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Myeloid-derived Mechanotransducive Signaling Modulates the Pathologic Foreign Body Response (FBR)
Andrew C. Hostler BS, William W. Hahn MBChBAO, Jonathan P. Yasmeh MS, Jenne Stensland MS, BME, PA(CE), Katharina S. Fischer MD, Maria Gracia Mora-Pinos MD, Jared S. Holley MD, Abdelrahman M. Alsharif, Fidel Saenz BS, Autumn Lester BS, Hudson Kussie BS, Eammon McKenna BS, Maia Granoski BS, Tiffany I. Cagle, Masiam Jafri BS, Aaron C. Mason MD, Kellen Chen PhD, Geoffrey C. Gurtner MD
University of Arizona College of Medicine - Tucson
2024-02-01
Presenter: Andrew C. Hostler
Affidavit:
I certify that the abstract submitted by Andrew represents all original work performed primarily by Andrew. The concept and design of the study were envisioned primarily by myself and Dr. Kellen Chen
Director Name: Geoffrey Gurtner
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: Breast (Aesthetic and Recon.)
Background:
The foreign body response (FBR) to biomedical implants causes premature device failure and affects ~30% of >70 million annually implanted medical devices. Biophysiochemical incompatibilities between the host tissues and device biomaterial induce inflammatory-fibrotic tissue repair pathways, although the process is incompletely understood. Here, we characterized this inflammatory-fibrotic crosstalk in human samples.
Methods:
Breast implant associated-capsule tissue was collected from patients. Capsular contracture was scored using the Baker scale and categorized into mild (B1/B2: n=8) and severe FBR (B3/B4: n=6). Histological analysis using H&E, Masson's trichrome, and picrosirius red was performed. CT-FIRE and CurveAlign was performed to characterize collagen architecture. Immunostaining was performed using CD68, a-SMA, and FAK.
Results:
Severe FBR demonstrated significantly increased capsule thickness compared to mild (p=0.0003). Collagen deposition (p=0.0049), fiber length (p=0.0099), and density (p=0.0062) were also significantly increased in severe FBR. Mean fiber distance (p=0.0401) was significantly decreased. Severe FBR caused an increase in CD68 (macrophage) and aSMA (myofibroblast) layering within the FBR capsule, shown by significantly increased co-localized expression of CD68 and aSMA (p<0.01) and co-localized CD68 and FAK (p=0.0465). More severe FBR also increased aSMA and immune cell numbers (p<0.009).
Conclusions:
Increased immune-mediate crosstalk between macrophages and myofibroblasts correlated with more severe capsule formation and fibrosis. Interestingly, severe FBR resulted in more colocalized macrophage-myofibroblast cellular layering, in addition to elevated mechanoresponsive myeloid cell presence. Since myeloid cells home to sites of tissue injury, targeting these mechanotransductive myeloid cells could lead to novel, preventative FBR therapeutics.
