Bioengineering Lungs for Transplantation

Key points

The scaffold: decellularized native extracellular matrix

In order to engineer solid organs with the biological complexity of their native counterparts and the capacity to regain appropriate physiologic functions following transplantation, the foundation on which to build is an important consideration. Much evidence has demonstrated that the process of whole organ decellularization can provide an ideal framework for regeneration. By accessing the organ’s native vascular network, detergents or other recellularizing agents can be delivered in a

Airway: regenerating lung epithelium

The successful regeneration of functional lung tissue through recellularization of the native scaffold will require the targeted replacement of specialized lung epithelial cell types in distinct anatomic locations. The human lung epithelium comprises many distinctive cell types,²⁷ which can be loosely categorized into proximal and distal phenotypes each with unique and important functions. The acellular scaffold structure allows for the direct delivery of large cell numbers through the main

Vasculature: regenerating the lung endothelium

The regeneration of functional pulmonary vasculature must, at minimum, allow for physiologic blood perfusion following implantation. The preservation of essential anatomic features in the decellularized lung scaffold allows for direct delivery of endothelial cells through the vascular outlets in order to reconstruct the vasculature network. The native matrix architecture also facilitates direct anastomosis of the graft to the recipient after regeneration.

Initial studies of lung bioengineering

From cell-seeded constructs to functional tissue: bioreactors and whole organ culture

To properly develop ex vivo methodologies for whole organ culture and regeneration, one must consider the native biological context. Basic lung function in vivo depends on specific mechanical events that facilitate the exchange of gases between the perfusing blood and inspired air. These parameters have direct effects on the organ, tissue, cellular, and subcellular scales. Therefore, recapitulating these biomimetic events ex vivo is a critical component of lung bioengineering. The 2 primary

Application: transplantation of regenerated lung constructs

A major aim of regenerative medicine is to develop clinically viable approaches to re-create human organs and tissues that recapitulate both the structure and the function of the native organ; this is of particular importance in the context of end-stage organ failure. Technologies such as cardiopulmonary bypass and extracorporeal membrane oxygenation are well developed in the clinical setting, but only provide short-term solutions and are nonambulatory. Although these options provide the basic

Summary

The ability to create an implantable gas exchange construct on demand, from patient-derived cells, would have significant benefit to patients. Much work is still required to fully coalesce the fields of matrix and cell biology with tissue engineering, but promising advances have already been realized. Important questions regarding cell source, expansion, and delivery are currently being addressed, in order to ultimately achieve functional tissue formation and construct implantation.