title: Attachment of flexible heparin chains to gelatin scaffolds improves endothelial cell infiltration.
abstract: Long-term survival of implanted cells requires oxygen and nutrients, the need for which is met by vascularization of the implant. The use of scaffolds with surface-attached heparin as anchoring points for angiogenic growth factors has been reported to improve this process. We examined the potential role of surface modification of gelatin scaffolds in promoting endothelial cell infiltration by using a unique macromolecular conjugate of heparin as a coating. Compared to other heparin coatings, this surface modification provides flexible heparin chains, representing a new concept in heparin conjugation. In vitro cell infiltration of scaffolds was assessed using a three-dimensional model in which the novel heparin surface, without growth factors, showed a 2.5-fold increase in the number of infiltrating endothelial cells when compared to control scaffolds. No additional improvement was achieved by adding growth factors (vascular endothelial growth factor and/or fibroblast growth factor-2) to the scaffold. In vivo experiments confirmed these results and also showed that the addition of angiogenic growth factors did not significantly increase the endothelial cell infiltration but increased the number of inflammatory cells in the implanted scaffolds. The endothelial cell-stimulating ability of the heparin surface alone, combined with its growth factor-binding capacity, renders it an interesting candidate surface treatment to create a prevascularized site prepared for implantation of cells and tissues, in particular those sensitive to inflammation but in need of supportive revascularization, such as pancreatic islets of Langerhans.
authors: The Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: Jonas
authors: J
authors: Leijon
authors: Fredrik
authors: F
authors: Carlsson
authors: Johan
authors: J
authors: Brännström
authors: Javier
authors: J
authors: Sanchez
authors: Rolf
authors: R
authors: Larsson
authors: Bo
authors: B
authors: Nilsson
authors: Peetra U
authors: PU
authors: Magnusson
authors: Magnus
authors: M
authors: Rosenquist
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D005780:Gelatin / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019919:Prosthesis Implantation; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005780:Gelatin; D006493:Heparin