Sustained Release Of Antibiotics Research Articles

Gentamicin and clindamycin antibiotic-eluting depot technology eradicates S. aureus in an implant-associated osteomyelitis pig model without systemic antibiotics.

The therapeutic challenges of orthopedic device-related infections and emerging antimicrobial resistance have attracted attention to drug delivery technologies. This study evaluates the preclinical efficacy of local single- and dual-antibiotic therapy against implant-associated osteomyelitis (IAO) using a drug-eluting depot technology, CarboCell, that provides sustained release of high-dose antibiotics and allows for strategic in situ placement in relation to infectious lesions. Clindamycin and gentamicin were formulated in CarboCell compositions. One-stage-revision of tibial Staphylococcus aureus IAO was conducted in 19 pigs. Pigs were treated locally with CarboCell containing either gentamicin alone for 1 week or a co-formulation of gentamicin and clindamycin for 1 or 3 weeks. Bone, soft tissue, and antibiotic depots were collected for microbiology, histology, and HPLC analyses. Supporting in vivo release studies of CarboCell formulations were performed on mice. Both single- and dual-antibiotic CarboCell formulations were developed and capable of eradicating the infectious bacteria in bone and preventing colonization of implants inserted at revision. Eradication in soft tissue was observed in all pigs after 3 weeks and in 6/9 pigs after 1 week of treatment. Neutrophil counts in bone tissue were below the infection cut-off in all pigs receiving the dual-antibiotic therapies, but above in all pigs receiving the single-antibiotic therapy. Histological signs of active bone reorganization and healing were observed at 3 weeks. In conclusion, all CarboCell formulations demonstrated strong therapeutic activity against IAO, eradicating S. aureus in bone tissue and preventing colonization of implants even without the addition of systemic antibiotic therapy.

Sustained Antibiotic Release from Biodegradable Gelatin–Silica Hybrid for Orthopedic Infections

AbstractAntibiotic‐loaded polymethylmethacrylate (PMMA) beads are commonly employed to treat prosthetic joint infections (PJI) and chronic osteomyelitis due to their excellent mechanical strength. However, PMMA's non‐degradability results in a burst release of antibiotics and potential renal toxicity, necessitating additional surgeries for bead removal. There is a critical need for infection control materials that can deliver antibiotics effectively, maintain adequate mechanical strength, and degrade uniformly. This study introduces a gelatin–silica hybrid antibiotic carrier, characterized by covalent bonds between the gelatin and silica networks. The incorporation of the silica network enhances the compressive strength to 32.53 ± 2.4 MPa and ensures uniform degradation over 6 months, aligning with clinical timelines. Furthermore, the gelatin–silica hybrid can support up to 10 wt% antibiotic loading without compromising its properties, making it a promising candidate for next‐generation infection control materials.

MOF-Modified Microrollers for Bioimaging and Sustained Antibiotic Delivery.

Central nervous system (CNS) infections caused by neurosurgery or intrathecal injection of contaminated cerebrospinal fluid are a common and difficult complication. Drug-delivery microrobots are among the latest solutions proposed for antibacterial applications. However, there is a lack of research into developing microrobots with the ability to sustain antibody delivery while can move efficiently in the CNS. Here, biocompatible antibacterial metal-organic framework (MOF)-modified microrollers (MMRs) to combat CNS infections are proposed. The MMRs are iron-based metal-organic framework (NH2-MIL-101(Fe)) modified for enhanced adsorption and Fe/Al coated for magnetic actuation and biocompatibility. The MMRs have demonstrated a faster and unhindered magnetically actuated motion on the uneven biological tissue surface in an organ-on-a-chip that mimicked the CNS compared to it on smooth surface. CFD results consistently align with the experimental findings. The MMRs can be loaded with rhodamine 6G for bioimaging, allowing them to be imaged through sections of the main human tissues by fluorescence microscopy, or tetracycline hydrochloride for antibiotic delivery, allowing them to inhibit the growth of Staphylococcus aureus biofilms by sustained release of antibiotics for 9 days. This study provides a strategy to integrate high-capacity adsorption material with magnetically actuated locomotion for long-term targeted antibacterial applications in biological environments.

PLGA Nanoparticles Formulations Loaded With Antibiotics Induce Sustained and Controlled Antibiotics Release for Prolonged Antibacterial Action Against MRSA, and Pseudomonas aeruginosa FRD1.

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e., 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e., ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e., methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e., PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605, MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e., 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes.

Magnetic-navigable silk fibroin microneedles for oral drug delivery: Ensuring long-lasting helicobacter pylori eradication and rapid hemostasis in the stomach

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

The synergic effect of nanosecond fiber laser and drug-loaded electrospun PVA coating on metallurgical and biological characteristics of Ti-6Al-4 V alloy

Nowadays, titanium-based implants are widely used to replace damaged or missing body organs. Poor chemical bonding with the bone and infection caused by formation of biofilm on the implant surface are the most common problems with them. So, antibacterial properties and osteoblast adhesion improvement have been intended to address these issues. The aim of this research is cell adhesion improvement and prevention of bacterial infection using surface roughness and in-situ antibiotic drug release. Here, micromachining (nanoseconds) laser with a groove distance of 10, 30, and 50 µm, was used to surface modification. X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), hardness, roughness, and wettability tests were used for physical and metallurgical characterization of surface-modified samples to find the optimum laser processing conditions. Roughness has increased as a result of laser surface modification and surface characteristics of alloy exhibit sensitivity to the groove distance. The lower groove distance indicated the higher roughness and wettability. Martensite phase, α phase, and, Ti3Al were observed in the fusion zone. Also, the dissolution of the beta phase has occurred in the fusion and the heat-affected zones. No oxidation was observed. All these occurred without any change in bulk. Then optimized sample surfaces were coated by the vancomycin-loaded polyvinyl alcohol solution using electrospinning process, and toxicity, cell adhesion, and drug release rate were evaluated. The results showed laser surface modification and coating did not hurt cell viability. Modified samples demonstrated high cell adhesion and improvement in drug release compared to the unmodified samples. The drug release rate was extended from 4 h to 25 h for modified samples. So, the modified implants could indicate a sustained release of antibiotics as well.

Fighting fibrin with fibrin: Vancomycin delivery into coagulase-mediated Staphylococcus aureus biofilms via fibrin-based nanoparticle binding.

Staphylococcus aureus skin and soft tissue infection is a common ailment placing a large burden upon global healthcare infrastructure. These bacteria are growing increasingly recalcitrant to frontline antimicrobial therapeutics like vancomycin due to the prevalence of variant populations such as methicillin-resistant and vancomycin-resistant strains, and there is currently a dearth of novel antibiotics in production. Additionally, S. aureus has the capacity to hijack the host clotting machinery to generate fibrin-based biofilms that confer protection from host antimicrobial mechanisms and antibiotic-based therapies, enabling immune system evasion and significantly reducing antimicrobial efficacy. Emphasis is being placed on improving the effectiveness of therapeutics that are already commercially available through various means. Fibrin-based nanoparticles (FBNs) were developed and found to interact with S. aureus through the clumping factor A (ClfA) fibrinogen receptor and directly integrate into the biofilm matrix. FBNs loaded with antimicrobials such as vancomycin enabled a targeted and sustained release of antibiotic that increased drug contact time and reduced the therapeutic dose required for eradicating the bacteria, both in vitro and in vivo. Collectively, these findings suggest that FBN-antibiotic delivery may be a novel and potent therapeutic tool for the treatment of S. aureus biofilm infections.

Effects of Vancomycin/Tobramycin-Doped Ceramic Composite (Polyvinyl Alcohol Composite–Vancomycin/Tobramycin–Polymeric Dicalcium Phosphate Dihydrate) in a Rat Femur Model Implanted With Contaminated Porous Titanium Cylinders

BackgroundPeriprosthetic joint infection (PJI) remains common and problematic. We hypothesized that using a bioceramic that provided rapid release of the antibiotics (vancomycin [VAN] or VAN and tobramycin [VAN and TOB]) from a polyvinyl-alcohol-composite (PVA) combined with a delayed and sustained antibiotic release from polymeric-dicalcium-phosphate-dihydrate (PDCPD) ceramic would inhibit S. aureus-associated implant infections. MethodsA total of 50 male Sprague Dawley rats were randomly divided into 5 groups—I: negative control; II: bacteria only; III: bacteria + saline wash; IV: bacteria + PVA-VAN-PDCPD, and V: bacteria + PVA-VAN-TOB-PDCPD. A porous titanium (Ti) implant was press-fit into the rat knee. S. aureus-containing broth was added into the joint space creating a PJI. After 1 week, the joints from groups III to V were washed with saline and the fluid collected for bacterial quantification. This was followed by saline irrigation treatment (groups III to V) and application of the antibiotic-loaded PVA-PDCPD bioceramic (groups IV and V). On day 21, joint fluid was collected, and the implants harvested for bacterial quantification. ResultsNo bacteria were isolated from the negative control (group I). The positive control (group II) was positive on both days 7 and 21. Bacteria were still present on day 21 in the fluid and implant in group III. Groups (IV and V) showed a decrease in the bacterial burden in the fluid and implant on day 21. There were significant differences in bacteria levels in the collected wash fluid and on the implant at day 21 between the saline wash (group III) and treatment groups (IV and V). ConclusionsIn this animal model of acute periprosthetic infection, treatment with PVA-VAN-PDCPD and PVA-VAN/TOB-PDCPD reduced bacterial load in the infected joint and the infected Ti implant. Application of PVA-VAN-PDCPD and/or PVA-VAN/TOB-PDCPD after saline irrigation could be used as an addition to the treatment of PJI.

Human-Derived collagen hydrogel as an antibiotic vehicle for topical treatment of bacterial biofilms.

The complexity of chronic wounds creates difficulty in effective treatments, leading to prolonged care and significant morbidity. Additionally, these wounds are incredibly prone to bacterial biofilm development, further complicating treatment. The current standard treatment of colonized superficial wounds, debridement with intermittent systemic antibiotics, can lead to systemic side-effects and often fails to directly target the bacterial biofilm. Furthermore, standard of care dressings do not directly provide adequate antimicrobial properties. This study aims to assess the capacity of human-derived collagen hydrogel to provide sustained antibiotic release to disrupt bacterial biofilms and decrease bacterial load while maintaining host cell viability and scaffold integrity. Human collagen harvested from flexor tendons underwent processing to yield a gellable liquid, and subsequently was combined with varying concentrations of gentamicin (50-500 mg/L) or clindamycin (10-100 mg/L). The elution kinetics of antibiotics from the hydrogel were analyzed using liquid chromatography-mass spectrometry. The gel was used to topically treat Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens in established Kirby-Bauer and Crystal Violet models to assess the efficacy of bacterial inhibition. 2D mammalian cell monolayers were topically treated, and cell death was quantified to assess cytotoxicity. Bacteria-enhanced in vitro scratch assays were treated with antibiotic-embedded hydrogel and imaged over time to assess cell death and mobility. Collagen hydrogel embedded with antibiotics (cHG+abx) demonstrated sustained antibiotic release for up to 48 hours with successful inhibition of both MRSA and C. perfringens biofilms, while remaining bioactive up to 72 hours. Administration of cHG+abx with antibiotic concentrations up to 100X minimum inhibitory concentration was found to be non-toxic and facilitated mammalian cell migration in an in vitro scratch model. Collagen hydrogel is a promising pharmaceutical delivery vehicle that allows for safe, precise bacterial targeting for effective bacterial inhibition in a pro-regenerative scaffold.

Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable In Situ-Forming Depot Antibiotics Delivery System.

Bone infections with Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics. CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology. CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9 of 12 and full eradication in 5 of 12 pigs. Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.

Novel Bioresorbable Drug-Eluting Mesh Scaffold for Therapy of Muscle Injury.

A novel bioresorbable drug-eluting polycaprolactone (PCL) mesh scaffold was developed, utilizing a solvent-cast additive manufacturing technique, to promote therapy of muscle injury. The degradation rate and mechanical properties strength of the PCL mesh were characterized after immersion in a buffer solution for different times. The in vitro release characteristics of vancomycin, ceftazidime, and lidocaine from the prepared mesh were evaluated using a high-performance liquid chromatography (HPLC) assay. In addition, the in vivo efficacy of PCL meshes for the repair of muscle injury was investigated on a rat model with histological examinations. It was found that the additively manufactured PCL meshes degraded by 13% after submission in buffered solution for four months. All PCL meshes with different pore sizes exhibited greater strength than rat muscle and survived through 10,000 cyclic loadings. Furthermore, the meshes could offer a sustained release of antibiotics and analgesics for more than 3 days in vitro. The results of this study suggest that drug-loaded PCL mesh exhibits superior ability to pure PCL mesh in terms of effectively promoting muscle repair in rat models. The histological assay also showed adequate biocompatibility of the resorbable meshes. The additively manufactured biodegradable drug-eluting meshes may be adopted in the future in humans for the therapy of muscle injuries.

Telodendrimer functionalized hydrogel platform for sustained antibiotics release in infection control

Wound infection commonly causes delayed healing, especially in the setting of chronic wounds. Local release of antibiotics is considered a viable approach to treat chronic wounds. We have developed a versatile telodendrimer (TD) platform for efficient loading of charged antibiotic molecules via a combination of multivalent and synergistic charge and hydrophobic interactions. The conjugation of TD in biocompatible hydrogel allows for topical application to provide sustained antibiotic release. Notably, a drug loading capacity as high as 20 % of the drug-to-resin dry weight ratio can be achieved. The payload content (PC) and release profile of the various antibiotics can be optimized by fine-tuning TD density and valency in hydrogel based on the charge and hydrophobic features of the drug, e.g., polymyxin B (PMB), gentamycin (GM), and daptomycin (Dap), for effective infection control. We have shown that hydrogel with moderately reduced TD density demonstrates a more favorable release profile than hydrogel with higher TD density. Antibiotics loaded in TD hydrogel have comparable antimicrobial potency and reduced cytotoxicity compared to the free antibiotics due to a prolonged, controlled drug release profile. In a mouse model of skin and soft tissue infection, the subcutaneous administration of PMB-loaded TD hydrogel effectively eliminated the bacterial burden. Overall, these results suggest that engineerable TD hydrogels have great potential as a topical treatment to control infection for wound healing. Statement of significanceWound infection causes a significant delay in the wound healing process, which results in a significant financial and resource burden to the healthcare system. PEGA-telodendrimer (TD) resin hydrogel is an innovative and versatile platform that can be fine-tuned to efficiently encapsulate different antibiotics by altering charged and hydrophobic structural moieties. Additionally, this platform is advantageous as the TD density in the resin can also be fine-tuned to provide the desired antibiotic payload release profile. Sustained antibiotics release through optimization of TD density provides a prolonged therapeutic window and reduces burst release-induced cytotoxicity compared to conventional antibiotics application. Studies in a preclinical mouse model of bacteria-induced skin and soft tissue infection demonstrated promising therapeutic efficacy as evidenced by effective infection control and prolonged antibacterial efficacy of antibiotics-loaded PEGA-TD resin. In conclusion, the PEGA-TD resin platform provides a highly customizable approach for effective antibiotics release with significant potential for topical application to treat various bacterial wound infections to promote wound healing.

Fabrication of CMC/PVA/Dextrin-Based Polymeric Membrane for Controlled Release of Cefixime With Enhanced Antibacterial Activity.

This study focuses on the investigation of the significance of polymers in drug delivery approaches. The carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA) and dextrin-based hydrogel membrane were prepared and employed for the sustained release of third-generation oral antibiotic (cefixime). Different proportions of CMC, PVA and dextrin were blended and hydrogel membranes were fabricated via solvent casting method. The prepared membrane was characterized by FTIR, SEM, UV-visible, TGA and swelling analysis. Cefixime drug was incorporated in the CMC/PVA/dextrin matrix and drug release was investigated. The sustained release of the tested drug (cefixime) was investigated and the drug was released in 120 min in the phosphate-buffered saline (PBS) solution. The antibacterial activity of the prepared membrane was promising against Proteus vulgaris, salmonella typhi, Escherichia coli and Bacillus subtilis strains. The swelling capabilities, thermal stability and non-toxic nature of the prepared CMC/PVA/dextrin membrane could have potential applications for cefixime drug in delivery in a controlled way for the treatment of infectious diseases.

A Nanoporous 3D-Printed Scaffold for Local Antibiotic Delivery.

Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery.

Enhancement of antibacterial and wound healing capabilities of cotton fabric through the covalent bonding of antibiotic-loaded hydrophobized mesoporous silica nanoparticles

Wound dressings are highly desirable for mitigating pathogenic bacterial infections. Sterilized cotton fabric is a widely used medical dressing, facilitating wound healing, mitigating pathogenic infections, and reducing treatment expenses. Nevertheless, untreated cotton fabric lacks intrinsic antibacterial properties. In this study, we introduced antibiotics-loaded aminopropyl and octadecyl grafted mesoporous silica nanoparticles onto the surface of hydrophobized cotton fabric. The obtained wound dressing exhibited remarkable antibacterial efficacy against Escherichia coli and Staphylococcus aureus through sustained antibiotic release. In vivo assessments verified that this intelligent cotton fabric dressing accelerates wound healing and prevents adhesion to skin tissues. Additionally, the reusability, hydrophobic nature, and straightforward synthesis methodology collectively provide an alternative solution to smart wound dressings for biomedical applications.© 2014 xxxxxxxx. Hosting by Elsevier B.V. All rights reserved.

Tailoring metallurgical and biological characteristics of Ti–6Al–4V alloy by synergetic application of Nd:YAG laser and drug-loaded electrospun PVA

Titanium alloys have been used extensively as implants. However, they generally suffer from low biocompatibility as well as antibacterial activity. To date, several strategies have been proposed to address these issues. It is of practical interest to synergistically increase both cellular adhesion and antimicrobial activity in titanium-based implants. Here, Ti–6Al–4V alloys were surface-modified by Nd:YAG laser with different scanning speeds ranging from 1 to 5 mm s−1 and subsequently coated by drug-loaded polymer nanofibers for prolonged drug release. The laser-modified samples were both physically and metallurgically characterized through XRD, OM, AFM, FESEM, hardness, and wettability tests to find the optimum laser processing conditions. Results showed that the surface characteristics of the alloys are sensitive to the scanning speed; the higher the scan velocity, the lower surface roughness and wettability were obtained. The enhanced formation of TiO and Ti6O oxides on the surfaces of laser-modified alloys was delineated. Then, a model polymer/drug system of polyvinyl alcohol/vancomycin was directly electrospun onto the optimized samples surfaces. The laser-modified, drug-loaded samples present an improved biocompatibility as the cellular adhesion and viability were increased in contact with these samples. Up to 39% increase in cell viability was obtained for the laser-modified samples by 5 mm s−1 scan speed in comparison with unmodified, uncoated samples. The increased biocompatibility was attributed to the formation of oxide layers which reduce the toxicity of vanadium and aluminum elements. Also, the drug release rate was extended from 4 h to 25 h for modified samples. So, the modified implants could present a sustained release of antibiotics as well.

A bioinspired antibacterial and photothermal membrane for stable and durable clean water remediation.

Solar-driven steam generation has been considered as a prevalent and sustainable approach to obtain clean fresh water. However, the presence of microorganisms in seawater may cause the biofouling and degradation of polymeric photothermal materials and clog the channels for water transportation, leading to a decrease in solar evaporation efficiency during long-term usage. Herein, we have reported a facile strategy to construct a robust cellulose membrane device coated by tobramycin-doped polydopamine nanoparticles (PDA/TOB@CA). The PDA/TOB@CA membrane not only exhibited synergistic antibacterial behaviors with long-term and sustained antibiotic release profiles, but also achieved a high water evaporation rate of 1.61 kg m-2 h-1 as well as an evaporation efficiency of >90%. More importantly, the high antibacterial activity endowed the PDA/TOB@CA membrane with superb durability for stable reuse over 20 cycles, even in microbe-rich environments. Therefore, we envision that this study could pave a new pathway towards the design and fabrication of robust antibacterial and photothermal materials for long-term and stable clean water production.

Unravelling the role of hemp straw derived cellulose in CMC/PVA hydrogel for sustained release of fluoroquinolone antibiotic

Cellulose fibres derived from hemp stalks, a prevalent biowaste in Northern India, were effectively converted into carboxymethyl cellulose (HS-CMC). Novel environmentally benign hydrogels were synthesized from HS-CMC and polyvinyl alcohol (PVA) using citric acid, a green crosslinker employing freeze-drying method. The HS-CMC/PVA hydrogels were successfully used for sustained release of fluoroquinolone antibiotic, norfloxacin. The hydrogels were characterized using FTIR, XRD, FE-SEM, EDS and thermal stability and evaluated for their carbonyl content, swelling ratio, in-vitro drug release behaviour and bactericidal properties. Successful isolation of cellulose from hemp stalks and its conversion into hydrogel with the presence of ester and carbonyl linkages was confirmed by FTIR. Thermal stability was impaired when cellulose fibres were converted into HS-CMC via carboxymethylation, as the crystalline structure was utterly disrupted. For the hydrogel, the equilibrium swelling ratios at pH -1.2 and 7.4 were assessed as 378.4 % and 538.7 %, respectively, higher than reported CMC hydrogels. The norfloxacin (NFX) encapsulated hydrogels exhibited good bactericidal properties with zone of inhibition of 19.2 ± 0.3 mm against E. coli and 16.4 ± 0.4 mm against S. aureus. The in-vitro release of NFX at pH 1.2 was 91 %, higher than pH 7.4 at 82 % with strong adherence to Higuchi kinetics model signifying that the release of NFX is via dissolution and diffusion. The release kinetics at different pH revealed Fickian behaviour establishing the potential of HS-CMC hydrogel for sustained release of norfloxacin.

Thermosensitive vancomycin@PLGA-PEG-PLGA/HA hydrogel as an all-in-one treatment for osteomyelitis

Osteomyelitis is a difficult-to-treat infectious disease. Treatment, which includes controlling the infection and removing necrotic tissues, is challenging. Considering the side effects and drug resistance of systemic antibiotics, local drug delivery systems are being explored. Antibiotic-loaded bone cement is the main treatment strategy; however, it has several disadvantages. Thus, based on its thermosensitive gelation properties, poly(D, L-lactide-co-glycolide)–poly(ethylene glycol)–poly(D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was used as a sustained-release drug carrier by calibrating its synthesis parameters. We prepared and characterized vancomycin@PLGA-PEG-PLGA/hydroxyapatite (HA) thermosensitive hydrogel with an LA/GA ratio of 15:1. The rheological characteristics, sol–gel phase-transition properties, and critical micelle concentration value of the PLGA-PEG-PLGA/HA complex confirmed that it undergoes a temperature-sensitive sol–gel phase transition. Furthermore, the HA in the composite increased the storage modulus of the system. FT-IR, XRD, and TEM findings showed that HA could be dispersed uniformly in the PLGA-PEG-PLGA polymer. Moreover, HA neutralized acidity during polymer degradation, improving in vitro cytocompatibility. In vitro and in vivo antibacterial experiments showed that the composite sustained-release system exhibited good bone repair characteristics owing to its efficacy in infection treatment. Therefore, vancomycin@PLGA-PEG-PLGA/HA allows sustained release of antibiotics and promotes bone tissue repair, showing potential for wide clinical applicability.

Antibiotic Cement Utilization for the Prophylaxis and Treatment of Infections in Spine Surgery: Basic Science Principles and Rationale for Clinical Use.

Antibiotic bone cement (ABC) is an effective tool for the prophylaxis and treatment of osteomyelitis due to the controlled, sustained release of local antibiotics. ABC has been proven to be effective in the orthopedic fields of arthroplasty and extremity trauma, but the adoption of ABC in spine surgery is limited. The characteristics of ABC make it an optimal solution for treating vertebral osteomyelitis (VO), a serious complication following spine surgery, typically caused by bacterial and sometimes fungal and parasitic pathogens. VO can be devastating, as infection can result in pathogenic biofilms on instrumentation that is dangerous to remove. New techniques, such as kyphoplasty and novel vertebroplasty methods, could amplify the potential of ABC in spine surgery. However, caution should be exercised when using ABC as there is some evidence of toxicity to patients and surgeons, antibiotic allergies, bone cement structural impairment, and possible development of antibiotic resistance. The purpose of this article is to describe the basic science of antibiotic cement utilization and review its usage in spine surgery.