Response of Primary Human Bone Marrow Mesenchymal Stromal Cells and Dermal Keratinocytes to Thermal Printer Materials In Vitro

Abstract

Advancement in thermal three-dimensional printing techniques has greatly increased the possible applications of various materials in medical applications and tissue engineering. Yet, potential toxic effects on primary human cells have been rarely investigated. Therefore, we compared four materials commonly used in thermal printing for bioengineering, namely thermally printed acrylonitrile butadiene styrene, MED610, polycarbonate, and polylactic acid, and investigated their effects on primary human adult skin epidermal keratinocytes and bone marrow mesenchymal stromal cells (BM-MSCs) in vitro. We investigated indirect effects on both cell types caused by potential liberation of soluble substances from the materials, and also analyzed BM-MSCs in direct contact with the materials. We found that even in culture without direct contact with the materials, the culture with MED610 (and to a lesser extent acrylonitrile butadiene styrene) significantly affected keratinocytes, reducing cell numbers and proliferation marker Ki67 expression, and increasing glucose consumption, lactate secretion, and expression of differentiation-associated genes. BM-MSCs had decreased metabolic activity, and exhibited increased cell death in direct culture on the materials. MED610 and acrylonitrile butadiene styrene induced the strongest expression of genes associated to differentiation and estrogen receptor activation. In conclusion, we found strong cell-type-specific effects of the materials, suggesting that materials for applications in regenerative medicine should be carefully selected not only based on their mechanical properties but also based on their cell-type-specific biological effects.Electronic supplementary materialThe online version of this article (doi:10.1007/s40846-016-0118-z) contains supplementary material, which is available to authorized users.

Biocompatibility of Photopolymers in 3D Printing

“…Oskui et al 9) and Leonhardt et al 29) reported improved biocompatibility outcomes for materials cleaned with isopropanol and post-cured. Schmelzer et al 11) , in contrast, reported in their in vitro study that ethanol treatment was ineffective in improving the biocompatibility of MED610. It is worth emphasizing that although in vitro tests are faster, less expensive, more reproducible, and more scalable than other types of tests, they may suffer from a lack of relevance to the clinical use of materials, and this weakness is not trivial 30) .…”

“…The quality of the AM-produced devices may consequently vary when identical parts are built using different 3D printers or even when the same 3D printer, parameters, process steps, and materials are used 2) . An issue of concern is recent studies highlighting their potential toxicity [8][9][10][11] . By being toxic, there is a relative ability of the materials to cause injury to biological tissues, ranging from improper biochemical function, organ damage, and cell destruction, to death 12) .…”

3D Printing Solutions for Microfluidic Chip-To-World Connections

“…In the case of bioanalysis applications, a strong influence on cellular behavior of mammalian cells and bacteria exposed to 3D-printed structures realized from liquid resins was observed [ 29 ]. The resins commonly used for stereolithography 3D printing contain UV-sensitive photo-initiators, which exhibit a pronounced cytotoxic effect [ 45 ]. Biocompatible classified resins such as E-Shell 300 from Envisiontec [ 39 ] or Med610 from Stratasys [ 46 ] need a thorough post-processing, including UV-flood exposure to cross-link residual monomers.…”

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“…Regarding of the advantages and disadvantages of the above materials, the future of 3D printing materials research will focus on the following aspects: Increasing the existing materials' mechanical properties and stability by modification; developing more new materials like PLGA; researching bioactive printing materials that have complex pore and structural composite [54,55].…”