Novel in vivo mouse model of shoulder implant infection

William L Sheppard; Gina M Mosich; Ryan A Smith; Christopher D Hamad; Howard Y Park; Stephen D Zoller; Rishi Trikha; Tatiana K McCoy; Rachel Borthwell; John Hoang; Nicole Truong; Nicolas Cevallos; Samuel Clarkson; Kellyn R Hori; Jan Maarten van Dijl; Kevin P Francis; Frank A Petrigliano; Nicholas M Bernthal

doi:10.1016/j.jse.2019.10.032

Novel in vivo mouse model of shoulder implant infection

J Shoulder Elbow Surg. 2020 Jul;29(7):1412-1424. doi: 10.1016/j.jse.2019.10.032. Epub 2020 Jan 31.

Authors

William L Sheppard¹, Gina M Mosich², Ryan A Smith³, Christopher D Hamad², Howard Y Park², Stephen D Zoller², Rishi Trikha¹, Tatiana K McCoy³, Rachel Borthwell³, John Hoang³, Nicole Truong³, Nicolas Cevallos³, Samuel Clarkson³, Kellyn R Hori³, Jan Maarten van Dijl⁴, Kevin P Francis⁵, Frank A Petrigliano¹, Nicholas M Bernthal⁶

Affiliations

¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
² Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
³ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
⁵ Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA; PerkinElmer, Hopkinton, MA, USA.
⁶ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA. Electronic address: nbernthal@mednet.ucla.edu.

Abstract

Background: Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement.

Methods: A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 μL of 1 × 10³ (e3), or 1 × 10⁴ (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 μL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed.

Results: Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence.

Discussion: Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII.

Conclusion: The development of this model provides a foundation to study new therapeutics, interventions, and host modifications.

Keywords: Shoulder; arthroplasty; implant; infection; osteolysis; osteomyelitis.

MeSH terms

Animals
Biofilms
Debridement
Disease Models, Animal
Female
Mice
Mice, Inbred C57BL
Postoperative Complications / microbiology*
Prosthesis-Related Infections / etiology*
Shoulder Joint*
Shoulder Prosthesis / adverse effects*
Staphylococcal Infections / microbiology*
Staphylococcus aureus

Abstract

MeSH terms

Grants and funding