title: Harnessing cellular-derived forces in self-assembled microtissues to control the synthesis and alignment of ECM.
abstract: The alignment and blend of extracellular matrix (ECM) proteins give a tissue its specific mechanical properties as well as its physiological function. Various tissue engineering methods have taken purified ECM proteins and aligned them into gels, sponges and threads. Although, each of these methods has created aligned ECM, they have had many limitations including loss of hierarchal collagen structure and poor mechanical performance. Here, we have developed a new method to control ECM synthesis using self-assembled cells. Cells were seeded into custom designed, scaffold-free, micro-molds with fixed obstacles that harnessed and directed cell-mediated stresses. Cells within the microtissue reacted to self-generated tension by aligning, elongating, and synthesizing an ECM whose organization was dictated by the strain field that was set by our micro-mold design. We have shown that through cell selection, we can create tissues with aligned collagen II or aligned elastin. We have also demonstrated that these self-assembled microtissues have mechanical properties in the range of natural tissues and that mold design can be used to further tailor these mechanical properties.
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology Brown University, Providence, RI, USA; Center for Biomedical Engineering, Brown University, Providence, RI, USA.
authors.forename: Jacquelyn Y
authors.initials: JY
authors.lastname: Schell
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology Brown University, Providence, RI, USA; Center for Biomedical Engineering, Brown University, Providence, RI, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Wilks
authors.affiliation: School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Mohak
authors.initials: M
authors.lastname: Patel
authors.affiliation: Center for Biomedical Engineering, Brown University, Providence, RI, USA; School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Franck
authors.affiliation: Department of Mechanical Engineering, University of Massachusetts Dartmouth, North Dartmouth, MA, USA.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Chalivendra
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Vivek B
authors.initials: VB
authors.lastname: Shenoy
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology Brown University, Providence, RI, USA; Center for Biomedical Engineering, Brown University, Providence, RI, USA. Electronic address: Jeffrey_Morgan@Brown.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Morgan
mesh_terms: D018929:Cell Culture Techniques / Q000295:instrumentation*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000648:ultrastructure; D024043:Collagen Type II / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004867:Equipment Design; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D009940:Organoids / Q000378:metabolism / Q000648:ultrastructure*; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
chemical_list: D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D004549:Elastin
keywords: Aligned ECM; Cell-derived ECM; Mechanical properties; Self-assembly; Spheroid; Strong tissues