TY - JOUR
T1 - A Collagen Based Cryogel Bioscaffold that Generates Oxygen for Islet Transplantation
AU - Razavi, Mehdi
AU - Primavera, Rosita
AU - Kevadiya, Bhavesh D.
AU - Wang, Jing
AU - Buchwald, Peter
AU - Thakor, Avnesh S.
N1 - Funding Information:
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIH) award to the Stanford Diabetes Research Center (P30DK116074), the Akiko Yamzaki and Jerry Yang Faculty Scholar Fund in Pediatric Translational Medicine and the Stanford Maternal and Child Health Research Institute, and the Society of Interventional Radiology Foundation Ring Development Grant. This work was also supported by the Stanford Nano Shared Facilities (SNSF) grant (1161726-146-DAARZ), as part of the grant supported by the National Science Foundation grant (ECCS-1542152), and the Stanford Neuroscience Microscopy Service grant (NIH NS069375). The authors also wish to acknowledge Dr. Mujib Ullah for performing Western blot analysis. All procedures were performed in accordance with the regulations approved by the Institutional Animal Care and Use Committee (IACUC) of Stanford University.
Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/4/1
Y1 - 2020/4/1
N2 - The aim of this article is to develop, characterize, and test a novel 3D bioscaffold matrix that can accommodate pancreatic islets and provide them with a continuous, controlled, and steady source of oxygen to prevent hypoxia-induced damage following transplantation. Hence, a collagen-based cryogel bioscaffold that incorporates calcium peroxide (CPO) into its matrix is made. The optimal concentration of CPO integrated into bioscaffolds is 0.25 wt% and this generates oxygen at 0.21 ± 0.02 × 10-3 m day-1 (day 1), 0.19 ± 0.01 × 10-3 m day-1 (day 6), 0.13 ± 0.03 × 10-3 m d-1 (day 14), and 0.14 ± 0.02 × 10-3 m d-1 (day 21). Accordingly, islets seeded into cryogel-CPO bioscaffolds have a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds; these findings are supported by data from quantitative computational modeling. When syngeneic islets are transplanted into the epididymal fat pad (EFP) of diabetic mice, the cryogel-0.25 wt%CPO bioscaffold improves islet function with diabetic animals re-establishing glycemic control. Mice transplanted with cryogel-0.25 wt%CPO bioscaffolds show faster responses to intraperitoneal glucose injections and have a higher level of insulin content in their EFP compared to those transplanted with islets alone (P < 0.05). The novel oxygen-generating bioscaffold (i.e., cryogel-0.25 wt%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra-hepatic sites of transplantation.
AB - The aim of this article is to develop, characterize, and test a novel 3D bioscaffold matrix that can accommodate pancreatic islets and provide them with a continuous, controlled, and steady source of oxygen to prevent hypoxia-induced damage following transplantation. Hence, a collagen-based cryogel bioscaffold that incorporates calcium peroxide (CPO) into its matrix is made. The optimal concentration of CPO integrated into bioscaffolds is 0.25 wt% and this generates oxygen at 0.21 ± 0.02 × 10-3 m day-1 (day 1), 0.19 ± 0.01 × 10-3 m day-1 (day 6), 0.13 ± 0.03 × 10-3 m d-1 (day 14), and 0.14 ± 0.02 × 10-3 m d-1 (day 21). Accordingly, islets seeded into cryogel-CPO bioscaffolds have a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds; these findings are supported by data from quantitative computational modeling. When syngeneic islets are transplanted into the epididymal fat pad (EFP) of diabetic mice, the cryogel-0.25 wt%CPO bioscaffold improves islet function with diabetic animals re-establishing glycemic control. Mice transplanted with cryogel-0.25 wt%CPO bioscaffolds show faster responses to intraperitoneal glucose injections and have a higher level of insulin content in their EFP compared to those transplanted with islets alone (P < 0.05). The novel oxygen-generating bioscaffold (i.e., cryogel-0.25 wt%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra-hepatic sites of transplantation.
KW - bioscaffold
KW - islet transplantation
KW - oxygen
KW - type 1 diabetes
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U2 - 10.1002/adfm.201902463
DO - 10.1002/adfm.201902463
M3 - Article
C2 - 33071709
AN - SCOPUS:85083621162
SN - 1616-301X
VL - 30
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 15
M1 - 1902463
ER -