Sustained Postnatal Skin Regeneration Upon Prenatal Application of Functionalized Collagen Scaffolds
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Publication year
2021Source
Tissue Engineering Part A, 27, 1-2, (2021), pp. 10-25ISSN
Publication type
Article / Letter to editor
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Organization
Radboudumc Extern
Urology
Biochemistry (UMC)
Journal title
Tissue Engineering Part A
Volume
vol. 27
Issue
iss. 1-2
Page start
p. 10
Page end
p. 25
Subject
Radboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 15: Urological cancers RIMLS: Radboud Institute for Molecular Life Sciences; Biochemistry - Radboud University Medical Center; Urology - Radboud University Medical CenterAbstract
Primary closure of fetal skin in spina bifida protects the spinal cord and improves clinical outcome, but is also associated with postnatal growth malformations and spinal cord tethering. In this study, we evaluated the postnatal effects of prenatally closed full-thickness skin defects in sheep applying collagen scaffolds with and without heparin/vascular endothelial growth factor/fibroblast growth factor 2, focusing on skin regeneration and growth. At 6 months, collagen scaffold functionalized with heparin, VEGF, and FGF2 (COL-HEP/GF) resulted in a 6.9-fold increase of the surface area of the regenerated skin opposed to 1.7 × for collagen only. Epidermal thickness increased 5.7-fold at 1 month, in line with high gene expression of S100 proteins, and decreased to 2.1 at 6 months. Increased adipose tissue and reduced scaffold degradation and number of myofibroblasts were observed for COL-HEP/GF. Gene ontology terms related to extracellular matrix (ECM) organization were enriched for both scaffold treatments. In COL-HEP/GF, ECM gene expression resembled native skin. Expression of hair follicle-related genes in COL-HEP/GF was comparable to native skin, and de novo hair follicle generation was indicated. In conclusion, in utero closure of skin defects using functionalized collagen scaffolds resulted in long-term skin regeneration and growth. Functionalized collagen scaffolds that grow with the child may be useful for prenatal treatment of closure defects like spina bifida. Impact statement Prenatal closure of fetal skin in case of spina bifida prevents damage to the spinal cord. Closure of the defect is challenging and may result in postnatal growth malformations. In this study, the postnatal effects of a prenatally applied collagen scaffold functionalized with heparin and vascular endothelial growth factor (VEGF)/fibroblast growth factor (FGF) were investigated. An increase of the surface area of regenerated skin ("growing with the child") and generation of hair follicles was observed. Gene expression levels resembled those of native skin with respect to the extracellular matrix and hair follicles. Overall, in utero closure of skin defects using heparin/VEGF/FGF functionalized collagen scaffolds results in long-term skin regeneration.
This item appears in the following Collection(s)
- Academic publications [246423]
- Electronic publications [134009]
- Faculty of Medical Sciences [93307]
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