title: Electrospun poly(hydroxybutyrate) scaffolds promote engraftment of human skin equivalents via macrophage M2 polarization and angiogenesis.
abstract: Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-ε-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Implantation of PHB scaffolds in healthy rats polarized macrophages to an M2-type that promoted constructive in vivo remodelling. Moreover, implantation of DE-PHB composites in a NOD/SCID mouse xenograft model resulted in engraftment accompanied by an increase in angiogenesis that favoured the survival of the human graft. Thus, PHB scaffolds are an attractive substrate for further exploration in skin reconstruction procedures, probably due in part to their greater angiogenic and M2 macrophage polarization properties. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.|Joint Unit for Cardiovascular Repair Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sanchis
authors.affiliation: Instituto Tecnológico Textil Aitex, Alcoy, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Blanes
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.
authors.forename: Mª Dolores
authors.initials: MD
authors.lastname: Pérez Del Caz
authors.affiliation: Departamento de Patología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz-Saurí
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.|Joint Unit for Cardiovascular Repair Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Piquer-Gil
authors.affiliation: Laboratory of Cell Therapy, Foundation for Applied Medical Research and Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.affiliation: Instituto Tecnológico Textil Aitex, Alcoy, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Marco
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.|Joint Unit for Cardiovascular Repair Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Nahuel
authors.initials: N
authors.lastname: Garcia
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.|Joint Unit for Cardiovascular Repair Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Imelda
authors.initials: I
authors.lastname: Ontoria-Oviedo
authors.affiliation: Instituto Tecnológico Textil Aitex, Alcoy, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Cambra
authors.affiliation: Laboratory of Cell Therapy, Foundation for Applied Medical Research and Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.affiliation: Instituto de Investigación Sanitaria la Fe, Regenerative Medicine and Heart Transplantation Unit, Valencia, Spain.|Joint Unit for Cardiovascular Repair Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Pilar
authors.identifier: 0000-0001-6071-7431
authors.initials: P
authors.lastname: Sepúlveda
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020405:Dermis / Q000166:cytology / Q000648:ultrastructure; D004817:Epidermis / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011108:Polymers / Q000737:chemistry; D000091402:Prohibitins; D017208:Rats, Wistar; D016038:Skin Transplantation; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D006885:Hydroxybutyrates; C000717328:PHB protein, human; C000717332:Phb protein, rat; D011108:Polymers; D000091402:Prohibitins
keywords: electrospinning; human skin xenograft; poly(hydroxybutyrate); skin equivalents