Title: Incorporation of a prolyl hydroxylase inhibitor into scaffolds : a strategy for stimulating vascularization
Authors : Sham, Adeline
Martinez, Eliana C.
Beyer, Sebastian
Trau, Dieter W.
Raghunath, Michael
Published in : Tissue engineering. Part A
Volume(Issue) : 21
Issue : 5-6
Publisher / Ed. Institution : Mary Ann Liebert
Issue Date: 2015
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subject (DDC) : 571: Physiology and related subjects
616: Internal medicine and diseases
Abstract: Clinical applications of tissue engineering are constrained by the ability of the implanted construct to invoke vascularization in adequate extent and velocity. To overcome the current limitations presented by local delivery of single angiogenic factors, we explored the incorporation of prolyl hydroxylase inhibitors (PHIs) into scaffolds as an alternative vascularization strategy. PHIs are small molecule drugs that can stabilize the alpha subunit of hypoxia-inducible factor-1 (HIF-1), a key transcription factor that regulates a variety of angiogenic mechanisms. In this study, we conjugated the PHI pyridine-2,4-dicarboxylic acid (PDCA) through amide bonds to a gelatin sponge (Gelfoam®). Fibroblasts cultured on PDCA-Gelfoam were able to infiltrate and proliferate in these scaffolds while secreting significantly more vascular endothelial growth factor than cells grown on Gelfoam without PDCA. Reporter cells expressing green fluorescent protein-tagged HIF-1α exhibited dose-dependent stabilization of this angiogenic transcription factor when growing within PDCA-Gelfoam constructs. Subsequently, we implanted PDCA-Gelfoam scaffolds into the perirenal fat tissue of Sprague Dawley rats for 8 days. Immunostaining of explants revealed that the PDCA-Gelfoam scaffolds were amply infiltrated by cells and promoted vascular ingrowth in a dose-dependent manner. Thus, the incorporation of PHIs into scaffolds appears to be a feasible strategy for improving vascularization in regenerative medicine applications.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific Journal
DOI : 10.1089/ten.TEA.2014.0077
ISSN: 1937-335X
1937-3341
URI: https://digitalcollection.zhaw.ch/handle/11475/12191
Appears in Collections:Publikationen Life Sciences und Facility Management

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