Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, with increasing incidence and mortality rates despite significant progress has been done in screening and treatment in the last decades. The role of the gut microbiota has recently been highlighted as one of the key players in CRC initiation and progression as certain microbial metabolites promote carcinogenesis or resistance to therapeutics. Such influence of the gut microbiota on CRC, underscores the need for innovative research models accounting for this, which is currently neglected.
Therefore, in order to advance CRC research, there is a pressing need to develop more physiologically relevant models in vitro that accurately represents the tumour microenvironment and the complex relationship between CRC and gut microbiota. Despite the increasing evidence of the role of microbial metabolites and specific bacteria in CRC development, current in vitro models fail to mimic these dynamics. This is in part due to the lack of models available that recapitulate in high detail the heterogenicity of gut microbiota.
In BIOMIMIC-CRC we propose the development of advanced in vitro platforms that combine CRC with highly representative models of healthy and pathological gut microbiota provided by our industrial partner, Bac3Gel, using bioprinting and microfluidic technologies. These platforms aim to replicate the complex dynamics between CRC and gut microbiota for its potential applications in drug screening and personalised medicine to elucidate the CRC-microbiota interactions.
In order to reach that aim, three main objectives have been established in BIOMIMIC-CRC which are directly related to the tasks of the project:
1. Development of healthy and pathological models of gut microbiota to evaluate the impact of specific microbial populations on CRC lines in static 2D conditions.
2. Formulation of bioinks and 3D bioprinting of bi-layered micropillars containing gut microbiota and CRC cells for the assessment of their dynamics in a more structurally accurate context and;
3. Development of a CRC-on-chip replicating the biophysical stimuli of the colon to provide a bio-inspired miniaturised platform for CRC research.
This multidisciplinary approach, combining tissue engineering, microbiology, and microfluidics, is expected to have significant scientific, technological, and societal impacts, from advancing CRC research to developing high-throughput systems for drug screening applications with potential to optimise treatment strategies and reduce healthcare burdens. Additionally, the strategy proposed in BIOMIMIC-CRC has the potential to be translated to other systems where an interaction between microbiota and mammalian cells occurs.
The team of BIOMIMIC-CRC is composed by a multidisciplinary team of young and motivated researchers, committed to the development of more accessible and physiologically relevant models that have the potential to propel CRC research.