Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization

Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrog...

Full description

Bibliographic Details
Main Authors: Hayeon Byun, Yujin Han, Eunhyung Kim, Indong Jun, Jinkyu Lee, Hyewoo Jeong, Seung Jae Huh, Jinmyoung Joo, Su Ryon Shin, Heungsoo Shin
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-06-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24000744
_version_ 1797272451557621760
author Hayeon Byun
Yujin Han
Eunhyung Kim
Indong Jun
Jinkyu Lee
Hyewoo Jeong
Seung Jae Huh
Jinmyoung Joo
Su Ryon Shin
Heungsoo Shin
author_facet Hayeon Byun
Yujin Han
Eunhyung Kim
Indong Jun
Jinkyu Lee
Hyewoo Jeong
Seung Jae Huh
Jinmyoung Joo
Su Ryon Shin
Heungsoo Shin
author_sort Hayeon Byun
collection DOAJ
description Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel. The composite hydrogel (G-TSrP) is created by combining gelatin methacryloyl (GelMA) and nanoparticles (TSrP) composed of tannic acid (TA) and Sr2+. These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation. G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype. It has been observed that the liberation of TA and Sr2+ from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages, and thereby, coordinate in vivo adapted degradation of the G-TSrP. Most significantly, G-TSrP accelerates angiogenesis despite the TA's inhibitory properties, which are counteracted by the released Sr2+. Moreover, G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth. Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel. Collectively, these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.
first_indexed 2024-03-07T14:28:24Z
format Article
id doaj.art-e3fde7a009c64d6887a67646b31fd012
institution Directory Open Access Journal
issn 2452-199X
language English
last_indexed 2024-03-07T14:28:24Z
publishDate 2024-06-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj.art-e3fde7a009c64d6887a67646b31fd0122024-03-06T05:28:27ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-06-0136185202Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularizationHayeon Byun0Yujin Han1Eunhyung Kim2Indong Jun3Jinkyu Lee4Hyewoo Jeong5Seung Jae Huh6Jinmyoung Joo7Su Ryon Shin8Heungsoo Shin9Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Cambridge, MA 02139, USADepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of KoreaDepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of KoreaEnvironmental Safety Group, Korea Institute of Science & Technology Europe (KIST-EUROPE), Saarbrücken 66123, GermanyDepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of KoreaDepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of KoreaDepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of KoreaDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of KoreaDivision of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Cambridge, MA 02139, USADepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; Institute of Nano Science and Technology, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; Corresponding author. Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel. The composite hydrogel (G-TSrP) is created by combining gelatin methacryloyl (GelMA) and nanoparticles (TSrP) composed of tannic acid (TA) and Sr2+. These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation. G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype. It has been observed that the liberation of TA and Sr2+ from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages, and thereby, coordinate in vivo adapted degradation of the G-TSrP. Most significantly, G-TSrP accelerates angiogenesis despite the TA's inhibitory properties, which are counteracted by the released Sr2+. Moreover, G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth. Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel. Collectively, these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.http://www.sciencedirect.com/science/article/pii/S2452199X24000744ImmunomodulationWound healingNeovascularizationMulti-functional nanoparticlesComposite hydrogels
spellingShingle Hayeon Byun
Yujin Han
Eunhyung Kim
Indong Jun
Jinkyu Lee
Hyewoo Jeong
Seung Jae Huh
Jinmyoung Joo
Su Ryon Shin
Heungsoo Shin
Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
Bioactive Materials
Immunomodulation
Wound healing
Neovascularization
Multi-functional nanoparticles
Composite hydrogels
title Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
title_full Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
title_fullStr Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
title_full_unstemmed Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
title_short Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
title_sort cell homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization
topic Immunomodulation
Wound healing
Neovascularization
Multi-functional nanoparticles
Composite hydrogels
url http://www.sciencedirect.com/science/article/pii/S2452199X24000744
work_keys_str_mv AT hayeonbyun cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT yujinhan cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT eunhyungkim cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT indongjun cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT jinkyulee cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT hyewoojeong cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT seungjaehuh cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT jinmyoungjoo cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT suryonshin cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization
AT heungsooshin cellhomingandimmunomodulatorycompositehydrogelsforeffectivewoundhealingwithneovascularization