Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration

Wound healing progresses through many key cellular activities, including fibroblast and keratinocyte proliferation and angiogenesis. This study explored the wound-healing potential of reactive oxygen species (ROS)-generating hyaluronic acid (HA) hydrogels. We fabricated a chlorin e6–conjugated HA (C...

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Main Authors: Seung Hee Hong, Ye Jin Park, Seo In Lee, Ki Chang Nam, Mi Hee Lee, Jong-Chul Park
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-09-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25001902
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author Seung Hee Hong
Ye Jin Park
Seo In Lee
Ki Chang Nam
Mi Hee Lee
Jong-Chul Park
author_facet Seung Hee Hong
Ye Jin Park
Seo In Lee
Ki Chang Nam
Mi Hee Lee
Jong-Chul Park
author_sort Seung Hee Hong
collection DOAJ
description Wound healing progresses through many key cellular activities, including fibroblast and keratinocyte proliferation and angiogenesis. This study explored the wound-healing potential of reactive oxygen species (ROS)-generating hyaluronic acid (HA) hydrogels. We fabricated a chlorin e6–conjugated HA (Ce6-HA) hydrogel that generates ROS when subjected to irradiation from an LED light source. In vitro studies revealed that the ROS generated by the Ce6-HA hydrogels enhanced the proliferation of fibroblasts and keratinocytes. Further, the fibroblasts were found to have high levels of intracellular ROS, elevated expression of p-ERK1/2, p-p38 MAPK, p-Akt, and cyclin D1 proteins, and enhanced collagen deposition. Moreover, the Ce6-HA hydrogel also promoted endothelial angiogenesis in vitro. In vivo studies demonstrated the ROS-generating HA hydrogels significantly improved wound closure and tissue regeneration compared to control groups. The Ce6-HA hydrogel-treated group exhibited accelerated wound healing, with enhanced fibroblast proliferation, increased keratinocyte proliferation, and better angiogenesis. Histopathological and immunohistochemical analyses showed elevated levels of key growth factors and signaling molecules, which are critical to wound healing. The controlled ROS generation from the Ce6-HA hydrogels activated broader molecular pathways necessary for effective skin tissue repair. Therefore, ROS-triggering HA hydrogels could be a viable approach to accelerate recovery and reduce scarring in clinical settings.
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spelling doaj-art-8ea024dbfc99402e93a6cb8ed55e78222025-08-20T03:18:15ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-09-015197799210.1016/j.bioactmat.2025.05.006Photodynamically tunable ROS-generating hydrogels for accelerated tissue regenerationSeung Hee Hong0Ye Jin Park1Seo In Lee2Ki Chang Nam3Mi Hee Lee4Jong-Chul Park5Department of Medical Engineering, Yonsei University, College of Medicine, Seoul 03722, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University, College of Medicine, Seoul, 03722, Republic of KoreaDepartment of Medical Engineering, Yonsei University, College of Medicine, Seoul 03722, Republic of KoreaDepartment of Medical Engineering, Yonsei University, College of Medicine, Seoul 03722, Republic of KoreaDepartment of Medical Engineering, Dongguk University, College of Medicine, Gyeonggi-do, 10326, Republic of KoreaDepartment of Medical Engineering, Yonsei University, College of Medicine, Seoul 03722, Republic of KoreaDepartment of Medical Engineering, Yonsei University, College of Medicine, Seoul 03722, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University, College of Medicine, Seoul, 03722, Republic of Korea; Corresponding author. Department of Medical Engineering, Yonsei University, College of Medicine, Seoul, 03722, Republic of Korea.Wound healing progresses through many key cellular activities, including fibroblast and keratinocyte proliferation and angiogenesis. This study explored the wound-healing potential of reactive oxygen species (ROS)-generating hyaluronic acid (HA) hydrogels. We fabricated a chlorin e6–conjugated HA (Ce6-HA) hydrogel that generates ROS when subjected to irradiation from an LED light source. In vitro studies revealed that the ROS generated by the Ce6-HA hydrogels enhanced the proliferation of fibroblasts and keratinocytes. Further, the fibroblasts were found to have high levels of intracellular ROS, elevated expression of p-ERK1/2, p-p38 MAPK, p-Akt, and cyclin D1 proteins, and enhanced collagen deposition. Moreover, the Ce6-HA hydrogel also promoted endothelial angiogenesis in vitro. In vivo studies demonstrated the ROS-generating HA hydrogels significantly improved wound closure and tissue regeneration compared to control groups. The Ce6-HA hydrogel-treated group exhibited accelerated wound healing, with enhanced fibroblast proliferation, increased keratinocyte proliferation, and better angiogenesis. Histopathological and immunohistochemical analyses showed elevated levels of key growth factors and signaling molecules, which are critical to wound healing. The controlled ROS generation from the Ce6-HA hydrogels activated broader molecular pathways necessary for effective skin tissue repair. Therefore, ROS-triggering HA hydrogels could be a viable approach to accelerate recovery and reduce scarring in clinical settings.http://www.sciencedirect.com/science/article/pii/S2452199X25001902Wound healingHyaluronic acidHydrogelReactive oxygen speciesAngiogenesisProliferation
spellingShingle Seung Hee Hong
Ye Jin Park
Seo In Lee
Ki Chang Nam
Mi Hee Lee
Jong-Chul Park
Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration
Bioactive Materials
Wound healing
Hyaluronic acid
Hydrogel
Reactive oxygen species
Angiogenesis
Proliferation
title Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration
title_full Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration
title_fullStr Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration
title_full_unstemmed Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration
title_short Photodynamically tunable ROS-generating hydrogels for accelerated tissue regeneration
title_sort photodynamically tunable ros generating hydrogels for accelerated tissue regeneration
topic Wound healing
Hyaluronic acid
Hydrogel
Reactive oxygen species
Angiogenesis
Proliferation
url http://www.sciencedirect.com/science/article/pii/S2452199X25001902
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AT seoinlee photodynamicallytunablerosgeneratinghydrogelsforacceleratedtissueregeneration
AT kichangnam photodynamicallytunablerosgeneratinghydrogelsforacceleratedtissueregeneration
AT miheelee photodynamicallytunablerosgeneratinghydrogelsforacceleratedtissueregeneration
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