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Seeding and Implantation of a Biosynthetic Tissue-engineered Tracheal Graft in a Mouse Model
Published on: April 1, 2019
Effect of cell seeding on neotissue formation in a tissue engineered trachea
Elizabeth S Clark1, Cameron Best2, Ekene Onwuka3
1Tissue 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.
Tissue-engineered tracheal grafts (TETGs) using vacuum-seeded bone marrow cells on nanofiber scaffolds show promise for airway repair. Seeded grafts demonstrated improved healing and reduced stenosis in an ovine model, warranting further research.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Surgical Innovation
Background:
- Tracheal reconstruction is challenged by limited tissue availability and synthetic graft failure.
- Tissue-engineered tracheal grafts (TETGs) offer a potential autologous solution with inherent growth capabilities.
Purpose of the Study:
- To develop and evaluate a TETG using vacuum-seeded bone marrow-derived mononuclear cells (BM-MNCs) on a nanofiber scaffold.
- To assess the impact of scaffold porosity on cell seeding efficiency.
- To determine the in vivo performance of seeded TETGs in an ovine tracheal interposition model.
Main Methods:
- Polymeric nanofiber scaffolds were fabricated and characterized for porosity.
- Bone marrow-derived mononuclear cells (BM-MNCs) were vacuum-seeded onto scaffolds.
- In vitro cell seeding efficiency was compared between normal porosity (NP) and high porosity (HP) scaffolds.
- NP scaffolds, seeded with BM-MNCs, were implanted as tracheal interposition grafts in an ovine model for 6 weeks.
Main Results:
- Normal porosity scaffolds exhibited significantly higher cell seeding efficiency compared to high porosity scaffolds (360.3 ± 69.19 × 10^3 cells/mm^2 vs. 133.7 ± 22.73 × 10^3 cells/mm^2, p<0.004).
- Seeded TETGs showed evidence of wound healing, epithelialization, and delayed stenosis post-implantation.
- Unseeded grafts experienced higher rates of early respiratory complications and stenosis compared to seeded grafts.
Conclusions:
- Vacuum seeding of BM-MNCs onto nanofiber scaffolds provides a viable method for generating TETGs for immediate implantation.
- The developed TETG technology demonstrates potential for tracheal reconstruction, showing improved graft performance.
- Further preclinical investigation is necessary to validate this approach for clinical application in tracheal disease management.

