Host response towards decellularised lung extracellular matrix reinforced bioinks for 3D bioprinting lung tissue for transplantation

Lung transplantation is the only option for end-stage lung diseases, but organ shortage remains problematic. Bioengineering lungs ex vivo could overcome shortages and 3D bioprinting can generate relevant custom structures, but, other criteria such as the immune responses of these constructs and their integration with the host vasculature are critical for successful clinical translation. Previously, we generated a tissue-specific hybrid bioink consisting of alginate, reinforced with extracellular matrix from decellularized lung tissue (rECM) to 3D bioprint human airways comprised of regionally specified primary cells which remained patent over time.1 3D bioprinted constructs generated using batch processed rECM bioinks prevent the foreign body response when transplanted into T-cell deficient mice, mimicking clinical immunosuppression for solid organ transplantation. However, one of the major potential benefits of organ bioengineering is that the cells could be sourced from the eventual transplant recipient, thus obviating the need for long term immunosuppression. Here we sought to investigate the biocompatibility and regenerative ability of 3D printed lung rECM alginate hydrogels in immunocompetent mice. We find that the 3D printed rECM constructs do not illicit negative immune responses when syngeneic transplanted into immunocompetent mice and integrate well in the surrounding tissue without evidence of a foreign body response. Furthermore, we find that the rECM is pro-angiogenic and supports de novo vasculature upon subcutaneous implantation. rECM bioinks are thus a promising new approach for generating functional human tissue using 3D bioprinting. 1De Santis, M. M, et al., Extracellular‐Matrix‐Reinforced Bioinks for 3D Bioprinting Human Tissue. Adv. Mater. 2020, 2005476.