Grants Funded

Abstract

Impact Statement: Patients undergo tissue expansion (TE) for many different clinical indications, and there is great potential to improve the experience of TE. Our preliminary studies on global changes in microRNA expression during TE indicate that miR-193a-5p is downregulated in expanded skin. By studying the role of miR-193a-5p in expanded skin samples and cultured skin cells, we hope to better elucidate its role in mechanically induced skin growth and regeneration during TE. Based on the obtained results, we plan to evaluate the potentially therapeutic role of a miR-193a-5p inhibitor in TE using a porcine model. This research could lead to the design of adjunctive treatments to improve TE efficacy and to facilitate expansion in compromised tissue beds.

Project Summary: Tissue expansion (TE) is a common procedure utilized in plastic surgery in order to promote skin growth when reconstructing a defect or deformity. This procedure involves the placement of a tissue expander beneath the skin, followed by serial injections of saline over the course of weeks to months to expand the overlying tissue and induce growth. Although the technique has been used for over 40 years, there has been little investigation into the genetic response of tissues to expansion, or how this knowledge may improve tissue expansion. TE could be improved by optimizing the ability of the skin to grow, allowing for faster, more efficient expansion while reducing complications. This would be especially of use when placing tissue expanders in areas of the body where the skin has minimal laxity or where the integrity of the skin has been compromised. One way to accomplish this would be to utilize an adjunctive pharmacologic therapy to augment the ability of skin cells to grow during the expansion process. However, to develop effective skin pretreatment, it is necessary to understand how biological processes, affected by mechanical forces, promote skin growth and regeneration during TE. Our preliminary results show a persistent decrease in expression of the microRNA ssc-miR-193a-5p between 1 hour and 7 days of expansion, suggesting that ssc-miR-193a-5p modulates the molecular response to tissue expansion and might play a significant role in stimulating skin growth and maintaining tissue homeostasis. In this proposal, we seek to identify the role of miR-193a-5p in skin growth and regeneration stimulated by mechanical forces during TE. Our first aim is to identify spatio-temporal changes in miR-193a-5p expression during TE in vivo on porcine skin and to investigate the effect of miR-193a-5p suppression in vitro on keratinocyte and fibroblast biology. Our second aim is to determine the mechanism of miR-193a-5p downregulation in TE. The results of this study will serve as a foundation for future research into the potential use of a miR-193a-5p inhibitor as an adjunctive therapy to optimize TE. The long-term objective of this study is to establish an evidence-based skin pretreatment to minimize TE complications and improve outcomes.

Biography
Dr. Joanna K. Ledwon, PhD, is a Research Assistant Professor of Pediatric Surgery at Northwestern University and Ann & Robert H. Lurie Children's Hospital. Dr. Ledwon earned a Bachelor’s degree in Biotechnology from the University of Szczecin and a Master's degree in Biotechnology from the University of Warsaw. She then earned a Doctorate of Medical Sciences degree in Medical Biology from the Centre of Postgraduate Medical Education in Poland. Her doctoral research was focused on the identification of genetic risk markers of breast, prostate and colon cancer using genome-wide association studies. Over the past six years in the Gosain Laboratory, Dr. Ledwon has supported the research team with her expertise in biomedical research and molecular biology on multiple projects. She has studied the genetic background and molecular mechanisms of craniosynostosis and used patient-derived MSC cell culture and zebrafish animal models. She has also provided technical skill and biological expertise to study the molecular response of skin during tissue expansion using a porcine model. Dr. Ledwon has also investigated the effect of ADM on mechanically induced skin growth and the dermal changes during tissue expansion in a porcine model. As a young faculty member with a strong academic interest in the molecular mechanisms of tissue growth and regeneration, Dr. Ledwon is passionate about advancing the field of plastic surgery through basic science and translational research.