Abstract
Mammalian cells have been widely shown to respond to nano- and microtopography that mimics the extracellular matrix. Synthetic nano- and micron-sized structures are therefore of great interest in the field of tissue engineering, where polymers are particularly attractive due to excellent biocompatibility and versatile fabrication methods. Ordered arrays of polymeric pillars provide a controlled topographical environment to study and manipulate cells, but processing methods are typically either optimized for the nano- or microscale. Here, we demonstrate polymeric nanopillar (NP) fabrication using 3D direct laser writing (3D DLW), which offers a rapid prototyping across both size regimes. The NPs are interfaced with NIH3T3 cells and the effect of tuning geometrical parameters of the NP array is investigated. Cells are found to adhere on a wide range of geometries, but the interface depends on NP density and length. The Cell Interface with Nanostructure Arrays (CINA) model is successfully extended to predict the type of interface formed on different NP geometries, which is found to correlate with the efficiency of cell alignment along the NPs. The combination of the CINA model with the highly versatile 3D DLW fabrication thus holds the promise of improved design of polymeric NP arrays for controlling cell growth.
Highlights
Pillar diameter structures are seen mainly for diameters in the microregime (≥1 μm)
We have demonstrated that 3D direct laser writing (3D DLW) can be used for fast and flexible prototyping of polymeric NPs from pentaerythritol triacrylate (PETIA), which allowed us to systematically study the effect of NP array geometry on the behavior of NIH3T3 cells
We have shown that the polymeric NPs generally provide a biocompatible environment for cell adhesion and sustained cell growth, and that the cells form a tight interface with the NPs through both direct membrane adhesion and actin remodeling around the NPs
Summary
Nina Buch-Månson 1, Arnaud Spangenberg[2], Laura Piedad Chia Gomez[2], Jean-Pierre Malval[2], Olivier Soppera2 & Karen L. Cell behavior on longer polymeric NPs or for NP diameters in the transition between nano- and microregimes remain only scarcely investigated In this context, 3D direct laser writing (3D DLW) by multi-photon polymerization offers an appealing approach to overcome these limitations. If the CINA model applies to this size regime, the ability to predict the cell-NP interface at a given geometry, which can potentially influence the cell response, would make screening and optimization of NP arrays even more rapid For this purpose, we tune both NP length and density and observe the effects on the interface and behavior of fibroblasts (NIH3T3), which are major players in wound healing[32] and known to respond to both nano- and microtopographical cues[33, 34]
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