A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion
Peng Wang,
Liping Qian,
Huixin Liang,
Jianhao Huang,
Jing Jin,
Chunmei Xie,
Bin Xue,
Jiancheng Lai,
Yibo Zhang,
Lifeng Jiang,
Lan Li,
Qing Jiang
Affiliations
Peng Wang
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
Liping Qian
Centre for Experimental Animals, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210008, China
Huixin Liang
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
Jianhao Huang
Jiangsu Engineering Research Center for 3D Bioprinting, Nanjing 210008, China; Institute of Medical 3D Printing, Nanjing University, Nanjing 210093, China
Jing Jin
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
Chunmei Xie
College of Aeroplane Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China
Bin Xue
National Laboratory of Solid State Microstructures, Department of Physics, Nanjing University, Nanjing 210093, China
Jiancheng Lai
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
Yibo Zhang
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
Lifeng Jiang
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; Corresponding authors.
Lan Li
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; Corresponding authors.
Qing Jiang
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; Corresponding authors.
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.
