# Engineering recombinant lubricin to combat orthopedic infection

> **NIH NIH R03** · CORNELL UNIVERSITY · 2022 · $78,500

## Abstract

PROJECT SUMMARY / ABSTRACT
This application seeks funding to support a NIAMS K08 recipient during her transition to research independence.
The broad objective is to investigate how lubricin attenuates orthopedic biofilms and to determine whether distinct
lubricin O-glycans mediate these anti-biofilm properties. The ability of many orthopedic implant-associated
bacteria to form biofilms renders these organisms resistant to antimicrobial therapy. Once established, implant-
associated biofilms typically require debridement, implant exchange or implant removal and can lead to severe
functional deterioration necessitating arthrodesis or even amputation. Therefore, prevention and treatment of
orthopedic-associated biofilms has been identified as a critical research priority in musculoskeletal infection.
Recent work has identified mucin biopolymers as potent antagonists of biofilm assembly and virulence gene
expression, raising the possibility that recombinant lubricin therapeutics could be an effective strategy for
clinically relevant biofilms. Our preliminary data demonstrate that the recombinant lubricin developed as part of
the applicant’s K08 research not only inhibits biofilm formation but also dissipates established P. aeruginosa
biofilms in vitro. In the current proposal, we will investigate the hypothesis that the dual properties of surface
adhesion (N- and C-terminal domains) and anti-adhesion (mucin O-glycan domains) make lubricin an ideal anti-
biofilm agent. In Aim 1, we will investigate the mechanisms by which lubricin inhibits biofilm formation and
induces dispersion of established biofilms in growth media, in synovial fluid, and on titanium alloy (Ti6Al4V). In
Aim 2, we will determine whether distinct O-glycans mediate these anti-biofilm functions and whether lubricin
functionality could be optimized through glycoengineering. As part of Aim 2, we will manipulate the expression
of key glycosyltransferase enzymes to produce recombinant lubricin with altered compositions of Core-1, Core-
2 and sialylated O-glycan structures.
This proposal builds upon the applicant’s K08 research, in which lubricin has been primarily investigated as a
tribological agent for the treatment of post-traumatic osteoarthritis. By investigating a new, anti-biofilm application
for lubricin therapy, this award will enable Dr. Reesink to branch into a new sub-discipline of orthopedic research
with the potential to integrate with the applicant’s clinical veterinary expertise in small and large animal models
of orthopedic infection. Dr. Reesink’s proposal is supported by an exceptional team, including experts in
glycoengineering, molecular characterization of bacteria-surface interactions, and in vivo models of
periprosthetic joint infection and clinical translation.

## Key facts

- **NIH application ID:** 10355887
- **Project number:** 1R03AR078961-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Heidi Reesink
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,500
- **Award type:** 1
- **Project period:** 2022-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355887

## Citation

> US National Institutes of Health, RePORTER application 10355887, Engineering recombinant lubricin to combat orthopedic infection (1R03AR078961-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10355887. Licensed CC0.

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