Modulation of the angiogenic potential in collagen matrices by immobilisation of heparin and loading with vascular endothelial growth factor

The vascularization of engineered tissues in many cases does not keep up with the ingrowth of cells. Nutrient and oxygen supply are not sufficient, which ultimately leads to the death of the invading cells. The enhancement of the angiogenic capabilities of engineered tissues therefore represents a major challenge in the field of tissue engineering. The immobilization of angiogenic growth factors may be useful for enhancing angiogenesis. The most potent angiogenic growth factor specific to endothelial cells, vascular endothelial growth factor (VEGF165), has a high angiogenic activity and a high affinity for heparin. In order to immobilize VEGF, I therefore decided to incorporate heparin molecules into collagen matrices by covalently cross-linking them to amino functions on the collagen. Physical binding of VEGF to the heparin may then prevent a rapid clearance from the implant, while the release rate may be coupled to the degradation of the collagen matrix. The modified matrices were characterized by determination of the extent of the heparin immobilization, the in vitro degradation rate by collagenase, the number of free amino functions and the moisture uptake. For testing the angiogenic properties non-modified and heparinized collagen specimen were - either loaded with VEGF or non-loaded - implanted on the chorioallantoic membrane of the chicken embryo and in subcutaneous tissue of the rat. Specimens were explanted after varying periods of implantation, the number of capillaries in the CAM and hemoglobin content in the specimens were evaluated: heparinized collagen matrices loaded with VEGF are vascularized to a substantially higher extent as the non-modified matrices loaded with the same amount of VEGF. These modifications may be of prime importance for future developments in the field of skin substitutes, in which the rate of vascularization is essential for the survival of seeded autologous or stem cells.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2003

Author dc:creator

• Yao, Chang

Contributors dc:contributor

• Pallua, Norbert

• info:eu-repo/classification/ddc/610
• Medizin
• Angiogenesis
• collagen
• heparin
• VEGF

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123539%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:61928