Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis

Abstract Achieving functional tissue regeneration hinges on the coordinated growth of intricate blood vessels and nerves within the defect area. However, current strategies do not offer a reliable and effective way to fulfill this critical need. To address this challenge, a three-dimensional (3D) ge...

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Main Authors: Junqing Liu, Jun Kang, Ting Zou, Mingxin Hu, Yuchen Zhang, Shulan Lin, Ye Liang, Jialin Zhong, Yi Zhao, Xi Wei, Chengfei Zhang
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03218-z
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author Junqing Liu
Jun Kang
Ting Zou
Mingxin Hu
Yuchen Zhang
Shulan Lin
Ye Liang
Jialin Zhong
Yi Zhao
Xi Wei
Chengfei Zhang
author_facet Junqing Liu
Jun Kang
Ting Zou
Mingxin Hu
Yuchen Zhang
Shulan Lin
Ye Liang
Jialin Zhong
Yi Zhao
Xi Wei
Chengfei Zhang
author_sort Junqing Liu
collection DOAJ
description Abstract Achieving functional tissue regeneration hinges on the coordinated growth of intricate blood vessels and nerves within the defect area. However, current strategies do not offer a reliable and effective way to fulfill this critical need. To address this challenge, a three-dimensional (3D) gelatin methacryloyl–multi-walled carbon nanotube/cobalt (GelMA–MWCNTs/Co) hydrogel with controlled release of cobalt (Co) ions was developed for hypoxia-mimicking and dual beneficial effects on promoting vasculogenesis and neurogenesis. GelMA–MWCNTs/Co hydrogel exhibited sustained release of Co ions, promoting laden cell viability and long-term cell survival. GelMA–MWCNTs/Co hydrogel effectively enhanced human umbilical vein endothelial cells (HUVECs) vasculogenesis when cocultured with stem cells from apical papilla (SCAP). Moreover, this hydrogel facilitated the interaction between the pre-formed vascular and neural-like structures generated by electrical stimulation-induced SCAP (iSCAP). Furthermore, our in vivo study revealed that the GelMA–MWCNTs/Co hydrogel remarkably enhanced neovascularization and accelerated anastomosis with the host vasculature. The pre-vascularized scaffolds boosted the presence of neural differentiated SCAP in the regenerated tissue. This study provided proof of integrating functional Co ions release materials and dental-derived stem cells within a hydrogel scaffold as a promising potential for achieving simultaneous vascularization and neurogenesis. Graphical abstract
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spelling doaj-art-e17ef38be19647b0b60508c83f3248cf2025-08-20T03:10:13ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123111910.1186/s12951-025-03218-zFunctional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesisJunqing Liu0Jun Kang1Ting Zou2Mingxin Hu3Yuchen Zhang4Shulan Lin5Ye Liang6Jialin Zhong7Yi Zhao8Xi Wei9Chengfei Zhang10Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of StomatologyRestorative Dental Sciences, Faculty of Dentistry, The University of Hong KongShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen Stomatology Hospital (Pingshan) of Southern Medical UniversityRestorative Dental Sciences, Faculty of Dentistry, The University of Hong KongDepartment of Obstetrics, The Third Affiliated Hospital of Zhengzhou UniversityRestorative Dental Sciences, Faculty of Dentistry, The University of Hong KongRestorative Dental Sciences, Faculty of Dentistry, The University of Hong KongRestorative Dental Sciences, Faculty of Dentistry, The University of Hong KongStrait Institute of Flexible Electronics (SIFE, Future Technologies), Fujian Key Laboratory of Flexible Electronics, Fujian Normal UniversityHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of StomatologyRestorative Dental Sciences, Faculty of Dentistry, The University of Hong KongAbstract Achieving functional tissue regeneration hinges on the coordinated growth of intricate blood vessels and nerves within the defect area. However, current strategies do not offer a reliable and effective way to fulfill this critical need. To address this challenge, a three-dimensional (3D) gelatin methacryloyl–multi-walled carbon nanotube/cobalt (GelMA–MWCNTs/Co) hydrogel with controlled release of cobalt (Co) ions was developed for hypoxia-mimicking and dual beneficial effects on promoting vasculogenesis and neurogenesis. GelMA–MWCNTs/Co hydrogel exhibited sustained release of Co ions, promoting laden cell viability and long-term cell survival. GelMA–MWCNTs/Co hydrogel effectively enhanced human umbilical vein endothelial cells (HUVECs) vasculogenesis when cocultured with stem cells from apical papilla (SCAP). Moreover, this hydrogel facilitated the interaction between the pre-formed vascular and neural-like structures generated by electrical stimulation-induced SCAP (iSCAP). Furthermore, our in vivo study revealed that the GelMA–MWCNTs/Co hydrogel remarkably enhanced neovascularization and accelerated anastomosis with the host vasculature. The pre-vascularized scaffolds boosted the presence of neural differentiated SCAP in the regenerated tissue. This study provided proof of integrating functional Co ions release materials and dental-derived stem cells within a hydrogel scaffold as a promising potential for achieving simultaneous vascularization and neurogenesis. Graphical abstracthttps://doi.org/10.1186/s12951-025-03218-zHypoxiaStem cells from apical papillaHydrogelVascularizationNeurogenesisTissue engineering
spellingShingle Junqing Liu
Jun Kang
Ting Zou
Mingxin Hu
Yuchen Zhang
Shulan Lin
Ye Liang
Jialin Zhong
Yi Zhao
Xi Wei
Chengfei Zhang
Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
Journal of Nanobiotechnology
Hypoxia
Stem cells from apical papilla
Hydrogel
Vascularization
Neurogenesis
Tissue engineering
title Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
title_full Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
title_fullStr Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
title_full_unstemmed Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
title_short Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
title_sort functional cobalt doped hydrogel scaffold enhances concurrent vascularization and neurogenesis
topic Hypoxia
Stem cells from apical papilla
Hydrogel
Vascularization
Neurogenesis
Tissue engineering
url https://doi.org/10.1186/s12951-025-03218-z
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