Grants Funded

Abstract

Project Summary: Capsular contracture remains a significant adverse outcome of implant-based breast reconstruction. Acellular dermal matrix (ADM) has been introduced as an adjunct in implant-based reconstruction and has been linked to reduced risk of capsular contracture. However, despite its near ubiquitous use in prepectoral implant reconstruction, there is currently no clear understanding of the specific mechanism by which ADM impacts peri-prosthetic capsular development over time, especially in the setting of pro-fibrotic insults that can lead to capsular contracture. As such, this study investigates the longitudinal impact of ADM on the peri-prosthetic capsular microenvironment after implant-based breast reconstruction, with a specific focus on known clinical risk factors for capsular contracture. Our preliminary work has demonstrated that ADM favorably modulates the breast implant environment in the immediate postoperative period, by downregulating the inflammatory response. In this study, we will build on this work by determining whether 1) ADM continues to support a favorable microenvironment in the acute setting of pro-fibrotic insults (e.g., radiation therapy, hematoma, seroma, infection), and whether 2) ADM continues to longitudinally modulate the peri-prosthetic microenvironment, which is important given that contracture occurs as the capsule matures over time. In this study, we will compare ADM versus native capsular samples from women undergoing expander/implant reconstruction. These samples will be characterized at the cellular/molecular level and compared between women who experience pro-fibrotic stimuli in the acute setting versus those who do not. Similarly, capsular samples from women undergoing downstream procedures for capsular contracture (capsulotomy, capsulectomy) will be compared to our prior data from the more immediate postoperative period. Taken together, these samples will allow us to determine how ADM impacts the peri-prosthetic environment 1) in the acute context of inflammatory insults and 2) longitudinally in the setting of capsular contracture. Ultimately, despite the use of ADM, capsular contracture remains an important clinical issue in implant-based breast reconstruction. Understanding how ADM modulates capsular development 1) in the context of inflammatory insults as well as 2) over time will provide greater insight into the peri-prosthetic environment. This will inform more targeted efforts addressing capsular contracture.

Impact Statement: Despite the continual evolution of implant-based breast reconstruction, there remain persistent limitations with this reconstructive modality, the most salient of which includes capsular contracture. Capsular contracture can be highly morbid, resulting in visible/painful deformity that can affect up to 70% of women with reconstructive implants. While ADM is linked to lower capsular contracture rates, the mechanism is largely unknown. This study will provide critical insight into this challenging complication of breast implants, helping to better delineate the indications for ADM. Furthermore, understanding the peri-prosthetic milieu in the context of pro-fibrotic stimuli may suggest targets for the design of next-generation ADM engineered to further augment implant-related wound healing.

Biography
Dr. Momeni, Associate Professor of Surgery at Stanford, is an experienced clinical outcomes and translational researcher in Plastic Surgery and the current Godina Fellow of the American Society for Reconstructive Microsurgery. He is a leader in breast reconstruction and has led multiple studies focused on improving outcomes of implant-based breast reconstruction, especially in high-risk populations (e.g., irradiated patients). A particular focus of Dr. Momeni's research is to understand the mechanism of capsular contracture in implant-based breast reconstruction. Dr. Momeni is recognized nationally and internationally for his research in breast reconstruction. He has authored over 200 peer-reviewed publications and numerous textbook chapters and is on the editorial board of leading surgical journals. Dr. Yesantharao, Co-Investigator, is a Stanford Plastic Surgery resident entering research year in July 2024. She completed a BS in Biochemistry/Bioengineering at Rice, an MS in Biostatistics at Stanford, and an MD from Johns Hopkins, during which time she was awarded a Dean’s Research Fellowship to study capsular fibrosis. She is passionate about translational research, with work recognized by the Clinton Global Initiative. She has published over 70 peer-reviewed manuscripts/book chapters, is a member of the PRS Resident Advisory Board, and is an editorial board member of the Annals of Breast Surgery. Pooja aims for a career in academic microsurgery/breast reconstruction.