Bi-Phasic, Regenerative Tracheal Implants from 3D-Printed Advanced Biomaterials with Integrated Vascularizing and Epithelializing Factors
Abstract
Topic Area: FY20 PRMRP Area of Encouragement under Respiratory Health: Development of novel emergency airway management devices/adjuncts such as cricothyrotomy kits, airway insertion equipment, and especially combination airway devices. Overview of Proposed Research: This research will lay the foundation for the development of an off-the-shelf, tissue-regenerative tracheal implant for long-term airway management. We propose the design and development of a tracheal implant technology that is highly tissue regenerative and can be rapidly manufactured into shelf-stable, ready-to-use form factors and also patient-matched structures for long-term treatment. This will be achieved through integration of two new advanced biomaterials in combination with a proprietary 3D-printing manufacturing platform that enables production of multi-material structures with embedded growth factors. These materials and manufacturing platform will be utilized to create bi-phasic tracheal implant products specifically designed to emulate the composition and microstructure of natural tracheal tissue. The proposed work will establish the methodology for creating tracheal implant structures in off-the-shelf form factors (i.e., tubes), demonstrate the ability to fabricate anatomically matched human-scale implants, and characterize the materials and structures through a series of cell and small animal experiments. Critical Problem: Tracheal injuries can be immediately life-threatening, compromising the ability to breathe and requiring emergency treatment and stabilization to prevent fatality. These injuries may result from trauma, including battlefield injuries, congenital defects, and head and neck cancers. Military Service Members are of particular risk; in Iraq and Afghanistan from 2011 to 2016, neck injuries comprised 18.8% of total above-the-torso injuries. Even with surgical intervention for long-term management, mortality rates reach 80%, as current treatment options are severely limited. Challenges include limited donor tissue supply, implant obstruction, and immune system rejection, among others. Attempts to manufacture synthetic trachea implants have shown some promise, but nothing has yet demonstrated rapid and adequate vascularization or epithelialization, two critical criteria for tracheal implants. An effective approach for treating tracheal injuries in both civilian and military populations is much needed. Innovation: Previous attempts to treat tracheal injuries have relied on inconsistent, difficult-to-source allografts from cadavers, xenografts from animals, or ineffective synthetic polymers and hydrogels formed into solid tubes, which have not been able to achieve adequate vascularization and epithelialization, even with cells added prior to implantation. Our approach overcomes the limitations of previous work and integrates a new advanced 3D-printing manufacturing process with two innovative biomaterials to create tracheal structures that resemble both the varying composition and micro- and nano-structures of the natural tissue. We propose that this system uniquely enables the rapid production of complex multi-material structural combinations that can be embedded with growth factors to produce tissue-regenerating tracheal implants. Applicability and Impact: The innovative approach proposed here has commercialization potential for both military and civilian use, addressing a sizable market with a significant unmet medical need. Successful completion of this work will establish the technology s promise and permit us to seek funding and support for large animal studies and eventually human clinical trials and U.S. Food and Drug Administration regulatory approval. Importantly, it will also serve to advance an innovative advanced manufacturing approach for creating multi-regional soft tissue regenerative structures through the combination of advanced biomaterial 3D-inks, growth factors, and tissue-specific gels, thereby establis
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110291
Entities
People
- Adam E. Jakus
Organizations
- United States Army