Challenges and Opportunities for Tissue-Engineering Polarized Epithelium

Abstract

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

Micropatterning Strategies to Engineer Controlled Cell and Tissue Architecture in Vitro

“…Soft lithography is used to generate an elastomeric polymer stamp containing features defined by the topography of a previously patterned wafer (45). In this case, the process becomes more convenient as no clean room is required and multiple stamps can be cast from the same original wafer (28).…”

Composite Hydrogels with Tunable Anisotropic Morphologies and Mechanical Properties

“…Since many tissues, e.g., striated muscle, 6 cartilage, 7 or cornea 8 , to name just a few examples, have anisotropic hierarchical morphologies, there is a growing interest in developing approaches for the fabrication of anisotropic hydrogels that exhibit direction-dependent pore shape, microstructure, stiffness, and conductivity. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] In tissue engineering, aside from biomimicry, anisotropic pore shape and hydrogel structure, in general, are important for cell guidance 22 and differentiation, 23 as well as mass transport of biofactors and nutrients throughout the scaffold. 19,24,25 In bioseparation, control over the shape anisotropy of hydrogel pores may enhance the selectivity of the filtration of biological species and/or minimize the pressure drop across the matrix.…”

Full‐thickness tissue engineered oral mucosa for genitourinary reconstruction: A comparison of different collagen‐based biodegradable membranes

“…Since only mature epithelia synthesize a basement membrane, 36 it appears that the epithelial layer of all TEOMs in the experimental models presented here formed a mature tissue‐like construct. The formation of a functioning basement membrane is vital for the epithelial layer and for the functionality of the engineered mucosal substitutes, since the basement membrane acts as an anchor for the epithelial layer to the extracellular matrix 7,36 . Thus, the basement membrane formation in the TEOMs is a sign of a stable epithelial coverage of the distinct scaffolds, an important characteristic with respect to further clinical applications.…”

“…The epithelial cells were able to spread, organize, and form a multi-stratified epithelial layer on the upper side of the various membranes, as shown by cytokeratin 13 immunostaining. This can only be achieved by seeding primary epithelial cells, since polarization is usually not achieved by using epithelial cell lines 36. Collagen IV, a component of the lamina densa of basement membrane,7 was detected on the interface between the multi-layered epithelial tissue on all various membranes.Since only mature epithelia synthesize a basement membrane,36 it appears that the epithelial layer of all TEOMs in the experimental models presented here formed a mature tissue-like construct.…”