Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting  

作　　者：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 

机构地区：[1]Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department,PLA General Hospital and PLA Medical College,28 Fu Xing Road,Beijing,100853,PR China [2]PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury,Repair and Regeneration,Research Unit of Trauma Care,Tissue Repair and Regeneration,Chinese Academy of Medical Sciences,2019RU051,51 Fu Cheng Road,Beijing,100048,PR China [3]Academy of Medical Engineering and Translational Medicine,Tianjin University,300072,PR China [4]Guangdong Cardiovascular Institute,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou,Guangdong,510100,PR China [5]General Surgery Department,Yangzhou Hongquan Hospital,Jiangsu,225200,PR China [6]Institute of Basic Medical Research,Inner Mongolia Medical University,Hohhot,Inner Mongolia,010110,PR China [7]College of Graduate,Tianjin Medical University,22 Qi Xiang Tai Road Tianjin,300050,PR China [8]MRC Human Immunology Unit,MRC Weatherall Institute of Molecular Medicine,University of Oxford,John Radcliffe Hospital,Oxford,OX39DU,UK

出　　处：《Bioactive Materials》2022年第4期247-254,共8页生物活性材料（英文）

基　　金：supported in part by the National Nature Science Foundation of China(81830064,81721092,32000969,82002056);Key Support Program for Growth Factor Research(SZYZ-TR-03);Chinese PLA General Hospital for Military Medical Innovation Research Project(CX-19026);the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059);the Military Medical Research and Development Projects(AWS17J005);National Key Research and Development Program of China(2018YFA0108700,2017YFA0105602).

摘　　要：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.

关 键 词：Hypertrophic scar model Preformed cell aggregates 3D bioprinting Microenvironmental cues Drug screening 

分 类 号：R619.6[医药卫生—外科学] R318[医药卫生—临床医学]