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Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis.

ABSTRACT: Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regeneration after sufficient debridement. Moreover, we could further characterize the postinfectious inflammatory state of bony defects after debridement with elevated osteoclasts and decreased bone formation despite the absence of bacteria. In this study, we investigated the positive effects of Wnt-pathway modulation on bone regeneration in our previous established mouse model. This was achieved by local application of Wnt3a, a recombinant activator of the canonical Wnt-pathway. Application of Wnt3a could enhance new bone formation, which was verified by histological and μ-CT analysis. Moreover, histology and western blots revealed enhanced osteoblastogenesis and downregulated osteoclasts in a RANKL-dependent manner. Further analysis of Wnt-pathway showed downregulation after bone infections were reconstituted by application of Wnt3a. Interestingly, Wnt-inhibitory proteins Dickkopf 1 (DKK1), sclerostin, and secreted frizzled protein 1 (sFRP1) were upregulated simultaneously to Wnt-pathway activation, indicating a negative feedback for active form of Beta-catenin. In this study, we could demonstrate enhanced bone formation in defects caused by post-traumatic osteomyelitis after Wnt3a application. KEY MESSAGES: Osteomyelitis decreases bone regeneration Wnt3a restores bone healing after infection Canonical Wnt-pathway activation with negative feedback.

SUBMITTER: Wagner JM

PROVIDER: S-EPMC8526481 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe purpose of this study was to evaluate the safety and efficacy of vancomycin-loaded calcium sulfate beads and negative-pressure wound therapy (NPWT) in treating children with acute hematogenous osteomyelitis (AHOM).MethodsA retrospective cohort study was conducted from January 2017 to January 2020 examining children (n = 60) with AHOM who were treated with surgical debridement followed by vancomycin-loaded calcium sulfate beads and NPWT (n = 32) and compared to treatment by conventional surgical debridement (n = 28) followed by NPWT. Conventional surgical treatment consisted of fenestration of necrotic infected bone, debridement of surrounding soft tissue, and washing of the medullary canal before the application of NPWT. In the vancomycin group, the antibiotic-loaded beads were implanted after washing the medullary canal and before the application of NPWT. Epidemiological factors, complications during the procedure, outcomes at last follow-up (30.0 ± 11.7 months, range 13-58 months), and laboratory parameters were documented and compared between the two groups.ResultsGood outcomes were achieved at last follow-up in 71.4% of the conventional treatment group and 75% of the vancomycin group. In the vancomycin group, it took a mean of 4.8 ± 2.5 days for CRP levels to decrease to 50% of initial inflammatory levels compared to 13 ± 9.6 days for the conventional treatment group (p = 0.001, t-test). The conventional group also had seven patients who underwent four or more surgeries whereas no patients in the vancomycin group underwent more than three surgeries (p = 0.013, chi-square test).ConclusionLocalized vancomycin delivery with NPWT effective for treating cases of AHOM that required. No perioperative adverse reactions or complications occurred from this treatment method. Based on the shortened recovery period of CRP levels, prolonged administration of post-operational parenteral antibiotics can possibly be reduced with this treatment method.

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Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis.

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