Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting

The therapeutic interventions of human hypertrophic scars (HHS) remain puzzle largely due to the lack of accepted models. Current HHS models are limited by their inability to mimic native scar architecture and associated pathological microenvironments. Here, we create a 3D functional HHS model by pr...

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Autores principales:	Yao Bin, Zhu Dongzhen, Cui Xiaoli, Enhe jirigala, Song Wei, Li Zhao, Hu Tian, Zhu Ping, Li Jianjun, Wang Yuzhen, Zhang Yijie, Fu Xiaobing, Huang Sha
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2022
Materias:	Hypertrophic scar model Preformed cell aggregates 3D bioprinting Microenvironmental cues Drug screening Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3189b26a3550452fbda9c0acabe746b4
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id	oai:doaj.org-article:3189b26a3550452fbda9c0acabe746b4
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spelling	oai:doaj.org-article:3189b26a3550452fbda9c0acabe746b42021-11-28T04:35:28ZModeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting2452-199X10.1016/j.bioactmat.2021.09.004https://doaj.org/article/3189b26a3550452fbda9c0acabe746b42022-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X2100414Xhttps://doaj.org/toc/2452-199XThe therapeutic interventions of human hypertrophic scars (HHS) remain puzzle largely due to the lack of accepted models. Current HHS models are limited by their inability to mimic native scar architecture and associated pathological microenvironments. Here, we create a 3D functional HHS model by preformed cellular aggregates (PCA) bioprinting, firstly developing bioink from scar decellularized extracellular matrix (ECM) and alginate-gelatin (Alg-Gel) hydrogel with suitable physical properties to mimic the microenvironmental factors, then pre-culturing patient-derived fibroblasts in this bioink to preform the topographic cellular aggregates for sequent printing. We confirm the cell aggregates preformed in bioink displayed well defined aligned structure and formed functional scar tissue self-organization after bioprinting, hence showing the potential of creating HHS models. Notably, these HHS models exhibit characteristics of early-stage HHS in gene and protein expression, which significantly activated signaling pathway related to inflammation and cell proliferation, and recapitulate in vivo tissue dynamics of scar forming. We also use the in vitro and in vivo models to define the clinically observed effects to treatment with concurrent anti-scarring drugs, and the data show that it can be used to evaluate the potential therapeutic target for drug testing. The ideal humanized scar models we present should prove useful for studying critical mechanisms underlying HHS and to rapidly test new drug targets and develop patient-specific optimal therapeutic strategies in the future.Yao BinZhu DongzhenCui XiaoliEnhe jirigalaSong WeiLi ZhaoHu TianZhu PingLi JianjunWang YuzhenZhang YijieFu XiaobingHuang ShaKeAi Communications Co., Ltd.articleHypertrophic scar modelPreformed cell aggregates3D bioprintingMicroenvironmental cuesDrug screeningMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 10, Iss , Pp 247-254 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hypertrophic scar model Preformed cell aggregates 3D bioprinting Microenvironmental cues Drug screening Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
spellingShingle	Hypertrophic scar model Preformed cell aggregates 3D bioprinting Microenvironmental cues Drug screening Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 Yao Bin Zhu Dongzhen Cui Xiaoli Enhe jirigala Song Wei Li Zhao Hu Tian Zhu Ping Li Jianjun Wang Yuzhen Zhang Yijie Fu Xiaobing Huang Sha Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting
description	The therapeutic interventions of human hypertrophic scars (HHS) remain puzzle largely due to the lack of accepted models. Current HHS models are limited by their inability to mimic native scar architecture and associated pathological microenvironments. Here, we create a 3D functional HHS model by preformed cellular aggregates (PCA) bioprinting, firstly developing bioink from scar decellularized extracellular matrix (ECM) and alginate-gelatin (Alg-Gel) hydrogel with suitable physical properties to mimic the microenvironmental factors, then pre-culturing patient-derived fibroblasts in this bioink to preform the topographic cellular aggregates for sequent printing. We confirm the cell aggregates preformed in bioink displayed well defined aligned structure and formed functional scar tissue self-organization after bioprinting, hence showing the potential of creating HHS models. Notably, these HHS models exhibit characteristics of early-stage HHS in gene and protein expression, which significantly activated signaling pathway related to inflammation and cell proliferation, and recapitulate in vivo tissue dynamics of scar forming. We also use the in vitro and in vivo models to define the clinically observed effects to treatment with concurrent anti-scarring drugs, and the data show that it can be used to evaluate the potential therapeutic target for drug testing. The ideal humanized scar models we present should prove useful for studying critical mechanisms underlying HHS and to rapidly test new drug targets and develop patient-specific optimal therapeutic strategies in the future.
format	article
author	Yao Bin Zhu Dongzhen Cui Xiaoli Enhe jirigala Song Wei Li Zhao Hu Tian Zhu Ping Li Jianjun Wang Yuzhen Zhang Yijie Fu Xiaobing Huang Sha
author_facet	Yao Bin Zhu Dongzhen Cui Xiaoli Enhe jirigala Song Wei Li Zhao Hu Tian Zhu Ping Li Jianjun Wang Yuzhen Zhang Yijie Fu Xiaobing Huang Sha
author_sort	Yao Bin
title	Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting
title_short	Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting
title_full	Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting
title_fullStr	Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting
title_full_unstemmed	Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting
title_sort	modeling human hypertrophic scars with 3d preformed cellular aggregates bioprinting
publisher	KeAi Communications Co., Ltd.
publishDate	2022
url	https://doaj.org/article/3189b26a3550452fbda9c0acabe746b4
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Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting

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