Towards embryonic-like scaffolds for skin tissue engineering: identification of effector molecules and construction of scaffolds

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 devel...

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Bibliographic Details
Published in:Journal of tissue engineering and regenerative medicine 2016-01, Vol.10 (1), p.E34-E44
Main Authors: Uijtdewilligen, P. J. E., Versteeg, E. M. M., Gilissen, C., van Reijmersdal, S. V., Schoppmeyer, R., Wismans, R. G., Daamen, W. F., van Kuppevelt, T. H.
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cattle
collagen
Collagen - pharmacology
Collagen Type I - pharmacology
Embryo, Mammalian - cytology
Embryo, Mammalian - drug effects
embryonic scaffold
Gene Expression Regulation, Developmental - drug effects
growth factors
Hedgehog Proteins - metabolism
heparin
Heparin - pharmacology
hyaluronan
Hyaluronic Acid - pharmacology
Immunohistochemistry
Insulin-Like Growth Factor II - pharmacology
Mice, Inbred C57BL
Regenerative medicine
Skin - metabolism
tissue engineered skin graft
Tissue engineering
Tissue Engineering - methods
Tissue Scaffolds - chemistry
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Summary: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. Copyright © 2013 John Wiley & Sons, Ltd.
ISSN:1932-6254
1932-7005
DOI:10.1002/term.1725