Computed Tomography-Guided Tissue Engineering of Upper Airway Cartilage

Abstract

Normal laryngeal function has a large impact on quality of life, and dysfunction can be life threatening. In general, airway obstructions arise from a reduction in neuromuscular function or a decrease in mechanical stiffness of the structures of the upper airway. These reductions decrease the ability of the airway to resist inspiratory or expiratory pressures, causing laryngeal collapse. We propose to restore airway patency through methods that replace damaged tissue and improve the stiffness of airway structures. A number of recent studies have utilized image-guided approaches to create cell-seeded constructs that reproduce the shape and size of the tissue of interest with high geometric fidelity. The objective of the present study was to establish a tissue engineering approach to the creation of viable constructs that approximate the shape and size of equine airway structures, in particular the epiglottis. Computed tomography images were used to create three-dimensional computer models of the cartilaginous structures of the larynx. Anatomically shaped injection molds were created from the three-dimensional models and were seeded with bovine auricular chondrocytes that were suspended within alginate before static culture. Constructs were then cultured for approximately 4 weeks post-seeding and evaluated for biochemical content, biomechanical properties, and histologic architecture. Results showed that the three-dimensional molded constructs had the approximate size and shape of the equine epiglottis and that it is possible to seed such constructs while maintaining 75%+ cell viability. Extracellular matrix content was observed to increase with time in culture and was accompanied by an increase in the mechanical stiffness of the construct. If successful, such an approach may represent a significant improvement on the currently available treatments for damaged airway cartilage and may provide clinical options for replacement of damaged tissue during treatment of obstructive airway disease.

Biomechanical and biochemical characterization of porcine tracheal cartilage

“…The engineering of tissues in vitro for use in the treatment of tracheal disease is particularly challenging because the trachea is structurally and geometrically complex, consisting of epithelium, connective tissue, smooth muscle, and C‐shaped cartilage rings . Recent innovations in image‐guided approaches to tissue engineering allow creation of three‐dimensional reconstructions of complex geometric shapes, such as the trachea from computed tomography scan sets, and can reproduce cartilaginous structures with high fidelity . In these approaches, the tissues are cultured in vitro until such time as they have sufficient functionality to serve as a transplant.…”

Real‐time robotic airway measurement: An additional benefit of a novel steady‐hand robotic platform

“…Eventually, tissueengineering applications with use of 3D printed scaffolds may also require precise airway measurements. 25,26 Real-time REMS-assisted measurements of airway dimensions were found to have a mean MOE of 0.306 ± 0.247 mm. To our knowledge, the resolution of this system is superior to any previously described method of real-time airway measurement by nearly tenfold.…”

“…The performance of more involved airway reconstruction procedures such as cricotracheal resections and slide tracheoplasties can also be assisted by knowing the length of the stenotic segments with a high degree of accuracy. Eventually, tissue‐engineering applications with use of 3D printed scaffolds may also require precise airway measurements …”

Fabrication of tissue engineered osteochondral grafts for restoring the articular surface of diarthrodial joints

“…has allowed the widespread realization of digital models. First introduced in the early 2000s as researchers looked for a way to create 3D organs with shape fidelity [59], new advances in 3D printing have been applied to osteochondral composites, allowing for spatial control of material and chemical properties through the depth of a tissue [60–62], as well as TMJ reconstruction [63,64], humeral head regeneration [65], and tissue-engineered epiglottis [66]. Recent advances include hybrid printing, allowing the simultaneous deposition of electrospun fibers with cell-seeded hydrogels to provide optimal mechanical and biological properties layer by layer [67].…”