Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss.Debate persists as to the optimal void filler for this“limb salvage”surgery,whet...Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss.Debate persists as to the optimal void filler for this“limb salvage”surgery,whether metal or allograft bone.Clinicians focus on optimizing important functional gains for patients,and the risk of devastating implant infection has been thought to be similar regardless of implant material.Recent insights into infection pathophysiology are challenging this equipoise,however,with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus(the most common infecting agent)into the host lacunar–canaliculi network,and also clinical data revealing a higher rate of infection of allograft over metal.The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal.Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal,and both microarchitecture of host implant and presence of host immune response were assessed.An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone.The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection.These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible,contributing to elevated risks of infection in cortical bone.The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.展开更多
基金the Musculoskeletal Transplant Foundation/Musculoskeletal Tumor Society grant number 20161236.Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under the Ruth L.Kirschstein National Research Service Award Number T32AR059033 and Award Number 5K08AR069112-01.+2 种基金The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Confocal laser scanning microscopy was performed at the CNSI Advanced Light Microscopy/Spectroscopy Shared Resource Facility at UCLA,supported with funding from NIH-NCRR shared resources grant(CJX1-443835-WS-29646)and NSF Major Research Instrumentation grant(CHE-0722519).Support for LysEGFP mice was provided by the Training Program in Pharmacology:From Bench to Bedside at the University of California,Davis,supported by Grant NIH T32 GM099608(to Leif S.Anderson).Statistical support was provided by Nicholas J.Jackson,Ph.D.MPH,and the research described was supported by NIH/National Center for Advancing Translational Science(NCATS)UCLA CTSI Grant Number UL1TR001881.
文摘Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss.Debate persists as to the optimal void filler for this“limb salvage”surgery,whether metal or allograft bone.Clinicians focus on optimizing important functional gains for patients,and the risk of devastating implant infection has been thought to be similar regardless of implant material.Recent insights into infection pathophysiology are challenging this equipoise,however,with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus(the most common infecting agent)into the host lacunar–canaliculi network,and also clinical data revealing a higher rate of infection of allograft over metal.The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal.Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal,and both microarchitecture of host implant and presence of host immune response were assessed.An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone.The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection.These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible,contributing to elevated risks of infection in cortical bone.The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.
