A Zwitterionic Polyurethane Nanoporous Device with Low Foreign-Body Response for Islet Encapsulation

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Polymer Chemistry

Background:

• Cell encapsulation is a key strategy for type 1 diabetes treatment.
• Current encapsulation devices face challenges with safety, foreign-body response, and mass transfer.

Purpose of the Study:

• To develop novel zwitterionic polyurethane (ZPU) encapsulation devices.
• To evaluate the safety, functionality, and therapeutic potential of ZPU devices for cell encapsulation.

Main Methods:

• Fabrication of ZPU encapsulation devices with tunable nanoporous structures via electrospinning.
• Assessment of device properties including hydrophilicity, fouling resistance, mechanical strength, cell containment, and mass transfer.
• In vivo evaluation of foreign-body response and therapeutic efficacy in mouse models of type 1 diabetes.
• Demonstration of scalability and retrievability in large animal models (pigs and dogs).

Main Results:

• ZPU devices exhibited robust mechanical properties, prevented cell escape, and allowed efficient mass transfer.
• ZPU devices showed significantly reduced foreign-body response and cellular overgrowth compared to non-zwitterionic controls in mice.
• Successful islet encapsulation and diabetes correction in mice for approximately 3 months.
• Proof-of-concept for scalability and retrievability in pigs and dogs.

Conclusions:

• Zwitterionic polyurethanes are effective materials for creating advanced cell encapsulation devices.
• ZPU devices overcome key limitations of current technologies, offering improved biocompatibility and functionality.
• These findings position ZPU devices as highly promising candidates for cell encapsulation therapies, particularly for type 1 diabetes treatment.