title: Directing three-dimensional multicellular morphogenesis by self-organization of vascular mesenchymal cells in hyaluronic acid hydrogels.
abstract: BACKGROUND
  Physical scaffolds are useful for supporting cells to form three-dimensional (3D) tissue. However, it is non-trivial to develop a scheme that can robustly guide cells to self-organize into a tissue with the desired 3D spatial structures. To achieve this goal, the rational regulation of cellular self-organization in 3D extracellular matrix (ECM) such as hydrogel is needed.
  
  
  RESULTS
  In this study, we integrated the Turing reaction-diffusion mechanism with the self-organization process of cells and produced multicellular 3D structures with the desired configurations in a rational manner. By optimizing the components of the hydrogel and applying exogenous morphogens, a variety of multicellular 3D architectures composed of multipotent vascular mesenchymal cells (VMCs) were formed inside hyaluronic acid (HA) hydrogels. These 3D architectures could mimic the features of trabecular bones and multicellular nodules. Based on the Turing reaction-diffusion instability of morphogens and cells, a theoretical model was proposed to predict the variations observed in 3D multicellular structures in response to exogenous factors. It enabled the feasibility to obtain diverse types of 3D multicellular structures by addition of Noggin and/or BMP2.
  
  
  CONCLUSIONS
  The morphological consistency between the simulation prediction and experimental results probably revealed a Turing-type mechanism underlying the 3D self-organization of VMCs in HA hydrogels. Our study has provided new ways to create a variety of self-organized 3D multicellular architectures for regenerating biomaterial and tissues in a Turing mechanism-based approach.
authors.affiliation: College of Mechanical and Electrical Engineering, Hohai University, Changzhou, Jiangsu 213022 China.|Mechanical and Aerospace Engineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Chemical and Biomolecular Engineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Shiva
authors.initials: S
authors.lastname: Gojgini
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
authors.forename: Ting-Hsuan
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Mechanical and Aerospace Engineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Fei
authors.affiliation: Mechanical and Aerospace Engineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Siyan
authors.initials: S
authors.lastname: Dong
authors.affiliation: Mechanical and Aerospace Engineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.|Bioengineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Ho
authors.affiliation: Chemical and Biomolecular Engineering Department, University of California Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Segura
keywords: Hyaluronic acid; Mesenchymal stem cell; Self-organization; Turing mechanism