of creatinine and BUN, and attenuated renal histologic damage, oxidative stress, and infiltration of neutrophils and macrophages compared with wild-type mice. Notably, necrotic cell death was attenuated in p53 KO ischemic kidneys as well as oxidant-injured p53-deficient primary PTCs and pifithrin-α-treated PTC lines. Reduced oxidative stress and diminished expression of PARP1 and Bax in p53 KO ischemic kidneys may account for the decreased necrosis. Apoptosis and expression of proapoptotic p53 targets, including Bid and Siva, were also significantly reduced, and cell cycle arrest at the G2/M phase was attenuated in p53 KO ischemic kidneys. Furthermore, IRI-induced activation of TGF-ß and the long-term development of inflammation and interstitial fibrosis were significantly reduced in p53 KO mice. In conclusion, specific deletion of p53 in the PTC protects kidneys from functional and histologic deterioration after IRI by decreasing necrosis, apoptosis, and inflammation and modulates the long-term sequelae of IRI by preventing interstitial fibrogenesis.

The submerged printing of cells onto a modified surface using a continuous flow microspotter.

The printing of cells for microarray applications possesses significant challenges including the problem of maintaining physiologically relevant cell phenotype after printing, poor organization and distribution of desired cells, and the inability to deliver drugs and/or nutrients to targeted areas in the array. Our 3D microfluidic printing technology is uniquely capable of sealing and printing arrays of cells onto submerged surfaces in an automated and multiplexed manner. The design of the microfluidic cell array (MFCA) 3D fluidics enables the printhead tip to be lowered into a liquid-filled well or dish and compressed against a surface to form a seal. The soft silicone tip of the printhead behaves like a gasket and is able to form a reversible seal by applying pressure or backing away. Other cells printing technologies such as pin or ink-jet printers are unable to print in submerged applications. Submerged surface printing is essential to maintain phenotypes of cells and to monitor these cells on a surface without disturbing the material surface characteristics. By printing onto submerged surfaces, cell microarrays are produced that allow for drug screening and cytotoxicity assessment in a multitude of areas including cancer, diabetes, inflammation, infections, and cardiovascular disease.

Molded polymer-coated composite bone void filler improves tobramycin controlled release kinetics.

Infection remains a significant problem associated with biomedical implants and orthopedic surgeries, especially in revision total joint replacements. Recent advances in antibiotic-releasing bone void fillers (BVF) provide new opportunities to address these types of device-related orthopedic infections that often lead to substantial economic burdens and reduced quality of life. We report improvements made in fabrication and scalability of an antibiotic-releasing polycaprolactone-calcium carbonate/phosphate ceramic composite BVF using a new solvent-free, molten-cast fabrication process. This strategy provides the ability to tailor drug release kinetics from the BVF composite based on modifications of the inorganic substrate and/or the polymeric component, allowing extended tobramycin release at bactericidal concentrations. The mechanical properties of the new BVF composite are comparable to many reported BVFs and validate the relative homogeneity of fabrication. Most importantly, fabrication quality controls are correlated with favorable drug release kinetics, providing bactericidal activity to 10 weeks in vitro when the polycaprolactone component exceeds 98% w/w of the total polymer fraction. Furthermore, in a time kill study, tobramycin-releasing composite fragments inhibited S. aureus growth over 48 h at inoculums as high as 10(9) CFU/mL. This customizable antibiotic-releasing BVF polymer-inorganic biomaterial should provide osseointegrative and osteoconductive properties while contributing antimicrobial protection to orthopedic sites requiring the use of bone void fillers.

Quantitative affinity electrophoresis of RNA-small molecule interactions by cross-linking the ligand to acrylamide.

We show that the affinity electrophoresis analysis of RNA-small molecule interactions can be made quantifiable by cross-linking the ligand to the gel matrix. Using an RNA-aminoglycoside model system to verify our method, we attached an acryloyl chloride molecule to the aminoglycosides paromomycin and neomycin B to synthesize an acrylamide-aminoglycoside monomer. This molecule was then used as a component in gel polymerization for affinity electrophoresis, covalently attaching an aminoglycoside molecule to the gel matrix. To test RNA binding to the cross-linked aminoglycosides, we used the aminoglycoside binding RNA molecule derived from thymidylate synthase messenger RNA (mRNA) that contains a C-C mismatch. Binding is indicated by the difference in RNA mobility between gels with cross-linked ligand, with ligand embedded during polymerization, and with no ligand present. Critically, the predicted straight line relationship between the reciprocal of the relative migration of the RNA and the ligand concentration is obtained when using cross-linked aminoglycosides, whereas a straight line is not obtained using embedded aminoglycosides. Average apparent dissociation constants are determined from the slope of the line from these plots. This method allows an easy quantitative comparison between different nucleic acid molecules for a small molecule ligand.

Scanning electron image analysis to monitor of implant degradation and host healing following implantation of a drug-eluting bone graft void filler - biomed 2013.

Osteomyelitis is most commonly caused by Staphylococcus aureus and often sourced during orthopedic surgical intervention. Successful treatment or prevention of this bone penetrating infection requires antibiotics be delivered in excess of the minimal inhibitory concentration to prohibit the growth of the causative organism for sufficient duration. Unfortunately, current standard-of-care antibiotic therapies, administered via intravenous or oral delivery, suffer not only from systemic toxicity and low patient compliance but also provide insufficient local concentrations for therapy. To overcome these clinical inadequacies, a synthetic bone graft material was coated with an antibiotic (tobramycin)-releasing polymer (polycaprolactone) matrix to create a polymer-controlled antibiotic- releasing combination therapy for use as a bone void filler in orthopedic surgeries. Even though this local delivery strategy allows antibiotic delivery over a clinically relevant time frame to prevent infection, complete healing requires the host bone to infiltrate and reabsorb the bone void filler, ultimately replacing the defect with healthy tissue. Unfortunately, the same polymer matrix that allows for controlled local antibiotic delivery may also discourage host bone healing. Efficient orthopedic healing requires the rate of polymer degradation to match the rate of host-bone infiltration. Current imaging techniques, such as histological staining and x-ray imaging, are insufficient to simultaneously assess polymer degradation and host bone integration. Alternative techniques relying on backscatter electron detection during scanning electron microscopy (SEM) imaging may allow a visual differentiation between host bone, synthetic bone, and polymer. Analysis of backscattered SEM images was automated using a custom MATLAB program to determine the ratio of bone to polymer based upon the contrast between the bone (white) and polymer (dark grey). By collecting images of the implant over time, a profile could be created to describe the rate of polymer degradation in conjunction with host-bone infiltration, allowing the intelligent tailoring of infectious osteomyelitis treatment/prevention and host-graft integration.

Polymer-controlled release of tobramycin from bone graft void filler.

Despite clinical, material, and pharmaceutical advances, infection remains a major obstacle in total joint revision surgery. Successful solutions must extend beyond bulk biomaterial and device modifications, integrating locally delivered pharmaceuticals and physiological cues at the implant site, or within large bone defects with prominent avascular spaces. One approach involves coating clinically familiar allograft bone with an antibiotic-releasing rate-controlling polymer membrane for use as a matrix for local drug release in bone. The kinetics of drug release from this system can be tailored via alterations in the substrate or the polymeric coating. Drug-loaded polycaprolactone coating releases bioactive tobramycin from both cadaveric-sourced cancellous allograft fragments and synthetic hybrid coralline ceramic bone graft fragments with similar kinetics over a clinically relevant 6-week timeframe. However, micron-sized allograft particulate provides extended bioactive tobramycin release. Addition of porogen polyethylene glycol to the polymer coating formulation changes tobramycin release kinetics without significant impact on released antibiotic bioactivity. Incorporation of oil-microencapsulated tobramycin into the polymer coating did not significantly modify tobramycin release kinetics. In addition to releasing inhibitory concentrations of tobramycin, antibiotic-loaded allograft bone provides recognized beneficial osteoconductive potential, attractive for decreasing orthopedic surgical infections with improved filling of dead space and new bone formation.