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Updated: Apr 1, 2026
A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Modulating Micrococcal Nuclease-Triggered Antibiotic Releases for One-Stage Revisions of Staphylococcus
Jordan D Skelly1, Feiyang Chen1, Jie Song1,2
1Department of Orthopedics and Physical Rehabilitation, UMass Chan Medical School, Worcester, Massachusetts 01655, United States.
Abstract:
Periprosthetic joint infections caused by Staphylococcus aureus (S. aureus) pose significant health risks and economic burdens. Following revisions of infected arthroplasty prostheses, the reinfection rate can be as high as 30%. We previously developed hydrogel coatings for intramedullary metallic pins where vancomycin or ampicillin was covalently attached through an oligonucleotide linker cleavable by micrococcal nuclease secreted by S. aureus. When these pins were implanted in S. aureus-inoculated rat femoral canals, the on-demand release of antibiotics from the coating prevented infections from developing. Here, we test the hypothesis that a combination coating with rapid and more sustained S. aureus-triggered antibiotic releases could mitigate infections following one-stage revisions of previously infected prostheses. We implemented varying degrees of phosphorothioate modification of the oligonucleotide linker tethering ampicillin to the coating to achieve rapid and more sustained on-demand antibiotic releases. We first demonstrated that rat femoral infections, established by the inoculation of 200 CFU S. aureus at the time of uncoated primary intramedullary pin insertion, could not be resolved after one-stage revision without a proper pin coating, consistent with clinically observed challenges. However, bacterial burdens were significantly reduced following a one-stage revision with intramedullary pins coated with ampicillin-releasing coatings, with the combination of rapid and more sustained releases proving the most effective. When the combination coating was augmented with a single systemic vancomycin injection at the time of revision, infection was eradicated, outperforming local or systemic treatment alone and achieving unprecedented revision outcomes.
Insights
New antibiotic coatings for orthopedic implants, triggered by Staphylococcus aureus, significantly reduced infection rates in rats. A combination coating with systemic vancomycin achieved complete infection eradication after revision surgery.
Area of Science:
- Biomaterials Science
- Infectious Disease Research
- Orthopedic Surgery
Background:
- Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus present significant clinical challenges and high reinfection rates (up to 30%) after revision arthroplasty.
- Current treatments for PJIs, especially after revision surgery, often face limitations in efficacy.
- Staphylococcus aureus secretes micrococcal nuclease, an enzyme that can be exploited for targeted drug delivery.
Purpose of the Study:
- To evaluate a novel combination hydrogel coating for intramedullary pins designed for on-demand, Staphylococcus aureus-triggered antibiotic release.
- To test the hypothesis that varied release kinetics of antibiotics from the coating can improve infection mitigation during one-stage revision of infected prostheses.
- To determine the efficacy of combining localized, triggered antibiotic release with systemic antibiotic administration.
Main Methods:
- Development of hydrogel coatings with covalently attached ampicillin via oligonucleotide linkers with varying phosphorothioate modifications to control release rates.
- Establishment of Staphylococcus aureus-induced femoral canal infections in rats.
- One-stage revision surgery utilizing coated intramedullary pins, with assessment of bacterial burden reduction.
- Comparison of different coating release profiles and combination therapy with systemic vancomycin.
Main Results:
- Uncoated pins failed to resolve established Staphylococcus aureus infections after one-stage revision.
- Ampicillin-releasing coatings significantly reduced bacterial burdens, with combination rapid and sustained release coatings being most effective.
- The combination coating, augmented with a single systemic vancomycin injection, eradicated infection, outperforming local or systemic treatments alone.
Conclusions:
- On-demand, triggered antibiotic release from hydrogel-coated intramedullary pins is a promising strategy for managing periprosthetic joint infections.
- A combination coating strategy with tailored release kinetics, alongside systemic antibiotics, offers superior efficacy for eradicating established infections during revision surgery.
- This approach demonstrates potential for improving outcomes in complex orthopedic infections.
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