PULMONARY PERSPECTIVES®: Is 3D printing of organs the future? Creating a biologic 3D trachea
3D printing and tracheal regeneration
In the setting of large segment tracheal pathologies, both benign and malignant, surgical resection and reconstruction may be challenging. Our lab has been working on creating a bioengineered tissue alternative for repair and/or replacement of large tracheal defects. The ideal material should have longitudinal flexibility, while maintaining lateral rigidity and concurrently supporting chondrogenesis, neovascularization, and re-epithelialization. Using a combination of mesenchymal stem cells, biologic collagen membranes, and 3D printing, we have achieved preliminary and encouraging results in large animal models. 3D-reconstructed CT scan of the neck and chest is obtained, and we isolate the tracheobronchial tree below the cricoid cartilage extending toward the carina and the major bronchi. Large tracheal defects, long segment airway stenosis, or tracheobronchomalacia can then be corrected virtually using CAD software applications. The improved anatomical 3D image is next converted to a (.STL) file readable by the printer, which generates the tracheal scaffold. The latter is subsequently incubated with mesenchymal stem cells, which are allowed to grow and differentiate to chondrogenic progenitor cells in a bioreactor in vitro. Chondrogenesis is a complex and well-orchestrated process. We incubate the stem cells in growth media containing a specific mixture of TGF-ß; BMP-2,-4, and -7; and FGF-2 to induce the formation of the chondrogenic lineage. Additionally, the scaffold with the adherent cells are mounted on a mandrel in a bioreactor and subjected to slow and continuous rotation to improve chondrogenesis via mechanical stimulation. In the early phases of differentiation, collagen I and fibronectin are deposited around the cells creating the earliest form of extracellular matrix for chondrocytes growth. With this approach, we have seen maintained cellular growth and differentiation of the stem cells into chondrogenic progenitors in vitro and chondrocytes in vivo in the animal model (Al-Ayoubi et al. Presented at the STS 51st Annual Meeting. Orlando, FL 2013). Current efforts are underway to understand the airway dynamics, mucosal epithelial function, and long-term effects of the bioengineered trachea.
Final word
3D printing is an exciting technology with significant impact on regenerative medicine. It particularly allows precise and customized reproduction of the engineered tissue while maintaining form and function. Further identification of suitable biomaterials is warranted, as well as the biological interactions of the stem cells with their potential environments. While substantial information remains to be discovered and technical challenges overcome, the field of tissue engineering is undoubtedly heading toward amazing findings, hoping to find cures for many debilitating illnesses.
Drs. Al-Ayoubi and Bhora are with the Department of Thoracic Surgery; Mount Sinai St. Luke’s Hospital and Mount Sinai Roosevelt Hospital; Icahn School of Medicine at Mount Sinai; New York, NY.
