A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model

Elizabeth F. Maughan, Colin R. Butler, Claire Crowley, Gui Zhen Teoh, Margot Den Hondt, Nicholas J. Hamilton, Robert E. Hynds, Peggy Lange, Tahera Ansari, Luca Urbani, Samuel M. Janes, Paolo De Coppi, Martin A. Birchall, Martin J. Elliott

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objectives/Hypothesis: Despite surgical advances, childhood tracheal stenosis is associated with high morbidity and mortality. Various tracheal scaffold strategies have been developed as the basis for bioengineered substitutes, but there is no consensus on which may be superior in vivo. We hypothesized that there would be no difference in morbidity and mortality between three competing scaffold strategies in rabbits. Study Design: Pilot preclinical study. Methods: Tracheal scaffolds were prepared by three methods that have been applied clinically and reported: preserved cadaveric ("Herberhold") allografts, detergent-enzymatically decellularized allografts, and synthetic scaffolds (nanocomposite polymer [polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU)]). Scaffolds were implanted into cervical trachea of New Zealand White rabbits (n = 4 per group) without cell seeding. Control animals (n = 4) received autotransplanted tracheal segments using the same technique. Animals underwent bronchoscopic monitoring of the grafts for 30 days. Macroscopic evaluation of tissue integration, graft stenosis, and collapsibility and histological examinations were performed on explants at termination. Results: All surgical controls survived to termination without airway compromise. Mild to moderate anastomotic stenosis from granulation tissue was detected, but there was evidence suggestive of vascular reconnection with minimal fibrous encapsulation. In contrast, three of the four animals in the Herberhold and POSS-PCU groups, and all animals receiving decellularized allografts, required early termination due to respiratory distress. Herberhold grafts showed intense inflammatory reactions, anastomotic stenoses, and mucus plugging. Synthetic graft integration and vascularization were poor, whereas decellularized grafts demonstrated malacia and collapse but had features suggestive of vascular connection or revascularization. Conclusions: There are mirror-image benefits and drawbacks to nonrecellularized, decellularized, and synthetic grafts, such that none emerged as the preferred option. Results from prevascularized and/or cell-seeded grafts (as applied clinically) may elucidate clearer advantages of one scaffold type over another.

Original languageEnglish (US)
JournalLaryngoscope
DOIs
StateAccepted/In press - 2017
Externally publishedYes

Fingerprint

Transplantation
Pediatrics
Rabbits
Transplants
Allografts
Nanocomposites
Pathologic Constriction
Blood Vessels
Polymers
Morbidity
Tracheal Stenosis
Granulation Tissue
Mortality
Mucus
Trachea
Detergents
poly(carbonate urea) urethane

Keywords

  • Pediatric airway
  • Tissue engineering
  • Tracheal stenosis
  • Tracheal transplantation

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Maughan, E. F., Butler, C. R., Crowley, C., Teoh, G. Z., Hondt, M. D., Hamilton, N. J., ... Elliott, M. J. (Accepted/In press). A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model. Laryngoscope. https://doi.org/10.1002/lary.26611

A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model. / Maughan, Elizabeth F.; Butler, Colin R.; Crowley, Claire; Teoh, Gui Zhen; Hondt, Margot Den; Hamilton, Nicholas J.; Hynds, Robert E.; Lange, Peggy; Ansari, Tahera; Urbani, Luca; Janes, Samuel M.; Coppi, Paolo De; Birchall, Martin A.; Elliott, Martin J.

In: Laryngoscope, 2017.

Research output: Contribution to journalArticle

Maughan, EF, Butler, CR, Crowley, C, Teoh, GZ, Hondt, MD, Hamilton, NJ, Hynds, RE, Lange, P, Ansari, T, Urbani, L, Janes, SM, Coppi, PD, Birchall, MA & Elliott, MJ 2017, 'A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model', Laryngoscope. https://doi.org/10.1002/lary.26611
Maughan, Elizabeth F. ; Butler, Colin R. ; Crowley, Claire ; Teoh, Gui Zhen ; Hondt, Margot Den ; Hamilton, Nicholas J. ; Hynds, Robert E. ; Lange, Peggy ; Ansari, Tahera ; Urbani, Luca ; Janes, Samuel M. ; Coppi, Paolo De ; Birchall, Martin A. ; Elliott, Martin J. / A comparison of tracheal scaffold strategies for pediatric transplantation in a rabbit model. In: Laryngoscope. 2017.
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AU - Maughan, Elizabeth F.

AU - Butler, Colin R.

AU - Crowley, Claire

AU - Teoh, Gui Zhen

AU - Hondt, Margot Den

AU - Hamilton, Nicholas J.

AU - Hynds, Robert E.

AU - Lange, Peggy

AU - Ansari, Tahera

AU - Urbani, Luca

AU - Janes, Samuel M.

AU - Coppi, Paolo De

AU - Birchall, Martin A.

AU - Elliott, Martin J.

PY - 2017

Y1 - 2017

N2 - Objectives/Hypothesis: Despite surgical advances, childhood tracheal stenosis is associated with high morbidity and mortality. Various tracheal scaffold strategies have been developed as the basis for bioengineered substitutes, but there is no consensus on which may be superior in vivo. We hypothesized that there would be no difference in morbidity and mortality between three competing scaffold strategies in rabbits. Study Design: Pilot preclinical study. Methods: Tracheal scaffolds were prepared by three methods that have been applied clinically and reported: preserved cadaveric ("Herberhold") allografts, detergent-enzymatically decellularized allografts, and synthetic scaffolds (nanocomposite polymer [polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU)]). Scaffolds were implanted into cervical trachea of New Zealand White rabbits (n = 4 per group) without cell seeding. Control animals (n = 4) received autotransplanted tracheal segments using the same technique. Animals underwent bronchoscopic monitoring of the grafts for 30 days. Macroscopic evaluation of tissue integration, graft stenosis, and collapsibility and histological examinations were performed on explants at termination. Results: All surgical controls survived to termination without airway compromise. Mild to moderate anastomotic stenosis from granulation tissue was detected, but there was evidence suggestive of vascular reconnection with minimal fibrous encapsulation. In contrast, three of the four animals in the Herberhold and POSS-PCU groups, and all animals receiving decellularized allografts, required early termination due to respiratory distress. Herberhold grafts showed intense inflammatory reactions, anastomotic stenoses, and mucus plugging. Synthetic graft integration and vascularization were poor, whereas decellularized grafts demonstrated malacia and collapse but had features suggestive of vascular connection or revascularization. Conclusions: There are mirror-image benefits and drawbacks to nonrecellularized, decellularized, and synthetic grafts, such that none emerged as the preferred option. Results from prevascularized and/or cell-seeded grafts (as applied clinically) may elucidate clearer advantages of one scaffold type over another.

AB - Objectives/Hypothesis: Despite surgical advances, childhood tracheal stenosis is associated with high morbidity and mortality. Various tracheal scaffold strategies have been developed as the basis for bioengineered substitutes, but there is no consensus on which may be superior in vivo. We hypothesized that there would be no difference in morbidity and mortality between three competing scaffold strategies in rabbits. Study Design: Pilot preclinical study. Methods: Tracheal scaffolds were prepared by three methods that have been applied clinically and reported: preserved cadaveric ("Herberhold") allografts, detergent-enzymatically decellularized allografts, and synthetic scaffolds (nanocomposite polymer [polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU)]). Scaffolds were implanted into cervical trachea of New Zealand White rabbits (n = 4 per group) without cell seeding. Control animals (n = 4) received autotransplanted tracheal segments using the same technique. Animals underwent bronchoscopic monitoring of the grafts for 30 days. Macroscopic evaluation of tissue integration, graft stenosis, and collapsibility and histological examinations were performed on explants at termination. Results: All surgical controls survived to termination without airway compromise. Mild to moderate anastomotic stenosis from granulation tissue was detected, but there was evidence suggestive of vascular reconnection with minimal fibrous encapsulation. In contrast, three of the four animals in the Herberhold and POSS-PCU groups, and all animals receiving decellularized allografts, required early termination due to respiratory distress. Herberhold grafts showed intense inflammatory reactions, anastomotic stenoses, and mucus plugging. Synthetic graft integration and vascularization were poor, whereas decellularized grafts demonstrated malacia and collapse but had features suggestive of vascular connection or revascularization. Conclusions: There are mirror-image benefits and drawbacks to nonrecellularized, decellularized, and synthetic grafts, such that none emerged as the preferred option. Results from prevascularized and/or cell-seeded grafts (as applied clinically) may elucidate clearer advantages of one scaffold type over another.

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