A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion ligands regulates 3D spatial organization of cells and tissue.
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 biomolecules 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.
Department of Chemical and Biomolecular Engineering, Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Min Kyung
MK
Lee
Department of Chemical and Biomolecular Engineering, Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Max H
MH
Rich
Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: jong@cau.ac.kr.
Jonghwi
J
Lee
Department of Chemical and Biomolecular Engineering, Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Chemical Engineering, Soongsil University, Seoul, Republic of Korea. Electronic address: hjkong06@illinois.edu.
Hyunjoon
H
Kong
D000818:Animals; D016880:Anisotropy; D001672:Biocompatible Materials / Q000737:chemistry*; D032701:Biomimetics; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008024:Ligands; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008863:Microspheres; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000737:chemistry; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001672:Biocompatible Materials; D020100:Hydrogels; D008024:Ligands; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C047981:arginyl-glycyl-aspartic acid
Bimodal hydrogels; Bio-inspired; Differentiation; Glial cells; Microchannels; Neuron; RGD peptides; Stem cells; Uniaxial freeze drying