A Novel Microneedle-Based, Sandwiched Structure for Effective Intraperitoneal Adhesion (IA) Prevention: Material Fabrication and Molecular Level Mechanism Exploration - Project Summary/ Abstract The objective of the proposed project work has two folds. First, it addresses significant challenges of intraperitoneal adhesions (IAs) following abdominal surgeries, with a focus on prevention of both early and late-stage IA formation and its extension as well as barrier displacement. Current anti-IA barriers face limitations in active interaction with tissues, leading to barrier displacement and infection. This study proposes a novel biodegradable sandwiched structure consisting of a core-shell electrospun nanofiber center and microneedle outer layers. The outer layers are made of chitosan and incorporated with Diltiazem, a calcium channel blocker, to enhance blood clotting and prevent mesothelial cell membrane bridge formation, respectively. Chitosan also has anti-infection effect. The core-shell center features a tannic acid (TA) core, a reactive oxygen species (ROS) scavenging agent, and a polylactic acid/polyethylene glycol shell to gradually release TA to counteract ROS in IA and its extension formation. Second, this application will develop an in- depth understanding of the mechanisms underlying early- and late-stage IA formation and its extension by hypothesizing that ROS play a pivotal role in both IA and its extension formation. The project aims to achieve two key objectives: Aim 1 involves designing and creating the sandwich-structured mechanical barrier and investigating its effectiveness in preventing IA formation and extension through in vitro and in vivo tests. Aim 2 focuses on gaining an in-depth understanding of the mechanisms involved in both early and late-stage IA formation and its extension. The study hypothesizes that ROS plays a key role in IA and extension formation, and TA is effective in scavenging ROS. The research integrates multidisciplinary expertise, combining material design, fabrication techniques, and detailed mechanism studies, providing a holistic and transformative approach to anti-IA treatment. The significance of the research lies in addressing a critical clinical challenge, with IA contributing to female infertility, chronic postoperative pain, and intestinal obstructions. In line with the goals of the NIH AREA research grant program, students performing the research funded by this proposal at Rowan University will not only gain knowledge in materials design, fabrication techniques, rigorous physiochemical and biological characterization methods, but also be trained in teamwork, creative thinking, project management, peer mentoring, report writing and presentation skills. These knowledge and skills will be crucial for them to continue to pursue higher degrees and/or enter leadership roles in the future. The completion of this research project at Rowan will result in a paradigm shifting improvement of the efficacy of anti-IA treatments. Additionally, this initiative will offer students unparalleled opportunities to participate in cutting-edge scientific practices, nurturing the growth of highly-trained contributors to the scientific community.
