Biomaterials and biosensors in intestinal organoid culture, a progress review

Abstract

As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their threedimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them. K E Y W O R D Sbiosensor, intestinal stem cell, organoid, regenerative medicine, scaffold design

Structurally Dynamic Hydrogels for Biomedical Applications: Pursuing a Fine Balance between Macroscopic Stability and Microscopic Dynamics

“…Over the past decade, one of the key advances in the field of stem cell research is the development of organoids generated from self-renewing stem cells, including both pluripotent and tissue-derived stem cells. − Organoids are unique 3D cell models with multicellular architectures, similar to those of organs, and can reproduce partial functions of the corresponding tissues such as intestine, optic cup, liver, brain, pancreas, and stomach. − Owing to their unique properties, organoids provide unprecedented opportunities for the basic study of organ development and disease pathogenesis, and they are powerful tools for drug screening as well as reliable sources for organ transplantation in the future. As in building ex vivo tumor models, Matrigel, a structurally dynamic hydrogel, is also widely used for establishing organoid models.…”

Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation

“…In the present work we used Matrigel as a scaffold to induce and promote spheroid formation by HAT-7 cells. Matrigel is a poorly defined basement membrane derivative extracted from Engelbreth–Holm–Swarm mouse sarcoma cells, thus its direct application in regenerative medicine is limited ( Huang et al, 2020 ). However, its use is well established in the culture of spheroids and organoids from various tissues, especially those of epithelial origin.…”

“…However, its use is well established in the culture of spheroids and organoids from various tissues, especially those of epithelial origin. This is mainly because of three key factors: first, the Matrigel provides anchoring molecules such as the arg-gly-asp (RGD) sequence for cell adhesion; second, it has optimal stiffness for housing the cells; and third, it contains laminin-111, an important extracellular component that can independently provide biological signals for spheroid/organoid formation and growth ( Huang et al, 2020 ). Using Matrigel, 3D spheroids and organoids have been created from intestinal epithelial cells ( Huang et al, 2019 ), pancreas ( Bakhti et al, 2019 ; Molnar et al, 2020 ), lacrimal glands ( Schonthal et al, 2000 ; Massie et al, 2018 ) and salivary glands ( Szlavik et al, 2008a ; Szlavik et al, 2008b ; Maria et al, 2011 ).…”

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19)

“…Hydrogel matrices were also used for organoid culture and supporting organoid growth [80]. There is a range of synthetic and natural hydrogels [81] that can potentially be used in organoid production. Synthetic hydrogels have generally higher mechanical strength than natural hydrogels, but they lack important bioactive moities needed to support cell adhesion and proliferation [82].…”

“…Synthetic hydrogels have generally higher mechanical strength than natural hydrogels, but they lack important bioactive moities needed to support cell adhesion and proliferation [82]. Natural hydrogels contain moities like arg-gly-asp (RGD) sequence and laminin that provide cell anchoring means and biological signals for organoid growth [81]. Synthetic hydrogels such as polyethylene glycol (PEG) [83], modified PEG using RGD and laminin [84], PEG-based hydrogels [85], alginate [86], hyaluronic acid, collagen, gelatin, and fibrin [81] can also be used to support the survival of organoids.…”