Polymicrobial Biofilm Inhibition Effects of Acetate‐Buffered Chitosan Sponge Delivery Device

Jennings, Jessica Amber; Beenken, Karen E.; Parker, Ashley Cox; Smith, J. Keaton; Courtney, Harry S.; Smeltzer, Mark S.; Haggard, Warren O.

doi:10.1002/mabi.201500347

Cited by 17 publications

(11 citation statements)

References 75 publications

(124 reference statements)

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“…Sponges for local and rapid treatment of osteomyelitis appears to be a growing area of interest, particularly in military applications, as they are readily available to pack into traumatic wounds and rapidly deliver therapeutics directly to the site of infection. 29 Reported materials of sponges include chitosan, chitosan-polycaprolactone blends, and collagen, which have been used to deliver gentamicin, 116,152 ciprofloxacin, 29,153 amikacin, 154,155 vancomycin, [154][155][156] rifampin, 29 and others. 157 In two comparative studies in humans, gentamicin loaded collagen sponges matched the efficacy of traditionally used PMMA beads in osteomyelitis treatment, while reducing the need for secondary surgical procedures.…”

Section: Spongesmentioning

confidence: 99%

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Cobb

McCabe

Priddy

2020

Journal Orthopaedic Research

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Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long‐term, systemic antibiotic administration, which contributes to the development of antibiotic‐resistant bacteria and has limited ability to eradicate challenging biofilm‐forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm‐forming, antibiotic‐resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.

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Section: Spongesmentioning

confidence: 99%

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Cobb

McCabe

Priddy

2020

Journal Orthopaedic Research

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“…The combination of two principles of drug loading, (a) drug incorporation within the fiber scaffold and (b) liquid-loading of the PFS pore-system with drug solutions, can turn them into versatile multi-drug carriers that can flexibly provide user-adjustable doses and drug combinations at the point-of-care ( Jennings et al, 2016 ; Parker et al, 2015 ). The fundamental processes prevailing inside of PFS, including liquid-uptake/loading and release mechanisms from the scaffold, are still hardly understood.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive characterization (EPR, μCT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery

Zech

Mäder

Gündel

et al. 2020

International Journal of Pharmaceutics: X

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Highly porous 3D-scaffolds, made from cut, electrospun PLA fibers, are relatively new and promising systems for controlled drug-delivery applications. Because knowledge concerning fundamental processes of drug delivery from those scaffolds is limited, we noninvasively characterized drug-loading and drug-release mechanisms of these polymer-fiber sponges (PFS). We screened simplified PFS-implantation scenarios with EPR and μCT to quantify and 3D-visualize the absorption of model-biofluids and an oil, a possible drug-loading liquid. Saturation of PFS (6 × 8 mm, h x d) is governed by the high hydrophobicity of the material and air-entrapment. It required up to 45 weeks for phosphate-buffered saline and 11 weeks for a more physiological, surface-active protein-solution, indicating the slow fluid-uptake of PFS as an effective mechanism to substantially prolong the release of a drug incorporated within the scaffold. Medium-chain triglycerides, as a good wetting liquid, saturated PFS within seconds, suggesting PFS potential to serve as carrier-vessels for immobilizing hydrophobic drug-solutions to define a liquid's 3D-interface. Oil-retention under mechanical stress was therefore investigated. 1 H NMR permitted insights into PFS-oil interaction, confirming surface-relaxation and restricted diffusion; both did not influence drug release from oil-loaded PFS. Results facilitate better understanding of PFS and their potential use in drug delivery.

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“…As such, a strong interest in local antibiotic delivery mechanisms by direct local application of antibiotic powders or via antibiotic carriers that allow a slower release of antibiotic over time is gaining in popularity [ 10 – 16 ]. Previous animal studies have shown that commercially available absorbable chitosan sponges are suitable carriers for single-agent antibiotic delivery and allow for reductions in bacteria with or without negative pressure wound therapy adjuncts when applied to a contaminated wound [ 10 , 17 ]. These bioabsorbable chitosan sponges are capable of time-releasing antibiotics directly into a wound bed while also acting as a space filler [ 10 , 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous animal studies have shown that commercially available absorbable chitosan sponges are suitable carriers for single-agent antibiotic delivery and allow for reductions in bacteria with or without negative pressure wound therapy adjuncts when applied to a contaminated wound [ 10 , 17 ]. These bioabsorbable chitosan sponges are capable of time-releasing antibiotics directly into a wound bed while also acting as a space filler [ 10 , 17 – 20 ]. However, many traumatic orthopedic wound infections are polymicrobial and may require multiple antibiotics for adequate treatment.…”

Section: Introductionmentioning

confidence: 99%

Local control of polymicrobial infections via a dual antibiotic delivery system

et al. 2018

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BackgroundContaminated traumatic open orthopedic wounds are frequently complicated by polymicrobial contamination and infection. In high-risk wounds, the standard of care comprises debridement and irrigation combined with antibiotics which can be applied directly or combined with systemic antibiotics. Recently, bioabsorbable chitosan sponges have been shown to be an effective single-agent delivery device for local antibiotics with and without negative pressure wound therapy (NPWT). Severely contaminated orthopedic wounds, however, are often complicated by polymicrobial infections, necessitating multiple antibiotic agents. As such, the purpose of this study was to determine if a chitosan sponge would provide a suitable delivery vehicle for multiple antibiotics for the treatment of a polymicrobial infection in a large animal polytraumatic extremity wound model.MethodsA complex polytraumatic extremity wound was created in 11 adult male Boer goats. Each wound was contaminated with a bioluminescent strain of S. aureus (1 ml of 108 colony forming units/ml) and of P. aeruginosa (1 ml of 108 CFU/ml) which are genetically engineered to allow quantification with a photon-counting camera. Six hours following initial wound creation and contamination, wounds were debrided and irrigated with low-pressure normal saline. The animals were randomized into one of two treatments: wet-to-dry dressings alone or a commercially available chitosan sponge loaded with 1 g vancomycin and 1.2 g of tobramycin. Each animal was then recovered and reimaged 48 h later for total bacteria content; tissue samples were taken from the wound bed to determine relative bacterial colonization.ResultsAll animals in the chitosan sponge group saw significant reductions in overall bacterial load of S. aureus and P. aeruginosa (p = 0.001). The bioluminescence was also significantly reduced compared to the wet-to-dry dressing group (p = 0.0001). Furthermore, whereas the antibiotic sponge group displayed near complete eradication of bacteria, the wounds treated with the wet-to-dry dressings alone displayed a significant 2-log increase in total bacteria at 48 h p = 0.0001). S. aureus was the predominant species found in the wounds, comprising 95 and 99% of all bacteria found in the chitosan sponge and wet-to-dry, respectively.ConclusionDual antimicrobial therapy loaded in a chitosan sponge is an effective way to reduce polymicrobial infections traumatic extremity wound.

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Polymicrobial Biofilm Inhibition Effects of Acetate‐Buffered Chitosan Sponge Delivery Device

Cited by 17 publications

References 75 publications

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Noninvasive characterization (EPR, μCT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery

Local control of polymicrobial infections via a dual antibiotic delivery system

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