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

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外文摘要：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 scaf-folds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acry-lamide 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 resis-tance 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 prop-erties 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 path-way 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.

外文关键词：

Polyvinyl alcohol/acrylamide hydrogelMechanical property enhancementParacrine effectSkin regenerationSignaling pathways

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

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作者单位：

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

Jiangsu Engineering Research Center for 3D Bioprinting,Nanjing 210008,China

Institute of Medical 3D Printing,Nanjing University,Nanjing 210093,China

Centre for Experimental Animals,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing University,Nanjing 210008,China

College of Aeroplane Engineering,Nanjing University of Aeronautics and Astronautics,Nanjing 210016,China

National Laboratory of Solid State Microstructures,Department of Physics,Nanjing University,Nanjing 210093,China

Department of Chemical Engineering,Stanford University,Stanford,CA 94305,USA

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

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Basic Research Program of ChinaNatural Science Foundation of Jiangsu ProvinceScience Program of Jiangsu Province Administration for Market RegulationJiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent Foundation

项目编号：

32271413322714082021YFA1201404BK20232023KJ2024010

出版年：

2024

DOI：

10.1016/j.eng.2024.02.005

工程(英文)

CSTPCDEI

ISSN：2095-8099

年,卷(期)：2024.37(6)