title: Rapid creation of skin substitutes from human skin cells and biomimetic nanofibers for acute full-thickness wound repair.
abstract: Creation of functional skin substitutes within a clinically acceptable time window is essential for timely repair and management of large wounds such as extensive burns. The aim of this study was to investigate the possibility of fabricating skin substitutes via a bottom-up nanofiber-enabled cell assembly approach and using such substitutes for full-thickness wound repair in nude mice. Following a layer-by-layer (L-b-L) manner, human primary skin cells (fibroblasts and keratinocytes) were rapidly assembled together with electrospun polycaprolactone (PCL)/collagen (3:1, w/w; 8%, w/v) nanofibers into 3D constructs, in which fibroblasts and keratinocytes were located in the bottom and upper portion respectively. Following culture, the constructs developed into a skin-like structure with expression of basal keratinocyte markers and deposition of new matrix while exhibiting good mechanical strength (as high as 4.0 MPa by 14 days). Treatment of the full-thickness wounds created on the back of nude mice with various grafts (acellular nanofiber meshes, dermal substitutes, skin substitutes and autografts) revealed that 14-day-cultured skin substitutes facilitated a rapid wound closure with complete epithelialization comparable to autografts. Taken together, skin-like substitutes can be formed by L-b-L assembling human skin cells and biomimetic nanofibers and they are effective to heal acute full-thickness wounds in nude mice.
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
authors.forename: Seyed Babak
authors.initials: SB
authors.lastname: Mahjour
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA; Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Fong
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA; Department of Biomedical Engineering, School of Engineering, King Faisal University, Al-Hofuf, Al-Ahsa, Saudi Arabia.
authors.forename: Farshid
authors.initials: F
authors.lastname: Sefat
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA. Electronic address: Hongjun.Wang@stevens.edu.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
mesh_terms: D062088:Acellular Dermis; D000818:Animals; D040761:Biomimetic Materials / Q000627:therapeutic use*; D049109:Cell Proliferation; D005347:Fibroblasts; D052816:Foreskin / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057139:Nanofibers / Q000627:therapeutic use*; D011091:Polyesters / Q000627:therapeutic use*; D012867:Skin / Q000293:injuries; D016038:Skin Transplantation; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D014182:Transplantation, Autologous; D014945:Wound Healing; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D011091:Polyesters; C016240:polycaprolactone
keywords: Layer-by-layer; PCL/collagen polyblend nanofibers; Skin tissue engineering; Wound healing