Elizabeth S Clark1, Cameron Best2, Ekene Onwuka3, Tadahisa Sugiura2, Nathan Mahler2, Brad Bolon4, Andrew Niehaus5, Iyore James2, Narutoshi Hibino6, Toshiharu Shinoka6, Jed Johnson7, Christopher K Breuer8. 1. Tissue Engineering and Surgical Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive - Suite WB4154, Columbus, OH 43205; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210. 2. Tissue Engineering and Surgical Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive - Suite WB4154, Columbus, OH 43205. 3. Tissue Engineering and Surgical Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive - Suite WB4154, Columbus, OH 43205; Department of Surgery, The Ohio State University, 395W. 12th Avenue - Suite 670, Columbus, OH 43210. 4. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210; Comparative Pathology and Mouse Phenotyping Shared Resource, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210. 5. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp Street, Columbus, OH 43210. 6. Tissue Engineering and Surgical Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive - Suite WB4154, Columbus, OH 43205; Department of Cardiothoracic Surgery, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205. 7. Nanofiber Solutions, Inc., 1275 Kinnear Road, Columbus, OH 43212. 8. Tissue Engineering and Surgical Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive - Suite WB4154, Columbus, OH 43205; Department of Pediatric Surgery, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205. Electronic address: Christopher.Breuer@NationwideChildrens.org.
Abstract
BACKGROUND: Surgical management of long segment tracheal disease is limited by a paucity of donor tissue and poor performance of synthetic materials. A potential solution is the development of a tissue-engineered tracheal graft (TETG) which promises an autologous airway conduit with growth capacity. METHODS: We created a TETG by vacuum seeding bone marrow-derived mononuclear cells (BM-MNCs) on a polymeric nanofiber scaffold. First, we evaluated the role of scaffold porosity on cell seeding efficiency in vitro. We then determined the effect of cell seeding on graft performance in vivo using an ovine model. RESULTS: Seeding efficiency of normal porosity (NP) grafts was significantly increased when compared to high porosity (HP) grafts (NP: 360.3 ± 69.19 × 10(3) cells/mm(2); HP: 133.7 ± 22.73 × 10(3) cells/mm(2); p<0.004). Lambs received unseeded (n=2) or seeded (n=3) NP scaffolds as tracheal interposition grafts for 6 weeks. Three animals were terminated early owing to respiratory complications (n=2 unseeded, n=1 seeded). Seeded TETG explants demonstrated wound healing, epithelial migration, and delayed stenosis when compared to their unseeded counterparts. CONCLUSION: Vacuum seeding BM-MNCs on nanofiber scaffolds for immediate implantation as tracheal interposition grafts is a viable approach to generate TETGs, but further preclinical research is warranted before advocating this technology for clinical application.
BACKGROUND: Surgical management of long segment tracheal disease is limited by a paucity of donor tissue and poor performance of synthetic materials. A potential solution is the development of a tissue-engineered tracheal graft (TETG) which promises an autologous airway conduit with growth capacity. METHODS: We created a TETG by vacuum seeding bone marrow-derived mononuclear cells (BM-MNCs) on a polymeric nanofiber scaffold. First, we evaluated the role of scaffold porosity on cell seeding efficiency in vitro. We then determined the effect of cell seeding on graft performance in vivo using an ovine model. RESULTS: Seeding efficiency of normal porosity (NP) grafts was significantly increased when compared to high porosity (HP) grafts (NP: 360.3 ± 69.19 × 10(3) cells/mm(2); HP: 133.7 ± 22.73 × 10(3) cells/mm(2); p<0.004). Lambs received unseeded (n=2) or seeded (n=3) NP scaffolds as tracheal interposition grafts for 6 weeks. Three animals were terminated early owing to respiratory complications (n=2 unseeded, n=1 seeded). Seeded TETG explants demonstrated wound healing, epithelial migration, and delayed stenosis when compared to their unseeded counterparts. CONCLUSION: Vacuum seeding BM-MNCs on nanofiber scaffolds for immediate implantation as tracheal interposition grafts is a viable approach to generate TETGs, but further preclinical research is warranted before advocating this technology for clinical application.
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