한빛사논문
Hae Sang Park 1,2,3, Ji Seung Lee 2, Chang-Beom Kim 4, Kwang-Ho Lee 5, In-Sun Hong 6, Harry Jung 3, Hanna Lee 2, Young Jin Lee 2, Olatunji Ajiteru 2, Md Tipu Sultan 2, Ok Joo Lee 2, Soon Hee Kim 2, Chan Hum Park 1,2
1Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, College of Medicine Hallym University Chuncheon Republic of Korea.
2Nano-Bio Regenerative Medical Institute, School of Medicine Hallym University Chuncheon Republic of Korea.
3Institute of New Frontier Research Team Hallym University, Hallym Clinical and Translation Science Institute Chuncheon Republic of Korea.
4Intelligent Robot Research Team Electronics and Telecommunications Research Institute Daejeon Republic of Korea.
5Department of Advanced Materials Science and Engineering, College of Engineering Kangwon National University Chuncheon Republic of Korea.
6Department of Molecular Medicine, School of Medicine Gachon University Incheon Republic of Korea.
Hae Sang Park and Ji Seung Lee equally contributed to this work as the first authors.
CORRESPONDING AUTHOR : Chan Hum Park
Abstract
Herein, we report the first study to create a three-dimensional (3D) bioprinted artificial larynx for whole-laryngeal replacement. Our 3D bio-printed larynx was generated using extrusion-based 3D bioprinter with rabbit's chondrocyte-laden gelatin methacryloyl (GelMA)/glycidyl-methacrylated hyaluronic acid (GMHA) hybrid bioink. We used a polycaprolactone (PCL) outer framework incorporated with pores to achieve the structural strength of printed constructs, as well as to provide a suitable microenvironment to support printed cells. Notably, we established a novel fluidics supply (FS) system that simultaneously supplies basal medium together with a 3D bioprinting process, thereby improving cell survival during the printing process. Our results showed that the FS system enhanced post-printing cell viability, which enabled the generation of a large-scale cell-laden artificial laryngeal framework. Additionally, the incorporation of the PCL outer framework with pores and inner hydrogel provides structural stability and sufficient nutrient/oxygen transport. An animal study confirmed that the transplanted 3D bio-larynx successfully maintained the airway. With further development, our new strategy holds great potential for fabricating human-scale larynxes with in vivo-like biological functions for laryngectomy patients.
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