title: Hydrogel-based biomimetic environment for in vitro modulation of branching morphogenesis.
abstract: The mechanical properties of the cellular microenvironment dramatically alter during tissue development and growth. Growing evidence suggests that physical microenvironments and mechanical stresses direct cell fate in developing tissue. However, how these physical cues affect the tissue morphogenesis remains a major unknown. We explain here that the physical properties of the cell and tissue microenvironment, biomimetically reproduced by using hydrogel, guide the tissue morphogenesis in the developmental submandibular gland (SMG). In particular, the softer gel enhances the bud expansion and cleft formation of SMG, whereas the stiffer gel attenuates them. These morphological changes in SMG tissue are led by soluble factors (FGF7/10) induction regulated by cell traction force derived from the tissue deformation. Our findings suggest that cells sense the mechanics of their surrounding environment and alter their properties for self-organization and the following tissue morphogenesis. Also, physically designed hydrogel material is a valuable tool for producing the biomimetic microenvironment to explore how physical cues affect tissue morphogenesis and to modulate tissue morphogenesis for in vitro tissue synthesis.
authors.affiliation: Department of Biomaterials Science, Osaka University, 1-8 Yamada-Oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyajima
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Sakai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: An
authors.forename: Makoto
authors.initials: M
authors.lastname: Abe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakisaka
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egusa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imazato
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D032701:Biomimetics; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003198:Computer Simulation; D004548:Elasticity; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D008422:Materials Testing; D009024:Morphogenesis / Q000187:drug effects*; D013314:Stress, Mechanical; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D020100:Hydrogels; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor