“Smart” Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy

Bacterial infections are a severe medical problem, especially in traumatology, orthopedics, and surgery. The local use of antibiotics-elution materials has made it possible to increase the effectiveness of acute infections treatment. However, the infection prevention problem remains unresolved. Here, we demonstrate the fabrication of polylactic acid (PLA) “smart” films with microchamber arrays. These microchambers contain ceftriaxone as a payload in concentrations ranging from 12 ± 1 μg/cm2 to 38 ± 8 μg/cm2, depending on the patterned film thickness formed by the different PLA concentrations in chloroform. In addition, the release profile of the antibiotic can be prolonged up to 72 h in saline. At the same time, on the surface of agar plates, the antibiotic release time increases up to 96 h, which has been confirmed by the growth suppression of the Staphylococcus aureus bacteria. The efficient loading and optimal release rate are obtained for patterned films formed by the 1.5 wt % PLA in chloroform. The films produced from 1.5 and 2 wt % PLA solutions (thickness—0.42 ± 0.12 and 0.68 ± 0.16 µm, respectively) show an accelerated ceftriaxone release upon the trigger of the therapeutic ultrasound, which impacted as an expansion of the bacterial growth inhibition zone around the samples. Combining prolonged drug elution with the on-demand release ability of large cargo amount opens up new approaches for personalized and custom-tunable antibacterial therapy.

Nanoparticles as Antimicrobial Agents and Drug Delivery Systems - A Review

The world is facing major issues related to antibiotic resistance, specific drugs targeting and its side effects. Such obstacles can be rectified by nanotechnology as they have essential characteristics with smaller size, target specificity, easy deliverable with lesser side effects. The prime nature of the nanoparticles are, it can probe into the cell wall of the pathogenic microbes and even have the capacity to intrude into cellular pathways. Nanoparticles themselves are capable of destroying unwanted foreign particles or toxic cells, which enter into our bodies. Nanoparticles can be treated as carriers, in which they combine with specific drugs and deliver to target specific cells with lesser side effects. Nanoparticles are used as a drug delivery agent for various kinds of diseases related to cancer. Nanoparticles with drugs increase the antibiotic release at the different target sites and these nanoparticles have a great tendency to deliver a large number of drugs to a cell. In this current review, we discuss the bright future of NPs as drug delivery agents as it can overcome all conventional problems.

An Additively Manufactured Sample Holder to Measure the Controlled Release of Vancomycin from Collagen Laminates

The controlled release of antibiotics prevents the spread of pathogens and thereby improves healing processes in regenerative medicine. However, high concentrations may interfere with healing processes. It is therefore advantageous to use biodegradable materials for a controlled release. In particular, multilayer materials enable differential release at different surfaces. For this purpose, collagen sheets of different properties can be bonded by photochemical crosslinking. Here, we present the development and application of an easily accessible, additively manufactured sample holder to study the controlled release of vancomycin from modularly assembled collagen laminates in two directions. As proof-of-concept, we show that laminates of collagen sheets covalently linked by rose bengal and green light crosslinking (RGX) can be tightly inserted into the device without leakage from the upper to lower cavity. We used this sample holder to detect the release of vancomycin from symmetrically and asymmetrically loaded two-layer and three-layer collagen laminates into the upper and lower cavity of the sample holder. We show that these collagen laminates are characterized by a collagen type-dependent vancomycin release, enabling the control of antibiotic release profiles as well as the direction of antibiotic release.

Cefuroxime-Loaded Hydrogels for Prevention and Treatment of Bacterial Contamination of Open Wounds

Dextran/Sulfodextran-graft-polyacrylamide- and polyacrylamide-based hydrogels were synthesized by radical polymerization and loaded with cefuroxime to obtain antimicrobial wound dressings. Antibiotic release from the antibiotic-loaded hydrogels into an aqueous solution was studied by the HPLC-UV method. It is shown that cefuroxime-loaded Dextran/Sulfodextran-graft-polyacrylamide hydrogels release the antibiotic more slowly compared to polyacrylamide hydrogel with the same density of cross-links. Antibacterial activity of the synthesized materials was tested in vitro against wild strains of S. aureus, E. coli, and Klebsiella spp. The possibility of using the obtained antimicrobial hydrogels for the treatment of infected wounds was confirmed in vivo in a rat model.

Investigation of Antibiotic Release from Bone Allograft in an Experiment on Rabbits

BACKGROUND: The treatment of chronic osteomyelitis, despite the use of new methods, is still an urgent problem. Local use of antibacterial drugs in combination with systemic antibiotic therapy has become popular in recent decades. Autologous bone grafts are considered ideal for bone defects filling. Different methods of allograft preparation may have differences in the rate and duration of antibiotic release. Moreover, it can affect the effectiveness of microbial agent eradication. The study analyzed the differences in the release of gentamicin from different types of allografts in dynamics and methods of preparation: «PerOssal» medium, whole bone allograft soaked in antibiotic, whole bone allograft, welded with an antibiotic, and perforated bone allograft soaked in an antibiotic solution. AIM: The objective of the study was to study the stability of antibiotic release and to determine the effectiveness of local transport systems. Evaluation of the difference in gentamicin release from different types of allografts in dynamics and methods of preparation had been realized: “PerOssal” medium, whole bone allograft soaked in antibiotic, whole bone allograft welded with an antibiotic, and perforated bone allograft, soaked in antibiotic solution. MATERIALS AND METHODS: The research was conducted between September 2020 and March 2021. The experiments were performed on 120 laboratory rabbits (weight – 3000–3500 g, age – 6–8 months), which were divided into four groups (30 animals in each group). Group 1 consisted of animals treated with “PerOssal.” The whole bone allograft soaked in an antibiotic was used in the treatment of animals of Group 2. The whole bone allograft, welded with an antibiotic, was used in the treatment of animals of Group 3. Perforated bone allograft soaked in an antibiotic was used in Group 4. Osteomyelitis of the proximal femur was formed in experimental animals. RESULTS AND DISCUSSION: Statistically insignificant decrease in the concentration of gentamicin was observed by the 7th day in all experimental groups. In rabbits whose bone defect was filled with a whole bone allograft welded with antibiotic and perforated bone allograft impregnated with an antibiotic (Groups 3 and 4), the most stable concentration of gentamicin was noted throughout the study period. Statistically significant differences were revealed between the experimental groups in relation to the dynamics of changes in the concentration of gentamicin in blood plasma. It was found that the group using the biodegradable material “PerOssal” on the 1st day showed a high concentration of the antibiotic in the blood plasma. However, by the 2nd day, a lower concentration of the antibiotic was recorded compared to all comparison groups of the bone allograft. CONCLUSIONS: The results of the analysis of the dynamics of gentamicin concentration may indicate significant differences between the methods of graft preparation, especially in the relationship with antibiotic release into the blood plasma. The most stable antibiotic concentration was registered in the groups of animals that underwent the filling of bone defect using a whole bone allograft welded with an antibiotic and a perforated bone allograft impregnated with antibiotic. A significant decrease of gentamicin concentration in the femur homogenate by the 7th day after transplantation was observed when using a whole bone allograft impregnated with an antibiotic. At the same time, a stable concentration of the antibiotic in the blood plasma was registered. The highest initial antibiotic concentration in the homogenate with a gradual decrease over 7 days was observed when using the antibiotic-impregnated biodegradable material “PerOssal.”

Infections @ Trauma/Orthopedic Implants: Recent Advances on Materials, Methods, and Microbes—A Mini-Review

Implants and materials are indispensable in trauma and orthopedic surgery. The continuous improvements of implant design have resulted in an optimized mechanical function that supports tissue healing and restoration of function. One of the still unsolved problems with using implants and materials is infection. Trauma and material implantation change the local inflammatory situation and enable bacterial survival and material colonization. The main pathogen in orthopedic infections is Staphylococcus aureus. The research efforts to optimize antimicrobial surfaces and to develop new anti-infective strategies are enormous. This mini-review focuses on the publications from 2021 with the keywords S. aureus AND (surface modification OR drug delivery) AND (orthopedics OR trauma) AND (implants OR nails OR devices). The PubMed search yielded 16 original publications and two reviews. The original papers reported the development and testing of anti-infective surfaces and materials: five studies described an implant surface modification, three developed an implant coating for local antibiotic release, the combination of both is reported in three papers, while five publications are on antibacterial materials but not metallic implants. One review is a systematic review on the prevention of stainless-steel implant-associated infections, the other addressed the possibilities of mixed oxide nanotubes. The complexity of the approaches differs and six of them showed efficacy in animal studies.