Abstract
Challenges for therapeutic manipulation of adult angiogenesis with exogenous growth factors are to counteract (1) aberrant vessel growth (2) vessel leakage (3) vessel regression. We describe tissue engineering solutions, based on fibrin or poly ethyleneglycol-peptide implant matrices, for localized and prolonged delivery of VEGF that help ensure localized growth of structurally normal and lasting vessels and minimize adverse side effects. These matrices bind VEGF such that decisions on dosage, location, and duration of released factor are coupled to cellular proteolytic activity at the treatment site, i.e. biological feedback regulation of release. We describe acute angiogenesis response to such schemes of cell-demanded release using video microscopy, morphometry, casting techniques and scanning electron microscopy. Further, we have used biophotonic measurements in transgenic Vegfr2-luc (Xenogen) to correlate transcriptional activation of angiogenesis with immunohistochemical analysis of lasting vessel growth at and around VEGF- releasing implants. We have used VEGF-fibrin matrices applied to the flow surface of synthetic ePTFE grafts in pig trials of spontaneous graft endothelialization. We report an unexpected, untoward effect of VEGF for increasing intimal thickening, indicative of an effect for smooth muscle cell activation. Sponsored by Gebert Rüf Foundation.
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