Early-stage organoid formation in biofunctionalized self-assembling peptide matrices combinations

Abstract

As the third most commonly diagnosed cancer in the world, colorectal cancer (CRC) has become a pressing and urgent problem, requiring the disease mechanism research and therapeutic development. The field of tissue engineering has considerably progressed since the advent of synthetic matrices for 3D cell culture, providing in vitro models for CRC disease research. Compared to animal-derived matrices such as matrigel, synthetic matrices have several advantages including controllable properties, avoiding ethical problems and batch-to-batch variation. Ultrashort self-assembly peptides of amphiphilic nature have recently proven to be excellent matrices for 3D cell culture of many types of cells. In this thesis, we aimed to use biofunctional peptides to promote the growth of colorectal cancer organoids in the early stage of development. A peptide-based biofunctional hydrogel for organoid culture has been developed for the purpose of establishing a reproducible colorectal cancer model. The hydrogel is composed of self-assembly peptides designed to induce cell-matrix interactions. The hydrogel is mechanically tunable with customizable cell-adhesive ligands and has the ability to promote the formation and growth of colorectal cancer organoids in vitro. One of these biofunctionalized peptide matrices was particularly suitable for CRC lumen development, apical protein expression, and cell differentiation level compared to the gold-standard ECM Matrigel.