Tissue engineering of the gastrointestinal tract: the historic path to translation

The gastrointestinal (GI) tract is imperative for multiple functions including digestion, nutrient absorption, and timely waste disposal. The central feature of the gut is peristalsis, intestinal motility, which facilitates all of its functions. Disruptions in GI motility lead to sub-optimal GI function, resulting in a lower quality of life in many functional GI disorders. Over the last two decades, tissue engineering research directed towards the intestine has progressed rapidly due to advances in cell and stem-cell biology, integrative physiology, bioengineering and biomaterials. Newer biomedical tools (including optical tools, machine learning, and nuanced regenerative engineering approaches) have expanded our understanding of the complex cellular communication within the GI tract that lead to its orchestrated physiological function. Bioengineering therefore can be utilized towards several translational aspects: (i) regenerative medicine to remedy/restore GI physiological function; (ii) in vitro model building to mimic the complex physiology for drug and pharmacology testing; (iii) tool development to continue to unravel multi-cell communication networks to integrate cell and organ-level physiology. Despite the significant strides made historically in GI tissue engineering, fundamental challenges remain including the quest for identifying autologous human cell sources, enhanced scaffolding biomaterials to increase biocompatibility while matching viscoelastic properties of the underlying tissue, and overall biomanufacturing. This review provides historic perspectives for how bioengineering has advanced over time, highlights newer advances in bioengineering strategies, and provides a realistic perspective on the path to translation.