期刊
BIOMATERIALS
卷 58, 期 -, 页码 26-34出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.04.014
关键词
Bimodal hydrogels; Microchannels; Bio-inspired; RGD peptides; Uniaxial freeze drying; Stem cells; Differentiation; Neuron; Glial cells
资金
- National Science Foundation [CBET-1340491]
- National Science Foundation (STC-EBICS) [CBET-0939511]
- UIUC-IGB Proof of Concept Award
- National Research Foundation - Korea Ministry of Science, ICT & Future Planning [NRF- 2014R1A2A1A11054206]
- National Research Foundation - Korea Ministry of Science, ICT & Future Planning (Engineering Research Center of Excellence Program) [NRF-2014-009799]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1403491] Funding Source: National Science Foundation
Bioactive hydrogels have been extensively studied as a platform for 3D cell culture and tissue regeneration. One of the key desired design parameters is the ability to control spatial organization of bio-molecules and cells and subsequent tissue in a 3D matrix. To this end, this study presents a simple but advanced method to spatially organize microchanneled, cell adherent gel blocks and non-adherent ones in a single construct. This hydrogel system was prepared by first fabricating a bimodal hydrogel in which the microscale, alginate gel blocks modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD peptides), and those free of RGD peptides, were alternatingly presented. Then, anisotropically aligned microchannels were introduced by uniaxial freeze-drying of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal cells to adhere to and differentiate into neuron and glial cells exclusively in microchannels of the alginate gel blocks modified with RGD peptides. Separately, the bimodal gel loaded with microparticles releasing vascular endothelial growth factor stimulated vascular growth solely into microchannels of the RGD-alginate gel blocks in vivo. These results were not attained by the bimodal hydrogel fabricated to present randomly oriented micropores. Overall, the bimodal gel system could regulate spatial organization of nerve-like tissue or blood vessels at sub-micrometer length scale. We believe that the hydrogel assembly demonstrated in this study will be highly useful in developing a better understanding of diverse cellular behaviors in 3D tissue and further improve quality of a wide array of engineered tissues. (C) 2015 Elsevier Ltd. All rights reserved.
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