Collagen-Heparin-FGF2-VEGF Scaffolds Induce a Regenerative Gene Expression Profile in a Fetal Sheep Wound Model.

Autor: Gansevoort M; Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Oostendorp C; Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.; HAN University of Applied Sciences, Arnhem, The Netherlands., Bouwman LF; Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.; Leiden University Medical Center, Leiden, The Netherlands., Tiemessen DM; Department of Urology, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Geutjes PJ; Department of Urology, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.; Canisius Wilhelmina Hospital, Nijmegen, The Netherlands., Feitz WFJ; Department of Urology, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., van Kuppevelt TH; Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Daamen WF; Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Willeke.Daamen@radboudumc.nl.
Jazyk: angličtina
Zdroj: Tissue engineering and regenerative medicine [Tissue Eng Regen Med] 2024 Aug 31. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1007/s13770-024-00667-9
Abstrakt: Background: The developmental abnormality spina bifida is hallmarked by missing tissues (e.g. skin) and exposure of the spinal cord to the amniotic fluid, which can negatively impact neurological development. Surgical closure of the skin in utero limits neurological damage, but in large defects this results in scarring and contractures. Stimulating skin regeneration in utero would greatly benefit treatment outcome. Previously, we demonstrated that a porous type I collagen (COL) scaffold, functionalized with heparin (HEP), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) (COL-HEP/GF) improved pre- and postnatal skin regeneration in a fetal sheep full thickness wound model. In this study we uncover the early events associated with enhanced skin regeneration.
Methods: We investigated the gene expression profiles of healing fetal skin wounds two weeks after implantation of the COL(-HEP/GF) scaffolds. Using laser dissection and microarrays, differentially expressed genes (DEG) were identified in the epidermis and dermis between untreated wounds, COL-treated wounds and wounds treated with COL-HEP/GF. Biological processes were identified using gene enrichment analysis and DEG were clustered using protein-protein-interaction networks.
Results: COL-HEP/GF influences various interesting biological processes involved in wound healing. Although the changes were modest, using protein-protein-interaction networks we identified a variety of clustered genes that indicate COL-HEP/GF induces a tight but subtle control over cell signaling and extracellular matrix organization.
Conclusion: These data offer a novel perspective on the key processes involved in (fetal) wound healing, where a targeted and early interference during wound healing can result in long-term enhanced effects on skin regeneration.
(© 2024. The Author(s).)
Databáze: MEDLINE
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