Nanofiber patch with gradient presentation of biomolecules for treatment of pediatric tracheal stenosis

This Project Grant award from the National Institute of Child Health and Human Development (NICHD), under the Child Health and Human Development Extramural Research program (CFDA 93.865), is funding the development of a nanofiber patch for the treatment of pediatric tracheal stenosis, a life-threatening condition involving airway narrowing. The $154,000 award to Colorado State University aims to create a synthetic trachea patch that can maintain airway patency and regenerate cartilage-like tissue, addressing limitations of current surgical options. The research will refine the patch's growth factor composition and evaluate it in animal models, with the goal of bringing this innovative tracheal stenosis treatment to market. This grant aligns with the NICHD program's focus on supporting research to explore fundamental biological mechanisms, clinical interventions, and translational solutions across maternal, child, and adolescent health domains.

Abstract

The long-term objective of this application is to bring a trachea patch to the market for treatment of pediatric tracheal stenosis, or narrowing of the airway, which left untreated can be a life-threatening condition. Currently, otolaryngologists have only two major options for treating tracheal stenosis. One is a complex surgical procedure known as slide tracheoplasty that few surgeons in the country are qualified to perform. The other is to cut and splay the trachea holding IT open using a graft of rib cartilage. Both are difficult, time-consuming procedures with potential complications. We have an issued U.S. Patent on the trachea patch biomaterial that overcomes the five major technical hurdles required to replace rib cartilage grafting: 1) mechanical integrity, 2) suturable, 3) resorbable, 4) air-tight, and 5) off-the-shelf. There is currently nothing on the market remotely resembling the idea of a synthetic patch for tracheal stenosis. While the academic tissue engineering community has focused primarily on regenerating an entire trachea with highly complex strategies, arguably leading to technology in search of an application, we have focused instead on identifying a specific patient indication with an unmet need and designed a technology to fill that void. The overall hypothesis is that mimicking the wound healing environment using reinforced electrospun scaffolds with gradient presentation of biological factors will maintain tracheal patency and regenerate cartilage- like tissue comparable to healthy tracheas. Two specific aims are proposed to determine the most attractive growth factor loading for mimicking specific stages of wound healing. Aim 1 will refine growth factor loading by evaluating multiple compositions in a subcutaneous model. The final device composition will then be evaluated in a capstone in vivo rabbit tracheal defect study in aim 2. Compared to rib cartilage grafting, our trachea patch holds the following advantages: 1) no surgery to remove rib tissue, saving operating room time and cost, and eliminating potential complication/infection and morbidity at the rib site (attractive to patients and insurance companies), 2) easy to use, as IT is "plug and play" for surgeons who perform rib cartilage grafting (attractive to surgeons), 3) the gradient design has the potential to improve functionality and accelerate regeneration, promoting vascularization, macrophage recruitment, and directed matrix synthesis. For several reasons, we focus initial clinical translation on the pediatric population with laryngotracheal stenosis. In the simplest terms, our goal is to fix tracheas for young children around the world with narrowed airways to help them survive and breathe normally again.