The Growing Medical Need for Tracheal Replacement: Reconstructive Strategies Should Overcome Their Limits

Abstract

Breathing, being predominantly an automatic action, is often taken for granted. However, respiratory diseases affect millions of people globally, emerging as one of the major causes of disability and death overall. Among the respiratory dysfunctions, tracheal alterations have always represented a primary challenge for clinicians, biologists, and engineers. Indeed, in the case of wide structural alterations involving more than 50% of the tracheal length in adults or 30% in children, the available medical treatments are ineffective or inapplicable. So far, a plethora of reconstructive approaches have been proposed and clinically applied to face this growing, unmet medical need. Unfortunately, none of them has become a well-established and routinely applied clinical procedure to date. This review summarizes the main clinical reconstructive attempts and classifies them as non-tissue engineering and tissue engineering strategies. The analysis of the achievements and the main difficulties that still hinder this field, together with the evaluation of the forefront preclinical experiences in tracheal repair/replacement, is functional to promote a safer and more effective clinical translation in the near future.

Keywords: allotransplantation; clinical outcomes; preclinical studies; regenerative medicine; tissue engineering; tracheal replacement; tracheal surgeries.

FIGURE 1

Examples of tracheal and main bronchi’s reconstructive strategies. (A) Synthetic prostheses: metallic meshes and silicone tube. (B) Aortic allotransplantation with a supporting stent. (C) Tracheal allotransplantation: two-step procedure with pre-vascularization in heterotopic position (forearm) followed by orthotopic transplantation. (D) Autologous tissue replacement: stripes of rib cartilage are inserted in a skin forearm free flap (graft assembling phase). Then, the graft is tubularized to reproduce the tracheal lumen. (E) An allogenic trachea is decellularized and then recellularized in a rotating bioreactor with autologous cells. (F) Synthetic tailored tracheal grafts seeded with autologous cells in a rotating bioreactor. (G) A graft composed of a nitinol stent inserted between two layers of porcine acellularized dermis matrix is seeded with autologous skin keratinocytes (graft assembling phase). Once transplanted, the graft is alternately perfused, through pumps and cannulas, with antibiotics, autologous cells, and growth factors (GFs).