The investigators used the engineered hydrogels to generate a 3D matrix that provides optimal physical and biochemical support for organoid growth. Current methods for generating HIOs rely on growth in an animal tumour-derived extracellular matrix, which severely limits their future application in humans.

Growing HIOs in the engineered hydrogel, on the other hand, opens up possibilities for research into clinical applications. "The fully defined nature of these synthetic bioengineered hydrogels could make them ideal for use in human patients, in the event that HIOs are used for therapy in the future," explained co-lead author Miguel Quirós.

The synthetic matrix, developed at Georgia Tech, can be easily modified to create the mechanical and biological properties that suit the needs of the cells being hosted. In this work, co-lead author Ricardo Cruz-Acuña determined that a hydrogel made up of 96% water and containing a particular cell adhesion peptide was ideal for the HIOs.

Using a tiny colonoscope, Cruz-Acuña and Quirós delivered the hydrogel, along with the organoids, into wounds in the intestines of immune-compromised mice. The implanted cells were labelled so that they could be detected later.

After four weeks, the HIOs had completely engrafted into the injured area, forming 3D structures that resembled normal tissue. The synthetic hydrogel had disappeared, replaced by natural extracellular matrix produced by the cells themselves.

"We have shown that the hydrogel matrix helps the HIOs engraft into the intestinal tissue, that they differentiate and accelerate the healing of the wound," said Georgia Tech's Andrés García. "This work provides a proof of principle for using stem cell-derived human intestinal organoids in a therapeutic setting."

Next, the researchers hope to test their hydrogel matrix in animals with normal immune systems and in disease models. They note that trials in large animals would likely be needed before any human trials could be considered. Beyond the intestinal applications, such as treating wounds caused by disorders such as inflammatory bowel disease, for example, the team is also studying the use of hydrogels to deliver organoids to damaged kidneys and lungs.