Development of oxygen-releasing PVA hydrogels for protecting pancreatic beta cells from the hypoxic damage in diabetes
5 affiliations
- 1Department of Biomedical Engineering, Faculty of Technology, Kocaeli University 41001 Kocaeli Turkey
- 2Department of Stem Cell, Institute of Health Sciences, Kocaeli University 41001 Kocaeli Turkey
- 3Department of ChemistryIzmir Institute of Technology Urla Izmir 35430 Turkey
- 4Institute for Quantitative Health Science and Engineering, Michigan State University East Lansing MI USA
- 5Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University 41001 Kocaeli Turkey
Abstract
Hypoxia during the early post-transplantation period remains a major challenge for pancreatic β-cell survival and function before adequate vascularization is established. In this study, multilayered oxygen-generating hydrogels were developed using physically crosslinked poly(vinyl alcohol) (PVA) incorporating calcium peroxide (CPO) to support pancreatic β-cells under hypoxic conditions. The hydrogels were fabricated through repeated freeze–thaw cycles, with a CPO-containing core positioned between two catalase-containing outer layers designed to reduce cellular exposure to peroxide intermediates. Dimethyl sulfoxide (DMSO) was employed during fabrication to limit premature CPO hydrolysis. The physicochemical properties of the hydrogels were evaluated through morphological, swelling, and mechanical analyses, while dissolved oxygen levels in the surrounding medium were monitored over 28 days. The developed formulations maintained elevated dissolved oxygen levels over the observation period, with differences depending on CPO loading. Biological evaluations using human pancreatic β-cells (1.1B4) under hypoxic conditions demonstrated that the formulation containing 0.1% (w/v) CPO exhibited higher relative metabolic activity, reaching 170.0 ± 9.1% on day 7, and supported glucose-stimulated insulin secretion. In contrast, the 0.5% (w/v) CPO formulation showed reduced metabolic activity at later time points, increased lactate dehydrogenase (LDH) release, and lower INS gene expression. Matched catalase-free controls exhibited lower metabolic activity and greater LDH release than their catalase-containing counterparts, supporting the protective contribution of the catalase-containing outer layers. Overall, these findings demonstrate that the multilayered PVA/CPO–catalase architecture can provide sustained oxygenation while supporting pancreatic β-cell metabolic activity and insulin secretory function under in vitro hypoxic conditions.
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BibTeX
@article{isayeva2026development,
title = {{Development of oxygen-releasing PVA hydrogels for protecting pancreatic beta cells from the hypoxic damage in diabetes}},
author = {Aygün Isayeva and Elif Beyza Eren and Nermin Seda Kehr and Nureddin Ashammakhi and Yusufhan Yazır and Gökhan Duruksu and Ahmet Erdem},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra10280h},
url = {https://europepmc.org/article/PMC/PMC13729013},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Development of oxygen-releasing PVA hydrogels for protecting pancreatic beta cells from the hypoxic damage in diabetes
AU - Aygün Isayeva
AU - Elif Beyza Eren
AU - Nermin Seda Kehr
AU - Nureddin Ashammakhi
AU - Yusufhan Yazır
AU - Gökhan Duruksu
AU - Ahmet Erdem
PY - 2026
DA - 2026/11/03
JO - RSC advances
DO - 10.1039/d6ra10280h
UR - https://europepmc.org/article/PMC/PMC13729013
AB - Hypoxia during the early post-transplantation period remains a major challenge for pancreatic β-cell survival and function before adequate vascularization is established. In this study, multilayered oxygen-generating hydrogels were developed using physically crosslinked poly(vinyl alcohol) (PVA) incorporating calcium peroxide (CPO) to support pancreatic β-cells under hypoxic conditions. The hydrogels were fabricated through repeated freeze–thaw cycles, with a CPO-containing core positioned between two catalase-containing outer layers designed to reduce cellular exposure to peroxide intermediates. Dimethyl sulfoxide (DMSO) was employed during fabrication to limit premature CPO hydrolysis. The physicochemical properties of the hydrogels were evaluated through morphological, swelling, and mechanical analyses, while dissolved oxygen levels in the surrounding medium were monitored over 28 days. The developed formulations maintained elevated dissolved oxygen levels over the observation period, with differences depending on CPO loading. Biological evaluations using human pancreatic β-cells (1.1B4) under hypoxic conditions demonstrated that the formulation containing 0.1% (w/v) CPO exhibited higher relative metabolic activity, reaching 170.0 ± 9.1% on day 7, and supported glucose-stimulated insulin secretion. In contrast, the 0.5% (w/v) CPO formulation showed reduced metabolic activity at later time points, increased lactate dehydrogenase (LDH) release, and lower INS gene expression. Matched catalase-free controls exhibited lower metabolic activity and greater LDH release than their catalase-containing counterparts, supporting the protective contribution of the catalase-containing outer layers. Overall, these findings demonstrate that the multilayered PVA/CPO–catalase architecture can provide sustained oxygenation while supporting pancreatic β-cell metabolic activity and insulin secretory function under in vitro hypoxic conditions.
SN - 2046-2069
ER -