Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering

Abstract Engineering bioscaffolds with tailored architectures and optimized physicochemical properties remains a crucial yet challenging goal in tissue engineering and regenerative medicine. In this study, the design of reinforced concrete‐inspired annealed granular hydrogel (GH) scaffolds that meet...

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Main Authors: Jing Zhang, Yijia Wang, Yue Liu, Guanfu Wu, Guilong Lu, Yue Li, Yu Shen, Caifeng Wang, Mehdi Khanmohammadi, Wojciech Święszkowski, Jing Wang, Ziyi Yu
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202415634
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author Jing Zhang
Yijia Wang
Yue Liu
Guanfu Wu
Guilong Lu
Yue Li
Yu Shen
Caifeng Wang
Mehdi Khanmohammadi
Wojciech Święszkowski
Jing Wang
Ziyi Yu
author_facet Jing Zhang
Yijia Wang
Yue Liu
Guanfu Wu
Guilong Lu
Yue Li
Yu Shen
Caifeng Wang
Mehdi Khanmohammadi
Wojciech Święszkowski
Jing Wang
Ziyi Yu
author_sort Jing Zhang
collection DOAJ
description Abstract Engineering bioscaffolds with tailored architectures and optimized physicochemical properties remains a crucial yet challenging goal in tissue engineering and regenerative medicine. In this study, the design of reinforced concrete‐inspired annealed granular hydrogel (GH) scaffolds that meet the essential yet often conflicting requirements for bioscaffolds: providing adequate mechanical strength while facilitating cell infiltration, nutrient exchange, and the formation of complex cellular networks. GH building blocks are synthesized using a binary macromonomer system of hyperbranched polyethylene glycol and thiolated gelatin within microfluidic droplets, benefiting from the molecular interface assembly and templating effects of the microdroplets, which possess highly reactive vinyl functional groups, thereby endowing the annealed GH scaffolds with highly customizable properties. The versatility of this platform is demonstrated by the creation of full‐thickness engineered skin tissues that support keratinocyte attachment and differentiation; the formation of a mature epidermis, complete with a developed stratum corneum, and the expression of key markers, such as keratin 10 and keratin 14, while minimizing contraction over long‐term culturing, a common limitation of traditional collagen‐based scaffolds. Owing to their biocompatibility, tunable mechanical properties, ease of surface functionalization, and compatibility with bioprinting, these scaffolds have significant potential for applications in tissue engineering, drug delivery, and bioprinting.
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spelling doaj-art-defa6f59017d48d498a46f7cbb237cb92025-08-20T03:24:39ZengWileyAdvanced Science2198-38442025-06-011221n/an/a10.1002/advs.202415634Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue EngineeringJing Zhang0Yijia Wang1Yue Liu2Guanfu Wu3Guilong Lu4Yue Li5Yu Shen6Caifeng Wang7Mehdi Khanmohammadi8Wojciech Święszkowski9Jing Wang10Ziyi Yu11State Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaFaculty of Materials Science and Engineering Warsaw University of Technology Warsaw 02507 PolandFaculty of Materials Science and Engineering Warsaw University of Technology Warsaw 02507 PolandReproductive Medicine Center Zhongshan Hospital Fudan University Shanghai 200032 P. R. ChinaState Key Laboratory of Materials‐Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University 30 Puzhu South Road Nanjing 211816 P. R. ChinaAbstract Engineering bioscaffolds with tailored architectures and optimized physicochemical properties remains a crucial yet challenging goal in tissue engineering and regenerative medicine. In this study, the design of reinforced concrete‐inspired annealed granular hydrogel (GH) scaffolds that meet the essential yet often conflicting requirements for bioscaffolds: providing adequate mechanical strength while facilitating cell infiltration, nutrient exchange, and the formation of complex cellular networks. GH building blocks are synthesized using a binary macromonomer system of hyperbranched polyethylene glycol and thiolated gelatin within microfluidic droplets, benefiting from the molecular interface assembly and templating effects of the microdroplets, which possess highly reactive vinyl functional groups, thereby endowing the annealed GH scaffolds with highly customizable properties. The versatility of this platform is demonstrated by the creation of full‐thickness engineered skin tissues that support keratinocyte attachment and differentiation; the formation of a mature epidermis, complete with a developed stratum corneum, and the expression of key markers, such as keratin 10 and keratin 14, while minimizing contraction over long‐term culturing, a common limitation of traditional collagen‐based scaffolds. Owing to their biocompatibility, tunable mechanical properties, ease of surface functionalization, and compatibility with bioprinting, these scaffolds have significant potential for applications in tissue engineering, drug delivery, and bioprinting.https://doi.org/10.1002/advs.202415634bioprintinggranular hydrogelsmicrodropletsmicrofluidictissue engineering
spellingShingle Jing Zhang
Yijia Wang
Yue Liu
Guanfu Wu
Guilong Lu
Yue Li
Yu Shen
Caifeng Wang
Mehdi Khanmohammadi
Wojciech Święszkowski
Jing Wang
Ziyi Yu
Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering
Advanced Science
bioprinting
granular hydrogels
microdroplets
microfluidic
tissue engineering
title Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering
title_full Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering
title_fullStr Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering
title_full_unstemmed Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering
title_short Reinforced Granular Hydrogels Scaffolds with Tunable Physicochemical Properties for Advanced Skin Tissue Engineering
title_sort reinforced granular hydrogels scaffolds with tunable physicochemical properties for advanced skin tissue engineering
topic bioprinting
granular hydrogels
microdroplets
microfluidic
tissue engineering
url https://doi.org/10.1002/advs.202415634
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