ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration

Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for an...

Full description

Saved in:
Bibliographic Details
Main Authors: Guanglong Li, Fei Gao, Donglei Yang, Lu Lin, Weijun Yu, Jiaqi Tang, Ruhan Yang, Min Jin, Yuting Gu, Pengfei Wang, Eryi Lu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-12-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24003736
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850178336907591680
author Guanglong Li
Fei Gao
Donglei Yang
Lu Lin
Weijun Yu
Jiaqi Tang
Ruhan Yang
Min Jin
Yuting Gu
Pengfei Wang
Eryi Lu
author_facet Guanglong Li
Fei Gao
Donglei Yang
Lu Lin
Weijun Yu
Jiaqi Tang
Ruhan Yang
Min Jin
Yuting Gu
Pengfei Wang
Eryi Lu
author_sort Guanglong Li
collection DOAJ
description Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.
format Article
id doaj-art-5e7b339f525048aab0779d9a9d64205a
institution OA Journals
issn 2452-199X
language English
publishDate 2024-12-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj-art-5e7b339f525048aab0779d9a9d64205a2025-08-20T02:18:46ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-12-014224125610.1016/j.bioactmat.2024.08.035ECM-mimicking composite hydrogel for accelerated vascularized bone regenerationGuanglong Li0Fei Gao1Donglei Yang2Lu Lin3Weijun Yu4Jiaqi Tang5Ruhan Yang6Min Jin7Yuting Gu8Pengfei Wang9Eryi Lu10Department of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaInstitute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaInstitute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, ChinaInstitute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, China; Corresponding author.Department of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, China; Corresponding author.Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.http://www.sciencedirect.com/science/article/pii/S2452199X24003736Composite hydrogelDNA hydrogelStress relaxationOsteogenesisVascularization
spellingShingle Guanglong Li
Fei Gao
Donglei Yang
Lu Lin
Weijun Yu
Jiaqi Tang
Ruhan Yang
Min Jin
Yuting Gu
Pengfei Wang
Eryi Lu
ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration
Bioactive Materials
Composite hydrogel
DNA hydrogel
Stress relaxation
Osteogenesis
Vascularization
title ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration
title_full ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration
title_fullStr ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration
title_full_unstemmed ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration
title_short ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration
title_sort ecm mimicking composite hydrogel for accelerated vascularized bone regeneration
topic Composite hydrogel
DNA hydrogel
Stress relaxation
Osteogenesis
Vascularization
url http://www.sciencedirect.com/science/article/pii/S2452199X24003736
work_keys_str_mv AT guanglongli ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT feigao ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT dongleiyang ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT lulin ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT weijunyu ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT jiaqitang ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT ruhanyang ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT minjin ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT yutinggu ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT pengfeiwang ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration
AT eryilu ecmmimickingcompositehydrogelforacceleratedvascularizedboneregeneration