Objectives. The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery. Materials and Methods. Ti and Ti6Al4V disks were prepared. To evaluate the bactericidal effect of UV irradiation, Staphylococcus aureus 834 suspension was seeded onto the disks, which were then exposed to UV light for 15 minutes at a dose of 9 J/cm. 2. To evaluate the antimicrobial activity of UV irradiation, bacterial suspensions were seeded onto the disks 0, 0.5, one, six, 24 and 48 hours, and three and seven days after UV irradiation as described above. In both experiments, the bacteria were then harvested, cultured, and the number of colonies were counted. Results. No colonies were observed when UV irradiation was performed after the bacteria were added to the disks. When the bacteria were seeded after UV irradiation, the amount of surviving bacteria on the Ti and Ti6Al4V disks decreased at 0 hours and then gradually increased. However, the antimicrobial activity was maintained for seven days after UV irradiation. Conclusion. Antimicrobial activity was induced for seven days after UV irradiation on both types of disk. Irradiated Ti6Al4V and Ti had similar antimicrobial properties. Cite this article: T. Itabashi, K. Narita, A. Ono, K. Wada, T. Tanaka, G. Kumagai, R. Yamauchi, A. Nakane, Y. Ishibashi. Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation. Bone Joint Res 2017;6:108–112. DOI: 10.1302/2046-3758.62.2000619

Nanotopographical cues on Ti surfaces have been shown to elicit different cell responses such as differentiation and selective growth. Bone remodelling is a continuous process requiring specific cues for optimal bone growth and implant fixation. In addition, the prevention of biofilm formation on surgical implants is a major challenge. We have identified nanopatterns on Ti surfaces that would be optimal for both bone remodelling and for reducing risk of bacterial infection. We used primary human osteoblast/osteoclast co-cultures and seeded them on flat Ti and three Ti nanosurfaces with increasing degrees of roughness, manufactured using anodisation under alkaline conditions (for 2, 2.5 and 3 hours). Cell growth and behaviour was assessed by scanning electron microscopy (SEM), immunofluorescence microscopy, histochemistry and quantitative RT-PCR methods. Bacterial growth on the nanowire surfaces was also assessed by confocal microscopy and SEM. From the three surfaces tested, the 2 h nanowire surface supported osteoblast and, to a lesser extent, osteoclast growth and differentiation. Bacterial viability was significantly reduced on the 2h surface. Hence the 2 h surface provided optimal bone remodelling conditions while reducing infection risk, making it a favourable candidate for future implant surfaces. This work was funded by EPSRC grant EP/K034898/1.

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive. We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples

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

Introduction. A modified anodisation technique where a titanium surface releases bactericidal concentrations of silver was developed and called Agluna. Our hypothesis was that silver incorporation was bactericidal and had no effects on the viability of fibroblasts and osteoblasts, would have no negative effect on interfacial shear strength and bone contact in an in vivo trans-cortical implant ovine model. Methods. In vitro: Titanium alloy discs were either polished (Ti), anodised (Ano), anodised or Agluna treated (Ag) or anodised and Agluna treated followed by a conditioning step (Ag C). Conditioning was achieved by incubating discs in culture fluid for 48 hrs. The bactericidal effect of these discs was tested by measuring the zone of inhibition of different bacteria grown on agar. Live/dead staining was carried out and silver levels measured using atomic emission spectroscopy. 8 implants were inserted into each sheep (60 in total (n=5)). Grit blasted Titanium alloy (Gb) and Agluna treated grit blasted titanium alloy (Ag) at a silver concentration of 4-6 micrograms/cm2 were compared at 6 weeks. Gb implants, Ag (at 4-6micrograms/cm2), high dose Agluna implants with silver concentrations at 15-20micrograms/cm2 (HdAg) and a grit blasted anodised titanium alloy (Ano) were compared at 12 weeks. Pullout strength and bone-implant contact was quantified. Results. On Ti, Ano and Ag C surfaces the number of live fibroblasts was significantly greater than on Ag (non-conditioned) surfaces. Data from pull out tests at 6 weeks showed a lower but significant interfacial shear strength in the Ag group (310.4N) when compared with the Gb group (561.2N) (p=0.01). At 12 weeks, there were no significant differences between each of the 4 treatment groups. Histological analysis showed no significant differences in bone-implant contact between groups at 6 and 12 weeks. Discussion. The initial non-conditioned Agluna surface is bactericidal and cytotoxic but on conditioning, osteoblasts and fibroblasts attached and remained viable. The condition Agluna surface remains bactericidal. Silver incorporation at a concentration up to 20 micrograms/cm2 has no adverse toxic effect on osteointegration and the interfacial shear strength of implants. This coating has been used clinically in situations where the infection rate is high

With an ever-increasing aging population, total hip and knee arthroplasty is projected to increase by 137% and 601%, respectively, between the period; 2005–2030. Prosthetic Join Infection (PJI) occurs in approximately 2% of total joint replacements (TJRs) in the U.S. PJI is primarily caused by adherence of bacteria to the surface of the prosthesis, ultimately forming an irreversibly attached community of sessile bacteria, known as a biofilm, highly tolerant to antibiotic treatment. Often the only resolution if the ensuing chronic infection is surgical removal of the implant – at high cost for the patient (increased morbidity), and for healthcare resources. Strategies to prevent bacterial adherence have significant potential for medical impact. Laser surface treatment using an automated continuous wave (CW) fiber laser system has shown promise in producing anti-adherent and bactericidal surfaces. Work presented here aims to investigate the effect of this approach on orthopaedic metals as a proof of concept, specifically Ti-6Al-4V (kindly supplied by Stryker Orthopaedics, Limerick). A coupon was surface treated using a laser (MLS-4030; Micro Lasersystems BV, Driel). Samples were incubated in Müller Hinton Broth (MHB) inoculated with methicillin resistant Staphylococcus aureus (MRSA; ATCC 43300) for 24h before Live/Dead staining (BacLight™ solution; Molecular Probes) and inspection by fluorescence microscopy (GXM-L3201 LED; GX Optical). Images were analysed using ImageJ software (NIH) and a significant reduction (p > 0.05, n=24) in total biofilm coverage and Live/Dead ratio was observed between the laser treated and as received surfaces. This data demonstrates the anti-adherent, and indeed bactericidal, effect of Laser-surface treatment

Prosthetic joint infections (PJI) occur infrequently, but they represent the most devastating complication with high morbidity and substantial cost. Staphylococcus aureus and coagulase-negative S. epidermidis are the most commonly infecting agents associated with PJI. Nowadays, Gram-negative species like Escherichia coli and Pseudomonas aeruginosa are gaining relevance. The use of TiO2 conical nanotubular doped with fluorine and phosphorous (FP-cNT) surfaces is an interesting approach to prevent surface bacterial colonization during surgery and favouring the osseointegration. Despite of there are serum markers related with PJI, to date there is described no biomaterial-related marker that allows detecting PJI. Here we describe the adherence and the bactericidal effect of FP-cNT and its capacity of marking the non-fermenting bacteria that have been in contact with it by Al. This metal is delivered by FP-cNT in non-toxic concentrations (between 25 and 29 ng/mL). F-P-cNT layers on Ti6Al4V alloy were produced as described previously by our group. Ti6Al4V chemical polishing (CP) samples without nanostructure were used as control and produced as described previously. S. aureus 15981, S. epidermidis ATCC 35984, E. coli ATCC 25922, and P. aeruginosa ATCC 27853 strains adherence study was performed using the protocol described by Kinnari et al. in 0.9% NaCl sterile saline with a 120 min incubation. After incubation, the samples were stained with LIVE/DEAD BacLight Bacterial Viability Kit. Proportion of live and dead bacteria was calculated and studied by using ImageJ software. The experiments were performed in triplicate. The aluminum concentration was estimated in the supernatant after incubation and in the 0.22 µm filtered supernatant by atomic absorption in graphite furnace. The statistical data were analyzed by nonparametric Kruskal-Walis test and by pairwise comparisons using the nonparametric unilateral Wilcoxon test with a level of statistical significance of p<0.05. The values are cited as medians. Our results show that the bacterial adherence of all tested species significantly decreased on FP-cNT compared to CP except P. aeruginosa ATCC 27853: 19.8% for S. aureus 15981, 45.3% for S. epidermidis ATCC 35984 and 8.1% for E. coli ATCC 25922. The bacterial viability decreased 2-fold for S. aureus 15981, and 5-fold for S. epidemidis ATCC 35984, but increased 95% for P. aeruginosa ATCC 27853 and there no was variation for E. coli ATCC 25922 on FP-cNT compared to CP. Only supernatant P. aeruginosa ATCC 27853 shows significant Al detection after 120 min incubation (p<0.05). In summary, F-P cNT is a promising biomaterial that besides favoring osseointegration and potential usefulness as drug carrier, present bactericidal, non-stick ability (at least for staphylococci and E. coli) and is able to mark P. aeruginosa with Al, which could be potentially monitored in serum and urine in patients with PJI

Background. The different biodegradable local antibiotic delivery systems are widely used in recent years. The aim of this study was to evaluate the bactericidal activity antibiotic loaded PerOssal pellet in vitro and its effectiveness in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Material and methods. MALDI-TOF have been applied to microbiological diagnosis in patient with osteomyelitis. In most cases, Staphylococcus aureus was isolated. In vitro Ceftriaxone-Loaded PerOssal pellet were placed in middle agar plate containing a stock strain of Staphylococcus aureus. Plates were incubated at 37ºC for 24 hours. The zones of bacterial inhibition were recorded after 24, 48 and 72 hours of incubation. In vivo evaluation was performed by prospectively studying of 21 patients with a clinically and bacteriologically diagnosed Staphylococcus aureus induced osteomyelitis. Mean age was 38±4,2(26 to 53)). After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal pellets loaded with different antibiotics depending from the antibiotic sensitivity test. Endpoints were the absence of clinical manifestation of infection or disease recurrence, no need for further surgery. Results. In vitro showed after 24 hrs inhibition zone was 4,2 х 4,9 cm, after 72 hrs the inhibition zone was increased till 7,6 х 8,4 cm. During the subsequent time, there were no changes. Results of the clinical study evidenced no signs of infection in 18 patients (86% (CI 69,8;100)) (p<0,05) at the follow up, while 3 (14%(CI 0;30,2)) (p<0,05) subjects showed infection recurrence at 6 months from operation and 2 of them needed further surgical procedures. Conclusion. PerOssal as an antibiotic carrier stabilizes the action of the antibiotic. This antibiotic carrier system allows to choose an antibiotic individually for each patient according to the antibiotic sensitivity test and can be successfully used in clinical cases of osteomyelitis

Prosthetic joint infections (PJI) occur infrequently, but they represent the most devastating complication with high morbidity and substantial cost. Staphylococcus aureus and coagulase-negative S. epidermidis are the most common infecting agents associated with PJI. During the past decades, novel materials have been developed to improve osseointegration of implants. Recently has been demonstrated that by using nanosized hydroxyapatite (HA) coatings, since it combines nanoroughness and bone-like chemistry in a synergistic effect, it promotes better osseointegration when compared to uncoated metal implants. In a further step, due to the known bactericidal properties of fluor, the aim of this study is to evaluate the biofilm development on fluorohydroxyapatite (FHA) compared to HA. Coatings were grown on stainless steel substrates by Pulsed Laser Deposition (PLD) technique using fluorohydroxyapatite targets of marine origin. A comprehensive physicochemical characterization of the coatings was performed using SEM, EDS, XPS and XRD. Biological in vitro tests using the pre-osteoblastic cell line (MC3T3-E1) demonstrated the non-cytotoxicity of FHA coatings, the healthy cell proliferation and their osteogenic activity. The S. aureus 15981 (Valle et al.) and S. epidermidis ATCC 35984 strains adherence study was performed introducing each probe in a well of 96-well plate with 200 µl containing 106 colony forming units (CFU/mL) intryptic soy broth supplemented with 1% glucose and was incubated at 37°C 5% CO2 for 24 hours. After incubation, the medium was removed and three washes with 0.9% NaCl sterile saline were performed. The biofilm was disrupted by sonication at 50–60 Hz for 5 min. The CFU/cm2 was estimated by drop plate method. All of the experiments were performed in triplicate. Statistical analysis was performed by non-parametric unilateral Wilcoxon”s test with a level of statistical significance of 0.05. The results showed a significant (p=0.02475) 2.4-fold reduction in S. epidermidis biofilm formation on FHA (logUFC/cm2 = 6.87) compared to HA (logUFC/cm2 = 7.25); and also a significant (p=0.042) 3.7-fold reduction in S. aureus 15981 biofilm formation. In conclusion, according our results FHA is a promising biomaterial that promotes osseointegration and decreases the staphylococcal biofilm that could avoid PJI. Further studies will be necessary

Healthcare associated infections (HAI) pose a major threat to patients admitted to hospitals, and infection rates following orthopaedic arthroplasty surgery are as high as 4%, while the infection rates are even higher after revision surgery. 405 nm High-Intensity Narrow Spectrum (HINS) light has been proven to reduce environmental contamination in hospital isolation rooms, and there is potential to develop this technology for application in orthopaedic surgery. Cultured rat osteoblasts were exposed to 405 nm light to investigate if bactericidal doses of light could be used safely in the presence of mammalian cells. Cell viability was measured by MTT reduction and microscopy techniques, function by alkaline phosphatase activity, and proliferation by the BrdU assay. Exposures of up to a dose of 36 J/cm. 2. had no significant effect on osteoblast cell viability, whilst exposure of a variety of clinically relevant bacteria, to 36 J/cm. 2. resulted in up to 100% kill. Exposure to a higher dose of 54 J/cm. 2. significantly affected the osteoblast cell viability, indicating dose dependency. Work also demonstrated that 405 nm light exposure induces reactive oxygen species (ROS) production in both mammalian and bacterial cells, as shown by fluorescence generated from 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate dye. The mammalian cells were significantly protected from dying at 54 J/cm. 2. by catalase, which detoxifies H. 2. O. 2. Bacterial cells were significantly protected by sodium pyruvate (H. 2. O. 2. scavenger) and by a combination of free radical scavengers (sodium pyruvate, dimethyl thiourea (·OH scavenger), catalase) at 162 and 324 J/cm. 2. Thus the cytotoxic mechanism of 405 nm light in mammalian cells and bacteria is likely oxidative stress involving predominantly H. 2. O. 2. generation, with other ROS contributing to the damage. Additional work describing the potential for incorporation of this antimicrobial light within operating theatre lighting systems will also be discussed, and this, coupled with the cell viability and cytotoxicity results, suggests that 405 nm light could have great potential for continual patient safe decontamination during orthopaedic replacement surgeries and thereby reduce the incidence of infections

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good. Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results

Summary Statement. Innovative nanocomposite carbon coating doped with Si can significantly improve the osseintegration of orthopaedics implants. Additionally, this kind of coating increases the mechanical resistance of the implants, what is especially important on case of joints (frictional pairs). Introduction. Use of layers of carbon-doped silicon, which leads to the synthesis of layers improving mechanical and biological characteristics, let obtain good strength by volume features. Suitable introduction to the structure of amorphous silicon dioxide layer allow for the production of higher adhesion to metallic substrates and consequently the increased thickness and hardness. The increased thickness of the layer leads to a stronger diffusion barrier to harmful metal ions from the implant material and thus consequently improving the biocompatibility of the implant. Moreover, a silicon beneficial effect on stress relaxation layer formed during the synthesis. This allows for improved biocompatibility, also affects other property obtained in the case of silicon carbide layers, the bacteriastability. This further protects the surface of the implant against the risk of bacterial colonization in both the implantation and subsequent use in the body, and preferably suppressing inflammation and faster healing of surgical wounds. The thus obtained product is much better than the biological and mechanical parameters of currently offered. Patients & Methods. In order to evaluate the fabricated coatings conditions examination of the basic physicochemical and mechanical properties were conducted (AFM, Raman, XPS, nanoindentation technique). The in vitro and in vivo tests were also conducted. As a biological material osteoblast Saos-2 cells and endothelial cells line EA. 926 were used. For the evaluation of proliferation and cytotoxicity a “live/dead” test was used. For testing bactericidal activity of the C/Si coatings, an exponential growth phase of E. coli strain DH5 α was used. Test of bacterial immediate toxicity and bacterial colonization were performed. A model of rabbits and guinea pigs were used to obtained results with reference to irritation, intradermal reactivity, sensitization, local effects after implantation with the histopathological examination, cytotoxicity test. Results. XPS results have shown that the silicon content for each group of samples, both steel and titanium alloy is about 3, 4 and 5 percent. Increasing the concentration of silicon above 5% results in the weakening of the mechanical properties of the layer and lead to delamination of the sterilization process. Addition of silicon in the range of 3–5% does not negatively affect the mechanical and structural properties of the modified surface and from this point of view, all the criterion of strength. Performed studies confirmed very good mechanical properties of C/Si coatings. In vitro studies have indicated the optimal concentration of silicon in the coating, where the material is biocompatible and also has good antibacterial properties. Biocompatibility of silicon coatings was also confirmed by irritation and sensitization testing in the in vivo model. Discussion/Conclusion. Final result of the surface modification C/Si coating depends on modification of two effects, i.e. the formation of the transition layer of the substrate material and the synthesis of the outer carbon coating. Results of in vitro and in vivo tests confirmed very good biological properties of coatings which proved the fact that it is possible to improve the parameters of the implant work at the same time adding to the intrinsic the antibactericidal properties

Objectives

Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?

Objectives

The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength.

Objectives

The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.

Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated.

The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres.

The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation.

Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.