Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration

Digital light processing (DLP) bioprinting has revolutionized tissue engineering by offering unprecedented speed and precision. However, its full biomedical potential is hindered by the scarcity of cell-laden bioinks that combine excellent printability with superior bioactivity. In this study, we in...

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Main Authors: Caihong Fu, Guangyu Liu, Yirui Fan, Lang Xiao, Wenhua Li, Xinyu Tian, Jianxi Xiao
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425004788
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author Caihong Fu
Guangyu Liu
Yirui Fan
Lang Xiao
Wenhua Li
Xinyu Tian
Jianxi Xiao
author_facet Caihong Fu
Guangyu Liu
Yirui Fan
Lang Xiao
Wenhua Li
Xinyu Tian
Jianxi Xiao
author_sort Caihong Fu
collection DOAJ
description Digital light processing (DLP) bioprinting has revolutionized tissue engineering by offering unprecedented speed and precision. However, its full biomedical potential is hindered by the scarcity of cell-laden bioinks that combine excellent printability with superior bioactivity. In this study, we introduce a novel cell-laden collagen-based bioink optimized for precise DLP bioprinting and diabetic wound regeneration. This bioink integrates methacrylated collagen (CMA) with dihydromyricetin (DHM) and selected additives, achieving a combination of low concentration, high printability, and superior cell bioactivity, along with antioxidant and anti-inflammatory effects. By employing a multi-crosslinking strategy that integrates free radical polymerization, Michael addition, Schiff base formation, and hydrogen bonding, the bioink achieves an ultra-fast gelation speed (375 % increase), a 161 % increase in stiffness, a 231 % improvement in mechanical resilience, and a 208 % enhancement in anti-biodegradation. These properties allow for the fabrication of intricate, cell-laden constructs with micron-scale precision, high cell viability, minimal swelling, and enhanced structural stability. The CMA-DHM system synergistically enhances 3D cell proliferation, mitigates oxidative stress, and modulates macrophage polarization, significantly outperforming conventional CMA hydrogels. Leveraging these properties, we developed biomimetic skin substitutes encapsulating human dermal fibroblasts (HDFs), which effectively facilitate diabetic wound progression through critical healing phases. These skin substitutes provide potent antioxidant and anti-inflammatory effects, accelerate re-epithelialization and collagen deposition, and enhance angiogenesis, thereby preventing chronic wound formation and facilitating efficient tissue regeneration. This study establishes a versatile, scalable DLP bioprinting platform, offering a rapid and effective solution for chronic wound treatment, representing a significant advancement in regenerative medicine.
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spelling doaj-art-ae0746088b4c47d99cb39b168d5f10722025-08-20T02:32:26ZengElsevierMaterials Today Bio2590-00642025-06-013210190810.1016/j.mtbio.2025.101908Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regenerationCaihong Fu0Guangyu Liu1Yirui Fan2Lang Xiao3Wenhua Li4Xinyu Tian5Jianxi Xiao6State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR ChinaState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR ChinaState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR ChinaState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR ChinaState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR ChinaState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR ChinaState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, 730000, PR China; Corresponding author. State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.Digital light processing (DLP) bioprinting has revolutionized tissue engineering by offering unprecedented speed and precision. However, its full biomedical potential is hindered by the scarcity of cell-laden bioinks that combine excellent printability with superior bioactivity. In this study, we introduce a novel cell-laden collagen-based bioink optimized for precise DLP bioprinting and diabetic wound regeneration. This bioink integrates methacrylated collagen (CMA) with dihydromyricetin (DHM) and selected additives, achieving a combination of low concentration, high printability, and superior cell bioactivity, along with antioxidant and anti-inflammatory effects. By employing a multi-crosslinking strategy that integrates free radical polymerization, Michael addition, Schiff base formation, and hydrogen bonding, the bioink achieves an ultra-fast gelation speed (375 % increase), a 161 % increase in stiffness, a 231 % improvement in mechanical resilience, and a 208 % enhancement in anti-biodegradation. These properties allow for the fabrication of intricate, cell-laden constructs with micron-scale precision, high cell viability, minimal swelling, and enhanced structural stability. The CMA-DHM system synergistically enhances 3D cell proliferation, mitigates oxidative stress, and modulates macrophage polarization, significantly outperforming conventional CMA hydrogels. Leveraging these properties, we developed biomimetic skin substitutes encapsulating human dermal fibroblasts (HDFs), which effectively facilitate diabetic wound progression through critical healing phases. These skin substitutes provide potent antioxidant and anti-inflammatory effects, accelerate re-epithelialization and collagen deposition, and enhance angiogenesis, thereby preventing chronic wound formation and facilitating efficient tissue regeneration. This study establishes a versatile, scalable DLP bioprinting platform, offering a rapid and effective solution for chronic wound treatment, representing a significant advancement in regenerative medicine.http://www.sciencedirect.com/science/article/pii/S25900064250047883D bioprintingDiabetic wound healingCollagen hydrogelsWound dressingsSkin substitutes
spellingShingle Caihong Fu
Guangyu Liu
Yirui Fan
Lang Xiao
Wenhua Li
Xinyu Tian
Jianxi Xiao
Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration
Materials Today Bio
3D bioprinting
Diabetic wound healing
Collagen hydrogels
Wound dressings
Skin substitutes
title Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration
title_full Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration
title_fullStr Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration
title_full_unstemmed Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration
title_short Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration
title_sort highly printable and multifunctional cell laden collagen based bioinks for precise dlp bioprinting and rapid diabetic wound regeneration
topic 3D bioprinting
Diabetic wound healing
Collagen hydrogels
Wound dressings
Skin substitutes
url http://www.sciencedirect.com/science/article/pii/S2590006425004788
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