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International Journal of Molecular... Jul 2023Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms... (Review)
Review
Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms can help microorganisms adhere to the surfaces of various medical devices, causing biofilm-associated infections on the surfaces of biomaterials such as venous ducts, joint prostheses, mechanical heart valves, and catheters. Biofilms provide a protective barrier for bacteria and provide resistance to antimicrobial agents, which increases the morbidity and mortality of patients. This review summarizes biofilm formation processes and resistance mechanisms, as well as the main features of clinically persistent infections caused by biofilms. Considering the various infections caused by clinical medical devices, we introduce two main methods to prevent and treat biomaterial-related biofilm infection: antibacterial coatings and the surface modification of biomaterials. Antibacterial coatings depend on the covalent immobilization of antimicrobial agents on the coating surface and drug release to prevent and combat infection, while the surface modification of biomaterials affects the adhesion behavior of cells on the surfaces of implants and the subsequent biofilm formation process by altering the physical and chemical properties of the implant material surface. The advantages of each strategy in terms of their antibacterial effect, biocompatibility, limitations, and application prospects are analyzed, providing ideas and research directions for the development of novel biofilm infection strategies related to therapeutic materials.
Topics: Humans; Biocompatible Materials; Biofilms; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bacterial Adhesion; Surface Properties
PubMed: 37511440
DOI: 10.3390/ijms241411680 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
ACS Central Science Jul 2023Implant-associated infections (IAIs) caused by can result in serious challenges after orthopedic surgery. Due to biofilm formation and antibiotic resistance, this...
Implant-associated infections (IAIs) caused by can result in serious challenges after orthopedic surgery. Due to biofilm formation and antibiotic resistance, this refractory infection is highly prevalent, and finding drugs to attenuate bacterial virulence is becoming a rational alternative strategy. In , the SaeRS two-component system (TCS) plays a key role in the production of over 20 virulence factors and the pathogenesis of the bacterium. Here, by conducting a structure-based virtual screening against SaeR, we identified that fenoprofen, a USA Food and Drug Administration (FDA)-approved nonsteroid anti-inflammatory drug (NSAID), had excellent inhibitory potency against the response regulator SaeR protein. We showed that fenoprofen attenuated the virulence of without drug resistance. In addition, it was helpful in relieving osteolysis and restoring the walking ability of mice in vitro and in implant-associated infection models. More importantly, fenoprofen treatment suppressed biofilm formation and changed the biofilm structure, which caused to form loose and porous biofilms that were more vulnerable to infiltration and elimination by leukocytes. Our results reveal that fenoprofen is a potent antivirulence agent with potential value in clinical applications and that SaeR is a drug target against implant-associated infections.
PubMed: 37521790
DOI: 10.1021/acscentsci.3c00499 -
Advanced Materials (Deerfield Beach,... Jun 2024In recent years, tremendous effort is devoted to developing platforms, such as implantable drug delivery systems (IDDSs), with temporally and spatially controlled drug... (Review)
Review
In recent years, tremendous effort is devoted to developing platforms, such as implantable drug delivery systems (IDDSs), with temporally and spatially controlled drug release capabilities and improved adherence. IDDSs have multiple advantages: i) the timing and location of drug delivery can be controlled by patients using specific stimuli (light, sound, electricity, magnetism, etc.). Some intelligent "closed-loop" IDDS can even realize self-management without human participation. ii) IDDSs enable continuous and stable delivery of drugs over a long period (months to years) and iii) to administer drugs directly to the lesion, thereby helping reduce dosage and side effects. iv) IDDSs enable personalized drug delivery according to patient needs. The high demand for such systems has prompted scientists to make efforts to develop intelligent IDDS. In this review, several common stimulus-responsive mechanisms including endogenous (e.g., pH, reactive oxygen species, proteins, etc.) and exogenous stimuli (e.g., light, sound, electricity, magnetism, etc.), are given in detail. Besides, several types of IDDS reported in recent years are reviewed, including various stimulus-responsive systems based on the above mechanisms, radio frequency-controlled IDDS, "closed-loop" IDDS, self-powered IDDS, etc. Finally, the advantages and disadvantages of various IDDS, bottleneck problems, and possible solutions are analyzed to provide directions for subsequent research.
Topics: Humans; Drug Delivery Systems; Animals; Drug Implants; Drug Liberation
PubMed: 38376369
DOI: 10.1002/adma.202312530 -
Advanced Healthcare Materials Oct 2023Bacterial infection caused by biomaterials is a very serious problem in the clinical treatment of implants. The emergence of antibiotic resistance has prompted other... (Review)
Review
Bacterial infection caused by biomaterials is a very serious problem in the clinical treatment of implants. The emergence of antibiotic resistance has prompted other antibacterial agents to replace traditional antibiotics. Silver is rapidly developing as an antibacterial candidate material to inhibit bone infections due to its significant advantages such as high antibacterial timeliness, high antibacterial efficiency, and less susceptibility to bacterial resistance. However, silver has strong cytotoxicity, which can cause inflammatory reactions and oxidative stress, thereby destroying tissue regeneration, making the application of silver-containing biomaterials extremely challenging. In this paper, the application of silver in biomaterials is reviewed, focusing on the following three issues: 1) how to ensure the excellent antibacterial properties of silver, and not easy to cause bacterial resistance; 2) how to choose the appropriate method to combine silver with biomaterials; 3) how to make silver-containing biomaterials in hard tissue implants have further research. Following a brief introduction, the discussion focuses on the application of silver-containing biomaterials, with an emphasis on the effects of silver on the physicochemical properties, structural properties, and biological properties of biomaterials. Finally, the review concludes with the authors' perspectives on the challenges and future directions of silver in commercialization and in-depth research.
Topics: Humans; Biocompatible Materials; Silver; Anti-Bacterial Agents; Bacterial Infections; Prostheses and Implants
PubMed: 37300754
DOI: 10.1002/adhm.202300932 -
Annals of Plastic Surgery Dec 2023In October 2021, the US Food and Drug Administration mandated patient decision checklists and new labeling for breast implants with the goal of improving the informed...
OBJECTIVES
In October 2021, the US Food and Drug Administration mandated patient decision checklists and new labeling for breast implants with the goal of improving the informed decision-making process for patients considering breast implantation. Given growing concerns over breast implant-associated anaplastic large cell lymphoma, breast implant-associated squamous cell carcinoma, and breast implant illness, patients should be able to easily review these resources to make a fully informed decision when considering surgery. This study seeks to elucidate the accessibility, and therefore the utility of the newly mandated literature for the average breast implant patient.
METHODS
Patient decision checklists and breast implant boxed warnings were obtained from the most used breast implant manufacturers in the United States-Allergan, Mentor, and Sientra. Readability analysis of all Food and Drug Administration required documents was performed using the Flesch Reading Ease Score, Flesch Kincaid Grade Level, Gunning-Fog Index, Coleman-Liau Index, Simplified Measure of Gobbledygook, and Automated Readability Index.
RESULTS
The overall readability of all Allergan, Mentor, and Sientra patient materials correlates with a college reading level. Documents from all 3 implant manufacturers were of a statistically significantly higher reading level than that recommended by the American Medical Association and US Department of Health and Human Services. No materials were found to be at or below the recommended sixth-grade level.
CONCLUSIONS
The newly mandated breast implant patient decision guides are written at a college reading level. These materials should be simplified to improve health literacy shared decision making.
Topics: Humans; United States; Female; Breast Implants; Breast Implantation; Surgery, Plastic; United States Food and Drug Administration; Health Literacy; Breast Neoplasms; Comprehension; Health Services Accessibility; Internet
PubMed: 37856237
DOI: 10.1097/SAP.0000000000003674 -
The Spine Journal : Official Journal of... Sep 2023Bacterial infection of spinal instrumentation is a significant challenge in spinal fusion surgery. Although the intraoperative local application of powdered vancomycin...
BACKGROUND CONTEXT
Bacterial infection of spinal instrumentation is a significant challenge in spinal fusion surgery. Although the intraoperative local application of powdered vancomycin is common practice for mitigating infection, the antimicrobial effects of this route of administration are short-lived. Therefore, novel antibiotic-loaded bone grafts as well as a reliable animal model to permit the testing of such therapies are needed to improve the efficacy of infection reduction practices in spinal fusion surgery.
PURPOSE
This study aims to establish a clinically relevant rat model of spinal implant-associated infection to permit the evaluation of antimicrobial bone graft materials used in spinal fusion.
STUDY DESIGN
Rodent study of chronic spinal implant-associated infection.
METHODS
Instrumentation anchored in and spanning the vertebral bodies of L4 and L5 was inoculated with bioluminescent methicillin-resistant Staphylococcus aureus bacteria (MRSA). Infection was monitored using an in vivo imaging system (IVIS) for 8 weeks. Spines were harvested and evaluated histologically, and colony-forming units (CFUs) were quantified in harvested implants and spinal tissue.
RESULTS
Postsurgical analysis of bacterial infection in vivo demonstrated stratification between MRSA and phosphate-buffered saline (PBS) control groups during the first 4 weeks of the 8-week infection period, indicating the successful establishment of acute infection. Over the 8-week chronic infection period, groups inoculated with 1 × 10 MRSA CFU and 1 × 10 MRSA CFU demonstrated significantly higher bioluminescence than groups inoculated with PBS control (p = 0.009 and p = 0.041 respectively). Histological examination at 8 weeks postimplantation revealed the presence of abscesses localized to implant placement in all MRSA inoculation groups, with the most pervasive abscess formation in samples inoculated with 1 × 10 MRSA CFU and 1 × 10 MRSA CFU. Quantification of CFU plated from harvested spinal tissue at 8 weeks post-implantation revealed the 1 × 10 MRSA CFU inoculation group as the only group with a significantly greater average CFU count compared to PBS control (p = 0.017). Further, CFU quantification from harvested spinal tissue was greater than CFU quantification from harvested implants across all inoculation groups.
CONCLUSION
Our model demonstrated that the inoculation dosage of 1 × 10 MRSA CFU exhibited the most robust chronic infection within instrumented vertebral bodies. This dosage had the greatest difference in bioluminescence signal from control (p < 0.01), the lowest mortality (0% compared to 50% for samples inoculated with 1 × 10 MRSA CFU), and a significantly higher amount of CFUs from harvested spine samples than CFUs from control harvested spine samples. Further, histological analysis confirmed the reliability of this novel rodent model of implanted-associated infection to establish infection and biofilm formation of MRSA for all inoculation groups.
CLINICAL SIGNIFICANCE
This model is intended to simulate the infection of instrumentation used in spinal fusion surgeries concerning implant locality and material. This model may evaluate potential antimicrobial and osteogenic biomaterials and investigate the relationship between implant-associated infection and failed fusion.
Topics: Rats; Animals; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Persistent Infection; Rodentia; Reproducibility of Results; Prosthesis-Related Infections; Anti-Bacterial Agents; Disease Models, Animal
PubMed: 37247639
DOI: 10.1016/j.spinee.2023.05.014 -
Journal of Functional Biomaterials Dec 2023Biomimetic dental implants are regarded as one of the recent clinical advancements in implant surface modification. Coatings with varying thicknesses and roughness may... (Review)
Review
Biomimetic dental implants are regarded as one of the recent clinical advancements in implant surface modification. Coatings with varying thicknesses and roughness may affect the dental implant surface's chemical inertness, cell adhesion, and antibacterial characteristics. Different surface coatings and mechanical surface changes have been studied to improve osseointegration and decrease peri-implantitis. The surface medication increases surface energy, leading to enhanced cell proliferation and growth factors, and, consequently, to a rise in the osseointegration process. This review provides a comprehensive update on the numerous biomimetic coatings used to improve the surface characteristics of dental implants and their applications in two main categories: coating to improve osseointegration, including the hydroxyapatite layer and nanocomposites, growth factors (BMPs, PDGF, FGF), and extracellular matrix (collagen, elastin, fibronectin, chondroitin sulfate, hyaluronan, and other proteoglycans), and coatings for anti-bacterial performance, covering drug-coated dental implants (antibiotic, statin, and bisphosphonate), antimicrobial peptide coating (GL13K and human beta defensins), polysaccharide antibacterial coatings (natural chitosan and its coupling agents) and metal elements (silver, zinc, and copper).
PubMed: 38248682
DOI: 10.3390/jfb15010015 -
Advanced Science (Weinheim,... Aug 2023The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune...
The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.
Topics: Mice; Animals; Immunoconjugates; Drug Liberation; Bacteria; Anti-Infective Agents; Biofilms
PubMed: 37290045
DOI: 10.1002/advs.202301340 -
BMC Oral Health Jan 2024Dental implantology has revolutionized oral rehabilitation, offering a sophisticated solution for restoring missing teeth. Despite advancements, issues like infection,... (Review)
Review
BACKGROUND AND AIM
Dental implantology has revolutionized oral rehabilitation, offering a sophisticated solution for restoring missing teeth. Despite advancements, issues like infection, inflammation, and osseointegration persist. Nano and biomaterials, with their unique properties, present promising opportunities for enhancing dental implant therapies by improving drug delivery systems. This review discussed the current applications of nano and biomaterials in drug delivery for dental implants.
METHOD
A literature review examined recent studies and advancements in nano and biomaterials for drug delivery in dental implantology. Various materials, including nanoparticles, biocompatible polymers, and bioactive coatings, were reviewed for their efficacy in controlled drug release, antimicrobial properties, and promotion of osseointegration.
RESULTS
Nano and biomaterials exhibit considerable potential in improving drug delivery for dental implants. Nanostructured drug carriers demonstrate enhanced therapeutic efficacy, sustained release profiles, and improved biocompatibility. Furthermore, bioactive coatings contribute to better osseointegration and reduced risks of infections.
CONCLUSION
Integrating current nano and biomaterials in drug delivery for dental implants holds promise for advancing clinical outcomes. Enhanced drug delivery systems can mitigate complications associated with dental implant procedures, offering improved infection control, reduced inflammation, and optimized osseointegration.
Topics: Humans; Anodontia; Biocompatible Materials; Dental Implants; Drug Delivery Systems; Inflammation
PubMed: 38267933
DOI: 10.1186/s12903-024-03911-9