Incorporation of a prolyl hydroxylase inhibitor into scaffolds: A strategy for stimulating vascularization

Adeline Sham, Eliana Cecilia Martinez Valencia, Sebastian Beyer, Dieter W. Trau, Michael Raghunath

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1106-1115
Number of pages10
JournalTissue Engineering - Part A
Volume21
Issue number5-6
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Fingerprint

Prolyl-Hydroxylase Inhibitors
Absorbable Gelatin Sponge
Scaffolds
Pyridine
Acids
Transcription factors
Angiogenesis Inducing Agents
Alpha Subunit Hypoxia-Inducible Factor 1
Transcription Factors
Cells
Hypoxia-Inducible Factor 1
Regenerative Medicine
Porifera
Fibroblasts
Gelatin
Tissue Engineering
Green Fluorescent Proteins
Oils and fats
Amides
Tissue engineering

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Incorporation of a prolyl hydroxylase inhibitor into scaffolds : A strategy for stimulating vascularization. / Sham, Adeline; Martinez Valencia, Eliana Cecilia; Beyer, Sebastian; Trau, Dieter W.; Raghunath, Michael.

In: Tissue Engineering - Part A, Vol. 21, No. 5-6, 01.03.2015, p. 1106-1115.

Research output: Contribution to journalArticle

Sham, Adeline ; Martinez Valencia, Eliana Cecilia ; Beyer, Sebastian ; Trau, Dieter W. ; Raghunath, Michael. / Incorporation of a prolyl hydroxylase inhibitor into scaffolds : A strategy for stimulating vascularization. In: Tissue Engineering - Part A. 2015 ; Vol. 21, No. 5-6. pp. 1106-1115.
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