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Jos A.G. van Strijp
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3 records found
1
Journal article
(2026)
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F. Ruben H.A. Nurmohamed, Mackenzie E. Malo, Michelle Buijs, Berend van der Wildt, Alex J. Poot, Jos A.G. van Strijp, Harrie Weinans, Bart C.H. van der Wal, Ekaterina Dadachova, More Authors
Indwelling medical implants are susceptible to developing biofilm-associated infections that are notoriously difficult to eradicate. These persistent infections often cannot be resolved with antibiotics alone and typically require surgical intervention for effective management. An alternative approach is radioimmunotherapy (RIT) which uses specific antibodies linked to radioisotopes to selectively destroy bacteria. This antimicrobial approach bypasses traditional antibiotic mechanisms, and RIT is hypothesized to enhance outcomes beyond antibiotic therapy alone. RIT bactericidal effects were studied in Wistar Han rats fitted with femoral rod implants covered by matured 3-day biofilms. The rats (six per group) were treated with either: RIT with 177Lu-labeled 4497 antibody to S. aureus teichoic wall acid (WTA) (116.6 MBq/kg), or vancomycin (88 mg/kg), or combination of RIT (116.8 MBq/kg) and vancomycin, or left untreated. To evaluate efficacy, bacterial counts were taken from the joint capsule, bone, and implant after 7 days. Uptake and biodistribution were assessed via non-invasive in vivo SPECT/CT imaging and ex vivo gamma counting. Single administration of RIT achieved a 2.7-log (99.78%) reduction of bacterial burden in the infected joint capsule, had no effect on the infected femur, and resulted in 72.5% reduction of bacterial burden on the infected implant when compared to untreated controls. RIT reduced bacterial burden and inflammation in experimental PJI with no side effects. These findings underscore the potential of RIT in the treatment of infected indwelling devices and warrant further study.
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Indwelling medical implants are susceptible to developing biofilm-associated infections that are notoriously difficult to eradicate. These persistent infections often cannot be resolved with antibiotics alone and typically require surgical intervention for effective management. An alternative approach is radioimmunotherapy (RIT) which uses specific antibodies linked to radioisotopes to selectively destroy bacteria. This antimicrobial approach bypasses traditional antibiotic mechanisms, and RIT is hypothesized to enhance outcomes beyond antibiotic therapy alone. RIT bactericidal effects were studied in Wistar Han rats fitted with femoral rod implants covered by matured 3-day biofilms. The rats (six per group) were treated with either: RIT with 177Lu-labeled 4497 antibody to S. aureus teichoic wall acid (WTA) (116.6 MBq/kg), or vancomycin (88 mg/kg), or combination of RIT (116.8 MBq/kg) and vancomycin, or left untreated. To evaluate efficacy, bacterial counts were taken from the joint capsule, bone, and implant after 7 days. Uptake and biodistribution were assessed via non-invasive in vivo SPECT/CT imaging and ex vivo gamma counting. Single administration of RIT achieved a 2.7-log (99.78%) reduction of bacterial burden in the infected joint capsule, had no effect on the infected femur, and resulted in 72.5% reduction of bacterial burden on the infected implant when compared to untreated controls. RIT reduced bacterial burden and inflammation in experimental PJI with no side effects. These findings underscore the potential of RIT in the treatment of infected indwelling devices and warrant further study.
Journal article
(2026)
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F. Ruben H.A. Nurmohamed, Kevin J.H. Allen, Harrie Weinans, Ekaterina Dadachova, Bart C.H.van der Wal, Connor Frank, Mackenzie E. Malo, J. Fred F.Hooning van Duyvenbode, Berend van der Wildt, Alex J. Poot, Marnix G.E.H. Lam, Jos A.G.van Strijp, H. Charles Vogely
Background: Early postoperative implant infections are difficult to diagnose due to overlapping symptoms with inflammation. However, prompt surgical intervention for an implant infection can prevent the need for repeated surgeries and improve the overall success of the treatment and preserving the implant. The primary objective of this study was to assess the sensitivity and specificity of a novel immuno-PET radiotracer for detecting Staphylococcus aureus bacteria and their biofilms in a preclinical rat model. Results: An antibody against wall teichoic acid a common surface component of S. aureus, was labeled with Zirconium-89- as the PET tracer. Wistar Han rats underwent surgery with a S. aureus-related biofilm-infected femoral implant on one side and a sterile femoral implant on the contralateral side. The diagnostic efficacy of this imaging modality was compared with clinically established nuclear imaging techniques for implant infections, including [99mTc]Tc-MDP SPECT/CT, [18F]FDG PET/CT, and [18F]NaF PET/CT. Furthermore, co-injection of unlabeled (“cold”) antibodies was performed to evaluate their impact on biodistribution. All animals with a biofilm-associated femoral implant infection showed significantly higher uptake of the novel ImmunoPET tracer in the infected side compared to the sterile side throughout the 13-day postoperative study duration. A dose-dependent increase in tracer accumulation was observed with co-injection of cold antibody, suggesting its potential to improve biodistribution. Conclusions: ImmunoPET with Zirconium-89-labeled antibodies specific for wall teichoic acid antigen demonstrates sensitive and specific diagnostic capabilities compared to conventional nuclear imaging modalities, offering a promising tool for early detection of postoperative chronic low-grade infections and septic implant loosening.
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Background: Early postoperative implant infections are difficult to diagnose due to overlapping symptoms with inflammation. However, prompt surgical intervention for an implant infection can prevent the need for repeated surgeries and improve the overall success of the treatment and preserving the implant. The primary objective of this study was to assess the sensitivity and specificity of a novel immuno-PET radiotracer for detecting Staphylococcus aureus bacteria and their biofilms in a preclinical rat model. Results: An antibody against wall teichoic acid a common surface component of S. aureus, was labeled with Zirconium-89- as the PET tracer. Wistar Han rats underwent surgery with a S. aureus-related biofilm-infected femoral implant on one side and a sterile femoral implant on the contralateral side. The diagnostic efficacy of this imaging modality was compared with clinically established nuclear imaging techniques for implant infections, including [99mTc]Tc-MDP SPECT/CT, [18F]FDG PET/CT, and [18F]NaF PET/CT. Furthermore, co-injection of unlabeled (“cold”) antibodies was performed to evaluate their impact on biodistribution. All animals with a biofilm-associated femoral implant infection showed significantly higher uptake of the novel ImmunoPET tracer in the infected side compared to the sterile side throughout the 13-day postoperative study duration. A dose-dependent increase in tracer accumulation was observed with co-injection of cold antibody, suggesting its potential to improve biodistribution. Conclusions: ImmunoPET with Zirconium-89-labeled antibodies specific for wall teichoic acid antigen demonstrates sensitive and specific diagnostic capabilities compared to conventional nuclear imaging modalities, offering a promising tool for early detection of postoperative chronic low-grade infections and septic implant loosening.
Evaluation of silver bio-functionality in a multicellular in vitro model
Towards reduced animal usage in implant-associated infection research
Journal article
(2023)
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Leonardo Cecotto, Daphne A.C. Stapels, Kok P.M. van Kessel, Michiel Croes, Zeldali Lourens, H. Charles Vogely, Bart C.H. van der Wal, Jos A.G. van Strijp, H.H. Weinans, Saber Amin Yavari
Background: Despite the extensive use of silver ions or nanoparticles in research related to preventing implant-associated infections (IAI), their use in clinical practice has been debated. This is because the strong antibacterial properties of silver are counterbalanced by adverse effects on host cells. One of the reasons for this may be the lack of comprehensive in vitro models that are capable of analyzing host-bacteria and host-host interactions.
Methods and results: In this study, we tested silver efficacy through multicellular in vitro models involving macrophages (immune system), mesenchymal stem cells (MSCs, bone cells), and S. aureus (pathogen). Our model showed to be capable of identifying each element of culture as well as tracking the intracellular survival of bacteria. Furthermore, the model enabled to find a therapeutic window for silver ions (AgNO3) and silver nanoparticles (AgNPs) where the viability of host cells was not compromised, and the antibacterial properties of silver were maintained. While AgNO3 between 0.00017 and 0.017 µg/mL retained antibacterial properties, host cell viability was not affected. The multicellular model, however, demonstrated that those concentrations had no effect on the survival of S. aureus, inside or outside host cells. Similarly, treatment with 20 nm AgNPs did not influence the phagocytic and killing capacity of macrophages or prevent S. aureus from invading MSCs. Moreover, exposure to 100 nm AgNPs elicited an inflammatory response by host cells as detected by the increased production of TNF-α and IL-6. This was visible only when macrophages and MSCs were cultured together.
Conclusions: Multicellular in vitro models such as the one used here that simulate complex in vivo scenarios can be used to screen other therapeutic compounds or antibacterial biomaterials without the need to use animals. ...
Methods and results: In this study, we tested silver efficacy through multicellular in vitro models involving macrophages (immune system), mesenchymal stem cells (MSCs, bone cells), and S. aureus (pathogen). Our model showed to be capable of identifying each element of culture as well as tracking the intracellular survival of bacteria. Furthermore, the model enabled to find a therapeutic window for silver ions (AgNO3) and silver nanoparticles (AgNPs) where the viability of host cells was not compromised, and the antibacterial properties of silver were maintained. While AgNO3 between 0.00017 and 0.017 µg/mL retained antibacterial properties, host cell viability was not affected. The multicellular model, however, demonstrated that those concentrations had no effect on the survival of S. aureus, inside or outside host cells. Similarly, treatment with 20 nm AgNPs did not influence the phagocytic and killing capacity of macrophages or prevent S. aureus from invading MSCs. Moreover, exposure to 100 nm AgNPs elicited an inflammatory response by host cells as detected by the increased production of TNF-α and IL-6. This was visible only when macrophages and MSCs were cultured together.
Conclusions: Multicellular in vitro models such as the one used here that simulate complex in vivo scenarios can be used to screen other therapeutic compounds or antibacterial biomaterials without the need to use animals. ...
Background: Despite the extensive use of silver ions or nanoparticles in research related to preventing implant-associated infections (IAI), their use in clinical practice has been debated. This is because the strong antibacterial properties of silver are counterbalanced by adverse effects on host cells. One of the reasons for this may be the lack of comprehensive in vitro models that are capable of analyzing host-bacteria and host-host interactions.
Methods and results: In this study, we tested silver efficacy through multicellular in vitro models involving macrophages (immune system), mesenchymal stem cells (MSCs, bone cells), and S. aureus (pathogen). Our model showed to be capable of identifying each element of culture as well as tracking the intracellular survival of bacteria. Furthermore, the model enabled to find a therapeutic window for silver ions (AgNO3) and silver nanoparticles (AgNPs) where the viability of host cells was not compromised, and the antibacterial properties of silver were maintained. While AgNO3 between 0.00017 and 0.017 µg/mL retained antibacterial properties, host cell viability was not affected. The multicellular model, however, demonstrated that those concentrations had no effect on the survival of S. aureus, inside or outside host cells. Similarly, treatment with 20 nm AgNPs did not influence the phagocytic and killing capacity of macrophages or prevent S. aureus from invading MSCs. Moreover, exposure to 100 nm AgNPs elicited an inflammatory response by host cells as detected by the increased production of TNF-α and IL-6. This was visible only when macrophages and MSCs were cultured together.
Conclusions: Multicellular in vitro models such as the one used here that simulate complex in vivo scenarios can be used to screen other therapeutic compounds or antibacterial biomaterials without the need to use animals.
Methods and results: In this study, we tested silver efficacy through multicellular in vitro models involving macrophages (immune system), mesenchymal stem cells (MSCs, bone cells), and S. aureus (pathogen). Our model showed to be capable of identifying each element of culture as well as tracking the intracellular survival of bacteria. Furthermore, the model enabled to find a therapeutic window for silver ions (AgNO3) and silver nanoparticles (AgNPs) where the viability of host cells was not compromised, and the antibacterial properties of silver were maintained. While AgNO3 between 0.00017 and 0.017 µg/mL retained antibacterial properties, host cell viability was not affected. The multicellular model, however, demonstrated that those concentrations had no effect on the survival of S. aureus, inside or outside host cells. Similarly, treatment with 20 nm AgNPs did not influence the phagocytic and killing capacity of macrophages or prevent S. aureus from invading MSCs. Moreover, exposure to 100 nm AgNPs elicited an inflammatory response by host cells as detected by the increased production of TNF-α and IL-6. This was visible only when macrophages and MSCs were cultured together.
Conclusions: Multicellular in vitro models such as the one used here that simulate complex in vivo scenarios can be used to screen other therapeutic compounds or antibacterial biomaterials without the need to use animals.