title: Micropatterning Alginate Substrates forin vitroCardiovascular Muscle on a Chip.
abstract: Soft hydrogels such as alginate are ideal substrates for building musclein vitrobecause they have structural and mechanical properties close to thein vivoextracellular matrix (ECM) network. However, hydrogels are generally not amenable to protein adhesion and patterning. Moreover, muscle structures and their underlying ECM are highly anisotropic, and it is imperative thatin vitromodels recapitulate the structural anisotropy in reconstructed tissues forin vivorelevance due to the tight coupling between sturcture and function in these systems. We present two techniques to create chemical and structural heterogeneities within soft alginate substrates and employ them to engineer anisotropic muscle monolayers: (i) microcontact printing lines of extracellular matrix proteins on flat alginate substrates to guide cellular processes with chemical cues, and (ii) micromolding of alginate surface into grooves and ridges to guide cellular processes with topographical cues. Neonatal rat ventricular myocytes as well as human umbilical artery vascular smooth muscle cells successfully attach to both these micropatterned substrates leading to subsequent formation of anisotropic striated and smooth muscle tissues. Muscular thin film cantilevers cut from these constructs are then employed for functional characterization of engineered muscular tissues. Thus, micropatterned alginate is an ideal substrate forin vitromodels of muscle tissue because it facilitates recapitulation of the anisotropic architecture of muscle, mimics the mechanical properties of the ECM microenvironment, and is amenable to evaluation of functional contractile properties.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA (USA).
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA (USA).
authors.forename: Yohan
authors.initials: Y
authors.lastname: Farouz
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA (USA).
authors.forename: Alexander Peyton
authors.initials: AP
authors.lastname: Nesmith
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA (USA).
authors.forename: Leila F
authors.initials: LF
authors.lastname: Deravi
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA (USA).
authors.forename: Megan Laura
authors.initials: ML
authors.lastname: McCain
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall 321, Cambridge, MA (USA).
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
keywords: Biomedical Applications; Hydrogels; Microcontact Printing; Surface Modification; Tissue Engineering