Three dimensional tubular structure self-assembled by vascular mesenchymal cells at stiffness interfaces of hydrogels

Xiaolu Zhu; Shiva Gojgini; Ting-Hsuan Chen; Fang Teng; Peng Fei; Siyan Dong; Tatiana Segura; Chih-Ming Ho

doi:10.1016/j.biopha.2016.08.018

Three dimensional tubular structure self-assembled by vascular mesenchymal cells at stiffness interfaces of hydrogels

Biomed Pharmacother. 2016 Oct:83:1203-1211. doi: 10.1016/j.biopha.2016.08.018. Epub 2016 Aug 23.

Authors

Xiaolu Zhu¹, Shiva Gojgini², Ting-Hsuan Chen³, Fang Teng⁴, Peng Fei⁵, Siyan Dong⁵, Tatiana Segura², Chih-Ming Ho⁶

Affiliations

¹ School of Mechanical and Electrical Engineering, Hohai University, Changzhou, Jiangsu 213022, China; Mechanical and Aerospace Engineering Department, University of California, Los Angeles, CA 90095, USA. Electronic address: zhuxxiaoluu@yeah.net.
² Chemical and Biomolecular Engineering Department, University of California, Los Angeles, CA 90095, USA.
³ Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong.
⁴ Department of Gynaecology and Obstetrics, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
⁵ Mechanical and Aerospace Engineering Department, University of California, Los Angeles, CA 90095, USA.
⁶ Mechanical and Aerospace Engineering Department, University of California, Los Angeles, CA 90095, USA; Bioengineering Department, University of California Los Angeles, Los Angeles, CA 90095, USA.

PMID: 27562720
DOI: 10.1016/j.biopha.2016.08.018

Abstract

In this study, we report a rational and robust methodology to construct three dimensional (3D) tubular-structures solely by self-assembly of vascular mesenchymal cells (VMCs). Using the cell-laden hyaluronic acid hydrogel surrounded by cell-free gel with a higher stiffness, VMCs spontaneously migrated across the interface and assembled into 3D tubes, which composes of numerous cells. Based on turing instability which describes the reaction-diffusion processes of inhibitors and activators, this result of 3D tubular structure formation agrees with theoretical predictions from simulations of the reaction-diffusion of morphogens and cells under the initial conditions of patterned cell-laden hydrogel. We showed that this combination of theoretical prediction and experiments is able to produce multi-cellular 3D tubes with desired dimensions and determinate orientation in hydrogel mimicking the 3D features of tubular tissue. This work provides a reliable methodology for creating tubular structures with controllable sizes inside the 3D hydrogel through multi-cellular self-organization.

Keywords: Hyaluronic acid; Mesenchymal stem cell; Self-organization; Turing instability.

MeSH terms

Cell Culture Techniques / methods*
Cells, Cultured
Endothelium, Vascular / chemistry*
Endothelium, Vascular / cytology*
Endothelium, Vascular / physiology
Humans
Hyaluronic Acid / chemistry*
Hydrogels / chemistry*
Mesenchymal Stem Cells / chemistry*
Mesenchymal Stem Cells / physiology
Surface Properties

Substances

Hydrogels
Hyaluronic Acid