Selmin, Giulia; (2024) Biofabrication of 3D human smooth muscle constructs for intestinal tissue engineering. Doctoral thesis (Ph.D), UCL (University College London).

Text Giulia_Selmin_PhD Thesis_G. Selmin.pdf - Submitted Version Access restricted to UCL open access staff until 1 December 2025. Download (7MB)

Abstract

Recent advances in intestinal tissue engineering have led to improved biomimicry in terms of biological composition. Nevertheless, the complex architecture is still far from being faithfully reproduced and, as it strictly relates to tissue function, is a necessary component that must be implemented into the engineered models to fully exploit their potential. Particularly challenging is recreating in vitro the orthogonal orientation of smooth muscle (SM) layers as seen in vivo because important functions (i.e., peristalsis) cannot occur without such specific alignment. The aim of this project is biofabricating a threedimensional (3D) highly organised SM structure resembling the gut’s longitudinal and circular architecture with a view to create a biologically relevant gut model. Human pericytes derived from muscle and intestinal biopsies, namely mesoangioblasts (MABs), were used as SM precursors, given their established differentiation potential toward this lineage. The 3D shape and orientation were provided to the cells by a biocompatible photo-crosslinkable gelatine-based scaffold designed ad hoc and fabricated with two-photon bioprinting technology. MABs showed successful adhesion to the printed surfaces and morphological adaptation to linear and circular patterns. Remarkably, cells seeded onto hollow cylindrical 3D scaffolds, where the inner and outer surfaces are orthogonally orientated, effectively positioned according to the patterns, while retaining their ability to differentiate and mature. The organoid technology was then exploited to increase the biomimicry of the gut model: intestinal organoids were added as the epithelial component to the 3D SM tubes. Lastly, in the view of creating a prenatal patient-specific 3D model, amniotic fluid stem cells were used as muscle source given their ability of SM differentiation in vitro, thus paving the way for disease modelling and personalised pharmacological studies in pre-natal settings. On a final note, such SM construct is a valid 3D system for the tissue engineering of other hollow organs (oesophagus and ureter).

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