Sphingosine-1-phosphate (S1P), a bioactive lipid, is a potent candidate for treatment of ischemic vascular disease. However, designing biomaterial systems for the controlled release of S1P to achieve therapeutic angiogenesis presents both biological and engineering challenges. Thus, the objective of this study was to design a hydrogel system that provides controlled and sustained release of S1P to establish local concentration gradients that promote neovascularization. Alginate hydrogels have been extensively studied and characterized for delivery of proangiogenic factors. We sought to explore if chitosan (0, 0.1, 0.5, or 1%) incorporation could be used as a means to control S1P release from alginate hydrogels. With increasing chitosan incorporation, hydrogels exhibited significantly denser pore structure and stiffer material properties. While 0.1 and 0.5% chitosan gels demonstrated slower respective release of S1P, release from 1% chitosan gels was similar to alginate gels alone. Furthermore, 0.5% chitosan gels induced greater sprouting and directed migration of outgrowth endothelial cells (OECs) in response to released S1P under hypoxia in vitro. Overall, this report presents a platform for a novel alginate-chitosan hydrogel of controlled composition and in situ gelation properties that can be used to control lipid release for therapeutic applications.
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We thank the American Heart Association (15BGIA25730057 and 15PRE22930044) and the Hellman Family for the funding support for this work. We also acknowledge Dr. J. Kent Leach and Dr. Scott Simon for the use of their equipment in acquiring this data. We thank Fred Hayes and the UC Davis Advanced Materials Characterization and Testing (AMCAT) facility for guidance with SEM imaging.
Associate Editor Michael Gower oversaw the review of this article.
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Williams, P.A., Campbell, K.T., Gharaviram, H. et al. Alginate-Chitosan Hydrogels Provide a Sustained Gradient of Sphingosine-1-Phosphate for Therapeutic Angiogenesis. Ann Biomed Eng 45, 1003–1014 (2017). https://doi.org/10.1007/s10439-016-1768-2
- Composite hydrogel
- Controlled release
- Outgrowth endothelial cell
- Proangiogenic factors
- Sphingosine-1-phosphate (S1P)