A Safe, Fibrosis-Mitigating, and Scalable Encapsulation Device Supports Long-Term Function of Insulin-Producing Cells

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Diabetes Research

Background:

• Cell encapsulation and transplantation offer a potential immunosuppression-free cure for type 1 diabetes (T1D).
• Current encapsulation biomaterials often trigger foreign body responses, leading to fibrosis and impaired cell function.
• Clinical translation requires devices that are safe, scalable, and retrievable.

Purpose of the Study:

• To develop a durable, safe, and fibrosis-mitigating encapsulation device for cell therapies.
• To enable scalable cell encapsulation without compromising mass transfer.
• To demonstrate long-term efficacy and safety for T1D treatment.

Main Methods:

• Fabrication of a nanofibrous device coated with a zwitterionic alginate hydrogel.
• Encapsulation of rat islets and human stem cell-derived beta (SC-β) cells within the device.
• In vivo testing in mouse models of diabetes and assessment of scalability/retrievability in dogs.

Main Results:

• The device demonstrated facile mass transfer and minimal fibrotic reactions.
• Long-term diabetes correction was achieved in mice using encapsulated rat islets (up to 399 days) and human SC-β cells (up to 238 days).
• Scalability and retrievability were successfully demonstrated in canine models.

Conclusions:

• The developed nanofibrous encapsulation device shows significant potential for cell-based therapies in treating type 1 diabetes.
• The device's design addresses key challenges in mass transfer, fibrosis, scalability, and retrievability.
• This technology could advance cell therapies for T1D and other diseases.