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Imaging-Guided Bioreactor for Generating Bioengineered Airway Tissue
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Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia.

Albert C Pai1, Anthony M Swatek1, Thomas J Lynch2

  • 1Department of Cardiothoracic Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.

Bioengineering (Basel, Switzerland)
|July 29, 2023
PubMed
Summary

Bioengineered tracheal grafts show promise for airway reconstruction. Implanted basal cells differentiated into functional epithelium, demonstrating potential for regenerative therapies in airway obstructions.

Keywords:
airway stem cellsbioreactorferrettracheal revascularizationtracheal transplant

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Area of Science:

  • Regenerative Medicine
  • Tissue Engineering
  • Surgical Innovation

Background:

  • Long-segment tracheal defects often require grafts after resection for airway obstructions.
  • Bioengineered grafts offer customizable solutions for tracheal reconstruction.
  • Previous work established a bioreactor for decellularizing and recellularizing ferret tracheas.

Purpose of the Study:

  • To assess the in vivo fate of bioengineered tracheal grafts transplanted orthotopically.
  • To investigate the role of vascular endothelial growth factor (VEGF) and immunosuppression (IS) in graft revascularization and viability.
  • To evaluate the long-term survival and epithelialization of the bioengineered grafts.

Main Methods:

  • Orthotopic transplantation of bioengineered ferret tracheal grafts.
  • Administration of VEGF-laden hydrogel and immunosuppression (IS) as procedural adjuncts.
  • Histological analysis and assessment of graft revascularization, viability, and epithelial differentiation.

Main Results:

  • Immunosuppression (IS) initially limited graft revascularization, but VEGF supplementation counteracted this effect.
  • Submucosal gland (SMG) loss was observed irrespective of the revascularization strategy.
  • Bioengineered tracheas survived for one month post-transplant, with implanted basal cells differentiating and integrating into a recipient-derived epithelium.

Conclusions:

  • Bioengineered tracheal grafts can survive orthotopic transplantation and achieve functional epithelialization.
  • VEGF supplementation can mitigate the negative impact of immunosuppression on graft revascularization.
  • Further research into regenerative therapies for airway reconstruction is warranted.