Effect of cell seeding on neotissue formation in a tissue engineered trachea

Elizabeth S. Clark, Cameron Best, Ekene Onwuka, Tadahisa Sugiura, Nathan Mahler, Brad Bolon, Andrew Niehaus, Iyore James, Narutoshi Hibino, Toshiharu Shinoka, Jed Johnson, Christopher K. Breuer

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 × 103 cells/mm2; HP: 133.7 ± 22.73 × 103 cells/mm2; 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.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalJournal of Pediatric Surgery
Volume51
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Trachea
Porosity
Transplants
Nanofibers
Vacuum
Tracheal Diseases
Bone Marrow
Wound Healing
Sheep
Pathologic Constriction
Tissue Donors
Technology
Growth
Research

Keywords

  • Bone marrow mononuclear cells
  • Electrospinning
  • Large animal model
  • Tissue engineering
  • Trachea
  • Vacuum seeding

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Effect of cell seeding on neotissue formation in a tissue engineered trachea. / Clark, Elizabeth S.; Best, Cameron; Onwuka, Ekene; Sugiura, Tadahisa; Mahler, Nathan; Bolon, Brad; Niehaus, Andrew; James, Iyore; Hibino, Narutoshi; Shinoka, Toshiharu; Johnson, Jed; Breuer, Christopher K.

In: Journal of Pediatric Surgery, Vol. 51, No. 1, 01.01.2016, p. 49-55.

Research output: Contribution to journalArticle

Clark, ES, Best, C, Onwuka, E, Sugiura, T, Mahler, N, Bolon, B, Niehaus, A, James, I, Hibino, N, Shinoka, T, Johnson, J & Breuer, CK 2016, 'Effect of cell seeding on neotissue formation in a tissue engineered trachea', Journal of Pediatric Surgery, vol. 51, no. 1, pp. 49-55. https://doi.org/10.1016/j.jpedsurg.2015.10.008
Clark, Elizabeth S. ; Best, Cameron ; Onwuka, Ekene ; Sugiura, Tadahisa ; Mahler, Nathan ; Bolon, Brad ; Niehaus, Andrew ; James, Iyore ; Hibino, Narutoshi ; Shinoka, Toshiharu ; Johnson, Jed ; Breuer, Christopher K. / Effect of cell seeding on neotissue formation in a tissue engineered trachea. In: Journal of Pediatric Surgery. 2016 ; Vol. 51, No. 1. pp. 49-55.
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AU - Bolon, Brad

AU - Niehaus, Andrew

AU - James, Iyore

AU - Hibino, Narutoshi

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AU - Breuer, Christopher K.

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N2 - 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 × 103 cells/mm2; HP: 133.7 ± 22.73 × 103 cells/mm2; 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.

AB - 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 × 103 cells/mm2; HP: 133.7 ± 22.73 × 103 cells/mm2; 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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