The problem
Ulcerative colitis is a form of inflammatory bowel disease that affects about 900,000 Americans. The immune system attacks the lining of the colon, causing pain, bleeding and fatigue, and a higher risk of colon cancer.
Treatment is mostly reactive. Steroids like prednisone have many side effects, more than half of patients on biologic drugs don't reach remission, and about 30% of patients end up needing surgery. There is no preventive therapy.
Our proposal
We proposed a hydrogel that can be sprayed onto the inside of the colon. It carries E. coli engineered to produce interleukin-10 (IL-10), a protein that calms inflammation.
IL-10 helps in inflammatory bowel disease at high IV doses, but it can't be taken by mouth because stomach acid destroys it. Making it on site solves that. E. coli already lives in the gut, the engineered strain isn't harmful, and because the bacteria keep growing, one application could treat the colon for longer.
Hypothesis
The hydrogel will reduce inflammation by delivering IL-10 directly to the inflamed tissue, while being safe for the surrounding cells and sticking firmly to the intestinal mucus layer.
How we'd test it
Porosity and diffusion. Image the gel's structure with atomic force microscopy and STED microscopy to measure pore size and void fraction, then track how quickly IL-10 diffuses through gels with different crosslink densities.
Biocompatibility. Run a direct-contact cytotoxicity test following ISO 10993-5 on normal human colon cells (NCM460), checking cell viability every 24 hours for 3 days against positive and negative controls.
Mucus adhesion. Coat a surface with simulated intestinal mucus, apply the gel, and expose it to fluid flow that mimics the gut, measuring how strongly it sticks and how long it stays.
Animal model. Test in humanized mice (CD34+ NSG-SGM3) with colitis induced by dextran sulfate sodium. One limitation is that the gel would be injected in mice rather than sprayed during an endoscopy.