Epithelial cell adhesion on films mimicking surface of polymeric scaffolds of artificial urethra compared to molecular modeling of integrin binding

Abstract

In this study, a combined experimental and computational study of long-term human bladder epithelial cell line HBLAK adhesion and proliferation on five different polymeric surfaces, namely hyaluronic acid, amylose, collagen, polyhydroxybutyrate, and polylactic acid, was performed with the goal to understand the nature of the attraction between various surface materials and a simplified model of the cell surface (transmembrane protein integrin). These biodegradable polymers are frequently used as scaffolds for tissue engineering. During formation of the new tissue, the scaffold polymers are gradually replaced by the natural extracellular matrix of the proliferating cells. Cell adhesion and proliferation experiments were carried out employing thin polymer films prepared by solvent casting while for the computational approach three-dimensional molecular models of layers of ordered polymeric fibers were used as quasi-planar nano-sized models of polymeric surface patches. Experimental results indicated a good capability of amylose, polyhydroxybutyrate, and hyaluronic acid polymer films to foster cell adhesion. Proliferation experiment, carried out by incubating cells with the investigated polymer films for 72 h, showed that all the investigated polymers are able to sustain a good proliferation of HBLAK cells almost comparable to plain glass. Computational estimate of molecular mechanic interaction energies between three-dimensional models of polymeric films and the collagen-binding α₂ I domain of the cell adhesion receptor integrin α₂β₁ confirmed elevated affinity to amylose and polyhydroxybutyrate that is related to higher polarity of function groups on the film surface as documented by the maps of molecular electrostatic potential. This combined experimental and modeling approach can contribute to rational design and surface modifications of polymeric material suitable for forming the scaffolds of human urethra that can be effectively colonized by stem cells.

Keywords

Regenerative medicine artificial human urethra cell adhesion and proliferation thin films polymeric scaffold surfaces molecular modeling human integrin binding affinity to surfaces

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