Please use this identifier to cite or link to this item: https://doi.org/10.1088/1758-5090/aba0c2
Title: Fabrication of vascularized tissue constructs under chemically defined culture conditions
Authors: Sriram, Gopu 
Handral, Harish K
Gan, Shu Uin 
Islam, Intekhab 
Rufaihah, Abdul Jalil 
Cao, Tong 
Keywords: Science & Technology
Technology
Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
vascularized tissue
3D culture
microvasculature
fibrin matrix
serum-free
chemically defined
PLURIPOTENT STEM-CELLS
SMOOTH-MUSCLE-CELLS
ENDOTHELIAL-CELLS
IN-VITRO
DIFFERENTIATION
ANGIOGENESIS
PERICYTES
NETWORKS
GENERATION
DERIVATION
Issue Date: 1-Oct-2020
Publisher: IOP PUBLISHING LTD
Citation: Sriram, Gopu, Handral, Harish K, Gan, Shu Uin, Islam, Intekhab, Rufaihah, Abdul Jalil, Cao, Tong (2020-10-01). Fabrication of vascularized tissue constructs under chemically defined culture conditions. BIOFABRICATION 12 (4). ScholarBank@NUS Repository. https://doi.org/10.1088/1758-5090/aba0c2
Abstract: Three-dimensional (3D) biofabrication techniques that enable the production of multicellular tissue equivalents for applications in basic biology, drug screening and regenerative medicne. Fabrication of these tissue constructs with in-built microvasculature enables recapitulation of the biological environment of the native tissues. Here, we present the fabrication of 3D vascularized tissue constructs containing microvascular networks using human embryonic stem cell (hESC)-derived endothelial cells (ECs) and pericytes encapsulated within a fibrin-based matrix and cultured under chemically defined conditions. Firstly, by manipulating the developmental signaling pathways under chemically defined culture conditions, hESCs were efficiently differentiated to hESC-ECs and hESC-pericytes through intermediate stages of lateral plate and paraxial mesoderm respectively. Next, encapsulation of these hESC-derived vascular cells within fibrin-based matrix and culture under chemically defined conditions, result in self-assembly of hESC-ECs into a network of microvessels within a period of 6-9 d. With the supporting influence of hESC-pericytes, the microvascular network with lumen was stable for at least 3 weeks. Quantification of the fractal dimensions of the microvascular networks demonstrate the increasing complexity of the vascular network with increasing endothelial cell densities. Dextran permeation studies in the presence or absence of vasodilating agent (histamine) showed the presence of hollow lumen, modulation of barrier properties of the microvasculature and its functional response to histamine. Hence, this versatile in vitro 3D model of vascularized constructs generated under chemically defined conditions is well suited to study early angiogenesis for in vitro drug testing applications and provide a clinically amenable, fundamental step towards fabrication of complex and functional tissues for regenerative applications in the future.
Source Title: BIOFABRICATION
URI: https://scholarbank.nus.edu.sg/handle/10635/219436
ISSN: 1758-5082
1758-5090
DOI: 10.1088/1758-5090/aba0c2
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