Three-dimensional laser micro- and nano-structuring of acrylated poly(ethylene glycol) materials and evaluation of their cytoxicity for tissue engineering applications
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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 200nm 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.
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Several research groups have investigated the potential of 2PP for biomedical applications with biocompatible resins such as PLA, PCL, PEG or the use of proteins as scaffold material, which have the potential for clinical application.
“Several research groups have been investigated the potential of 2PP for biomedical applications with biocompatible resins such as PLA [28], PCL [29], PEG [30] or the use of proteins as scaffold material [31,32], which have the potential for clinical application [33].”
From <i>In vitro</i> degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization (2016) · cites this paper as [30]
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- Authors
- Ovsianikov, A., Malinauskas, M., Schlie, S., Chichkov, B., Gittard, S., Narayan, R., Löbler, M., Sternberg, K., Schmitz, K.-P., & Haverich, A.
- Affiliations
- Laser Zentrum Hannover (DE)
- University of North Carolina at Chapel Hill (US)
- University of Rostock (DE)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Ovsianikov, A.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 7
- Issue
- 3
- Pages
- 967-974
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC3034306
- OpenAlex
- W2101304102
- Cited by
- 234
- References
- 36
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 15 · 2021: 14 · 2020: 14 · 2019: 16 · 2018: 17 · 2017: 11 · 2016: 16 · 2015: 14 · 2014: 24 · 2013: 25 · 2012: 23
- FWCI
- 12.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Deutsche Forschungsgemeinschaft (Transregio 37)
- National Institute on Drug Abuse (R21DA026980)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nonlinear Optical Materials Studies
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Computational Mechanics › Laser Material Processing Techniques
- Keywords
- poly(ethylene glycol) diacrylate, two-photon polymerization, 3D scaffolds, tissue engineering, laser-induced nanostructuring, cytotoxicity, photoinitiators, aqueous extract, fibroblasts, biocompatibility, spatial resolution, molecular weight effects, microfabrication
- MeSH terms
- Acrylates, Cell Survival, Lasers, Polyethylene Glycols, Microscopy, Confocal, Spectroscopy, Near-Infrared, Tissue Engineering, Nanotechnology
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