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The effects of heparin releasing hydrogels on vascular smooth muscle cell phenotype.

Abstract：

:Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractile smooth muscle cell (SMC) phenotype via controlled release of heparin. The scaffold design was evaluated by quantifying the effects of free heparin on SMC phenotype, engineering hydrogels to provide controlled release of heparin, and synthesizing cell-adhesive, heparin releasing hydrogels to promote contractile SMC phenotype. Heparin inhibited SMC proliferation and up-regulated expression of contractile SMC phenotype markers, including smooth muscle alpha-actin, calponin, and SM-22alpha, in a dose-dependent fashion (6 microg/ml to 3.2mg/ml). Heparin release from PEGDA hydrogels was controlled by altering PEGDA molecular weight (MW 1000-6000) and concentration at polymerization (10-30% w/w), yielding release profiles ranging from hours to weeks in duration. Heparin released from PEGDA gels, formulated for optimized heparin loading and release kinetics (30% w/w PEGDA, MW 3000), stimulated SMCs to up-regulate contractile marker mRNA. A cell-instructive scaffold construct was prepared by polymerizing a thin hydrogel film, with pendant RGD peptides for cell attachment, over the optimized hydrogel depots. SMCs seeded on these constructs had elevated levels of contractile marker mRNA after 3 d of culture compared with SMCs on control constructs. These results indicate that RGD-modified, heparin releasing PEGDA gels can act as cell-instructive scaffolds that promote contractile SMC phenotype.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Beamish JA,Geyer LC,Haq-Siddiqi NA,Kottke-Marchant K,Marchant RE

doi

10.1016/j.biomaterials.2009.08.004

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

6286-94

issue

31

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(09)00811-4

journal_volume

30

pub_type

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