Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels

Mehdi Nikkhah, Nouran Eshak, Pinar Zorlutuna, Nasim Annabi, Marco Castello, Keekyoung Kim, Alireza Dolatshahi-Pirouz, Faramarz Edalat, Hojae Bae, Yunzhi Yang, Ali Khademhosseini

Research output: Contribution to journalArticle

155 Scopus citations

Abstract

Engineering of organized vasculature is a crucial step in the development of functional and clinically relevant tissue constructs. A number of previous techniques have been proposed to spatially regulate the distribution of angiogenic biomolecules and vascular cells within biomaterial matrices to promote vascularization. Most of these approaches have been limited to two-dimensional (2D) micropatterned features or have resulted in formation of random vasculature within three-dimensional (3D) microenvironments. In this study, we investigate 3D endothelial cord formation within micropatterned gelatin methacrylate (GelMA) hydrogels with varying geometrical features (50-150 μm height). We demonstrated the significant dependence of endothelial cells proliferation, alignment and cord formation on geometrical dimensions of the patterned features. The cells were able to align and organize within the micropatterned constructs and assemble to form cord structures with organized actin fibers and circular/elliptical cross-sections. The inner layer of the cord structure was filled with gel showing that the micropatterned hydrogel constructs guided the assembly of endothelial cells into cord structures. Notably, the endothelial cords were retained within the hydrogel microconstructs for all geometries after two weeks of culture; however, only the 100 μm-high constructs provided the optimal microenvironment for the formation of circular and stable cord structures. Our findings suggest that endothelial cord formation is a preceding step to tubulogenesis and the proposed system can be used to develop organized vasculature for engineered tissue constructs.

Original languageEnglish (US)
Pages (from-to)9009-9018
Number of pages10
JournalBiomaterials
Volume33
Issue number35
DOIs
Publication statusPublished - Dec 2012
Externally publishedYes

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Keywords

  • Cords
  • Endothelial cells
  • Gelatin methacrylate
  • Hydrogel
  • Microfabrication

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Nikkhah, M., Eshak, N., Zorlutuna, P., Annabi, N., Castello, M., Kim, K., ... Khademhosseini, A. (2012). Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials, 33(35), 9009-9018. https://doi.org/10.1016/j.biomaterials.2012.08.068