Abstract
Cell macroencapsulation circumvents the host immune system response against foreign tissue, bearing enormous potential as a safeguard for cell-based therapies for diabetes treatment. With this technology, pancreatic islets can safely be transplanted without immunosuppression, facilitating islet survival and function by embedding these in a customised matrix. So far, no islet encapsulation device has been shown to be fully functional in a clinical trial. In this project, we aim to overcome the limitations of current approaches of cell encapsulation. By the application of advanced additive manufacturing technologies to the prototyping process, a modular encapsulation device has been designed. The design of this geometry focusses on sufficient oxygen availability and optimal diffusion characteristics to the islets in various means. The encapsulation device comprises three modules: a membrane holder, a skeleton and an islet housing module.The membrane module carries a newly developed immunoisolating membrane with enhanced biocompatibility and vascularisation properties. To prevent immune-mediated rejection of the encapsulated cells, a composite membrane tuned to only allow passage of molecules smaller than 11.4 nm (exclusion of antibodies), while allowing diffusion of secreted hormones such as insulin. This composite membrane consists of modified polytetrafluoroethylene and a biohybrid heparin-starPEG hydrogel. The applied hydrogel can gradually bind and release growth factors and has previously been shown to mediate wound inflammation and stimulate angiogenesis. The skeleton module holds an oxygen-generating scaffold, which transiently provides endogenous oxygen inside the implant. During the initial post implantation period, it allows for adequate oxygen supply to the cell graft until vascularisation around the device has been sufficiently achieved. The distinguishing feature of the developed device geometry is the islet housing module comprising a microwell array, which separates single islets in a monolayer at defined distances and therefore is expected to create optimal diffusion characteristics for oxygen and effector hormones.
In summary, a novel macroencapsulation device for pancreatic islets down to the micro- and nanoscale has been designed covering the most critical aspects of immunoisolation, a clinically scalable device geometry, intrinsic oxygenation and a tailored matrix supporting long-term islet survival and function.
| Date of Award | 1 Jan 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Barbara Ludwig (Supervisor), Carsten Werner (Supervisor), Petra B. Welzel (Supervisor) & Peter Jones (Supervisor) |