title: Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model.
abstract: There is a need for better wound dressings that possess the requisite angiogenic capacity for rapid in situ healing of full-thickness skin wounds. Borate bioactive glass microfibers are showing a remarkable ability to heal soft tissue wounds but little is known about the process and mechanisms of healing. In the present study, wound dressings composed of borate bioactive glass microfibers (diameter = 0.4-1.2 μm; composition 6Na2O, 8K2O, 8MgO, 22CaO, 54B2O3, 2P2O5; mol%) doped with 0-3.0 wt.% CuO were created and evaluated in vitro and in vivo. When immersed in simulated body fluid, the fibers degraded and converted to hydroxyapatite within ∼7 days, releasing ions such as Ca, B and Cu into the medium. In vitro cell culture showed that the ionic dissolution product of the fibers was not toxic to human umbilical vein endothelial cells (HUVECs) and fibroblasts, promoted HUVEC migration, tubule formation and secretion of vascular endothelial growth factor (VEGF), and stimulated the expression of angiogenic-related genes of the fibroblasts. When used to treat full-thickness skin defects in rodents, the Cu-doped fibers (3.0 wt.% CuO) showed a significantly better capacity to stimulate angiogenesis than the undoped fibers and the untreated defects (control) at 7 and 14 days post-surgery. The defects treated with the Cu-doped and undoped fibers showed improved collagen deposition, maturity and orientation when compared to the untreated defects, the improvement shown by the Cu-doped fibers was not markedly better than the undoped fibers at 14 days post-surgery. These results indicate that the Cu-doped borate glass microfibers have a promising capacity to stimulate angiogenesis and heal full-thickness skin defects. They also provide valuable data for understanding the role of the microfibers in healing soft tissue wounds.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China.
authors.forename: Shichang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Cheng
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
authors.forename: Nai
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409-0340, USA. Electronic address: rahaman@mst.edu.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Rahaman
authors.affiliation: Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Zhongtang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China. Electronic address: shzhangchangqing@163.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001458:Bandages; D001672:Biocompatible Materials; D001881:Borates; D003300:Copper; D004195:Disease Models, Animal; D005898:Glass; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries*; D014945:Wound Healing; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D001672:Biocompatible Materials; D001881:Borates; D003300:Copper
keywords: Angiogenesis; Bioactive glass microfibers; Copper-doped borate bioactive glass; Skin regeneration; Wound healing