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Regulation of In Vivo Angiogenesis by Heparin‐controlled Dual Growth Factor Release from Hyaluronan Hydrogels
Author(s) -
Peattie Robert A.,
Fuegy Peter W.,
Riley Celeste M.,
Cai Shenshen,
Yu Bolan,
Firpo Matthew A.,
Shu Xiao Zheng,
Prestwich Glenn D.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a479-a
Subject(s) - in vivo , self healing hydrogels , chemistry , angiogenesis , growth factor , in vitro , microvessel , polyethylene glycol , biophysics , tissue engineering , peg ratio , biopolymer , gelatin , biomedical engineering , microbiology and biotechnology , biochemistry , biology , polymer , polymer chemistry , cancer research , medicine , receptor , organic chemistry , finance , economics
Synthetic biopolymer matrices can serve as scaffolds for cell and tissue growth if functional capillary networks can be developed within them. On the hypothesis that mature microvessel beds can be elicited by sequential delivery of multiple growth factors (GFs) in vivo , we have investigated the ability of small amounts of heparin (Hp) to control GF release from hydrogels based on chemically modified hyaluronan (HA‐DTPH) and gelatin (Gtn‐DTPH) crosslinked with polyethylene glycol diacrylate, without loss of bioactivity. The rate of GF release was evaluated in vitro by ELISA, and the angiogenic capacity of GF combinations tested in vivo in a mouse ear pinna. The total mass released in vitro varied from only 1.8% for PDGF to 90.2% for bFGF. As little as 0.3% Hp in the gels caused released mass to vary in the order bFGF > TGF‐β > KGF > VEGF > Ang‐1 > PDGF. Vessel networks produced in vivo by co‐delivery of two GFs were more mature than control cases. Quantitatively, the most effective treatment group was also delivery of two GFs, for which mean vascularization was 29% greater than cases delivering a single GF ( p < 0.04). These data strongly suggest that incorporation of small amounts of Hp in the gels can lead to a coordinated sequence of GF releases that generate continuous development of new microvessels over at least a 14 day period. Supported by NIH award 1R21EB004514, and by a Centers of Excellence award from the state of Utah.