Lecture Series

42 - Tracheal Reconstruction With Mscs And Scaffolds Focusing On Mucosal Regeneration

Writer :
ITREN (2015-08-01)
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Speaker : Seong Keun Kwon, M.D., PhD. (Department of Otorhinolaryngology - Head and Neck Surgery, Dongguk University International  Hospital)

Date : 2013-01-04

Location : Room 106 Pharmacy Hall, Dankook University

Abstract : Disorders affecting the trachea may be curable by surgical resection of the affected segment and a subsequent end-to-end anastomosis. However, this standard approach is possible only when the diseased portion of the airway does not exceed approximately half (6 cm) of the total length of the trachea in an adult or one-third of the total length in a child. 

A conventional allotransplantation of a clinically relevant tracheal segment (>6 cm) is surgically challenging and requires lifelong immunosuppression. Almost all the early clinical efforts documented have resulted in allograft necrosis, infection, and death in patients due to inadequate graft revascularization, contact with inhaled air, and infection and mediastinitis.   

Autologous autografts have been clinically applied for small defects in the airway; however, for large disorders of the trachea, the optimal solution remains elusive. Cadaveric allografts have been used mainly for tracheal reconstruction in children, but the technical feasibility is overshadowed by a high rate of major complications and uncertainty regarding the long term. 

Artificial prostheses have also been used to replace the trachea, but this has always been associated with material migration, rupture, infection, stenosis, nonepithelialized endoluminal surface and related contamination, and consequent disintegration. 

In current general clinical practice, the use of artificial grafts is limited to temporary or palliative approaches using endoluminal stents or definitive tracheotomy. New therapeutic options are therefore necessary; however, even after decades of intensive research in this field, an optimal solution is still lacking.

The selection of the most reasonable scaffold is highly important for a suitable engineering process and subsequent in situ tissue/organ function. For instance, for replacing the trachea, a scaffold should meet with basic tracheal  characteristics such as being bioactive, capable of hosting the seeded cells, nonimmunogenic, nontoxic, and noncarcinogenic/nonteratogenic. In addition, an optimal tracheal scaffold is characterized by air- and liquid tight seals as well as adequate structural support (lateral rigidity and longitudinal flexibility) to maintain airway patency and allow rapid epithelialization. 

The cell type used for seeding the scaffold may be autologous or allogenic and can range from differentiated to stem or progenitor origin. Consideration needs to be given to the specific advantages and disadvantages of each cell type, and ethical concerns must be discussed. Moreover, the cell seeding and culture processes require tissue-specific conditions to mimic the physiologic environment. Conventional static dish culture conditions usually cannot provide these requirements, and the utilization of cell sheet technology or a bioreactor is necessary.