PMID- 25370818
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20211021
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Print)
IS  - 1937-3341 (Linking)
VI  - 21
IP  - 5-6
DP  - 2015 Mar
TI  - Incorporation of a prolyl hydroxylase inhibitor into scaffolds: a strategy for 
      stimulating vascularization.
PG  - 1106-15
LID - 10.1089/ten.TEA.2014.0077 [doi]
AB  - 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((R))). 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-1alpha 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.
FAU - Sham, Adeline
AU  - Sham A
AD  - 1 Department of Biomedical Engineering, Faculty of Engineering, National 
      University of Singapore , Singapore, Singapore .
FAU - Martinez, Eliana C
AU  - Martinez EC
FAU - Beyer, Sebastian
AU  - Beyer S
FAU - Trau, Dieter W
AU  - Trau DW
FAU - Raghunath, Michael
AU  - Raghunath M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150114
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Prolyl-Hydroxylase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 499-80-9 (2,4-pyridinedicarboxylic acid)
SB  - IM
MH  - Animals
MH  - Cell Death/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cryoultramicrotomy
MH  - Fibroblasts/drug effects/metabolism
MH  - Gelatin Sponge, Absorbable/pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Male
MH  - Neovascularization, Physiologic/*drug effects
MH  - Porosity
MH  - Prolyl-Hydroxylase Inhibitors/*pharmacology
MH  - Proteolysis/drug effects
MH  - Pyridines/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Spectrophotometry, Ultraviolet
MH  - Tissue Scaffolds/*chemistry
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC4356217
EDAT- 2014/11/06 06:00
MHDA- 2015/12/17 06:00
PMCR- 2016/03/01
CRDT- 2014/11/06 06:00
PHST- 2014/11/06 06:00 [entrez]
PHST- 2014/11/06 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 10.1089/ten.tea.2014.0077 [pii]
AID - 10.1089/ten.TEA.2014.0077 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2015 Mar;21(5-6):1106-15. doi: 10.1089/ten.TEA.2014.0077. Epub 
      2015 Jan 14.