The effect of hyaluronic acid incorporation on fibroblast spreading and proliferation within PEG-diacrylate based semi-interpenetrating networks

Abstract The nanometer-scale mesh size of many synthetic crosslinked hydrogel networks restricts encapsulated cells to a rounded morphology that can inhibit cellular processes such as proliferation and migration that are essential for the early stages of remodeling and tissue formation. The objectiv...

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Published in:Biomaterials 2007-11, Vol.28 (33), p.4928-4938
Main Authors: Kutty, Jaishankar K, Cho, Eunhee, Soo Lee, Jeoung, Vyavahare, Naren R, Webb, Ken
Format: Article
Language:English
Subjects:
Acrylates - chemistry
Advanced Basic Science
Biocompatible Materials - chemistry
Cell Culture Techniques - instrumentation
Cell Culture Techniques - methods
Cell Proliferation
Cell spreading
Cell Survival
Dentistry
Elasticity
Fibroblast
Fibroblasts - metabolism
Humans
Hyaluronic acid
Hyaluronic Acid - chemistry
Hydrogel
Magnetic Resonance Spectroscopy
Microscopy, Confocal
Neovascularization, Physiologic
Polyethylene Glycols - chemistry
Tissue Engineering - methods
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Summary:Abstract The nanometer-scale mesh size of many synthetic crosslinked hydrogel networks restricts encapsulated cells to a rounded morphology that can inhibit cellular processes such as proliferation and migration that are essential for the early stages of remodeling and tissue formation. The objective of these studies was to investigate an approach for accelerating cellular remodeling based on the creation of semi-interpenetrating networks (IPNs) composed of hydrolytically degradable poly(ethylene glycol) (PEG) diacrylate macromers and native, enzymatically degradable extracellular matrix (ECM) components (collagen, gelatin and hyaluronic acid (HA)). Among the three ECM components investigated, addition of HA at concentrations of 0.12% w/v and greater supported fibroblast spreading throughout the three-dimensional network and significantly increased proliferation relative to control hydrogels without HA. Incorporation of HA resulted in relatively small changes in hydrogel physical/chemical properties such as swelling, degradation rate, and elastic modulus. Fibroblast spreading was eliminated by the addition of hyaluronidase inhibitors, demonstrating that cell-mediated enzymatic degradation of HA is a necessary mechanism responsible for the observed increases in fibroblast activity. By accelerating early cellular remodeling and growth, these semi-IPNs may be useful vehicles for cell transplantation in a variety of tissue engineering applications.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2007.08.007