A micron-scale surface topography design reducing cell adhesion to implanted materials

Francesco Robotti,Anna Mallone,Giovanni Pellegrini,Volkmar Falk,Federica Fraschetti,Simone Bottan,Christoph Starck,Nicole Lindenblatt,Aldo Ferrari,Dimos Poulikakos

doi:10.1038/s41598-018-29167-2

Francesco Robotti, Anna Mallone + Show 8 more

Open Access

https://doi.org/10.1038/s41598-018-29167-2

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Abstract

The micron-scale surface topography of implanted materials represents a complementary pathway, independent of the material biochemical properties, regulating the process of biological recognition by cells which mediate the inflammatory response to foreign bodies. Here we explore a rational design of surface modifications in micron range to optimize a topography comprised of a symmetrical array of hexagonal pits interfering with focal adhesion establishment and maturation. When implemented on silicones and hydrogels in vitro, the anti-adhesive topography significantly reduces the adhesion of macrophages and fibroblasts and their activation toward effectors of fibrosis. In addition, long-term interaction of the cells with anti-adhesive topographies markedly hampers cell proliferation, correlating the physical inhibition of adhesion and complete spreading with the natural progress of the cell cycle. This solution for reduction in cell adhesion can be directly integrated on the outer surface of silicone implants, as well as an additive protective conformal microstructured biocellulose layer for materials that cannot be directly microstructured. Moreover, the original geometry imposed during manufacturing of the microstructured biocellulose membranes are fully retained upon in vivo exposure, suggesting a long lasting performance of these topographical features after implantation.

Highlights

The non-specific adhesion of cells and tissues to synthetic substrates is at the origin of adverse responses to body implants, including those associated with foreign body reaction[1]
The bacterial fermentation process generating biocellulose offers an easy access to the modification of several material properties such as density[15], chemistry[16], and surface topography[17]
The criteria for selection encompassed the biological effect, the ability to transfer the topographical elements on the target materials through established lithography protocols, and the ability to upscale the process to large surfaces

Summary

Introduction

The non-specific adhesion of cells and tissues to synthetic substrates is at the origin of adverse responses to body implants, including those associated with foreign body reaction[1]. Silicon-based interfaces (e.g. drivelines of ventricular assist devices VADs, pacemakers, gastric and deep brain stimulators, breast implants) generate hotspots for the onset of fibrotic responses upon deployment[9] To mitigate this problem, several surface treatments have been tested, including www.nature.com/scientificreports/. Modification of artificial substrates with nano-scale topographies has shown the ability to reduce protein absorption[10] These non-fouling surfaces can demote cell adhesion blocking integrin-mediated surface recognition. A promising alternative approach is represented by the application of an intervening protective layer between the device and the hosting tissue In this direction, bio-synthesized cellulose (i.e. biocellulose) is attracting growing interest due to its favorable properties, which include the long-term stability and the low inflammatory response elicited in vivo[11,12,13,14]. The bacterial fermentation process generating biocellulose offers an easy access to the modification of several material properties such as density[15], chemistry[16], and surface topography[17]

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