# The joint environment and periprosthetic joint infection

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2024 · $686,259

## Abstract

ABSTRACT
Peri-prosthetic joint infections (PJI) are devastating complications of joint replacements. Prevention of infection
remains the best strategy as once a PJI has established, it is difficult to cure and recurrence rates exceed 17%.
Immediately following surgery, the joint implants are bathed in a post-operative serosanguinous fluid (SSF)
which over time changes to a viscous, protein- and proteoglycan-rich joint fluid. Our data show differences in
antibiotic sensitivity, bacterial adhesion, and myeloid cell function between synovial fluid (SynF), serum, and
serum dilutions that approximate wound fluid/SSF. Importantly, our data suggest that the fluid composition
across this evolution differentially modulates bacterial adherence, antibiotic sensitivity, and by implication,
immune response. Excitingly, our data further suggest that application of ultrasound-triggered microbubble
disruption (UTMD) can impact bacterial metabolism to enhance the antibiotic sensitivity that was lost with the
evolution of the joint fluid. Thus, we hypothesize that a “golden window” exists in which the post-operative SSF
permits eradication of contaminating bacteria through the combined actions of antibiotics and the immune
response while the transition to SynF limits the efficacy of both. We further propose that this golden window
can be enhanced and extended through the use of UTMD to activate bacterial metabolism. We will (1) determine
the effects of SSF and SynF fluid on antibiotic activity and myeloid cell function, (2) determine UTMD effects on
bacterial eradication and myeloid function in SSF and SynF joint fluid and (3) prevent PJI in vivo through
combined microbubble/antibiotic treatments. This information will be used to create combination therapies that
will prevent PJI in vivo. Importantly, our novel strategy will seamlessly integrate with current clinical infection
mitigation strategies and can be immediate translated into a new therapeutic approach for prevention of PJI.

## Key facts

- **NIH application ID:** 10899591
- **Project number:** 5R01AR082038-02
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Noreen J Hickok
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $686,259
- **Award type:** 5
- **Project period:** 2023-08-04 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899591

## Citation

> US National Institutes of Health, RePORTER application 10899591, The joint environment and periprosthetic joint infection (5R01AR082038-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10899591. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*