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Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and...
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Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "The Global Need for Effective Antibiotics".

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 41387

Special Issue Editors

Prof. Dr. Débora C. Coraça-Huber

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Guest Editor
Research Laboratory for Biofilms and Implant Associated Infections (BIOFILM LAB), Experimental Orthopedics, Department of Orthopedic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Interests: biofilms; implant-infections; antimicrobials; local delivery systems
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Eliana Aparecida de Rezende Duek

E-Mail Website
Guest Editor
Department of Physiological Sciencesb, Faculty of Medical and Health Sciences, Pontifical Catholic University of São Paulo, Sorocaba, SP, Brazil
Interests: biomedical engineering; biomaterials; polimers; local delivery systems
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marina Angélica Marciano da Silva

E-Mail Website
Guest Editor
Department of Restorative Dentistry, School of Dentistry of Piracicaba, State University of Campinas - FOP/UNICAMP, Piracicaba, SP, Brazil
Interests: dental medicine; bone cements; endodontics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Implantable medical devices, such as prosthetics, catheters, and several other devices, have revolutionized medicine, but they increase the risk of infection. Indeed, implant infection is one of the most frequent and severe complications associated with the use of biomaterials. Implant infections count as nosocomial infections, being a major cause of death and increased morbidity among hospitalized patients. Those infections are difficult to treat, often requiring surgical implant replacement. The mortality rates for periprosthetic joint infections are equivalent to the rates for breast cancer and melanoma. The most commonly cultured microorganisms in implant infections are Coagulase-Negative Staphylococci (CoNS; primarily S. epidermidis), followed by S. aureus and mixed flora. In previous decades, commercially available antibiotics lost their ability to fight against CoNS and several other microorganisms. CoNS of both animal and human origins represent an important reservoir of genetic elements that lead to resistance not only to beta-lactam antibiotics but also to other antibiotic classes. One additional mechanism contributing to this phenomenon and negatively affecting the antimicrobial susceptibility of CoNS is the potential of these bacteria to produce biofilms. The presence of biofilm results in antibiotic tolerance by bacteria because many of them cannot sufficiently penetrate through biofilms. There is an urgent need to investigate alternatives to antibiotic substances. Local antimicrobial therapies can contribute to better outcomes during infection treatments. The investigation of biomaterials able to deliver antibiotics, natural antimicrobial substances or antibiotic-boosting substances is of great interest.

This Special Issue seeks manuscript submissions that further investigate such substances in association with biomaterials for use in all areas of implantology. Submissions on local delivery systems, smart implants associated with antibiotic boosting substances, natural antimicrobials, and new antimicrobial substances are especially encouraged.

Prof. Dr. Débora C. Coraça-Huber
Prof. Dr. Eliana Aparecida de Rezende Duek
Prof. Dr. Marina Angélica Marciano da Silva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Biofilms
  • Implant infections
  • Antimicrobials
  • Biomedical engineering
  • Biomaterials
  • Bolymers
  • Local delivery systems
  • Dental medicine
  • Bone cements
  • Endodontics

Published Papers (15 papers)

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11 pages, 1836 KiB  
Article
Nifedipine Potentiates Susceptibility of Salmonella Typhimurium to Different Classes of Antibiotics
by David Haschka, Manuel Grander, Johannes Eibensteiner, Stefanie Dichtl, Sabine Koppelstätter and Günter Weiss
Antibiotics 2021, 10(10), 1200; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10101200 - 01 Oct 2021
Cited by 2 | Viewed by 1982
Abstract
The calcium channel blocker nifedipine induces cellular iron export, thereby limiting the availability of the essential nutrient iron for intracellular pathogens, resulting in bacteriostatic activity. To study if nifedipine may exert a synergistic anti-microbial activity when combined with antibiotics, we used the mouse [...] Read more.
The calcium channel blocker nifedipine induces cellular iron export, thereby limiting the availability of the essential nutrient iron for intracellular pathogens, resulting in bacteriostatic activity. To study if nifedipine may exert a synergistic anti-microbial activity when combined with antibiotics, we used the mouse macrophage cell line RAW267.4, infected with the intracellular bacterium Salmonella Typhimurium, and exposed the cells to varying concentrations of nifedipine and/or ampicillin, azithromycin and ceftriaxone. We observed a significant additive effect of nifedipine in combination with various antibiotics, which was not observed when using Salmonella, with defects in iron uptake. Of interest, increasing intracellular iron levels increased the bacterial resistance to treatment with antibiotics or nifedipine or their combination. We further showed that nifedipine increases the expression of the siderophore-binding peptide lipocalin-2 and promotes iron storage within ferritin, where the metal is less accessible for bacteria. Our data provide evidence for an additive effect of nifedipine with conventional antibiotics against Salmonella, which is partly linked to reduced bacterial access to iron. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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20 pages, 5065 KiB  
Article
An Enzybiotic Regimen for the Treatment of Methicillin-Resistant Staphylococcus aureus Orthopaedic Device-Related Infection
by Eric T. Sumrall, Marloes I. Hofstee, Daniel Arens, Christian Röhrig, Susanne Baertl, Dominic Gehweiler, Mathias Schmelcher, Martin J. Loessner, Stephan Zeiter, R. Geoff Richards and T. Fintan Moriarty
Antibiotics 2021, 10(10), 1186; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10101186 - 29 Sep 2021
Cited by 6 | Viewed by 2701
Abstract
Orthopaedic device-related infection (ODRI) presents a significant challenge to the field of orthopaedic and trauma surgery. Despite extensive treatment involving surgical debridement and prolonged antibiotic therapy, outcomes remain poor. This is largely due to the unique abilities of Staphylococcus aureus, the most [...] Read more.
Orthopaedic device-related infection (ODRI) presents a significant challenge to the field of orthopaedic and trauma surgery. Despite extensive treatment involving surgical debridement and prolonged antibiotic therapy, outcomes remain poor. This is largely due to the unique abilities of Staphylococcus aureus, the most common causative agent of ODRI, to establish and protect itself within the host by forming biofilms on implanted devices and staphylococcal abscess communities (SACs). There is a need for novel antimicrobials that can readily target such features. Enzybiotics are a class of antimicrobial enzymes derived from bacteria and bacteriophages, which function by enzymatically degrading bacterial polymers essential to bacterial survival or biofilm formation. Here, we apply an enzybiotic-based combination regimen to a set of in vitro models as well as in a murine ODRI model to evaluate their usefulness in eradicating established S. aureus infection, compared to classical antibiotics. We show that two chimeric endolysins previously selected for their functional efficacy in human serum in combination with a polysaccharide depolymerase reduce bacterial CFU numbers 10,000-fold in a peg model and in an implant model of biofilm. The enzyme combination also completely eradicates S. aureus in a SAC in vitro model where classical antibiotics are ineffective. In an in vivo ODRI model in mice, the antibiofilm effects of this enzyme regimen are further enhanced when combined with a classical gentamicin/vancomycin treatment. In a mouse model of methicillin-resistant S. aureus (MRSA) ODRI following a fracture repair, a combined local enzybiotic/antibiotic treatment regimen showed a significant CFU reduction in the device and the surrounding soft tissue, as well as significant prevention of weight loss. These outcomes were superior to treatment with antibiotics alone. Overall, this study demonstrates that the addition of enzybiotics, which are distinguished by their extremely rapid killing efficacy and antibiofilm activities, can enhance the treatment of severe MRSA ODRI. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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18 pages, 15817 KiB  
Article
Activity of N-Chlorotaurine against Long-Term Biofilms of Bacteria and Yeasts
by Victoria Grimus, Débora C. Coraça-Huber, Stephan J. M. Steixner and Markus Nagl
Antibiotics 2021, 10(8), 891; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10080891 - 22 Jul 2021
Cited by 4 | Viewed by 2344
Abstract
Background: N-chlorotaurine (NCT), an antiseptic that originates from the human defense system, has broad-spectrum microbicidal activity and is well tolerated by human tissue and applicable to sensitive body regions. Bacteria in short-term biofilms, too, have been shown to be killed by NCT. [...] Read more.
Background: N-chlorotaurine (NCT), an antiseptic that originates from the human defense system, has broad-spectrum microbicidal activity and is well tolerated by human tissue and applicable to sensitive body regions. Bacteria in short-term biofilms, too, have been shown to be killed by NCT. It was the aim of the present study to demonstrate the activity of NCT against bacteria and yeasts in longer-lasting biofilms, including their co-culture. Materials and methods: Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella variicola biofilms were grown for 14 weeks in MBECTM inoculator with 96 well base. Some pegs were pinched off weekly and incubated in 1% NCT in PBS (PBS only for controls) at pH 7.1 and 37 °C, for 30 and 60 min. Subsequently, bacteria were resuspended by ultrasonication and subjected to quantitative cultures. Similar tests were conducted with C. albicans biofilms grown on metal (A2-steel) discs for 4 weeks. Mixed co-cultures of C. albicans plus each of the three bacterial strains on metal discs were grown for 5–7 weeks and weekly evaluated, as mentioned above. Results: Single biofilms of S. aureus, P. aeruginosa, and K. variicola grew to approximately 1 × 106 colony forming units (CFU)/mL and C. albicans to 1 × 105 CFU/mL. In combined biofilms, the CFU count was about 1 log10 lower. Viable counts of biofilms of single bacteria were reduced by 2.8 to 5.6 log10 in 1% NCT after 60 min (0.9 to 4.7 log10 after 30 min) with Gram-negative bacteria being more susceptible than S. aureus. Significant reduction of C. albicans by 2.0 to 2.9 log10 occurred after 4 h incubation. In combined biofilms, viable counts of C. albicans were reduced by 1.1 to 2.4 log10 after 4 h, while they reached the detection limit after 1 to 2 h with bacteria (2.0 to > 3.5 log10 reduction). Remarkably, older biofilms demonstrated no increase in resistance but constant susceptibility to NCT. This was valid for all tested pathogens. In electron microscopy, morphological differences between NCT-treated and non-treated biofilms could be found. Conclusions: NCT is active against long-term biofilms of up to several months irrespective of their age. Combined biofilm cultures of yeasts and bacteria show a similar susceptibility pattern to NCT as single ones. These results contribute to the explanation of the clinical efficacy of NCT, for instance, in infected chronic wounds and purulently coated crural ulcerations. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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12 pages, 17508 KiB  
Article
Free-Floating Aggregate and Single-Cell-Initiated Biofilms of Staphylococcus aureus
by Tripti Thapa Gupta, Niraj K. Gupta, Peter Burback and Paul Stoodley
Antibiotics 2021, 10(8), 889; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10080889 - 21 Jul 2021
Cited by 5 | Viewed by 2659
Abstract
Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the common bacteria responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form free-floating aggregates in [...] Read more.
Periprosthetic joint infection (PJI) occurring after artificial joint replacement is a major clinical issue requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus is the common bacteria responsible for PJI. Recent in vitro research has shown that staphylococcal strains rapidly form free-floating aggregates in the presence of synovial fluid (SF) with biofilm-like resistance to antimicrobial agents. However, the development of biofilms formed from these aggregates under shear have not been widely investigated. Thus, in this study, we examined the progression of attached biofilms from free-floating aggregates. Biofilms were grown for 24 h in flow cells on titanium discs after inoculation with either pre-aggregated or single planktonic cells. Image analysis showed no significant difference between the biofilm formed from aggregates vs. the planktonic cells in terms of biomass, surface area, and thickness. Regarding antibiotic susceptibility, there were 1 and 2 log reductions in biofilms formed from single cells and aggregates, respectively, when treated with vancomycin for 24 h. Thus, this study demonstrates the formation of biofilm from free-floating aggregates and follows a similar developmental time period and shows similar antibiotic tolerance to more traditionally inoculated in vitro flow cell biofilms. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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13 pages, 1728 KiB  
Article
Staphylococcal Biofilm on the Surface of Catheters: Electron Microscopy Evaluation of the Inhibition of Biofilm Growth by RNAIII Inhibiting Peptide
by Adilson de Oliveira, Luiza Pinheiro-Hubinger, Valéria Cataneli Pereira, Danilo Flávio Moraes Riboli, Katheryne Benini Martins, Letícia Calixto Romero and Maria de Lourdes Ribeiro de Souza da Cunha
Antibiotics 2021, 10(7), 879; https://doi.org/10.3390/antibiotics10070879 - 20 Jul 2021
Cited by 2 | Viewed by 2620
Abstract
Staphylococcus aureus and coagulase-negative staphylococci (CoNS) have become the main causative agents of medical device-related infections due to their biofilm-forming capability, which protects them from the host’s immune system and from the action of antimicrobials. This study evaluated the ability of RNA III [...] Read more.
Staphylococcus aureus and coagulase-negative staphylococci (CoNS) have become the main causative agents of medical device-related infections due to their biofilm-forming capability, which protects them from the host’s immune system and from the action of antimicrobials. This study evaluated the ability of RNA III inhibiting peptide (RIP) to inhibit biofilm formation in 10 strains isolated from clinical materials, including one S. aureus strain, two S. epidermidis, two S. haemolyticus, two S. lugdunensis, and one isolate each of the following species: S. warneri, S. hominis, and S. saprophyticus. The isolates were selected from a total of 200 strains evaluated regarding phenotypic biofilm production and the presence and expression of the ica operon. The isolates were cultured in trypticase soy broth with 2% glucose in 96-well polystyrene plates containing catheter segments in the presence and absence of RIP. The catheter segments were observed by scanning electron microscopy. The results showed inhibition of biofilm formation in the presence of RIP in all CoNS isolates; however, RIP did not interfere with biofilm formation by S. aureus. RIP is a promising tool that might be used in the future for the prevention of biofilm-related infections caused by CoNS. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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16 pages, 895 KiB  
Article
Sesquiterpene Lactones from Cotula cinerea with Antibiotic Activity against Clinical Isolates of Enterococcus faecalis
by Alessio Cimmino, Emanuela Roscetto, Marco Masi, Angela Tuzi, Imene Radjai, Chakali Gahdab, Rossella Paolillo, Amedeo Guarino, Maria Rosaria Catania and Antonio Evidente
Antibiotics 2021, 10(7), 819; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070819 - 06 Jul 2021
Cited by 8 | Viewed by 1957
Abstract
Cotula cinerea, belonging to the tribe Anthemideae, is a plant widespread in the Southern hemisphere. It is frequently used in folk medicine in North African countries for several of its medical properties, shown by its extracts and essential oils. The dichloromethane extract [...] Read more.
Cotula cinerea, belonging to the tribe Anthemideae, is a plant widespread in the Southern hemisphere. It is frequently used in folk medicine in North African countries for several of its medical properties, shown by its extracts and essential oils. The dichloromethane extract obtained from its aerial parts demonstrated antibiotic activity against Enterococcus faecalis and was fractionated by bioguided purification procedures affording five main sesquiterpene lactones. They were identified by spectroscopic methods (NMR and ESIMS data) as guaiantrienolides, i.e., 6-acetoxy-1β-,6-acetoxy-1α-, and 6-acetoxy-10-β-hydroxyguaiantrienolide (1–3), and germacrenolides, i.e., haagenolide and 1,10-epoxyhaagenolide (4 and 5). The absolute configuration was assigned by applying the advanced Mosher’s method to haagenolide and by X-ray diffraction analysis to 1,10-epoxyhaagenolide. The specific antibiotic and antibiofilm activities were tested toward the clinical isolates of Enterococcus faecalis. The results showed that compounds 3–5 have antibacterial activity against all the strains of E. faecalis, while compound 2 exhibited activity only toward some strains. Compound 1 did not show this activity but had only antibiofilm properties. Thus, these metabolites have potential as new antibiotics and antibiofilm against drug resistant opportunistic pathogens. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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14 pages, 343 KiB  
Article
Effectiveness of Oil-Based Denture Dentifrices-Organoleptic Characteristics, Physicochemical Properties and Antimicrobial Action
by Andrezza C. M. dos Santos, Viviane C. Oliveira, Ana P. Macedo, Jairo K. Bastos, Mário S. Ogasawara, Evandro Watanabe, Isabela M. Chaguri, Cláudia H. Silva-Lovato and Helena F. O. Paranhos
Antibiotics 2021, 10(7), 813; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070813 - 04 Jul 2021
Cited by 3 | Viewed by 2585
Abstract
Denture dentifrices must be effective and not deleterious to prosthetic devices. This study formulated and evaluated dentifrices based on oils of Copaifera officinalis, Eucalyptus citriodora, Melaleuca alternifolia, Pinus strobus, and Ricinus communis. Organoleptic characteristics (appearance, color, odor, taste), physicochemical [...] Read more.
Denture dentifrices must be effective and not deleterious to prosthetic devices. This study formulated and evaluated dentifrices based on oils of Copaifera officinalis, Eucalyptus citriodora, Melaleuca alternifolia, Pinus strobus, and Ricinus communis. Organoleptic characteristics (appearance, color, odor, taste), physicochemical properties (pH, density, consistency, rheological, abrasiveness, weight loss, and surface roughness) and antimicrobial (Hole-Plate Diffusion–HPD)/anti-biofilm (Colony Forming Units–CFU) action against Staphylococcus aureus, Streptococcus mutans, and Candida albicans were evaluated. Formulations were compared with water (negative control) and a commercial dentifrice (positive control). The data were analyzed by Kruskal-Wallis and Dunn tests (α = 0.05). The organoleptic and physicochemical properties were adequate. All dentifrices promoted weight losses, with high values for C. officinalis and R. communis, and an increase in surface roughness, without differing from each other. For antimicrobial action, C. officinalis and E. citriodora dentifrices were similar to positive control showing effectiveness against S. mutans and C. albicans and no dentifrice was effective against S. aureus; regarding the anti-biofilm action, the dentifrices were not effective, showing higher CFU counts than positive control for all microorganisms. The dentifrices presented satisfactory properties; and, although they showed antimicrobial action when evaluated by HPD, they showed no effective anti-biofilm action on multispecies biofilm. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
20 pages, 3892 KiB  
Article
Influence of Nutrient Media Compared to Human Synovial Fluid on the Antibiotic Susceptibility and Biofilm Gene Expression of Coagulase-Negative Staphylococci In Vitro
by Stephan Josef Maria Steixner, Christopher Spiegel, Dietmar Dammerer, Alexander Wurm, Michael Nogler and Débora Cristina Coraça-Huber
Antibiotics 2021, 10(7), 790; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070790 - 29 Jun 2021
Cited by 6 | Viewed by 2051
Abstract
Bacterial antibiotic resistance and biofilm formation are mechanisms usually involved in the pathogeny of implant-related infections. Worldwide, antibiotic susceptibility tests are usually carried out using nutrient-rich media. Clinical routine laboratories and even research centers use for example EUCAST or CLSI for guidelines. In [...] Read more.
Bacterial antibiotic resistance and biofilm formation are mechanisms usually involved in the pathogeny of implant-related infections. Worldwide, antibiotic susceptibility tests are usually carried out using nutrient-rich media. Clinical routine laboratories and even research centers use for example EUCAST or CLSI for guidelines. In this study, we investigated the effect of different nutrient media on the antibiotic susceptibility and icaADBC gene expression of bacteria in biofilm. As media, Müller-Hinton Bouillon (MHB), Tryptic Soy Broth (TSB) and human synovial fluid (SF) diluted 1:4 in phosphate buffered saline (PBS), each also supplemented with 1% glucose, were used. The influence of different nutrient media on the antibiotic susceptibility of coagulase-negative staphylococci (CoNS) was evaluated by counting of colony-forming units (CFU) and by checking the metabolic activity of the bacteria. We used reverse transcriptase and real-time qPCR to investigate the influence of nutrient media on the biofilm gene expression. We used two-way analysis of variance (ANOVA). p < 0.05 was considered to be statistically significant. Significant differences in growth and antibiotic susceptibility were detected in all strains tested among the different media used. The nutrient media showed influence on the cell viability of all bacteria after antibiotic treatment. IcaADBC gene expression was significantly influenced by glucose and all nutrient media. The results highlight the influence of glucose on the antibiotic susceptibility, growth and gene expression of all strains tested. For all strains, a significant difference in bacterial recovery, viability and gene expression were found when compared to biofilm grown in SF. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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17 pages, 8823 KiB  
Article
A New Dermal Substitute Containing Polyvinyl Alcohol with Silver Nanoparticles and Collagen with Hyaluronic Acid: In Vitro and In Vivo Approaches
by Dario Mendes Júnior, Moema A. Hausen, Jéssica Asami, Akemi M. Higa, Fabio L. Leite, Giovanni P. Mambrini, Andre L. Rossi, Daniel Komatsu and Eliana A. de Rezende Duek
Antibiotics 2021, 10(6), 742; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060742 - 19 Jun 2021
Cited by 15 | Viewed by 2953
Abstract
The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match [...] Read more.
The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match for PVA as a dressing, as it focuses on creating a physical barrier to avoid wound dehydration. When associated with extracellular components, such as the collagen matrix, the device obtained can create the desired biological conditions to act as a skin substitute. This study aimed to analyze the anti-microbiological activity and the in vitro and in vivo responses of a bilaminar device of PVA containing AgNPs associated with a membrane of collagen–hyaluronic acid (col-HA). Additionally, mesenchymal stem cells were cultured in the device to evaluate in vitro responses and in vivo immunomodulatory and healing behavior. The device morphology revealed a porous pattern that favored water retention and in vitro cell adhesion. Controlled wounds in the dorsal back of rat skins revealed a striking skin remodeling with new epidermis fulfilling all previously injured areas after 14 and 28 days. No infections or significant inflammations were observed, despite increased angiogenesis, and no fibrosis-markers were identified as compared to controls. Although few antibacterial activities were obtained, the addition of AgNPs prevented fungal growth. All results demonstrated that the combination of the components used here as a dermal device, chosen according to previous miscellany studies of low/mid-cost biomaterials, can promote skin protection avoiding infections and dehydration, minimize the typical wound inflammatory responses, and favor the cellular healing responses, features that give rise to further clinical trials of the device here developed Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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15 pages, 2834 KiB  
Article
Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency
by Marina Pekmezovic, Melina Kalagasidis Krusic, Ivana Malagurski, Jelena Milovanovic, Karolina Stępień, Maciej Guzik, Romina Charifou, Ramesh Babu, Kevin O’Connor and Jasmina Nikodinovic-Runic
Antibiotics 2021, 10(6), 737; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060737 - 18 Jun 2021
Cited by 12 | Viewed by 3195
Abstract
Novel biodegradable and biocompatible formulations of “old” but “gold” drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form [...] Read more.
Novel biodegradable and biocompatible formulations of “old” but “gold” drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form of films (~50 µm). Thermal properties and stability of the materials were not significantly altered by the incorporation of polyenes in mcl-PHA, but polyene containing materials were more hydrophobic. These formulations were tested in vitro against a panel of pathogenic fungi and for antibiofilm properties. The films containing 0.1 to 2 weight % polyenes showed good activity and sustained polyene release for up to 4 days. A PHA monomer, namely 3-hydroxydecanoic acid (C10-OH), was added to the films to achieve an enhanced synergistic effect with polyenes against fungal growth. Mcl-PHA based polyene formulations showed excellent growth inhibitory activity against both Candida yeasts (C. albicans ATCC 1023, C. albicans SC5314 (ATCC MYA-2876), C. parapsilosis ATCC 22019) and filamentous fungi (Aspergillus fumigatus ATCC 13073; Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102). All antifungal PHA film preparations prevented the formation of a C. albicans biofilm, while they were not efficient in eradication of mature biofilms, rendering them suitable for the transdermal application or as coatings of implants. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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16 pages, 8515 KiB  
Article
Development of Bisphosphonate-Conjugated Antibiotics to Overcome Pharmacodynamic Limitations of Local Therapy: Initial Results with Carbamate Linked Sitafloxacin and Tedizolid
by Emmanuela Adjei-Sowah, Yue Peng, Jason Weeks, Jennifer H. Jonason, Karen L. de Mesy Bentley, Elysia Masters, Yugo Morita, Gowrishankar Muthukrishnan, Philip Cherian, X. Eric Hu, Charles E. McKenna, Frank H. Ebetino, Shuting Sun, Edward M. Schwarz and Chao Xie
Antibiotics 2021, 10(6), 732; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060732 - 17 Jun 2021
Cited by 12 | Viewed by 3909
Abstract
The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a “target and release” [...] Read more.
The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a “target and release” approach to deliver antibiotics to bone infection sites. A fluorescent bisphosphonate probe was used to demonstrate bone surface labeling adjacent to bacteria in a S. aureus infected mouse tibiae model. Bisphosphonate and hydroxybisphosphonate conjugates of sitafloxacin and tedizolid (BCA) were synthesized using hydroxyphenyl and aminophenyl carbamate linkers, respectively. The conjugates were adequately stable in serum. Their cytolytic activity versus parent drug on MSSA and MRSA static biofilms grown on hydroxyapatite discs was established by scanning electron microscopy. Sitafloxacin O-phenyl carbamate BCA was effective in eradicating static biofilm: no colony formation units (CFU) were recovered following treatment with 800 mg/L of either the bisphosphonate or α-hydroxybisphosphonate conjugated drug (p < 0.001). In contrast, the less labile tedizolid N-phenyl carbamate linked BCA had limited efficacy against MSSA, and MRSA. CFU were recovered from all tedizolid BCA treatments. These results demonstrate the feasibility of BCA eradication of S. aureus biofilm on OLCN bone surfaces and support in vivo drug development of a sitafloxacin BCA. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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13 pages, 6436 KiB  
Article
Elution Kinetics from Antibiotic-Loaded Calcium Sulfate Beads, Antibiotic-Loaded Polymethacrylate Spacers, and a Powdered Antibiotic Bolus for Surgical Site Infections in a Novel In Vitro Draining Knee Model
by Kelly Moore, Rebecca Wilson-van Os, Devendra H. Dusane, Jacob R. Brooks, Craig Delury, Sean S. Aiken, Phillip A. Laycock, Anne C. Sullivan, Jeffrey F. Granger, Matthew V. Dipane, Edward J. McPherson and Paul Stoodley
Antibiotics 2021, 10(3), 270; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030270 - 08 Mar 2021
Cited by 5 | Viewed by 3343
Abstract
Antibiotic-tolerant bacterial biofilms are notorious in causing PJI. Antibiotic loaded calcium sulfate bead (CSB) bone void fillers and PMMA cement and powdered vancomycin (VP) have been used to achieve high local antibiotic concentrations; however, the effect of drainage on concentration is poorly understood. [...] Read more.
Antibiotic-tolerant bacterial biofilms are notorious in causing PJI. Antibiotic loaded calcium sulfate bead (CSB) bone void fillers and PMMA cement and powdered vancomycin (VP) have been used to achieve high local antibiotic concentrations; however, the effect of drainage on concentration is poorly understood. We designed an in vitro flow reactor which provides post-surgical drainage rates after knee revision surgery to determine antibiotic concentration profiles. Tobramycin and vancomycin concentrations were determined using LCMS, zones of inhibition confirmed potency and the area under the concentration–time curve (AUC) at various time points was used to compare applications. Concentrations of antibiotcs from the PMMA and CSB initially increased then decreased before increasing after 2 to 3 h, correlating with decreased drainage, demonstrating that concentration was controlled by both release and flow rates. VP achieved the greatest AUC after 2 h, but rapidly dropped below inhibitory levels. CSB combined with PMMA achieved the greatest AUC after 2 h. The combination of PMMA and CSB may present an effective combination for killing biofilm bacteria; however, cytotoxicity and appropriate antibiotic stewardship should be considered. The model may be useful in comparing antibiotic concentration profiles when varying fluid exchange is important. However, further studies are required to assess its utility for predicting clinical efficacy. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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13 pages, 2815 KiB  
Article
Incorporation of Hybrid Nanomaterial in Dental Porcelains: Antimicrobial, Chemical, and Mechanical Properties
by Carla L. Vidal, Izabela Ferreira, Paulo S. Ferreira, Mariana L. C. Valente, Ana B. V. Teixeira and Andréa C. Reis
Antibiotics 2021, 10(2), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020098 - 20 Jan 2021
Cited by 9 | Viewed by 2070
Abstract
Biofilm formation on biomaterials is a challenge in the health area. Antimicrobial substances based on nanomaterials have been proposed to solve this problem. The aim was to incorporate nanostructured silver vanadate decorated with silver nanoparticles (β-AgVO3) into dental porcelains [...] Read more.
Biofilm formation on biomaterials is a challenge in the health area. Antimicrobial substances based on nanomaterials have been proposed to solve this problem. The aim was to incorporate nanostructured silver vanadate decorated with silver nanoparticles (β-AgVO3) into dental porcelains (IPS Inline and Ex-3 Noritake), at concentrations of 2.5% and 5%, and evaluate the surface characteristics (by SEM/EDS), antimicrobial activity (against Streptococcus mutans, Streptococcus sobrinus, Aggregatibacter actinomycetemcomitans, and Pseudomonas aeruginosa), silver (Ag+) and vanadium (V4+/V5+) ions release, and mechanical properties (microhardness, roughness, and fracture toughness). The β-AgVO3 incorporation did not alter the porcelain’s components, reduced the S. mutans, S. sobrinus and A. actinomycetemcomitans viability, increased the fracture toughness of IPS Inline, the roughness for all groups, and did not affect the microhardness of the 5% group. Among all groups, IPS Inline 5% released more Ag+, and Ex-3 Noritake 2.5% released more V4+/V5+. It was concluded that the incorporation of β-AgVO3 into dental porcelains promoted antimicrobial activity against S. mutans, S. sobrinus, and A. actinomycetemcomitans (preventing biofilm formation), caused a higher release of vanadium than silver ions, and an adequate mechanical behavior was observed. However, the incorporation of β-AgVO3 did not reduce P. aeruginosa viability and increased the surface roughness of dental porcelains. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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Review

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12 pages, 2052 KiB  
Review
Antimicrobial Activity of Calcium Silicate-Based Dental Materials: A Literature Review
by Ana Cristina Padilha Janini, Gabriela Fernanda Bombarda, Lauter Eston Pelepenko and Marina Angélica Marciano
Antibiotics 2021, 10(7), 865; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070865 - 16 Jul 2021
Cited by 12 | Viewed by 2901
Abstract
Endodontic biomaterials have significantly improved dental treatment techniques in several aspects now that they can be used for vital pulp treatments, as temporary intracanal medication, in definitive fillings, in apical surgeries, and for regenerative procedures. Calcium silicate-based cement is a class of dental [...] Read more.
Endodontic biomaterials have significantly improved dental treatment techniques in several aspects now that they can be used for vital pulp treatments, as temporary intracanal medication, in definitive fillings, in apical surgeries, and for regenerative procedures. Calcium silicate-based cement is a class of dental material that is used in endodontics in direct contact with the dental structures, connective tissue, and bone. Because the material interacts with biological tissues and stimulates biomineralization processes, its properties are of major importance. The main challenge in endodontic treatments is the elimination of biofilms that are present in the root canal system anatomical complexities, as it remains even after chemical-mechanical preparation and disinfection procedures. Thus, an additional challenge for these biomaterials is to exert antimicrobial activity while maintaining their biological properties in parallel. This article reviews the literature for studies considering the antimicrobial properties of calcium silicate-based dental biomaterials used in endodontic practice. Considering the reviewed studies, it can be affirmed that the reduced antimicrobial effect exhibited by calcium silicate-based endodontic materials clearly emphasizes that all clinical procedures prior to their use must be carefully performed. Future studies for the evaluation of these materials, and especially newly proposed materials, under poly-microbial biofilms associated with endodontic diseases will be necessary. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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13 pages, 498 KiB  
Review
Sensitivity of Staphylococcal Biofilm to Selected Compounds of Plant Origin
by Denis Swolana, Małgorzata Kępa, Agata Kabała-Dzik, Radosław Dzik and Robert D. Wojtyczka
Antibiotics 2021, 10(5), 607; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050607 - 20 May 2021
Cited by 7 | Viewed by 2494
Abstract
Staphylococcus epidermidis is a bacterium that belongs to the human microbiota. It is most plentiful on the skin, in the respiratory system, and in the human digestive tract. Moreover, it is the most frequently isolated microorganism belonging to the group of Coagulase Negative [...] Read more.
Staphylococcus epidermidis is a bacterium that belongs to the human microbiota. It is most plentiful on the skin, in the respiratory system, and in the human digestive tract. Moreover, it is the most frequently isolated microorganism belonging to the group of Coagulase Negative Staphylococci (CoNS). In recent years, it has been recognized as an important etiological factor of mainly nosocomial infections and infections related to the cardiovascular system. On the other hand, Staphylococcus aureus, responsible for in-hospital and out-of-hospital infections, is posing an increasing problem for clinicians due to its growing resistance to antibiotics. Biofilm produced by both of these staphylococcal species in the course of infection significantly impedes therapy. The ability to produce biofilm hinders the activity of chemotherapeutic agents—the only currently available antimicrobial therapy. This also causes the observed significant increase in bacterial resistance. For this reason, we are constantly looking for new substances that can neutralize microbial cells. In the present review, 58 substances of plant origin with antimicrobial activity against staphylococcal biofilm were replaced. Variable antimicrobial efficacy of the substances was demonstrated, depending on the age of the biofilm. An increase in the activity of the compounds occurred in proportion to increasing their concentration. Appropriate use of the potential of plant-derived compounds as an alternative to antibiotics may represent an important direction of change in the support of antimicrobial therapy. Full article
(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)
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