title: Upregulating Hif-1α by Hydrogel Nanofibrous Scaffolds for Rapidly Recruiting Angiogenesis Relative Cells in Diabetic Wound.
abstract: Nonhealing chronic wounds on foot are one of the most dreaded complications of diabetes, and biomedical scaffolds remain an attractive option for repairing or regenerating tissues. Accelerating angiogenesis in the early stage after injury is critical to wound healing process; however, the scaffolds accelerate the angiogenesis in the beginning but with the acceleration of vessel network formation the scaffold network hinders the process. In this study, the water soluble drugs-loaded hydrogel nanofibrous scaffolds are designed for rapidly recruiting angiogenesis relative cells and promoting wound healing. The sustained release profile of desferrioxamine (DFO), which continues for about 72 h, leads to significantly increase of neovascularization. The majority of the scaffold is degraded in 14 d, leaving enough space for cell proliferation and vessel formation. The in vitro results show that the scaffolds upregulate the expression of Hif-1α and vascular endothelial growth factor, and enhance the interaction between fibroblasts and endothelial cells. The in vivo studies show a higher expression of angiogenesis related cytokines. This study demonstrates that the DFO released from hydrogel nanofibrous scaffolds of quick degradation can interfere with the required prolyl-hydroxylases cofactors by acting as Fe(2+) chelator and upregulate the expression of Hif-1α, leading to a significant increase of the neovascularization.
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Soochow, Jiangsu, 215004, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jia
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.|Harvard John A. Paulson School of Applied Science and Engineering, Harvard University, Cambridge, MA, 02138, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Rapid Manufacturing Engineering Center of Shanghai University, 99 Shangda Road, Shanghai, 200444, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Burn and Plastic surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Peilang
authors.initials: P
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Orthopaedics, Qian Fo Shan Hospital, Shan Dong University, 16766 Jingshi Road, Ji Nan, Shandong, 250014, P. R. China.
authors.forename: Guilai
authors.initials: G
authors.lastname: Zuo
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: Rapid Manufacturing Engineering Center of Shanghai University, 99 Shangda Road, Shanghai, 200444, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou, Jiangsu, 215006, P. R. China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Cui
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatmentof Bone and Joint Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
authors.forename: Lianfu
authors.initials: L
authors.lastname: Deng
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use; D020405:Dermis / Q000166:cytology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D065546:Drug Liberation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D005453:Fluorescence; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D001672:Biocompatible Materials; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011142:Polyvinyl Alcohol; D048271:Chitosan; D003676:Deferoxamine
keywords: angiogenesis; diabetic wounds; drug release; hydrogel nanofibers; vessel regeneration