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Novel in vivo mouse model of shoulder implant infection.
Sheppard, William L; Mosich, Gina M; Smith, Ryan A; Hamad, Christopher D; Park, Howard Y; Zoller, Stephen D; Trikha, Rishi; McCoy, Tatiana K; Borthwell, Rachel; Hoang, John; Truong, Nicole; Cevallos, Nicolas; Clarkson, Samuel; Hori, Kellyn R; van Dijl, Jan Maarten; Francis, Kevin P; Petrigliano, Frank A; Bernthal, Nicholas M.
Affiliation
  • Sheppard WL; 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.
  • Mosich GM; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
  • Smith RA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hamad CD; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
  • Park HY; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
  • Zoller SD; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA.
  • Trikha R; 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.
  • McCoy TK; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Borthwell R; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hoang J; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Truong N; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Cevallos N; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Clarkson S; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hori KR; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • van Dijl JM; Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Francis KP; Department of Orthopedic Surgery, University of California, Los Angeles, Santa Monica, CA, USA; PerkinElmer, Hopkinton, MA, USA.
  • Petrigliano FA; 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.
  • Bernthal NM; 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.
J Shoulder Elbow Surg ; 29(7): 1412-1424, 2020 Jul.
Article in En | MEDLINE | ID: mdl-32014357
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Postoperative Complications / Shoulder Joint / Staphylococcal Infections / Prosthesis-Related Infections / Shoulder Prosthesis Type of study: Qualitative_research Limits: Animals Language: En Journal: J Shoulder Elbow Surg Journal subject: ORTOPEDIA Year: 2020 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Postoperative Complications / Shoulder Joint / Staphylococcal Infections / Prosthesis-Related Infections / Shoulder Prosthesis Type of study: Qualitative_research Limits: Animals Language: En Journal: J Shoulder Elbow Surg Journal subject: ORTOPEDIA Year: 2020 Document type: Article Affiliation country: United States