Effect of antibiotic infused calcium sulfate/hydroxyapatite (CAS/HA) insets on implant-associated osteitis in a femur fracture model in mice

Oezel, Lisa; Büren, Carina; Scholz, A; Windolf, Joachim; Windolf, Ceylan D.

doi:10.1371/journal.pone.0213590

Cited by 19 publications

(17 citation statements)

References 30 publications

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“…Therefore, it was concluded that the application of the antimicrobial-impregnated material in an acute implant-associated infection did not cure the lesion. 10 This corresponds to the findings of the present preclinical study. In accordance with our observations, biofilm formation in antimicrobial-loaded carriers has also been described in the clinic.…”

Section: Discussionsupporting

confidence: 91%

“…In a recent preclinical study, the effect of CERAMENT|G was evaluated in a murine fracture model of implant-related S. aureus osteitis. 10 Lavage and debridement was performed before implantation of the product, and a final lavage was obtained again on the day of euthanization. 10 Although based on lavage, and not bone tissue samples, all samples were positive for bacteria.…”

Section: Discussionmentioning

confidence: 99%

“… 10 Lavage and debridement was performed before implantation of the product, and a final lavage was obtained again on the day of euthanization. 10 Although based on lavage, and not bone tissue samples, all samples were positive for bacteria. Therefore, it was concluded that the application of the antimicrobial-impregnated material in an acute implant-associated infection did not cure the lesion.…”

Section: Discussionmentioning

confidence: 99%

“… 7 , 8 The ideal antimicrobial-loaded bone void filler possesses properties such as biodegradability, biocompatibility, providing an osteoconductive and osteoinductive scaffold for healing, and elution of high levels of antimicrobials. 6 , 9 , 10 CERAMENT|G (BoneSupport AB, Lund, Sweden) is an injectable bone void filler composed of 60 wt% calcium sulphate and 40 wt% calcium hydroxyapatite (HA). 9 - 11 Calcium sulphate (CS) is resorbed quickly and is thereby quickly replaced by newly formed osteoid and is effective at delivering high levels of antimicrobials.…”

Section: Introductionmentioning

confidence: 99%

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Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis

Blirup-Plum

Bjarnsholt

Jensen

et al. 2020

Bone & Joint Research

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Aims CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis

Blirup-Plum

Bjarnsholt

Jensen

et al. 2020

Bone & Joint Research

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“…The incidence of infections and osteomyelitis after complex fractures is high, ranging from 1 to 55% in primary fracture stabilization, especially in open fractures with extensive tissue damage [4][5][6][7][8]. Staphylococcus aureus is the most common pathogen associated with infected metal implants [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

A new sequential animal model for infection-related non-unions with segmental bone defect

Helbig

Guehring

Titze

et al. 2020

BMC Musculoskelet Disord

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Background: The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects. Methods: After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 10 3 CFU Staphylococcus aureus (infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable reosteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis. Results: We developed and presented a new two-stage non-union animal model through a targeted S. aureus infection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and noninfected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculated S. aureus strain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the μ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001). Conclusions: We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.

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Plate-associated localized osteitis in mini-pig by biofilm-forming Methicillin-resistant Staphylococcus aureus (MRSA): establishment of a novel experimental model

Jaekel

Windolf

Sager

et al. 2022

Eur J Trauma Emerg Surg

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Purpose The increasing number of implant-associated infections during trauma and orthopedic surgery caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance of conventional antibiotics requires new therapeutic strategies. One possibility could be testing for different therapeutic strategies with differently coated plates. Therefore, a clinically realistic model is required. The pig offers the best comparability to the human situation, thus it was chosen for this model. The present study characterizes a novel model of a standardized low-grade acute osteitis with bone defect in the femur in mini-pigs, which is stabilized by a titanium locking plate to enable further studies with various coatings. Methods A bone defect was performed on the femur of 7 Aachen mini-pigs and infected with Methicillin-resistant S. aureus (MRSA ATCC 33592). The defect zone was stabilized with a titanium plate. After 14 days, a plate change, wound debridement and lavage were performed. Finally, after 42 days, the animals were lavaged and debrided again, followed by euthanasia. The fracture healing was evaluated radiologically and histologically. Results A local osteitis with radiologically visible lysis of the bone could be established. The unchanged high Colony-forming Units (CFU) in lavage, the significant differences in Interleukin (IL)-6 in blood compared to lavage and the lack of increase in Alkaline Phosphates (ALP) in serum over the entire observation period show the constant local infection. Conclusion The study shows the successful induction of local osteitis with lysis of the bone and the lack of enzymatic activity to mineralize the bone. Therefore, this standardized mini-pig model can be used in further clinical studies, to investigate various coated implants, bone healing, biofilm formation and immune response in implant-associated osteitis.

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Effect of antibiotic infused calcium sulfate/hydroxyapatite (CAS/HA) insets on implant-associated osteitis in a femur fracture model in mice

Cited by 19 publications

References 30 publications

Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis

Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis

A new sequential animal model for infection-related non-unions with segmental bone defect

Plate-associated localized osteitis in mini-pig by biofilm-forming Methicillin-resistant Staphylococcus aureus (MRSA): establishment of a novel experimental model

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