Interactions of human blood and tissue cell types with 95-nm-high nanotopography

Two of the major concerns for tissue engineering materials are inflammatory responses from blood cells and fibrous encapsulation by the body in order to shield the implant from blood reaction. A further hurdle is that of vascularization. In order to develop new tissues, or to repair parts of the vascular system, nutrients need to be carried to the basal cell layers. If a material promotes tissue formation, but not vascularization, necrosis will be observed as multilayered cells develop. In this paper, polymer demixed island topography with a 95-nm Z axis was tested using human mononuclear blood cells, platelets, fibroblasts, and endothelial cells. The results showed no difference in blood response between the islands and the flat controls, suggesting that in vivo there would be negligible immunological difference. Fibroblasts reacted by changing morphology into a rounded shape with thick processes and poorly developed cytoskeleton. Retardation of fibroblast growth may be an advantageous, as it is this cell type that forms the fibrous capsule, preventing growth of the required tissue type. Finally, endothelial cells were seen to form arcuate, or curved, morphologies in response to the islands. This is the normal, in vivo, morphology for vascular endothelium. This result suggests that the nano-features are promoting a more phenotypically correct morphology.

I. Introduction

Cells are known to react to the shape of their environment in vivo. These topographical cues may come from surrounding extracellular matrix (ECM), such as collagen fibers and neighboring cell morphologies [1]. In vitro, cells have been observed to respond to micro-scale topographies, with many cell types altering their morphologies and cytoskeletons in response to both highly defined topographies and random roughness [2]– [6]. The development of technologies used in the electronics industry, such as the progression from photolithography to electron-beam lithography, have allowed the first in vitro glimpses of cell reactions to defined nano-topographies [7]. These surfaces are, however, very expensive to produce both in terms of writing cost and time of manufacture.