A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion  

作　　者：Peng Wang Liping Qian Huixin Liang Jianhao Huang Jing Jin Chunmei Xie Bin Xue Jiancheng Lai Yibo Zhang Lifeng Jiang Lan Li Qing Jiang 

机构地区：[1]State Key Laboratory of Pharmaceutical Biotechnology,Division of Sports Medicine and Adult Reconstructive Surgery,Department of Orthopedic Surgery,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing University,Nanjing 210008,China [2]Jiangsu Engineering Research Center for 3D Bioprinting,Nanjing 210008,China [3]Institute of Medical 3D Printing,Nanjing University,Nanjing 210093,China [4]Centre for Experimental Animals,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing University,Nanjing 210008,China [5]College of Aeroplane Engineering,Nanjing University of Aeronautics and Astronautics,Nanjing 210016,China [6]National Laboratory of Solid State Microstructures,Department of Physics,Nanjing University,Nanjing 210093,China [7]Department of Chemical Engineering,Stanford University,Stanford,CA 94305,USA [8]Department of Orthopedic Surgery,The Second Affiliated Hospital Zhejiang University School of Medicine,Orthopedic Research Institute of Zhejiang University,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province,Hangzhou 310009,China

出　　处：《Engineering》2024年第6期138-151,共14页工程（英文）

基　　金：supported by the National Natural Science Foundation of China(32271413 and 32271408);the National Basic Research Program of China(2021YFA1201404);the Natural Science Foundation of Jiangsu Province(BK20232023);the Science Program of Jiangsu Province Administration for Market Regulation(KJ2024010);the Jiangsu Provincial Key Medical Center Foundation,and the Jiangsu Provincial Medical Outstanding Talent Foundation.

摘　　要：Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

关 键 词：Polyvinyl alcohol/acrylamide hydrogel Mechanical property enhancement Paracrine effect Skin regeneration Signaling pathways 

分 类 号：R318.08[医药卫生—生物医学工程]