Francesco Segreto1, Simone Carotti2, Giovanni Francesco Marangi3, Daniele Tosi1, Maria Zingariello2, Alfonso Luca Pendolino1, Laura Sancillo4, Sergio Morini2, Paolo Persichetti1. 1. Department of Plastic, Reconstructive and Aesthetic Surgery, "Campus Bio-Medico di Roma" University, Via Alvaro del Portillo, 200, 00128 Rome, Italy. 2. Center for Integrated Biomedical Research (CIR), Laboratory of Microscopic and Ultrastructural Anatomy, "Campus Bio-Medico di Roma" University, Via Alvaro del Portillo, 200, 00128 Rome, Italy. 3. Department of Plastic, Reconstructive and Aesthetic Surgery, "Campus Bio-Medico di Roma" University, Via Alvaro del Portillo, 200, 00128 Rome, Italy. Electronic address: g.marangi@unicampus.it. 4. Medicine and Aging Sciences, University G. D'Annunzio of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Abstract
BACKGROUND: Capsular contracture is the most common complication following breast implant placement. The multiple factors unbalancing the physiological response to the foreign body have not been fully elucidated. The aim of this study was to investigate the role of neo-angiogenesis, inflammation and estrogen receptors in peri-prosthetic tissue development and remodeling. METHODS: The study enrolled 31 women who underwent expander substitution with definitive implant. Specimens were stained with hematoxylin/eosin, Masson trichrome, immunohistochemistry and immunofluorescence for alpha-smooth muscle actin, estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), Collagen type I and III, CD31 (as a marker of neo-angiogenesis) and vascular endothelial growth factor (VEGF). Inflammatory infiltration was quantified and analyzed. Transmission electron microscopy was performed for ultrastructural evaluation. RESULTS: Myofibroblasts, mainly localized in the middle layer of capsular tissue, expressed VEGF, ER-α and ER-β. ER-β expression positively correlated with Collagen type I deposition (p= 0.025). Neo-angiogenesis was predominant in the middle layer. CD31 expression positively correlated with Collagen type I expression (p=0.009) and inflammatory infiltration grade (p= 0.004). The degree of inflammatory infiltration negatively correlated with the time from implantation (p = 0.022). DISCUSSION: The middle layer is key in the development and remodeling of capsular tissue. Myofibroblasts produce VEGF, that induces neo-angiogenesis. New vessels formation is also correlated to the inflammatory response. Collagen deposition is associated with ER-β expression and neo-angiogenesis. These findings may prelude to targeted pharmacologic therapies able to control such interactions, thus hampering the self-sustaining loop promoting the progression of physiologic fibrosis toward pathologic contracture.
BACKGROUND: Capsular contracture is the most common complication following breast implant placement. The multiple factors unbalancing the physiological response to the foreign body have not been fully elucidated. The aim of this study was to investigate the role of neo-angiogenesis, inflammation and estrogen receptors in peri-prosthetic tissue development and remodeling. METHODS: The study enrolled 31 women who underwent expander substitution with definitive implant. Specimens were stained with hematoxylin/eosin, Masson trichrome, immunohistochemistry and immunofluorescence for alpha-smooth muscle actin, estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), Collagen type I and III, CD31 (as a marker of neo-angiogenesis) and vascular endothelial growth factor (VEGF). Inflammatory infiltration was quantified and analyzed. Transmission electron microscopy was performed for ultrastructural evaluation. RESULTS: Myofibroblasts, mainly localized in the middle layer of capsular tissue, expressed VEGF, ER-α and ER-β. ER-β expression positively correlated with Collagen type I deposition (p= 0.025). Neo-angiogenesis was predominant in the middle layer. CD31 expression positively correlated with Collagen type I expression (p=0.009) and inflammatory infiltration grade (p= 0.004). The degree of inflammatory infiltration negatively correlated with the time from implantation (p = 0.022). DISCUSSION: The middle layer is key in the development and remodeling of capsular tissue. Myofibroblasts produce VEGF, that induces neo-angiogenesis. New vessels formation is also correlated to the inflammatory response. Collagen deposition is associated with ER-β expression and neo-angiogenesis. These findings may prelude to targeted pharmacologic therapies able to control such interactions, thus hampering the self-sustaining loop promoting the progression of physiologic fibrosis toward pathologic contracture.
Authors: Francesco Segreto; Simone Carotti; Giovanni Francesco Marangi; Maria Francesconi; Luca Scaramuzzino; Marco Gratteri; Erika Caldaria; Sergio Morini; Paolo Persichetti Journal: Int Wound J Date: 2020-07-25 Impact factor: 3.315
Authors: Jorge A Belgodere; Connor T King; Jacob B Bursavich; Matthew E Burow; Elizabeth C Martin; Jangwook P Jung Journal: Front Bioeng Biotechnol Date: 2018-05-24