Advances in bioreactors for lung bioengineering: From scalable cell culture to tissue growth monitoring

Abstract

Lung bioengineering has emerged to resolve the current lung transplantation limitations and risks, including the shortage of donor organs and the high rejection rate of transplanted lungs. One of the most critical elements of lung bioengineering is MAHFOUZI ET AL.

Bioengineering lungs: An overview of current methods, requirements, and challenges for constructing scaffolds

“…Amongst the most versatile engineering approaches that allow for custom-made 3D designs in tissue engineering is 3D-bioprinting, which has emerged as a powerful technique in producing synthetic scaffolds for organs ( Rider et al, 2018 ). 3D bioprinting has been an attractive tool that is being explored to engineer organs with the ultimate goal of producing transplantable tissues, and in the case of the lung, for creating artificial lung scaffolds ( Mahfouzi et al, 2021a ). Significant progress has been made that allows for the 3D bioprinting of the trachea and bronchus, but the challenge remains in choosing appropriate manufacturing methods, that allow bioprinting at a microscale resolution to achieve key features of lung tissues ( Frejo and Grande, 2019 ; Galliger et al, 2019 ; Xie et al, 2020 ).…”

“…Speed, precision, and resolution parameters are key factors in choosing the bioprinting methods (e.g. extrusion, microfluidics, inkjet, laser-assisted) ( Ozbolat and Yu, 2013 ; Murphy and Atala, 2014 ; Mandrycky et al, 2016 ; Mahfouzi et al, 2021a ). In regard to the bioprinting of lung parenchyma, stereolithography has been used to provide highly precise construct with high resolution.…”

“…Additionally, selecting a proper bioink is a critical step in 3D bioprinting. Bioinks that provide proper properties related to mechanical strength, flexibility, biocompatibility, biodegradability, bioabsorbability, and printability are essential to achieve a functioning organ ( Mahfouzi et al, 2021a ). They should also have properties needed to allow for specific biological cues that guide cell growth, differentiation, and migration ( Mahfouzi et al, 2021b ; Doyle and O’grady, 2013 ).…”

“…Due to the unique lung anatomy and physiology, the use of bioreactors is crucial to biofabricate lung scaffolds, both artificial and biological. They provide controlled and prespecified environmental settings, allowing the biological processes needed to occur to support cell growth and differentiation, tissue decellularization and recellularization, and monitoring cell cultures ( Farré et al, 2018 ; Mahfouzi et al, 2021a ). They expose re-seeded scaffolds to physical and biochemical stimuli, allowing cells to undergo differentiation and regeneration within developing scaffolds.…”

“…Some examples include bioreactor systems for decellularization of scaffolds by perfusion and recellularization by perfusion and ventilation ( Talò et al, 2020 ; Mahfouzi et al, 2021b ). Others are systems used for large-scale cell cultures, which are composed of rotating bioreactors that differentiate epithelium cells for lung bioengineering by exposing cells to air and liquid ( Ghaedi et al, 2014 ; Mahfouzi et al, 2021a ). However, in regard to bioreactors involved in re- and decellularization of lungs, further limitations need to be addressed, such as achieving a uniform temperature across the chamber, sterile environment, pH control, and proper waste removal ( Mahfouzi et al, 2021b ).…”