TY - JOUR

T1 - Three-dimensional laser micro- and nano-structuring of acrylated poly(ethylene glycol) materials and evaluation of their cytoxicity for tissue engineering applications

AU - Ovsianikov, A.

AU - Malinauskas, M.

AU - Schlie, S.

AU - Chichkov, B.

AU - Gittard, S.

AU - Narayan, R.

AU - Löbler, M.

AU - Sternberg, K.

AU - Schmitz, K. P.

AU - Haverich, A.

N1 - Funding information: The presented work was supported by the DFG Excellence Cluster “Rebirth” and the SFB Transregio 37, “Mikro- und Nanosysteme in der Medizin – Rekonstruktion biologischer Funktionen”.

PY - 2010/10/25

Y1 - 2010/10/25

N2 - The natural cell environment is characterized by complex three-dimensional structures, which contain features at multiple length scales. Many in vitro studies of cell behavior in three dimensions rely on the availability of artificial scaffolds with controlled three-dimensional topologies. In this paper, we demonstrate fabrication of three-dimensional scaffolds for tissue engineering out of poly(ethylene glycol) diacrylate (PEGda) materials by means of two-photon polymerization (2PP). This laser nanostructuring approach offers unique possibilities for rapid manufacturing of three-dimensional structures with arbitrary geometries. The spatial resolution dependence on the applied irradiation parameters is investigated for two PEGda formulations, which are characterized by molecular weights of 302 and 742. We demonstrate that minimum feature sizes of 200 nm are obtained in both materials. In addition, an extensive study of the cytotoxicity of the material formulations with respect to photoinitiator type and photoinitiator concentration is undertaken. Aqueous extracts from photopolymerized PEGda samples indicate the presence of water-soluble molecules, which are toxic to fibroblasts. It is shown that sample aging in aqueous medium reduces the cytotoxicity of these extracts; this mechanism provides a route for biomedical applications of structures generated by 2PP microfabrication and photopolymerization technologies in general. Finally, a fully biocompatible combination of PEGda and a photoinitiator is identified. Fabrication of reproducible scaffold structures is very important for systematic investigation of cellular processes in three dimensions and for better understanding of in vitro tissue formation. The results of this work suggest that 2PP may be used to polymerize poly(ethylene glycol)-based materials into three-dimensional structures with well-defined geometries that mimic the physical and biological properties of native cell environments.

AB - The natural cell environment is characterized by complex three-dimensional structures, which contain features at multiple length scales. Many in vitro studies of cell behavior in three dimensions rely on the availability of artificial scaffolds with controlled three-dimensional topologies. In this paper, we demonstrate fabrication of three-dimensional scaffolds for tissue engineering out of poly(ethylene glycol) diacrylate (PEGda) materials by means of two-photon polymerization (2PP). This laser nanostructuring approach offers unique possibilities for rapid manufacturing of three-dimensional structures with arbitrary geometries. The spatial resolution dependence on the applied irradiation parameters is investigated for two PEGda formulations, which are characterized by molecular weights of 302 and 742. We demonstrate that minimum feature sizes of 200 nm are obtained in both materials. In addition, an extensive study of the cytotoxicity of the material formulations with respect to photoinitiator type and photoinitiator concentration is undertaken. Aqueous extracts from photopolymerized PEGda samples indicate the presence of water-soluble molecules, which are toxic to fibroblasts. It is shown that sample aging in aqueous medium reduces the cytotoxicity of these extracts; this mechanism provides a route for biomedical applications of structures generated by 2PP microfabrication and photopolymerization technologies in general. Finally, a fully biocompatible combination of PEGda and a photoinitiator is identified. Fabrication of reproducible scaffold structures is very important for systematic investigation of cellular processes in three dimensions and for better understanding of in vitro tissue formation. The results of this work suggest that 2PP may be used to polymerize poly(ethylene glycol)-based materials into three-dimensional structures with well-defined geometries that mimic the physical and biological properties of native cell environments.

KW - Cytotoxicity

KW - PEG

KW - Polymer

KW - Scaffolds

KW - Tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=79251648820&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2010.10.023

DO - 10.1016/j.actbio.2010.10.023

M3 - Article

C2 - 20977947

AN - SCOPUS:79251648820

VL - 7

SP - 967

EP - 974

JO - Acta biomaterialia

JF - Acta biomaterialia

SN - 1742-7061

IS - 3

ER -