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 pr...

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Bibliographic Details
Published in:Biomaterials 2009-10, Vol.30 (31), p.6286-6294
Main Authors: Beamish, Jeffrey A, Geyer, Leah C, Haq-Siddiqi, Nada A, Kottke-Marchant, Kandice, Marchant, Roger E
Format: Article
Language:English
Subjects:
Advanced Basic Science
Arterial tissue engineering
Biocompatible Materials - chemistry
Blotting, Western
Cell Differentiation - drug effects
Cell Proliferation - drug effects
Cells, Cultured
Dentistry
Heparin - chemistry
Heparin - pharmacology
Humans
Hydrogel
Hydrogels - chemistry
Muscle, Smooth, Vascular - cytology
Myocytes, Smooth Muscle - cytology
Myocytes, Smooth Muscle - drug effects
Reverse Transcriptase Polymerase Chain Reaction
Scaffold
Smooth muscle cell
Tissue Engineering - methods
Tissue Scaffolds - chemistry
Vascular graft
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Summary: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 α-actin, calponin, and SM-22α, in a dose-dependent fashion (6 μg/ml to 3.2 mg/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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2009.08.004