C-Shaped Cartilage Development Using Wharton's Jelly-Derived Hydrogels to Assemble a Highly Biomimetic Neotrachea for use in Circumferential Tracheal Reconstruction |
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Authors: | Erji Gao Yao Wang Pengli Wang Qianyi Wang Yuxuan Wei Daiying Song Huangfang Xu Jinghao Ding Yong Xu Huitang Xia Ru Chen Liang Duan |
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Institution: | 1. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430 China;2. Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200041 China;3. Department of Foot and Ankle Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630 China;4. Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011 China;5. Department of Breast Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311 China;6. Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, The First Affiliated Hospital of Shandong First Medical University, Shandong, 250013 China |
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Abstract: | A highly biomimetic neotrachea with C-shaped cartilage rings has promising clinical applications in the treatment of circumferential tracheal defects (CTDs) owing to its structure and physiological function. However, to date, most fabricated tracheal cartilages are O-shaped. In this study, finite element analysis demonstrates C-shaped cartilage rings that exhibit better compliance than O-shaped. Hydrogel is developed using methacryloyl-modified decellularized Wharton's jelly matrix (DWJMA) for the regeneration of C-shaped cartilage rings. This novel hydrogel possesses adjustable physicochemical properties and favorable cytocompatibility. When loaded with chondrocytes, DWJMA hydrogels support the optimal cartilage regeneration both in vitro and in vivo. More importantly, a highly biomimetic neotrachea simultaneously simulating the structural and physiological properties of the normal trachea is regenerated via modular assembly of several individual C-shaped cartilage rings. The results demonstrate the highly biomimetic neotrachea have better patency (88.6 ± 6.1% vs 74.4 ± 9.4%, p < 0.05), improve the survival rate, alleviate weight loss and mucoid impaction, than its O-shaped counterpart when used for the treatment of CTDs in a rabbit model. Therefore, this study proposes a novel hydrogel for the regeneration of C-shaped cartilage and provides new insights into the treatment of CTDs using a highly biomimetic neotrachea with C-shaped cartilage rings. |
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Keywords: | C-shaped cartilages decellularized wharton's jelly matrix highly biomimetic development photo-cross-linked hydrogels tracheal reconstruction |
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