title: Combined chemical and structural signals of biomaterials synergistically activate cell-cell communications for improving tissue regeneration.
abstract: Biomaterials are only used as carriers of cells in the conventional tissue engineering. Considering the multi-cell environment and active cell-biomaterial interactions in tissue regeneration process, in this study, structural signals of aligned electrospun nanofibers and chemical signals of bioglass (BG) ionic products in cell culture medium are simultaneously applied to activate fibroblast-endothelial co-cultured cells in order to obtain an improved skin tissue engineering construct. Results demonstrate that the combined biomaterial signals synergistically activate fibroblast-endothelial co-culture skin tissue engineering constructs through promotion of paracrine effects and stimulation of gap junctional communication between cells, which results in enhanced vascularization and extracellular matrix protein synthesis in the constructs. Structural signals of aligned electrospun nanofibers play an important role in stimulating both of paracrine and gap junctional communication while chemical signals of BG ionic products mainly enhance paracrine effects. In vivo experiments reveal that the activated skin tissue engineering constructs significantly enhance wound healing as compared to control. This study indicates the advantages of synergistic effects between different bioactive signals of biomaterials can be taken to activate communication between different types of cells for obtaining tissue engineering constructs with improved functions.
  
  
  
  Tissue engineering can regenerate or replace tissue or organs through combining cells, biomaterials and growth factors. Normally, for repairing a specific tissue, only one type of cells, one kind of biomaterials, and specific growth factors are used to support cell growth. In this study, we proposed a novel tissue engineering approach by simply using co-cultured cells and combined biomaterial signals. Using a skin tissue engineering model, we successfully proved that the combined biomaterial signals such as surface nanostructures and bioactive ions could synergistically stimulate the cell-cell communication in co-culture system through paracrine effects and gap junction activation, and regulated expression of growth factors and extracellular matrix proteins, resulting in an activated tissue engineering constructs that significantly enhanced skin regeneration.
authors.affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
authors.forename: Yachen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Peng
authors.affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China. Electronic address: jchang@mail.sic.ac.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
mesh_terms: D000818:Animals; D002450:Cell Communication; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057139:Nanofibers / Q000737:chemistry / Q000627:therapeutic use; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D017768:Skin, Artificial; D014945:Wound Healing
keywords: Chemical signals; Co-cultures; Skin tissue regeneration; Structural signals; Tissue engineering