Fabrication of cell container arrays with overlaid surface topographies

Abstract

This paper presents cell culture substrates in the form of microcontainer arrays with overlaid surface topographies, and a technology for their fabrication. The new fabrication technology is based on microscale thermoforming of thin polymer films whose surfaces are topographically prepatterned on a micro- or nanoscale. For microthermoforming, we apply a new process on the basis of temporary back moulding of polymer films and use the novel concept of a perforated-sheet-like mould. Thermal micro- or nanoimprinting is applied for prepatterning. The novel cell container arrays are fabricated from polylactic acid (PLA) films. The thin-walled microcontainer structures have the shape of a spherical calotte merging into a hexagonal shape at their upper circumferential edges. In the arrays, the cell containers are arranged densely packed in honeycomb fashion. The inner surfaces of the highly curved container walls are provided with various topographical micro- and nanopatterns. For a first validation of the microcontainer arrays as in vitro cell culture substrates, C2C12 mouse premyoblasts are cultured in containers with microgrooved surfaces and shown to align along the grooves in the three-dimensional film substrates. In future stem-cell-biological and tissue engineering applications, microcontainers fabricated using the proposed technology may act as geometrically defined artificial microenvironments or niches.Electronic supplementary materialThe online version of this article (doi:10.1007/s10544-011-9588-5) contains supplementary material, which is available to authorized users.

Mimicking the biological world: Methods for the 3D structuring of artificial cellular environments

“…With additional flexible solid layers, acting as transfer membrane, it is also possible to form porous substrates that have great advantages in application as cell culturing scaffold [9]. Structures vary from simple line structures with different ratios to complex hexagonal or honeycomb structures [32,49], which can be perfused or super fused by cell culturing media inside of bioreactor systems.…”

“…Recent publications and patents are showing that thermoforming technology is well suited to create complex, multilayered material systems [49,50,113,114] (Schober, A., Weise, F., Fernekorn, U., Hildmann, C. et al, Verfahren zur Herstellung eines mikrostrukturierten Formkörpers, DE 10 2012DE 10 103 174.6, 2012. One possible way to realize these complex multiscale structures is to thermoform premanufactured submicron and nanostructured foil.…”

“…Currently limits are set by the lack of suitable dropon-demand devices, biocompatibility of polymers, and by long process times. Nevertheless, the fusion of different disciplines is [41] Poly(ethyleneoxide terephthalate)-poly (butyleneterephthalate) (PEOT/PBT) copolymers [18] • Multiphoton polymerization of hydrogels/ polymers [42][43][44] -Inkjet printing -Organ printing [15,[45][46][47] Biofunctionalization of 3D substrates Chemical functionalization by patterning [48][49][50][51][52][53] Patterning of hydrogels [16,17,54] Biological application…”

Combination of Microstereolithography and Electrospinning to Produce Membranes Equipped with Niches for Corneal Regeneration

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Effect of Surface Morphology of Poly(ϵ‐caprolactone) Scaffolds on Adipose Stem Cell Adhesion and Proliferation

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