A new antibacterial carrier of hyaluronic acid gel

Matsuno, Hiroaki; Yudoh, Kazuo; Hashimoto, Masamichi; Himeda, Yasukazu; Miyoshi, Takushi; Yoshida, Kaoru; Kano, Syogo

doi:10.1007/s00776-006-1059-0

Cited by 24 publications

(21 citation statements)

References 14 publications

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“…Previously, mouse models of implant-associated osteomyelitis have been limited to intramedullary [9, 20, 24] or trans-cortical pins [17, 25]. These models are beneficial for studying the general etiology of osteomyelitis and biofilm formation [24] or systemic treatment strategies such as various antibiotic regimens [20] and immunization [26].…”

Section: Discussionmentioning

confidence: 99%

“…Studies that have evaluated local antibiotic delivery in small animal models primarily evaluated prophylactic intervention rather than treatment of a well established infection [7, 8], or used small models that cannot readily accommodate debridement and placement of antibiotic-laden spacers [9]. Large animal models that could replicate clinical scenarios of established infections are costly and typically require strict ethical justifications, which limit their use in exploratory research [10].…”

Section: Introductionmentioning

confidence: 99%

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A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

Inzana

Schwarz

Kates

et al. 2015

Bone

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Mice are the small animal model of choice in biomedical research due to the low cost and availability of genetically engineered lines. However, the devices utilized in current mouse models of implant-associated bone infection have been limited to intramedullary or trans-cortical pins, which are not amenable to treatments involving extensive debridement of a full-thickness bone loss and placement of a segmental antibiotic spacer. To overcome these limitations, we developed a clinically faithful model that utilizes a locking fracture fixation plate to enable debridement of an infected segmental bone defect (full-thickness osteotomy) during a revision surgery, and investigated the therapeutic effects of placing an antibiotic-laden spacer in the segmental bone defect. To first determine the ideal time point for revision following infection, a 0.7 mm osteotomy in the femoral mid-shaft was stabilized with a radiolucent PEEK fixation plate. The defect was inoculated with bioluminescent Staphylococcus aureus, and the infection was monitored over 14 days by bioluminescent imaging (BLI). Osteolysis and reactive bone formation were assessed by X-ray and micro-computed tomography (micro-CT). The active bacterial infection peaked by 5 days post-inoculation, however the stability of the implant fixation became compromised by 10–14 days post-inoculation due to osteolysis around the screws. Thus, day 7 was defined as the ideal time point to perform the revision surgery. During the revision surgery, the infected tissue was debrided and the osteotomy was widened to 3 mm to place a poly-methyl methacrylate spacer, with or without vancomycin. Half of the groups also received systemic vancomycin for the remaining 21 days of the study. The viable bacteria remaining at the end of the study were measured using colony forming unit assays. Volumetric bone changes (osteolysis and reactive bone formation) were directly measured using micro-CT image analysis. Mice that were treated with local or systemic vancomycin did not display gross pathology at the end of the study. While localized vancomycin delivery alone tended to decrease the bacterial burden and osteolysis, these effects were only significant when combined with systemic antibiotic therapy. This novel mouse model replicates key features of implant-associated osteomyelitis that make treatment extremely difficult, such as biofilm formation and osteolysis, and imitates the clinical practice of placing an antibiotic-laden spacer after infected tissue debridement. In addition, the model demonstrates the limitations of current PMMA spacers and could be an invaluable tool for evaluating alternative antimicrobial treatments for implant-associated bone infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

Inzana

Schwarz

Kates

et al. 2015

Bone

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“…As an critical material in the joint arthroplasty, HA can serve as local antibiotic carrier [41,42]. Thus, the Ag nanoparticle-highly loaded HA-PDDA multilayered film developed by us could provide a great potential in antimicrobial applications, particularly in an implantable biomaterial applications in artificial bones [43].…”

Section: Stability and Antibacterial Activitymentioning

confidence: 99%

In situ fabrication of silver nanoarrays in hyaluronan/PDDA layer-by-layer assembled structure

Cui

Bao

et al. 2008

Journal of Colloid and Interface Science

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“…In addition, the HA 2 /MS þ PIC hydrogel resulted in a lower inflammatory response when compared with a collagen hydrogel in vivo. Matsuno et al (2006) developed a novel bioabsorbable antibacterial carrier using HA gel for the prevention and treatment of orthopedic infections. In this study, they investigated the in vivo antibacterial effects of the two forms of this new material: an HA gel sponge and an HA gel film.…”

Section: Applications Of Ha In Dosage Form In the Drug Delivery Systemmentioning

confidence: 99%

An insight on hyaluronic acid in drug targeting and drug delivery

Yadav

Mishra

Agrawal

2008

Journal of Drug Targeting

111

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Hyaluronic acid (HA) has recently been studied for its use in drug delivery applications. Medically, HA is used as a surgical aid in ophthalmology. It also possesses therapeutic potential in the treatment of arthritis and wound healing. HA-binding receptors, CD44 and receptor for hyaluronan-mediated motility have attracted much enthusiasm, mainly because they are believed to be involved in cancer metastasis. This review unravels the role of HA in drug delivery and targeting. Designing of various novel drug delivery systems using HA as a biopolymer will also be reviewed in the present article.

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A new antibacterial carrier of hyaluronic acid gel

Abstract: Our bioabsorbable carrier of antibiotic-containing HA gel is effective for prophylactic treatment or treatment of an actual deep infection following total joint arthroplasty.

Cited by 24 publications

References 14 publications

A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

In situ fabrication of silver nanoarrays in hyaluronan/PDDA layer-by-layer assembled structure

An insight on hyaluronic acid in drug targeting and drug delivery

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