Search

Hybrid porous polymers based on poly-EGDMA and polylactide containing vancomycin, the concentration of which in the polymer varied by two orders of magnitude, were synthesized. The processes of polymer biodegradation and vancomycin release were studied in the following model media: phosphate-buffered saline (PBS), trypsin-Versene solution, and trypsin-PBS solution. The maximum antibiotic release was recorded during the first 3 h of extraction. The duration of antibiotic escape from the polymer samples in trypsin-containing media varied from 3 to 22 days, depending on the antibiotic content of the polymer. Keeping samples of the hybrid polymer in trypsin-containing model media resulted in acidification of the solutions—after 45 days, up to a pH of 1.84 in the trypsin-Versene solution and up to pH 1.65 in the trypsin-PBS solution. Here, the time dependences of the vancomycin release from the polymer into the medium and the decrease in pH of the medium correlated. These data are also consistent with the results of a study of the dynamics of sample weight loss during extraction in the examined model media. However, while the polymer porosity increased from ~53 to ~60% the pore size changed insignificantly, over only 10 μm. The polymer samples were characterized by their antibacterial activity against Staphylococcus aureus, and this activity persisted for up to 21 days during biodegradation of the material, regardless of the medium type used in model. Surface-dependent human cells (dermal fibroblasts) adhere well, spread out, and maintain high viability on samples of the functionalized hybrid polymer, thus demonstrating its biocompatibility in vitro. [ABSTRACT FROM AUTHOR]

The early loss of dental implants can be avoided with systemic antibiotics, however there are potentially significant side effects. Consequently, the use of local drug administration techniques is necessary to make dental implant therapy more practical. In this study, Y-branched nanotubes were prepared by non-expensive and simple anodization in two steps. Tests were performed to highlight their potential for local antibiotic administration. Y-branched nanotubes were able to incorporate a dose of Tetracycline and ensure its electrochemical stability. The presence of tetracycline significantly enhanced antibacterial efficacy, resulting in an increase of up to 55% for Escherichia coli and Pseudomonas aeruginosa and 50% for Staphylococcus aureus. The comparable antibacterial effects of the nanostructured surfaces highlight the potential of tetracycline in promoting antimicrobial action. Moreover, the addition of tetracycline does not influence the structural, morphological and stability properties of the nanostructured deposited TiO2 films. [ABSTRACT FROM AUTHOR]

Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC). [ABSTRACT FROM AUTHOR]

The objective was to explore the dynamics and duration of antibiotic elution in samples based on polymer hydrogel and PMMA. Material and methods The samples impregnated with vancomycin, rifampicin and cefazolin at various concentrations were placed in phosphate-buffered saline and incubated at 37 °C. The medium was completely replaced at 1, 3, 7, 14, 21 and 28 days. Spectrophotometry was used to measure concentration of drugs in solution and the release profiles. The median and 95 % CI were employed to statistically describe data obtained from 5 parallel studies. Results Concentrations of the antibiotics eluted from the polymer hydrogel were 7 times greater than those released from PMMA on day 1; 15 times greater on days 2 and 3; 6.6 times greater on day 7 and 3 times or more in the following days of observation. The rate of antibiotic release from hydrogel volumes also differed markedly. Discussion The drug release was more than 70% of the total amount for all hydrogel samples in contrast to PMMA with elution not exceeding 10 %. Despite the fact that a burst release was observed with 80 % of the antibiotic released in the first 5 days as seen in the case of bone cement, the concentration of the drug eluted from hydrogels was several times higher and exceeded the MIC throughout the observation period. The release of the antimicrobial agent from hydrogels was caused by diffusion of the particles from the entire volume of the matrix demonstrating an important advantage over PMMA with the potential being limited by surface depletion. Conclusion At this point, we have shown the possibility of creating potential depot systems based on unsaturated PVA derivatives with controlled release of antibiotics and characteristics being superior to PMMA.

Hybrid porous polymers based on poly-EGDMA and polylactide containing vancomycin, the concentration of which in the polymer varied by two orders of magnitude, were synthesized. The processes of polymer biodegradation and vancomycin release were studied in the following model media: phosphate-buffered saline (PBS), trypsin-Versene solution, and trypsin-PBS solution. The maximum antibiotic release was recorded during the first 3 h of extraction. The duration of antibiotic escape from the polymer samples in trypsin-containing media varied from 3 to 22 days, depending on the antibiotic content of the polymer. Keeping samples of the hybrid polymer in trypsin-containing model media resulted in acidification of the solutions—after 45 days, up to a pH of 1.84 in the trypsin-Versene solution and up to pH 1.65 in the trypsin-PBS solution. Here, the time dependences of the vancomycin release from the polymer into the medium and the decrease in pH of the medium correlated. These data are also consistent with the results of a study of the dynamics of sample weight loss during extraction in the examined model media. However, while the polymer porosity increased from ~53 to ~60% the pore size changed insignificantly, over only 10 μm. The polymer samples were characterized by their antibacterial activity against Staphylococcus aureus, and this activity persisted for up to 21 days during biodegradation of the material, regardless of the medium type used in model. Surface-dependent human cells (dermal fibroblasts) adhere well, spread out, and maintain high viability on samples of the functionalized hybrid polymer, thus demonstrating its biocompatibility in vitro.

Polymer nanofibers possess a range of attractive features that make them highly suitable for various biomedical application, including their high surface area/volume ratio, mechanical flexibility, porosity and potential for surface or bulk functionalization. Besides, such nanofibers can be used to encapsulate antibiotics to fabricate slow-release systems, but in this case the nanofibers should be fabricated with biocompatible and biodegradable polymers. Here we developed a novel nanocarrier system based on polyvinylpyrrolidone (PVP)/chitosan (CHI) electrospun nanofibers containing cloxacillin benzathine (CLO). PVP was chosen because of its ability to form nanofibers, while a small amount of chitosan was added to help control the CLO release, which antibiotic is widely employed to treat bacterial infections. The as-produced CLO-containing electrospun nanofibers were characterized regarding their morphological features and antibiotic release profile. SEM images revealed homogeneous and defects-free nanofibers, exhibiting no discernible morphological variations between the CLO-containing and CLO-non-containing nanofibers. FTIR results indicate hydrogen bonds formation between carboxyl and carboxylate groups from CLO and hydroxyl groups from CHI. The antimicrobial properties of antibiotic-loaded nanofibers were investigated against Gram-positive bacteria S. aureus, yielding inhibition zone diameters of 12.5 ± 1.6 mm and 29.8 ± 1.3 mm for PVP/CHI/CLO and PVP/CLO nanofibers, respectively. Besides, the drug release kinetics study indicates that the nanocarrier system formed by PVP/CHI can release the antibiotics more slowly due to the chemical interactions between CHI and CLO compounds. Our results suggest that drug activity was preserved after encapsulation by electrospinning, and the difference in the inhibition zone diameter was corroborated by drug release mechanism experiments, indicating the system as a potential material to treat infections caused by S. aureus. [ABSTRACT FROM AUTHOR]

The early loss of dental implants can be avoided with systemic antibiotics, however there are potentially significant side effects. Consequently, the use of local drug administration techniques is necessary to make dental implant therapy more practical. In this study, Y-branched nanotubes were prepared by non-expensive and simple anodization in two steps. Tests were performed to highlight their potential for local antibiotic administration. Y-branched nanotubes were able to incorporate a dose of Tetracycline and ensure its electrochemical stability. The presence of tetracycline significantly enhanced antibacterial efficacy, resulting in an increase of up to 55% for Escherichia coli and Pseudomonas aeruginosa and 50% for Staphylococcus aureus. The comparable antibacterial effects of the nanostructured surfaces highlight the potential of tetracycline in promoting antimicrobial action. Moreover, the addition of tetracycline does not influence the structural, morphological and stability properties of the nanostructured deposited TiO2 films.

Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC).

Infection of the periodontal pocket presents two major challenges for drug delivery: administration into the periodontal pocket and a high fluid clearance rate in the pocket. The current study aimed to develop and study a novel hydrogel system for delivery of the antibiotic drug metronidazole directly into the periodontal pocket via injection followed by in situ gelation. The natural polymers gelatin and alginate served as basic materials, and their crosslinking using a carbodiimide resulted in a dual hydrogel network. The study focused on the effects of the hydrogel's formulation parameters on the drug release profile and the hydrogel's physical and mechanical properties. A cell viability test was conducted on human fibroblasts. The metronidazole-loaded hydrogels demonstrated a decreasing release rate with time, where most of the drug eluted within 24 h. These hydrogels exhibited fibroblast viability of at least 75% after 24 and 48 h, indicating that they are highly biocompatible. Although the alginate concentration used in this study was relatively low, it had a strong effect on the physical as well as the mechanical properties of the hydrogel. An increase in the alginate concentration increased the crosslinking rate and enabled enhanced entanglement of the 3D structure, resulting in a decrease in the gelation time (less than 10 s) and swelling degree, which are both desired for the studied periodontal application. Increasing the gelatin concentration without changing the crosslinker concentration resulted in significant changes in the physical properties and slight changes in the mechanical properties. Metronidazole incorporation slightly decreased the hydrophilicity of the hydrogel and therefore also its viscosity, and affected the sealing ability and the tensile and compression moduli. The developed hydrogels exhibited controllable mechanical and physical properties, can target a wide range of conditions, and are therefore of high significance in the field of periodontal treatment. [ABSTRACT FROM AUTHOR]

• The stimuli leading to drug release can be either external or internal. • Nanoparticles are promising agents for targeted stimuli-dependent antibiotic drugs delivery. • Targeted antibiotic release at desired site minimizes the resistance and side effects associated with systematic release of drug(s). Site-specific delivery of antibiotics has always been a high-priority area in pharmaceutical research. Conventionally used antibiotics suffer several limitations, such as low accumulation and penetration in diseased cells/tissues, limited bioavailability of drugs, drug resistance, and off-target toxicity. To overcome these limitations, several strategies have been exploited for delivering antibiotics to the site of infection, such as the use of stimuli-responsive antibiotic delivery systems, which can release antibiotics in a controlled and timely fashion. These stimuli can either be exogenous (light, magnetism, ultrasound, and electrical) or endogenous (pH, redox reactions, and enzymatic). In this review, we present a summary of recent developments in the field of stimuli-based targeted drug delivery systems for the site-specific release of antibiotics. [ABSTRACT FROM AUTHOR]

Both antibiotic‐impregnated poly(methyl acrylate, methyl methacrylate) (PMMA) and antibiotic‐impregnated calcium sulfate have been successfully used as local antibiotic delivery vehicles for the management of chronic osteomyelitis. Here, we examined the antibiotic elution characteristics and antibacterial properties of a composite drug delivery system consisting of PMMA/calcium sulfate carrying vancomycin (dual carrier‐v) against Staphylococcus aureus, with PMMA loaded with vancomycin (PMMA‐v) as a control. Vancomycin gradually degraded from dual carrier‐v and PMMA‐v up to about 8 and 6 weeks, respectively. At different elution time points, the inhibition zones of the dual carrier‐v were larger than the inhibition zones of the PMMA‐v (P

The development of chitosan–gelatin (CS‐G) hydrogels embedded with ampicillin‐loaded hyaluronic acid nanoparticles (HA‐NPs) for wound dressing is proposed. It was aimed to provide controlled ampicillin delivery by incorporation of HA‐NPs into biocompatible CS‐G hydrogel structure. According to in vitro ampicillin release studies, 55% of ampicillin was released from CS‐G/HA‐NPs hydrogels after 5 days. Antibacterial performance of CS‐G/HA‐NPs hydrogels was proven with agar disc diffusion test. For cytotoxicity assay, fibroblast cell viability increased in CS‐G/HA‐NPs hydrogels compared with CS‐G group after 24 hr incubation. Consequently, the potential ability of CS‐G/HA‐NPs hydrogels as a controlled drug delivery system has been verified. [ABSTRACT FROM AUTHOR]

Polymers derived from natural sources are of interest in the scientific and medical communities, especially soy protein which exhibits low immunogenicity and good mechanical properties, and supports cell proliferation. Soy protein is cost-effective compared to other natural polymers and is attractive also due to its non-animal origin and relatively long storage stability. In the current study, hybrid film structures were developed and studied as a novel wound dressing platform with controlled release of three bioactive agents. The dense top layer is designed to provide mechanical support, control the water vapor permeability and to elute the antibiotic drug cloxacillin and the analgesic drug bupivacaine to the wound site. The porous sub-layer is designed to absorb the wound exudates and release the hemostatic agent tranexamic acid for bleeding control. The results show that the formulation parameters, i.e. crosslinker and plasticizer concentrations, affected the mechanical properties of the wound dressings as well as relevant physical properties (water vapor transmission rate and swelling kinetics), but had almost no effect on the drug-release profiles. While the antibiotic drug and the analgesic drug were released within several hours, the hemostatic agent was released within several minutes, according to the well designed hybrid structure. In conclusion, our novel soy protein hybrid wound dressings are biocompatible, can deliver various drugs simultaneously in a controlled fashion for each drug individually, and can be adjusted to suit various types of wounds by altering their properties through formulation effects. [ABSTRACT FROM AUTHOR]

This study deals with the development of a polypropylene (PP) artificial abdominal wall prosthesis textile with improved biological and antibiotic delivery properties. This added functionality was obtained by finishing of PP prosthesis textile with chitosan (CS), synthesized per-amino-cyclodextrin (CD-NH2) and polyacrylic acid (PAA). The finishing process involved polymerization between the three last mentioned reactants, which generated a cross-linked polymer that coated the PP surface meshes. Then different characterizations were performed on our wash-resistant functionalization to evaluate its efficiency. Firstly, wettability performance, for various grafting rates of the PP biomaterials, was assessed via the drop contact angle technique. Then, a mechanical characterization through an evaluation of the tensile strength revealed no influence of our grafting procedure on these properties. Scanning electron microscopy analysis was performed to evaluate the grafting mode and its effectiveness. Inclusion complex formation between the ciprofloxacin and both CD-NH2 and its polymer were studied via isothermal titration calorimetry measurements. Antibiotic sorption capacities of treated and untreated textile samples were then studied by batch assessments coupled with spectrophotometric analysis. The biological and microbiological properties of the PP mesh functionalized with the CS-CD-NH2 polymer and charged by selected antibiotic were assessed by cell culture analysis. After 3 and 6 days of cell contact, the results revealed an improved proliferation and adhesion of NIH3T3 fibroblastic cells and no obvious cytotoxicity on the chemical functionalized substrate. Finally, in vitro antimicrobial activity of the CS-CD-NH2-grafted PP biomaterial previously loaded with antibiotic was evaluated against the different bacteria strains, Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. Results revealed a greatly superior activity with the functionalized PP meshes compared to that of the untreated PP within a 24 h batch experiment in human blood plasma medium. In summary, the different results from the present study provide an insight into the efficient performance of CS/CD-NH2 polymer as drug delivery system for various applications in the field of medical biomaterials. [ABSTRACT FROM AUTHOR]

Both antibiotic‐impregnated poly(methyl acrylate, methyl methacrylate) (PMMA) and antibiotic‐impregnated calcium sulfate have been successfully used as local antibiotic delivery vehicles for the management of chronic osteomyelitis. Here, we examined the antibiotic elution characteristics and antibacterial properties of a composite drug delivery system consisting of PMMA/calcium sulfate carrying vancomycin (dual carrier‐v) against Staphylococcus aureus, with PMMA loaded with vancomycin (PMMA‐v) as a control. Vancomycin gradually degraded from dual carrier‐v and PMMA‐v up to about 8 and 6 weeks, respectively. At different elution time points, the inhibition zones of the dual carrier‐v were larger than the inhibition zones of the PMMA‐v (P < 0.05). The colony inhibition rate of the dual carrier‐v was 95.57%, whereas it was 77.87% for PMMA‐v. Scanning electron microscopy was used to demonstrate biofilm formation on the surface of plates treated with vancomycin‐unloaded PMMA, whereas there was no biofilm formation on the surface of plates treated with dual carrier‐v or PMMA‐v. The dual carrier‐v was more effective at antibacterial adhesion at each time point after immersion in simulated body fluid as compared with PMMA‐v (P < 0.05). In conclusion, our results suggest that the dual carrier‐v can release higher concentrations of antibiotics and inhibit bacteria growth more effectively in vitro as compared with PMMA‐v. The dual carrier‐v thus may have potential as an alternative strategy for osteomyelitis management. [ABSTRACT FROM AUTHOR]

A degradable, poly (lactic-co-glycolic acid) (PLGA), gentamicin-loaded prophylactic coating for hydroxyapatite (HA)-coated cementless hip prostheses is developed with similar antibacterial efficacy as offered by gentamicin-loaded cements for fixing traditional, cemented prostheses in bone. We describe the development pathway, from in vitro investigation of antibiotic release and antibacterial properties of this PLGA-gentamicin-HA-coating in different in vitro models to an evaluation of its efficacy in preventing implant-related infection in rabbits. Bone in-growth in the absence and presence of the coating was investigated in a canine model. The PLGA-gentamicin-HA-coating showed high-burst release, with antibacterial efficacy in agar-assays completely disappearing after 4 days, minimising risk of inducing antibiotic resistance. Gentamicin-sensitive and gentamicin-resistant staphylococci were killed by the antibiotic-loaded coating, in a simulated prosthesis-related interfacial gap. PLGA-gentamicin-HA-coatings prevented growth of bioluminescent staphylococci around a miniature-stem mounted in bacterially contaminated agar, as observed using bio-optical imaging. PLGA-gentamicin-HA-coated pins inserted in bacterially contaminated medullary canals in rabbits caused a statistically significant reduction in infection rates compared to HA-coated pins without gentamicin. Bone ingrowth to PLGA-gentamicin-HA-coated pins, in condylar defects of Beagle dogs was not impaired by the presence of the degradable, gentamicin-loaded coating. In conclusion, the PLGA-gentamicin-HA-coating constitutes an effective strategy for infection prophylaxis in cementless prostheses.

Hydrogel/honey hybrids manifest an attractive design with an exclusive therapeutic property that promotes wound healing process. The greater the concentration of honey within the formulation, the better the biomedical properties that will be achieved. However, an increase in the percentage of honey can negatively affect the physico-chemical and mechanical properties of hybrid hydrogels. The need exists, therefore, to prepare wound dressings that contain high honey density with optimal biomedical, mechanical and physicochemical properties. In this study, a simple method for the preparation of a highly concentrated honey/PVA hybrid hydrogel with borax as the crosslinking agent is reported. Comprehensive evaluations of the morphology, swelling kinetics, permeability, bio-adhesion, mechanical characteristics, cytotoxicity, antibacterial property, cell proliferation ability and their controlling release properties were conducted as a function of crosslinking density. All the borax-induced hydrogels showed acceptable biocompatibility, and the incorporation of 1% borax in the hydrogel formulation produced optimal behaviours for wound addressing applications. [ABSTRACT FROM AUTHOR]

Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria. Short-term release into an agar gel was evaluated using a fluorescent tracer (fluorescein) incorporated in the carrier materials calcium sulfate (CaSO 4 ) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO 4 beads were evaluated. Mechanical properties of fluorescein-incorporated beads were analyzed. Efficacy of the antibiotics vancomycin (VAN) or tobramycin (TOB) alone and in combination was evaluated against lawn biofilms of bioluminescent strains of Staphylococcus aureus and Pseudomonas aeruginosa . Zones of inhibition of cultures (ZOI) were measured visually and using an in-vivo imaging system (IVIS). The influence of body fluids on release was assessed using CaSO 4 beads that contained fluorescein or antibiotics and were pre-coated with human blood or synovial fluid. The spread from the beads followed a square root of time relationship in all cases. The loading concentration had no influence on short-term fluorescein release and pre-coating of beads with body fluids did not affect short-term release or antibacterial activity. Compared to PMMA, CaSO 4 had a more rapid short term rate of elution and activity against planktonic and lawn biofilms. This study highlights the importance of considering antibiotic loading and packing density when investigating the clinical application of bone cements for infection management. [ABSTRACT FROM AUTHOR]

• The development of novel antibiotic-free strategies, like biomaterial NIR-responsive, which act in synergy with antibiotics and increase their efficiency is a promising approach to circumvent antibiotic resistance of MDR pathogens. • Photothermal microparticles coated with polydopamine are a key to simultaneously obtaining an antibacterial and a radical scavenging activity to ensure wound healing. • Injectable hydrogels based on Gellan Gum with shear-thinning, self-healing and adhesiveness capabilities can repair damage and restore structural and functional properties of the tissue. [Display omitted] The development of wound dressings with combined antioxidant, antibacterial and tissue adhesion functions has been a difficult medical task for the treatment of wound infections. We synthetized a dopamine and PEG functionalized Gellan Gum (GG) to produce an injectable hydrogel with radical scavenging activity having both specific and aspecific antibiotic/antimicrobial properties. Using starting GG with different molecular weights, we obtained two derivatives that have been used to prepare the gel precursor dispersion, that undergoes gelation in the presence of colistin and dried microparticles (MPs) functionalized on the surface with polydopamine (pDA). Both were used to dope the hydrogel, increase the radical scavenger activity and impart near-infrared light (NIR) responsiveness. Indeed, with an irradiation of 810 nm, the incorporated microparticles exhibit photothermal transformation properties and improve the release of antibiotics on demand. The combination of photothermal and antibiotic therapy with synergistic antibacterial action acts on Pseudomonas aeruginosa and leads to a bactericidal effect in a few hours, while on Staphylococcus aureus there is an effect of inhibition of growth over time due only to the hyperthermic effect. We believe this study provides a promising method for fabricating a multifunctional injectable hydrogel for the potential treatment of infected skin wounds. [ABSTRACT FROM AUTHOR]

In this work we try to address the large interest existing nowadays in the better understanding of the interaction between microbial biofilms and metallic implants. Our aimed was to identify a new preventive strategy to control drug release, biofilm formation and contamination of medical devices with microbes. The transfer and printing of novel bioactive glass-polymer-antibiotic composites by Matrix-Assisted Pulsed Laser Evaporation into uniform thin films onto 316 L stainless steel substrates of the type used in implants are reported. The targets were prepared by freezing in liquid nitrogen mixtures containing polymer and antibiotic reinforced with bioglass powder. The cryogenic targets were submitted to multipulse evaporation by irradiation with an UV KrF* (λ = 248 nm, τFWHM ≤ 25 ns) excimer laser source. The prepared structures were analyzed by infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and profilometry, before and after immersion in physiological fluids. The bioactivity and the release of the antibiotic have been evaluated. We showed that the incorporated antibiotic underwent a gradually dissolution in physiological fluids thus supporting a high local treatment efficiency. Electrochemical measurements including linear sweep voltammetry and impedance spectroscopy studies were carried out to investigate the corrosion resistance of the coatings in physiological environments. The in vitro biocompatibility assay using the MG63 mammalian cell line revealed that the obtained nanostructured composite films are non-cytotoxic. The antimicrobial effect of the coatings was tested against Staphylococcus aureus and Escherichia coli strains, usually present in implant-associated infections. An anti-biofilm activity was evidenced, stronger against E. coli than the S. aureus strain. The results proved that the applied method allows for the fabrication of implantable biomaterials which shield metal ion release and possess increased biocompatibility and resistance to microbial colonization and biofilm growth. [ABSTRACT FROM AUTHOR]

Space maintainers (SMs) used for craniofacial reconstruction function to preserve the void space created upon bone loss and promote soft tissue healing over the defect. Polymethylmethacrylate-based SMs present several drawbacks including implant exposure, secondary removal surgeries, and potential bacterial contamination during implantation. To address these issues, a novel composite material comprising poly(propylene fumarate) (PPF) with N-vinyl pyrrolidone (NVP) as the crosslinking agent, carboxymethylcellulose (CMC) hydrogel as a porogen, and antibiotic loaded poly(lactic- co-glycolic acid) (PLGA) microparticles as antibiotic carriers and porogen was fabricated. CMC was incorporated at 40 wt % to impart rapid porosity while PLGA microparticles were incorporated at 30 or 40 wt % to release either clindamycin or colistin. This study was designed to examine the effects of PPF:NVP ratio, PLGA wt %, and the drug dose on the mass loss, temporal porosity change and drug release kinetics of the composite construct. Mass loss decreased significantly in constructs containing 3:2 PPF:NVP ratio with 30 wt % PLGA (63.2 ± 0.8%) compared to the 2:3 PPF:NVP ratio (80.3 ± 1.0% and 85.3 ± 1.3% for 30 and 40 wt % PLGA content, respectively) at 8 weeks. In formulations with 3:2 PPF:NVP ratio, incorporation of 40 versus 30 wt % PLGA significantly increased the porosity at 8 weeks under accelerated degradation conditions. Constructs released clindamycin or colistin at concentrations above the minimum inhibitory concentration for target pathogens for 45 and 77 days, respectively. This study demonstrates that the composition of PPF/CMC/PLGA constructs can be modulated to achieve properties suitable for craniofacial degradable space maintenance applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1485-1497, 2015. [ABSTRACT FROM AUTHOR]

In this work we try to address the large interest existing nowadays in the better understanding of the interaction between microbial biofilms and metallic implants. Our aimed was to identify a new preventive strategy to control drug release, biofilm formation and contamination of medical devices with microbes. The transfer and printing of novel bioactive glass-polymer-antibiotic composites by Matrix-Assisted Pulsed Laser Evaporation into uniform thin films onto 316 L stainless steel substrates of the type used in implants are reported. The targets were prepared by freezing in liquid nitrogen mixtures containing polymer and antibiotic reinforced with bioglass powder. The cryogenic targets were submitted to multipulse evaporation by irradiation with an UV KrF* (λ = 248 nm, τFWHM ≤ 25 ns) excimer laser source. The prepared structures were analyzed by infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and profilometry, before and after immersion in physiological fluids. The bioactivity and the release of the antibiotic have been evaluated. We showed that the incorporated antibiotic underwent a gradually dissolution in physiological fluids thus supporting a high local treatment efficiency. Electrochemical measurements including linear sweep voltammetry and impedance spectroscopy studies were carried out to investigate the corrosion resistance of the coatings in physiological environments. The in vitro biocompatibility assay using the MG63 mammalian cell line revealed that the obtained nanostructured composite films are non-cytotoxic. The antimicrobial effect of the coatings was tested against Staphylococcus aureus and Escherichia coli strains, usually present in implant-associated infections. An anti-biofilm activity was evidenced, stronger against E. coli than the S. aureus strain. The results proved that the applied method allows for the fabrication of implantable biomaterials which shield metal ion release and possess increased biocompatibility and resistance to microbial colonization and biofilm growth.

Antibiotic incorporation into hydroxyapatite (HA) coatings by co-precipitation and the impact of bone relevant doping elements on the adsorption kinetics are investigated from both theoretical and experimental points of view. Tobramycin interactions with bioactive TiO 2 and HA surfaces are analyzed using density functional theory. According to the calculations, the drug molecule has larger adsorption energy than the Ca + ion on both surfaces under study in Phosphate Buffered Saline (PBS). The results support the experimental observations that HA nucleation and growth are strongly limited on TiO 2 surfaces in the presence of clinically relevant antibiotic concentrations in PBS. The drug molecule is more likely to adopt parallel arrangement onto the HA surface, as the adsorption energy of such arrangement is higher compared to a perpendicular one. Strontium substitution of the HA surface is found to results in a weaker drug–surface interaction, and leads also to a decrease in coating thickness. However, the presence of strontium gives rise to a coating morphology with enhanced drug incorporation capacity and slower antibiotic release compared to non-substituted, co-precipitated counterparts. Our theoretical calculation results were found to be in excellent agreement with experimental data and provide a powerful tool to understand the interaction mechanism between drug and different surface chemistries necessary for development of future versatile orthopedic and dental implant surfaces. [ABSTRACT FROM AUTHOR]

Abstract: Currently the safe and responsible use of antibiotics is a world-wide concern as it promotes prevention of the increasing emergence of multiresistant bacterial strains. Considering that there is a noticeable decline of the available antibiotic pipeline able to combat emerging resistance in serious infection a major concern grows around the prosthetic joint infections once the available commercial antibiotic loaded polymethylmethacrylate bone cements (BC) are inadequate for local antibiotic treatment, especially against MRSA, the most commonly isolated and antibiotic-resistant pathogen in bone infections. In this paper a novel modified BC matrix loaded with minocycline is proposed. A renewed interest in this tetracycline arises due to its broad-spectrum of activity against the main organisms responsible for prosthetic joint infections, especially against MRSA. The modified BC matrices were evaluated concerning minocycline release profile, biomechanical properties, solid-state characterization, antimicrobial stability and biocompatibility under in vitro conditions. BC matrix loaded with 2.5% (w/wBC ) of minocycline and 10.0% (w/wBC ) of lactose presented the best properties since it completely released the loaded minocycline, maintained the mechanical properties and the antimicrobial activity against representative strains of orthopedic infections. In vitro biocompatibility was assessed for the elected matrix and neither minocycline nor lactose loading enhanced BC cytotoxicity. [Copyright &y& Elsevier]

A bioactive glass and its corresponding glass-ceramic have been used to investigate the possibility to load a common antibiotic (carbenicillin) on their surface during the reactivity processes which occur by dipping these materials in a simulated body fluid. The materials bioactivity in the early stage of simulated body fluid treatment has been investigated by means of scanning electron microscopy (SEM-EDS) and X-ray diffraction. The uptake of carbenicillin has been performed by dipping the samples in simulated body fluid solution with a drug concentration of 500 mg/l for 6, 12 and 24 h. Some glass samples underwent a pre-treatment in simulated body fluid, for different time frames, in order to form a silica gel layer before the surface exposition to antibiotic. The carbenicillin release has been measured in water up to 36 h. The amount of incorporated and released antibiotic has been estimated by UV visible spectrophotometer. All samples were able to incorporate a significant amount of antibiotic and it was possible to tailor the drug release by modifying the simulated body fluid pre-treatment. [ABSTRACT FROM AUTHOR]