Hyaluronic Acid and Its Composites as a Local Antimicrobial/Antiadhesive Barrier

Abstract. Living in biofilms is probably the most common condition for bacteria and fungi and biofilm-related infections account for the majority of bacterial infectious diseases worldwide.Among others biofilm-related infections, those associated with implanted biomaterials have an enormous and still largely underestimated impact in orthopaedics and trauma, cardio-surgery and several other surgical disciplines.Given the limited efficacy of existing antibiotics in the prevention and treatment of bacterial biofilms, new strategies are needed to protect implants and host tissues, overcoming the striking ability of the microorganisms to adhere on different surfaces and to immediately protect themselves by forming the biofilm matrix.Adhesion is a necessary first step in microbial colonization and pathogenesis and provides a potential target for new preventive and treatment approach.Among various polymers, tested as antibacterial coatings, hyaluronic acid and some of its composites do offer a well-established long-term safety profile and a proven ability to reduce bacterial adhesion and biofilm formation.Aim of the present review is to summarize the available evidence concerning the antiadhesion/antibiofilm activity of hyaluronic acid and some of its derivatives to reduce/prevent bacterial adhesion and biofilm formation in various experimental and clinical settings.

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Preventing S. aureus biofilm formation on titanium surfaces by the release of antimicrobial β-peptides from polyelectrolyte multilayers

10.1101/431205 ◽

2018 ◽

Cited By ~ 1

Author(s):

Angélica de L. Rodríguez López ◽

Myung-Ryul Lee ◽

Riley Whitehead ◽

David M. Lynn ◽

Sean P. Palecek

Keyword(s):

Thin Films ◽

Hyaluronic Acid ◽

Antimicrobial Peptides ◽

Biofilm Formation ◽

Titanium Implants ◽

Orthopaedic Implant ◽

Localized Delivery ◽

Titanium Substrates ◽

New Strategies

ABSTRACTStaphylococcus aureus infections represent the major cause of titanium based-orthopaedic implant failure. Current treatments for S. aureus infections involve the systemic delivery of antibiotics and additional surgeries, increasing health-care costs and affecting patient’s quality of life. As a step toward the development of new strategies that can prevent these infections, we build upon previous work demonstrating that the colonization of catheters by the fungal pathogen Candida albicans can be prevented by coating them with thin polymer multilayers composed of chitosan (CH) and hyaluronic acid (HA) designed to release a β-amino acid-based peptidomimetic of antimicrobial peptides (AMPs). We demonstrate here that this β-peptide is also potent against S. aureus (MIC = 4 µg/mL) and characterize its selectivity toward S. aureus biofilms. We demonstrate further that β-peptide-containing CH/HA thin-films can be fabricated on the surfaces of rough planar titanium substrates in ways that allow mammalian cell attachment and permit the long-term release of β-peptide. β-Peptide loading on CH/HA thin-films was then adjusted to achieve release of β-peptide quantities that selectively prevent S. aureus biofilms on titanium substrates in vitro for up to 24 days and remained antimicrobial after being challenged sequentially five times with S. aureus inocula, while causing no significant MC3T3-E1 preosteoblast cytotoxicity compared to uncoated and film-coated controls lacking β-peptide. We conclude that these β-peptide-containing films offer a novel and promising localized delivery approach for preventing orthopaedic implant infections. The facile fabrication and loading of β-peptide-containing films reported here provides opportunities for coating other medical devices prone to biofilm-associated infections.STATEMENT OF SIGNIFICANCETitanium (Ti) and its alloys are used widely in internal fixation devices due to their mechanical strength and long-term biocompatibility. However, these devices are susceptible to bacterial colonization and the subsequent formation of biofilms. Here we report a chitosan and hyaluronic acid polyelectrolyte multilayer-based approach for the localized delivery of helical, cationic, globally amphiphilic β-peptide mimetics of antimicrobial peptides to inhibit S. aureus colonization and biofilm formation. Our results reveal that controlled release of this β-peptide can selectively kill S. aureus cells without exhibiting toxicity toward MC3T3-E1 preosteoblast cells. Further development of this polymer-based coating could result in new strategies for preventing orthopaedic implant-related infections, improving outcomes of these titanium implants.

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The Impact of Incorporating Antimicrobials into Implant Surfaces

Journal of Dental Research ◽

10.1177/0022034517731768 ◽

2017 ◽

Vol 97 (1) ◽

pp. 14-22 ◽

Cited By ~ 13

Author(s):

N.J. Hickok ◽

I.M. Shapiro ◽

A.F. Chen

Keyword(s):

Antimicrobial Activity ◽

Bacterial Adhesion ◽

Biofilm Formation ◽

Antimicrobial Properties ◽

Joint Replacements ◽

Structured Surfaces ◽

Antimicrobial Surfaces ◽

The Impact

With the increase in numbers of joint replacements, spinal surgeries, and dental implantations, there is an urgent need to combat implant-associated infection. In addition to stringent sterile techniques, an efficacious way to prevent this destructive complication is to create new implants with antimicrobial properties. Specifically, these implants must be active in the dental implant environment where the implant is bathed in the glycoprotein-rich salivary fluids that enhance bacterial adhesion, and propagation, and biofilm formation. However, in designing an antimicrobial surface, a balance must be struck between antimicrobial activity and the need for the implant to interact with the bone environment. Three types of surfaces have been designed to combat biofilm formation, while attempting to maintain osseous interactions: 1) structured surfaces where topography, usually at the nanoscale, decreases bacterial adhesion sufficiently to retard establishment of infection; 2) surfaces that actively elute antimicrobials to avert bacterial adhesion and promote killing; and 3) surfaces containing permanently bonded agents that generate antimicrobial surfaces that prevent long-term bacterial adhesion. Both topographical and elution surfaces exhibit varying, albeit limited, antimicrobial activity in vitro. With respect to covalent coupling, we present studies on the ability of the permanent antimicrobial surfaces to kill organisms while fostering osseointegration. All approaches have significant drawbacks with respect to stability and efficacy, but the permanent surfaces may have an edge in creating a long-term antibacterial environment.

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Faculty Opinions recommendation of Long-term followup of dextranomer/hyaluronic acid injection for vesicoureteral reflux: late failure warrants continued followup.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1160004.620267 ◽

2009 ◽

Author(s):

Bradley Kropp

Keyword(s):

Hyaluronic Acid ◽

Vesicoureteral Reflux ◽

Hyaluronic Acid Injection ◽

Acid Injection ◽

Late Failure

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Confocal and SEM imaging to demonstrate food pathogen- biofilm biocontrol by pyocyanin from Pseudomonas aeruginosa BTRY1

International Journal of Bioassays ◽

10.21746/ijbio.2017.01.007 ◽

2016 ◽

Vol 6 (01) ◽

pp. 5218

Author(s):

Laxmi Mohandas ◽

Anju T. R. ◽

Sarita G. Bhat*

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Laser Scanning ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Antibiofilm Activity ◽

Opportunistic Pathogens ◽

Redox Active ◽

Sem Imaging ◽

The Impact

An assortment of redox-active phenazine compounds like pyocyanin with their characteristic blue-green colour are synthesized by Pseudomonas aeruginosa, Gram-negative opportunistic pathogens, which are also considered one of the most commercially valuable microorganisms. In this study, pyocyanin from Pseudomonas aeruginosa BTRY1 from food sample was assessed for its antibiofilm activity by micro titer plate assay against strong biofilm producers belonging to the genera Bacillus, Staphylococcus, Brevibacterium and Micrococcus. Pyocyanin inhibited biofilm activity in very minute concentrations. This was also confirmed by Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM). Both SEM and CLSM helped to visualize the biocontrol of biofilm formation by eight pathogens. The imaging and quantification by CLSM also established the impact of pyocyanin on biofilm-biocontrol mainly in the food industry.

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Surface Immobilization of Nano-Silver on Polymeric Medical Devices to Prevent Bacterial Biofilm Formation

Pathogens ◽

10.3390/pathogens8030093 ◽

2019 ◽

Vol 8 (3) ◽

pp. 93 ◽

Cited By ~ 8

Author(s):

Riau ◽

Aung ◽

Setiawan ◽

Yang ◽

Yam ◽

...

Keyword(s):

Medical Devices ◽

Biofilm Formation ◽

Culture Media ◽

Silver Ions ◽

Bacterial Biofilm ◽

Surface Immobilization ◽

Nano Silver ◽

Gram Positive Bacteria ◽

Tissue Microenvironment

: Bacterial biofilm on medical devices is difficult to eradicate. Many have capitalized the anti-infective capability of silver ions (Ag+) by incorporating nano-silver (nAg) in a biodegradable coating, which is then laid on polymeric medical devices. However, such coating can be subjected to premature dissolution, particularly in harsh diseased tissue microenvironment, leading to rapid nAg clearance. It stands to reason that impregnating nAg directly onto the device, at the surface, is a more ideal solution. We tested this concept for a corneal prosthesis by immobilizing nAg and nano-hydroxyapatite (nHAp) on poly(methyl methacrylate), and tested its biocompatibility with human stromal cells and antimicrobial performance against biofilm-forming pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Three different dual-functionalized substrates—high Ag (referred to as 75:25 HAp:Ag); intermediate Ag (95:5 HAp:Ag); and low Ag (99:1 HAp:Ag) were studied. The 75:25 HAp:Ag was effective in inhibiting biofilm formation, but was cytotoxic. The 95:5 HAp:Ag showed the best selectivity among the three substrates; it prevented biofilm formation of both pathogens and had excellent biocompatibility. The coating was also effective in eliminating non-adherent bacteria in the culture media. However, a 28-day incubation in artificial tear fluid revealed a ~40% reduction in Ag+ release, compared to freshly-coated substrates. The reduction affected the inhibition of S. aureus growth, but not the P. aeruginosa. Our findings suggest that Ag+ released from surface-immobilized nAg diminishes over time and becomes less effective in suppressing biofilm formation of Gram-positive bacteria, such as S. aureus. This advocates the coating, more as a protection against perioperative and early postoperative infections, and less as a long-term preventive solution.

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Extract from phyllosphere bacteria with antibiofilm and quorum quenching activity to control several fish pathogenic bacteria

BMC Research Notes ◽

10.1186/s13104-021-05612-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Olivia Nathalia ◽

Diana Elizabeth Waturangi

Keyword(s):

Streptococcus Agalactiae ◽

Aeromonas Hydrophila ◽

Biofilm Formation ◽

Pathogenic Bacteria ◽

Vibrio Harveyi ◽

Quorum Quenching ◽

Indicator Bacteria ◽

Antibiofilm Activity ◽

Fish Pathogen ◽

Phyllosphere Bacteria

Abstract Objective The objective of this research were to screen quorum quenching activity compound from phyllosphere bacteria as well as antibiofilm activity against several fish pathogen bacteria such as Aeromonas hydrophila, Streptococcus agalactiae, and Vibrio harveyi. Results We found eight phyllosphere bacteria isolates with potential quorum quenching activity to inhibit Chromobacterium violaceum as indicator bacteria. Crude extracts (20 mg/mL) showed various antibiofilm activity against fish pathogenic bacteria used in this study. Isolate JB 17B showed the highest activity to inhibit biofilm formation of A. hydrophila and V. harveyi, meanwhile isolate JB 3B showed the highest activity to inhibit biofilm of S. agalactiae. From destruction assay, isolate JB 8F showed the highest activity to disrupt biofilm of A. hydrophila isolate JB 20B showed the highest activity to disrupt biofilm of V. harveyi, isolate JB 17B also showed the highest activity to disrupt biofilm of S. agalactiae.

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Effect of Titanium Dioxide Nanoparticles on the Expression of Efflux Pump and Quorum-Sensing Genes in MDR Pseudomonas aeruginosa Isolates

Antibiotics ◽

10.3390/antibiotics10060625 ◽

2021 ◽

Vol 10 (6) ◽

pp. 625

Author(s):

Fatma Y. Ahmed ◽

Usama Farghaly Aly ◽

Rehab Mahmoud Abd El-Baky ◽

Nancy G. F. M. Waly

Keyword(s):

Titanium Dioxide ◽

Quorum Sensing ◽

Biofilm Formation ◽

Antimicrobial Agents ◽

Efflux Pump ◽

Titanium Dioxide Nanoparticles ◽

Sol Gel ◽

Efflux Pumps ◽

Antibiofilm Activity ◽

The Impact

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production.

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Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy

Crystals ◽

10.3390/cryst11040321 ◽

2021 ◽

Vol 11 (4) ◽

pp. 321

Author(s):

Shenghui Zhong ◽

Peng Liu ◽

Jinsong Ding ◽

Wenhu Zhou

Keyword(s):

Rheumatoid Arthritis ◽

Hyaluronic Acid ◽

Targeted Delivery ◽

High Dose ◽

One Pot ◽

Inflammatory Site ◽

Pei Nanoparticles ◽

Toxic Reactions

Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.

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Bond Strengthening in Oral Bacterial Adhesion to Salivary Conditioning Films

Applied and Environmental Microbiology ◽

10.1128/aem.01119-08 ◽

2008 ◽

Vol 74 (17) ◽

pp. 5511-5515 ◽

Cited By ~ 40

Author(s):

Henny C. van der Mei ◽

Minie Rustema-Abbing ◽

Joop de Vries ◽

Henk J. Busscher

Keyword(s):

Bacterial Adhesion ◽

Biofilm Formation ◽

Specific Interactions ◽

Adhesion Forces ◽

Bacterial Strains ◽

Bacterial Interactions ◽

Initial Adhesion ◽

Conditioning Film ◽

Interacting Surfaces ◽

Conditioning Films

ABSTRACT Transition from reversible to irreversible bacterial adhesion is a highly relevant but poorly understood step in initial biofilm formation. We hypothesize that in oral biofilm formation, irreversible adhesion is caused by bond strengthening due to specific bacterial interactions with salivary conditioning films. Here, we compared the initial adhesion of six oral bacterial strains to salivary conditioning films with their adhesion to a bovine serum albumin (BSA) coating and related their adhesion to the strengthening of the binding forces measured with bacteria-coated atomic force microscopy cantilevers. All strains adhered in higher numbers to salivary conditioning films than to BSA coatings, and specific bacterial interactions with salivary conditioning films were accompanied by stronger initial adhesion forces. Bond strengthening occurred on a time scale of several tens of seconds and was slower for actinomyces than for streptococci. Nonspecific interactions between bacteria and BSA coatings strengthened twofold faster than their specific interactions with salivary conditioning films, likely because specific interactions require a closer approach of interacting surfaces with the removal of interfacial water and a more extensive rearrangement of surface structures. After bond strengthening, bacterial adhesion forces with a salivary conditioning film remained stronger than those with BSA coatings.

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Pediatric Antiphospholipid Syndrome: from Pathogenesis to Clinical Management

Current Rheumatology Reports ◽

10.1007/s11926-020-00976-7 ◽

2021 ◽

Vol 23 (2) ◽

Author(s):

Silvia Rosina ◽

Cecilia Beatrice Chighizola ◽

Angelo Ravelli ◽

Rolando Cimaz

Keyword(s):

Antiphospholipid Syndrome ◽

Fluid Phase ◽

Multiple Organ ◽

Clinical Settings ◽

Glycoprotein I ◽

Long Term Follow Up ◽

Pediatric Populations ◽

Cellular Components

Abstract Purpose of Review Elucidating the pathogenic mechanisms mediated by antiphospholipid antibodies (aPL) might exert important clinical implications in pediatric antiphospholipid syndrome (APS). Recent Findings aPL are traditionally regarded as the main pathogenic players in APS, inducing thrombosis via the interaction with fluid-phase and cellular components of coagulation. Recent APS research has focused on the role of β2 glycoprotein I, which bridges innate immunity and coagulation. In pediatric populations, aPL should be screened in appropriate clinical settings, such as thrombosis, multiple-organ dysfunction, or concomitant systemic autoimmune diseases. Children positive for aPL tests often present non-thrombotic non-criteria manifestations or asymptomatic aPL positivity. In utero aPL exposure has been suggested to result in developmental disabilities, warranting long-term follow-up. Summary The knowledge of the multifaceted nature of pediatric APS should be implemented to reduce the risk of underdiagnosing/undertreating this condition. Hopefully, recent pathogenic insights will open new windows of opportunity in the management of pediatric APS.

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