Oxygen-enhanced assembloid-based vascularized intestinal-on-a-chip for radioprotective drug evaluation

Area of Science:

• Biomedical Engineering
• Gastroenterology
• Radiation Biology

Background:

• The intestine is crucial for digestion, immunity, and metabolism but vulnerable to radiation.
• Existing 3D intestinal models suffer from hypoxia, limiting their accuracy.
• Improving oxygenation in in vitro intestinal models is essential for advanced research.

Purpose of the Study:

• To create a physiologically relevant in vitro intestinal model with enhanced oxygen mass transfer.
• To improve structural organization and functional maturation of 3D intestinal constructs.
• To apply the model for studying radiation-induced injury and evaluating radioprotective agents.

Main Methods:

• A microengineered 3D cell-assembly platform was used, organizing intestinal epithelial cells, endothelial cells, and fibroblasts.
• An oxygen-permeable microwell system was implemented to alleviate hypoxia and promote epithelial differentiation.
• A vascularized chip was created by incorporating self-assembled microvascular networks within a hydrogel matrix.

Main Results:

• The model demonstrated characteristic radiation injury symptoms, including reduced cell viability and impaired barrier integrity.
• Treatment with dimethyloxalylglycine (DMOG) effectively mitigated radiation-induced damage.
• The model's response confirmed its utility for assessing radioprotective drugs.

Conclusions:

• The developed vascularized intestinal-on-a-chip model accurately mimics the human intestinal microenvironment.
• This model provides a robust platform for studying radiation-induced intestinal injury.
• The system has significant applications in radiation protection and regenerative medicine research.