Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering

Hydrogel scaffolds play a crucial role in tissue engineering; however, traditional bulk hydrogel scaffolds (BHS) often suffer from insufficiently sized pores (nanoscales), impeding cellular infiltration, development, and expansion. This limitation affects oxygen and nutrient exchange efficiency, in...

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Main Authors: Yaqi Guo, Shan Mou, Litao Suo, Yingqian Zhou, Shuang Wu, Xinfang Xie, Di Sun, Bingqian Wang, Zhenxing Wang, Raymund E. Horch, Jie Yang, Jiaming Sun
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425005769
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author Yaqi Guo
Shan Mou
Litao Suo
Yingqian Zhou
Shuang Wu
Xinfang Xie
Di Sun
Bingqian Wang
Zhenxing Wang
Raymund E. Horch
Jie Yang
Jiaming Sun
author_facet Yaqi Guo
Shan Mou
Litao Suo
Yingqian Zhou
Shuang Wu
Xinfang Xie
Di Sun
Bingqian Wang
Zhenxing Wang
Raymund E. Horch
Jie Yang
Jiaming Sun
author_sort Yaqi Guo
collection DOAJ
description Hydrogel scaffolds play a crucial role in tissue engineering; however, traditional bulk hydrogel scaffolds (BHS) often suffer from insufficiently sized pores (nanoscales), impeding cellular infiltration, development, and expansion. This limitation affects oxygen and nutrient exchange efficiency, in which case it relies extensively on liquid permeation and bulk hydrogels swelling. In contrast, hydrogel microparticles (HMPs) have proven to be both printable and injectable, allowing the development of modular thick constructs with interconnected pores. This study introduces a novel method of fabricating porous granular hydrogel scaffolds (GHS) by printing thermo-crosslinked gelatin methacryloyl (GelMA) HMPs granular hydrogels before chemical crosslinking (dual-crosslinking). The scaffolds exhibit an average pore fraction ranging from 14 % to 23 % and an average pore size varying from 4923 μm2 to 8185 μm2 (with equivalent circular diameter of 80–102 μm). In vitro experiments demonstrated the effective infiltration, adhesion, proliferation, and adipogenic differentiation of human adipose-derived stem cells (hADSCs) within the scaffold pores. Additionally, in vivo observations confirmed the presence of differentiated adipose cells within the central pores after 4 weeks. These results collectively suggest the proposed microspheres printing technique holds significant promise for fabricating microporous scaffolds and further applications in tissue engineering.
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spelling doaj-art-ebeebd3f6de04724a974de5dcbe3bb9e2025-08-20T03:27:05ZengElsevierMaterials Today Bio2590-00642025-08-013310200610.1016/j.mtbio.2025.102006Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineeringYaqi Guo0Shan Mou1Litao Suo2Yingqian Zhou3Shuang Wu4Xinfang Xie5Di Sun6Bingqian Wang7Zhenxing Wang8Raymund E. Horch9Jie Yang10Jiaming Sun11Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China; Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of ChinaDepartment of Plastic and Hand Surgery and Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich Alexander University of Erlangen-Nürnberg, FAU, Schlossplatz 4, Erlangen, 91054, Bavaria, Germany; Corresponding author.Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China; Corresponding author.Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China; Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China; Corresponding author. Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.Hydrogel scaffolds play a crucial role in tissue engineering; however, traditional bulk hydrogel scaffolds (BHS) often suffer from insufficiently sized pores (nanoscales), impeding cellular infiltration, development, and expansion. This limitation affects oxygen and nutrient exchange efficiency, in which case it relies extensively on liquid permeation and bulk hydrogels swelling. In contrast, hydrogel microparticles (HMPs) have proven to be both printable and injectable, allowing the development of modular thick constructs with interconnected pores. This study introduces a novel method of fabricating porous granular hydrogel scaffolds (GHS) by printing thermo-crosslinked gelatin methacryloyl (GelMA) HMPs granular hydrogels before chemical crosslinking (dual-crosslinking). The scaffolds exhibit an average pore fraction ranging from 14 % to 23 % and an average pore size varying from 4923 μm2 to 8185 μm2 (with equivalent circular diameter of 80–102 μm). In vitro experiments demonstrated the effective infiltration, adhesion, proliferation, and adipogenic differentiation of human adipose-derived stem cells (hADSCs) within the scaffold pores. Additionally, in vivo observations confirmed the presence of differentiated adipose cells within the central pores after 4 weeks. These results collectively suggest the proposed microspheres printing technique holds significant promise for fabricating microporous scaffolds and further applications in tissue engineering.http://www.sciencedirect.com/science/article/pii/S2590006425005769Hydrogel microparticlesGranular hydrogel scaffoldsExtrusion printinghADSCsBreast tissue engineering
spellingShingle Yaqi Guo
Shan Mou
Litao Suo
Yingqian Zhou
Shuang Wu
Xinfang Xie
Di Sun
Bingqian Wang
Zhenxing Wang
Raymund E. Horch
Jie Yang
Jiaming Sun
Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering
Materials Today Bio
Hydrogel microparticles
Granular hydrogel scaffolds
Extrusion printing
hADSCs
Breast tissue engineering
title Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering
title_full Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering
title_fullStr Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering
title_full_unstemmed Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering
title_short Porous granular hydrogel scaffolds biofabricated from dual-crosslinked hydrogel microparticles for breast tissue engineering
title_sort porous granular hydrogel scaffolds biofabricated from dual crosslinked hydrogel microparticles for breast tissue engineering
topic Hydrogel microparticles
Granular hydrogel scaffolds
Extrusion printing
hADSCs
Breast tissue engineering
url http://www.sciencedirect.com/science/article/pii/S2590006425005769
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