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A RHAMM Peptide Mimetic Reduces Capsule Fibrosis in a Novel Rodent Model of Radiation-Induced Capsular Contracture
Kathryn L H Minkhorst1,2,3, Natalia J Lewandowski2, Cornelia Tolg3
1Division of Plastic and Reconstructive Surgery, Western University, London, ON.
Plastic and Reconstructive Surgery
|March 10, 2026
Summary
A novel rat model for radiation-induced capsular contracture was developed. A RHAMM peptide mimetic, NP-110, effectively reduced fibrosis in this model, offering potential therapeutic strategies for breast reconstruction patients.
Area of Science:
- Biomedical Engineering
- Oncology
- Plastic Surgery
Background:
- Capsular contracture is a frequent complication following breast reconstruction surgery.
- Radiation therapy significantly increases the challenge of capsular contracture.
- Developing effective treatments for radiation-induced capsular contracture is crucial.
Purpose of the Study:
- To establish a new rat model for studying radiation-induced capsular contracture.
- To assess the efficacy of a RHAMM (Receptor for Hyaluronic Acid Mediated Motility) function-blocking peptide mimetic, NP-110, in mitigating fibrosis within this model.
Main Methods:
- A silicone implant was placed in Sprague Dawley rats, followed by targeted ionizing radiation (26 Gy) to induce capsular contracture.
- A cohort of rats received NP-110 or a control peptide, alongside radiation, to evaluate therapeutic effects.
- Histological and biochemical analyses were performed to quantify fibrotic changes.
Main Results:
- The developed rat model successfully demonstrated clinically, histologically, and biochemically measurable capsule fibrosis post-radiation.
- NP-110 treatment led to a significant reduction in collagen deposition and bundling (p <0.001).
- NP-110 treated animals exhibited significantly less alpha-smooth muscle actin (aSMA) expression (p=0.02) compared to controls.
Conclusions:
- A novel, orthotopic, and reproducible animal model for radiation-induced capsular contracture has been successfully established.
- RHAMM inhibition using NP-110 shows promise as a therapeutic strategy to prevent post-radiotherapy capsular contracture.
- This research identifies RHAMM as a potential therapeutic target for managing capsular contracture complications.
