ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment

Mesenchymal stem cell (MSC) transplantation is widely recognized as a promising treatment for peripheral artery diseases because of their unique ability to secrete multiple growth factors and immunomodulatory cytokines. However, direct administration of MSCs frequently results in insufficient therap...

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Main Authors: Seungjun Lee, Goeun Choe, Jongdarm Yi, Junghyun Kim, Sun Hong Lee, Jin Jeon, Hee Seok Yang, Jae Young Lee
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424003508
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author Seungjun Lee
Goeun Choe
Jongdarm Yi
Junghyun Kim
Sun Hong Lee
Jin Jeon
Hee Seok Yang
Jae Young Lee
author_facet Seungjun Lee
Goeun Choe
Jongdarm Yi
Junghyun Kim
Sun Hong Lee
Jin Jeon
Hee Seok Yang
Jae Young Lee
author_sort Seungjun Lee
collection DOAJ
description Mesenchymal stem cell (MSC) transplantation is widely recognized as a promising treatment for peripheral artery diseases because of their unique ability to secrete multiple growth factors and immunomodulatory cytokines. However, direct administration of MSCs frequently results in insufficient therapeutic efficacy due to low viability and poor retention at the implantation site. The delivery of MSCs in microsized hydrogels allows for simple injection, improved retention, and enhanced cell protection. However, the high oxidative stress present in ischemic tissues significantly impairs the viability and therapeutic activity of transplanted MSCs. This study aimed to develop a simple and effective method for fabricating reactive oxygen species (ROS)-scavenging microgels to enhance the MSC efficacy for ischemic hindlimb treatment. Specifically, tip-sonicated graphene oxide (GO)/alginate (sGO/alginate) microgels exhibited significantly increased antioxidizing activity against various ROS compared with pristine GO/alginate microgels. MSCs encapsulated in sGO/alginate microgels (MSC/sGO/alginate) demonstrated higher viability than those encapsulated in alginate or GO/alginate microgels under various oxidative stress conditions. Furthermore, human umbilical vein endothelial cells co-cultured with MSCs encapsulated in sGO/alginate microgels formed more tubes under both normal and H2O2-treated conditions, implying enhanced pro-angiogenic potential of the MSCs. In vivo experiments using hindlimb ischemia mouse models revealed significant improvements in blood perfusion, limb salvage, vascularization, and MSC survival in the MSC/sGO/alginate group compared with the other groups (MSC, MSC/alginate, and MSC/GO/alginate). The strategy developed in this study offers a straightforward and powerful method for treating various ROS-related diseases, including ischemia.
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spelling doaj-art-e51263a8fb764f048f8a591aebc130392025-08-20T01:55:30ZengElsevierMaterials Today Bio2590-00642024-12-012910128910.1016/j.mtbio.2024.101289ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatmentSeungjun Lee0Goeun Choe1Jongdarm Yi2Junghyun Kim3Sun Hong Lee4Jin Jeon5Hee Seok Yang6Jae Young Lee7School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of KoreaSchool of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of KoreaSchool of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of KoreaSchool of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of KoreaDepartment of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of KoreaDepartment of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of KoreaDepartment of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomedical Science & Engineering, Dankook University, Cheonan, 31116, Republic of KoreaSchool of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of Korea; Corresponding author.Mesenchymal stem cell (MSC) transplantation is widely recognized as a promising treatment for peripheral artery diseases because of their unique ability to secrete multiple growth factors and immunomodulatory cytokines. However, direct administration of MSCs frequently results in insufficient therapeutic efficacy due to low viability and poor retention at the implantation site. The delivery of MSCs in microsized hydrogels allows for simple injection, improved retention, and enhanced cell protection. However, the high oxidative stress present in ischemic tissues significantly impairs the viability and therapeutic activity of transplanted MSCs. This study aimed to develop a simple and effective method for fabricating reactive oxygen species (ROS)-scavenging microgels to enhance the MSC efficacy for ischemic hindlimb treatment. Specifically, tip-sonicated graphene oxide (GO)/alginate (sGO/alginate) microgels exhibited significantly increased antioxidizing activity against various ROS compared with pristine GO/alginate microgels. MSCs encapsulated in sGO/alginate microgels (MSC/sGO/alginate) demonstrated higher viability than those encapsulated in alginate or GO/alginate microgels under various oxidative stress conditions. Furthermore, human umbilical vein endothelial cells co-cultured with MSCs encapsulated in sGO/alginate microgels formed more tubes under both normal and H2O2-treated conditions, implying enhanced pro-angiogenic potential of the MSCs. In vivo experiments using hindlimb ischemia mouse models revealed significant improvements in blood perfusion, limb salvage, vascularization, and MSC survival in the MSC/sGO/alginate group compared with the other groups (MSC, MSC/alginate, and MSC/GO/alginate). The strategy developed in this study offers a straightforward and powerful method for treating various ROS-related diseases, including ischemia.http://www.sciencedirect.com/science/article/pii/S2590006424003508Hindlimb ischemiaGraphene oxideAntioxidantMesenchymal stem cellsSonication
spellingShingle Seungjun Lee
Goeun Choe
Jongdarm Yi
Junghyun Kim
Sun Hong Lee
Jin Jeon
Hee Seok Yang
Jae Young Lee
ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
Materials Today Bio
Hindlimb ischemia
Graphene oxide
Antioxidant
Mesenchymal stem cells
Sonication
title ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
title_full ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
title_fullStr ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
title_full_unstemmed ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
title_short ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
title_sort ros scavenging ultrasonicated graphene oxide alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment
topic Hindlimb ischemia
Graphene oxide
Antioxidant
Mesenchymal stem cells
Sonication
url http://www.sciencedirect.com/science/article/pii/S2590006424003508
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