Trachea

A tissue engineered trachea has received much attention as a clinically viable solution in long-segment tracheal replacement. However, attempts to regenerate a functional trachea using naturally derived scaffolds and exogenous cells have seen mixed success and recent clinical studies have cast doubt on its feasibility (70). Nonetheless, work with trachea regeneration offers pertinent insights that can be applied to multi-tissue recellularization needed in VCA engineering. Using the pig as a clinically relevant animal model, Haykal et al. applied a novel double chamber perfusion bioreactor to seed long-segment decellularized tracheal scaffolds with separate luminal and external compartments for seeding of tracheal epithelial cells and bone marrow-derived MSCs, respectively. Over an ex vivo maturation period of 72 h, recellularization of the trachea within this double-chamber perfusion bioreactor showed improved cell attachment and distribution compared to traditional static-seeding methods without perfusion (9). Additional advancement of porcine trachea regeneration by Aoki et al. described a chimeric trachea recellularization approach characterized by partial decellularization of the donor tracheal epithelium while preserving an immune-privileged cartilage compartment (10). Subsequent re-epithelialization of the trachea scaffold using exogenous human bronchial epithelial cells matured in an ex vivo perfusion bioreactor over 7 days facilitated cell attachment, viability and growth. Altogether, these two descriptions of tracheal engineering that utilize dynamic perfusion seeding within a double chamber bioreactor and a recellularization approach based on donor-recipient tissue chimerism are potential concepts that may be adopted to the broader scope of recellularization of other complex VCA tissues.