Engineered Tissue Development in Biofabricated 3D Geometrical Confinement–A Review

Abstract

Living tissue is a complex, heterogeneous structure where spatially organized ECMs present embedded cells with a variety of biochemical and mechanical signals. These signals are important to the formation of tissue structures and maintaining tissue homeostasis and physiological functions. Recent advances in biofabrication technologies have allowed the creation of 3D geometrical patterns that can guide the dynamic interaction between cells and ECM, leading to the formation of morphologically controlled engineered tissues that recapitulate the structure and function of native tissues. In this work, we first review advanced biofabrication technologies including lithography-based microfabrication and bioprinting that have been adopted to create a variety of geometrical confinements such as microgrooves and microribs, microwells, micropillar arrays, and microfibers. For each confinement type, we review geometrically guided formation and maturation of a variety of tissue types, including skeletal and cardiac muscles, epithelial tissue, endothelial tissue, and fibrous tissue. Geometrical confinements are important microenvironmental cues that can be utilized to promote the formation of biomimetic structures in engineered tissues.

Microfibrous extracellular matrix enhances in vitro modeling of the liver hepatocytes by modulating metabolism and integrin expression

“…An aliquot of 200 µL of the lysate was taken for BCA protein assay, as a measurement of cell numbers in each well for subsequent data normalization. The remaining lysates was mixed with 800 µL acetonitrile/methanol (50/50; v/v) containing 10 µM 13 C-threonine (as internal standard for LC-MS analyses, purchased from Cambridge Isotope Laboratories, Inc. Tewksbury, MA) and vortex mixed for 30s. Then samples were incubated for 1h at -20 °C to precipitate proteins, which were then centrifuged at 14,000 rpm (Eppendorf, Centrifuge 5424R, Hauppauge, NY) at 4 °C.…”

Engineering Biomaterials and Approaches for Mechanical Stretching of Cells in Three Dimensions

“…The custom-designed elastic micropillars (termed as microfabricated tissue gauges) are not only used to constrain the engineered microtissues but also to report forces generated by them in real time. Such approach has attracted great interests in the past decade ( Jason et al, 2014 ; Liu et al, 2014 ; Mills et al, 2017 ; Ronaldson-Bouchard et al, 2018 ; Chen and Zhao, 2019 ). Recently, a similar approach has been reported by using elastic microwires instead of micropillars to constrain and monitor microtissues, showing great promises in heteropolar microtissue construction and disease modeling ( Mastikhina et al, 2019 ; Wang E. Y. et al, 2019 ; Zhao Y. et al, 2019 ).…”

Compressive Buckling Fabrication of 3D Cell‐Laden Microstructures

“…[ 4 , 5 , 6 , 7 ] Lithography‐based techniques such as microfluidic channels and microtissue patterning have been developed in recent years and have become the workhorse in tissue engineering for the creation of biomimetic tissue structures. [ 8 , 9 , 10 , 11 ] Microfluidic‐based organ‐on‐chip systems are currently at the main stage for the modeling of diseases and the preclinical testing of a variety of drugs. [ 6 , 12 , 13 ] However, despite their success and widespread use, lithography‐generated biomimetic structures are predominantly two‐dimensional (2D) and only represent very limited out‐of‐plane tissue structure.…”