Severe capsular contracture of breast implants may result from localized pathological changes: An intra-capsular comparative analysis.

[BACKGROUND] Capsular contracture is the most common complication following breast implant surgery. Its incidence has been associated with implant- and surgery-related factors. We observed significant regional differences in capsular thickness within the same specimen, suggesting that localized pathology, rather than uniform tightening, may drive contracture. We verified these findings by analyzing controlled samples and proposed a novel pathophysiologic mechanism.

[METHODS] We collected samples from contracted and uncontracted capsules across four quadrants of the top and bottom surfaces. In each contracted specimen, we compared the thickest and thinnest areas, using uncontracted capsules as controls. Histological analysis (H&E and Masson's trichrome) assessed thickness and collagen deposition. Immunohistochemistry evaluated α-SMA, TGF-β1, and CD68 expression. RNA sequencing identified differentially expressed genes and related pathways.

[RESULTS] Histology revealed significant variability in capsule thickness, with increased fibrosis in lower quadrant regions. Immunohistochemistry showed elevated α-SMA, TGF-β1, and CD68 in areas of severe contracture, indicating enhanced myofibroblast activity, pro-fibrotic signaling, and macrophage infiltration. RNA-seq revealed that differences between contracted and uncontracted capsules were linked to immune responses, whereas differences between thick and thin regions involved metabolic pathways. ITGB6 was identified as a key gene in localized contracture.

[CONCLUSIONS] Capsular contracture is primarily driven by local factors within the capsular cavity, not systemic immune responses or implant surface alone. Individual immune baselines and local stimuli jointly influence contracture formation. ITGB6 may serve as a molecular marker for diagnosis and treatment, while minimizing intraoperative trauma may help prevent contracture.

[CLINICAL RELEVANCE STATEMENT] Understanding that capsular contracture stems from localized capsular factors, rather than systemic responses or implant surface alone, highlights the importance of minimizing intraoperative trauma and local inflammation, and suggests ITGB6 as a potential diagnostic and therapeutic target.