1. Bioreactor-based manufacturing of engineered grafts
The manufacturing processes for the production of engineered tissue grafts for clinical applications are typically based on conventional manual cell culture methods. These procedures require a large number of labor-intensive manipulations that ultimately pose challenges in terms of regulatory compliance, up-scaling, and cost effectiveness. As an alternative, bioreactor-based production systems, which automate and control the bioprocesses, have the potential to overcome these limitations, facilitating the translation of engineered tissue products towards wide-spread clinical use. Based on the state-of-the-art bioreactor systems and novel bioprocesses that we have developed over the last 15 years, we are currently establishing a regulatory compliant bioreactor system, which we aim to use for the production of cartilage grafts in an unprecedented Phase I clinical trial.
Tonnarelli B et al. Streamlined bioreactor-based production of human cartilage tissues. Eur Cells Mater, 2016. Pubmed.
Santoro R et al. Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing. Biomaterials, 2010. Pubmed.
Martin I et al. Bioreactor-based roadmap for the translation of tissue engineering strategies into clinical products. Trends Biotechnol, 2009. Pubmed.
Wendt D et al. Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions. Biorheology, 2006. Pubmed.
2. Bioreactor-based 3D cell culture models
In addition to serving as the foundation for automated manufacturing systems, bioreactor systems can also play a key role in establishing 3D in vitro model systems supporting fundamental investigations of cell function and tissue development. In this context, bioreactors are being utilized to establish 3D models for fundamental studies of chondrogenic and osteogenic differentiation of chondrocytes and mesenchymal stromal cells in our laboratory. In addition, our collaborations reaching outside of the BCRS have led to the establishment of 3D models of a thymic organoid to study thymic epithelial cell function (Professor Georg Hollander, Pediatric Immunology) as well as a 3D model of the optic nerve microenvironment to investigate the effects of compartmentalization on meningothelial cell metabolism (Dr. Albert Neutzner, Ocular Pharmacology and Physiology).
Hoch AI et al. Expansion of bone marrow mesenchymal stromal cells in perfused 3D ceramic scaffolds enhances in vivo bone formation. Biotechnol J, 2017. Pubmed.
Hoffmann W et al. Novel Perfused Compression Bioreactor System as an in vitro Model to Investigate Fracture Healing. Front Bioeng Biotechnol, 2015. Pubmed.
Santoro R et al. On-line monitoring of oxygen as a non-destructive method to quantify cells in engineered 3D tissue constructs. J Tissue Eng Regen Med, 2012. Pubmed.
Cioffi M et al. Computational evaluation of oxygen and shear stress distributions in 3D perfusion culture systems: macro-scale and micro-structured models. J Biomech, 2008. Pubmed.
3. CELLEC Biotek AG
Based on our perfusion bioreactors developed over the last 15 years, and the resulting high impact bioreactor-based research conducted by the tissue engineering laboratory, in February 2011 we founded CELLEC Biotek AG, a lab spin-out for the development and commercialization of bioreactor systems for 3D cell culture and tissue generation.