title: Towards embryonic-like scaffolds for skin tissue engineering: identification of effector molecules and construction of scaffolds.
abstract: Autologous skin grafts are the gold standard for the treatment of burn wounds. In a number of cases, treatment with autologous tissue is not possible and skin substitutes are used. The outcome, however, is not optimal and improvements are needed. Inspired by scarless healing in early embryonic development, we here set out a strategy for the design and construction of embryonic-like scaffolds for skin tissue engineering. This strategy may serve as a general approach in the construction of embryonic-like scaffolds for other tissues/organ. As a first step, key effector molecules upregulated during embryonic and neonatal skin formation were identified using a comparative gene expressing analysis. A set of 20 effector molecules was identified, from which insulin-like growth factor 2 (IGF2) and sonic hedgehog (SHH) were selected for incorporation into a type I collagen-heparin scaffold. Porous scaffolds were constructed using purified collagen fibrils and 6% covalently bound heparin (to bind and protect the growth factors), and IGF2 and SHH were incorporated either individually (~0.7 and 0.4 µg/mg scaffolds) or in combination (combined ~1.5 µg/mg scaffolds). In addition, scaffolds containing hyaluronan (up to 20 µg/mg scaffold) were prepared, based on the up- or downregulation of genes involved in hyaluronan synthesis/degradation and its suggested role in scarless healing. In conclusion, based on a comprehensive gene expression analysis, a set of effector molecules and matrix molecules was identified and incorporated into porous scaffolds. The scaffolds thus prepared may create an 'embryonic-like' environment for cells to recapitulate embryonic events and for new tissues/organs.
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: P J E
authors.initials: PJ
authors.lastname: Uijtdewilligen
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: E M M
authors.initials: EM
authors.lastname: Versteeg
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Gilissen
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: S V
authors.initials: SV
authors.lastname: van Reijmersdal
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Schoppmeyer
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Wismans
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: W F
authors.initials: WF
authors.lastname: Daamen
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: T H
authors.initials: TH
authors.lastname: van Kuppevelt
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D024042:Collagen Type I / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D012867:Skin / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D024042:Collagen Type I; D053823:Hedgehog Proteins; D007335:Insulin-Like Growth Factor II; D006820:Hyaluronic Acid; D006493:Heparin; D003094:Collagen
keywords: collagen; embryonic scaffold; growth factors; heparin; hyaluronan; tissue engineered skin graft