Abstract
The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets.
| Original language | English |
|---|---|
| Article number | 120449 |
| Number of pages | 13 |
| Journal | Biomaterials |
| Volume | 267 |
| DOIs | |
| Publication status | Published - Jan 2021 |
Funding
This research has received funding from the Dutch Province of Limburg, from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 694801 ), and from the Juvenile Diabetes Research Foundation (grant agreement No 3-SRA-2016-256-S-B and No 3-SRA-2017-428-S-B ). In addition, it is supported by the partners of Regenerative Medicine Crossing Borders (RegMed XB), a public–private partnership that uses regenerative medicine strategies to cure common chronic diseases. This collaboration project is financed by the Dutch Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public–private partnerships. The funding sources had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. We would like to thank Tonny Bosman (SupraPolix, the Netherlands) for providing us the UPy-PC material and Hang Nguyen (Maastricht University, the Netherlands) for her help revising the manuscript.
| Funders | Funder number |
|---|---|
| European Union's Horizon 2020 - Research and Innovation Framework Programme | |
| Ministerie van Economische Zaken en Klimaat | |
| European Union's Horizon 2020 - Research and Innovation Framework Programme | 694801 |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Keywords
- Biomaterials
- Clinical islet transplantation
- Islet encapsulation device
- Oxidative stress
- Type 1 diabetes
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