Skip to main content
SpringerLink
Log in

Femtosecond Laser-Assisted Nanoscale 3D Printing of Hydrogels

  • Living reference work entry
  • First Online:
Handbook of Laser Micro- and Nano-Engineering

  • 125 Accesses

Abstract

Nanoscale 3D printing can be achieved by femtosecond laser-triggered two-photon polymerization. Hydrogels that mimic the native extracellular matrix (ECM) environment are one of the most promising materials in cell biology and tissue engineering. It has been demonstrated that hydrogels’ 3D geometrical cues have a strong influence on cell behaviors. Natural cellular environment has complex 3D structure in micro- and nanoscale. Thus it is important to create hydrogels with micro- and nanoscale features to mimic the natural environment. Two-photon polymerization-based 3D printing technique enables fabrication of sub-micron resolution hydrogel structures. The design and fabrication of 3D hydrogels for tissue engineering and drug delivery has been an important research area of TPP fabrication. This chapter reviews the basics of this technique and some of its biomedical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Alge DL, Anseth KS (2013) Bioactive hydrogels: lighting the way. Nat Mater 12:950–952. https://doi.org/10.1038/nmat3794

    Article  ADS  Google Scholar 

  • Amato L, Gu Y, Bellini N et al (2012) Integrated three-dimensional filter separates nanoscale from microscale elements in a microfluidic chip. Lab Chip 12:1135–1142

    Article  Google Scholar 

  • Annabi N, Nichol JW, Zhong X et al (2010) Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng Part B Rev 16:371–383

    Article  Google Scholar 

  • Annabi N, Tamayol A, Uquillas JA et al (2014) 25th anniversary article: rational design and applications of hydrogels in regenerative medicine. Adv Mater 26:85–124

    Article  Google Scholar 

  • Basu S, Campagnola PJ (2004) Properties of crosslinked protein matrices for tissue engineering applications synthesized by multiphoton excitation. J Biomed Mater Res A 71:359–368

    Article  Google Scholar 

  • Basu S, Cunningham LP, Pins GD et al (2005a) Multiphoton excited fabrication of collagen matrixes cross-linked by a modified benzophenone dimer: bioactivity and enzymatic degradation. Biomacromolecules 6:1465–1474

    Article  Google Scholar 

  • Basu S, Rodionov V, Terasaki M, Campagnola PJ (2005b) Multiphoton-excited microfabrication in live cells via Rose Bengal cross-linking of cytoplasmic proteins. Opt Lett 30:159–161

    Article  ADS  Google Scholar 

  • Berg A, Wyrwa R, Weisser J et al (2011) Synthesis of photopolymerizable hydrophilic macromers and evaluation of their applicability as reactive resin components for the fabrication of three-dimensionally structured hydrogel matrices by 2-photon-polymerization. Adv Eng Mater 13:B274–B284. https://doi.org/10.1002/adem.201080092

    Article  Google Scholar 

  • Berry DB, You S, Warner J et al (2017) A 3D tissue-printing approach for validation of diffusion tensor imaging in skeletal muscle. Tissue Eng A 23:980–988. https://doi.org/10.1089/ten.tea.2016.0438

    Article  Google Scholar 

  • Bhatnagar D, Simon M, Rafailovich MH (2016) Hydrogels for regenerative medicine. In: Parveen FK (ed) Recent advances in biopolymers. InTech, Rijeka

    Google Scholar 

  • Bian W, Liau B, Badie N, Bursac N (2009) Mesoscopic hydrogel molding to control the 3D geometry of bioartificial muscle tissues. Nat Protoc 4:1522–1534

    Article  Google Scholar 

  • Buwalda SJ, Boere KWM, Dijkstra PJ et al (2014) Hydrogels in a historical perspective: from simple networks to smart materials. J Control Release 190:254–273. https://doi.org/10.1016/j.jconrel.2014.03.052

    Article  Google Scholar 

  • Chen M, Zhong M, Johnson JA (2016) Light-controlled radical polymerization: mechanisms, methods, and applications. Chem Rev 116:10167–10211. https://doi.org/10.1021/acs.chemrev.5b00671

    Article  Google Scholar 

  • Cicha K, Li Z, Stadlmann K et al (2011) Evaluation of 3D structures fabricated with two-photon-photopolymerization by using FTIR spectroscopy. J Appl Phys 110:064911

    Article  ADS  Google Scholar 

  • Ciuciu AI, CywiĹ„ski PJ (2014) Two-photon polymerization of hydrogels–versatile solutions to fabricate well-defined 3D structures. RSC Adv 4:45504–45516

    Article  ADS  Google Scholar 

  • Claeyssens F, Hasan EA, Gaidukeviciute A et al (2009) Three-dimensional biodegradable structures fabricated by two-photon polymerization. Langmuir 25:3219–3223

    Article  Google Scholar 

  • Cunningham LP, Veilleux MP, Campagnola PJ (2006) Freeform multiphoton excited microfabrication for biological applications using a rapid prototyping CAD-based approach. Opt Express 14:8613–8621

    Article  ADS  Google Scholar 

  • DeForest CA, Anseth KS (2011) Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photoconjugation and photocleavage reactions. Nat Chem 3:925–931

    Article  Google Scholar 

  • Dinca V, Kasotakis E, Catherine J et al (2008) Directed three-dimensional patterning of self-assembled peptide fibrils. Nano Lett 8:538–543. https://doi.org/10.1021/nl072798r

    Article  ADS  Google Scholar 

  • Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337–4351. https://doi.org/10.1016/S0142-9612(03)00340-5

    Article  Google Scholar 

  • Engelhardt S, Hoch E, Borchers K et al (2011) Fabrication of 2D protein microstructures and 3D polymer–protein hybrid microstructures by two-photon polymerization. Biofabrication 3:025003

    Article  ADS  Google Scholar 

  • Farsari M, Filippidis G, Fotakis C (2005) Fabrication of three-dimensional structures by three-photon polymerization. Opt Lett 30:3180. https://doi.org/10.1364/OL.30.003180

    Article  ADS  Google Scholar 

  • Farsari M, Filippidis G, Sambani K et al (2006) Two-photon polymerization of an eosin Y-sensitized acrylate composite. J Photochem Photobiol A-Chem 181:132–135. https://doi.org/10.1016/j.jphotochem.2005.11.005

    Article  Google Scholar 

  • Guo R, Xiao S, Zhai X et al (2006) Micro lens fabrication by means of femtosecond two photon photopolymerization. Opt Express 14:810–816

    Article  ADS  Google Scholar 

  • Hahn MS, Miller JS, West JL (2006) Three-dimensional biochemical and biomechanical patterning of hydrogels for guiding cell behavior. Adv Mater 18:2679–2684

    Article  Google Scholar 

  • Hong S, Sycks D, Chan HF et al (2015) 3D printing of highly stretchable and tough hydrogels into complex, cellularized structures. Adv Mater 27:4035–4040

    Article  Google Scholar 

  • Hribar KC, Choi YS, Ondeck M et al (2014) Digital plasmonic patterning for localized tuning of hydrogel stiffness. Adv Funct Mater 24:4922–4926

    Article  Google Scholar 

  • Hribar KC, Meggs K, Liu J et al (2015) Three-dimensional direct cell patterning in collagen hydrogels with near-infrared femtosecond laser. Sci Rep 5:1–7

    Google Scholar 

  • Huang S, Heikal AA, Webb WW (2002) Two-photon fluorescence spectroscopy and microscopy of NAD (P) H and flavoprotein. Biophys J 82:2811–2825

    Article  Google Scholar 

  • Hwang HH, Zhu W, Victorine G et al (2018) 3D-printing of functional biomedical microdevices via light- and extrusion-based approaches. Small Methods 2:1700277. https://doi.org/10.1002/smtd.201700277

    Article  Google Scholar 

  • Jhaveri SJ, McMullen JD, Sijbesma R et al (2009) Direct three-dimensional microfabrication of hydrogels via two-photon lithography in aqueous solution. Chem Mater 21:2003–2006

    Article  Google Scholar 

  • Juodkazis S, Mizeikis V, Misawa H (2009) Three-dimensional microfabrication of materials by femtosecond lasers for photonics applications. J Appl Phys 106:051101. https://doi.org/10.1063/1.3216462

    Article  ADS  Google Scholar 

  • Kadic M, BĂĽckmann T, Stenger N et al (2012) On the practicability of pentamode mechanical metamaterials. Appl Phys Lett 100:191901. https://doi.org/10.1063/1.4709436

    Article  ADS  Google Scholar 

  • Kadic M, Milton GW, van Hecke M, Wegener M (2019) 3D metamaterials. Nat Rev Phys 1:198–210. https://doi.org/10.1038/s42254-018-0018-y

    Article  Google Scholar 

  • Kaehr B, Shear JB (2008) Multiphoton fabrication of chemically responsive protein hydrogels for microactuation. Proc Natl Acad Sci 105:8850–8854

    Article  ADS  Google Scholar 

  • Kaehr B, Allen R, Javier DJ et al (2004) Guiding neuronal development with in situ microfabrication. Proc Natl Acad Sci U S A 101:16104–16108

    Article  ADS  Google Scholar 

  • Kloxin AM, Kasko AM, Salinas CN, Anseth KS (2009) Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324:59–63

    Article  ADS  Google Scholar 

  • Kufelt O, El-Tamer A, Sehring C et al (2014) Hyaluronic acid based materials for scaffolding via two-photon polymerization. Biomacromolecules 15:650–659

    Article  Google Scholar 

  • Li Z, Pucher N, Cicha K et al (2013) A straightforward synthesis and structure–activity relationship of highly efficient initiators for two-photon polymerization. Macromolecules 46:352–361. https://doi.org/10.1021/ma301770a

    Article  ADS  Google Scholar 

  • Li M, Yang Q, Liu H et al (2016) Capillary origami inspired fabrication of complex 3D hydrogel constructs. Small 12:4492–4500

    Article  Google Scholar 

  • Liao H, Munoz-Pinto D, Qu X et al (2008) Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype. Acta Biomater 4:1161–1171

    Article  Google Scholar 

  • Loebel C, Broguiere N, Alini M et al (2015) Microfabrication of photo-cross-linked hyaluronan hydrogels by single-and two-photon tyramine oxidation. Biomacromolecules 16:2624–2630

    Article  Google Scholar 

  • Lu W-E, Dong X-Z, Chen W-Q et al (2011) Novel photoinitiator with a radical quenching moiety for confining radical diffusion in two-photon induced photopolymerization. J Mater Chem 21:5650–5659. https://doi.org/10.1039/c0jm04025h

    Article  Google Scholar 

  • Maruo S, Fourkas JT (2008) Recent progress in multiphoton microfabrication. Laser Photonics Rev 2:100–111

    Article  ADS  Google Scholar 

  • Maruo S, Nakamura O, Kawata S (1997) Three-dimensional microfabrication with two-photon-absorbed photopolymerization. Opt Lett 22:132–134

    Article  ADS  Google Scholar 

  • Nguyen QT, Hwang Y, Chen AC et al (2012) Cartilage-like mechanical properties of poly (ethylene glycol)-diacrylate hydrogels. Biomaterials 33:6682–6690

    Article  Google Scholar 

  • Olsen MH, Hjortø GM, Hansen M et al (2013) In-chip fabrication of free-form 3D constructs for directed cell migration analysis. Lab Chip 13:4800. https://doi.org/10.1039/c3lc50930c

    Article  Google Scholar 

  • Ovsianikov A, Schlie S, Ngezahayo A et al (2007) Two-photon polymerization technique for microfabrication of CAD-designed 3D scaffolds from commercially available photosensitive materials. J Tissue Eng Regen Med 1:443–449. https://doi.org/10.1002/term.57

    Article  Google Scholar 

  • Ovsianikov A, Gruene M, Pflaum M et al (2010) Laser printing of cells into 3D scaffolds. Biofabrication 2:014104

    Article  ADS  Google Scholar 

  • Ovsianikov A, Deiwick A, Van Vlierberghe S et al (2011a) Laser fabrication of 3D gelatin scaffolds for the generation of bioartificial tissues. Materials 4:288–299

    Article  ADS  Google Scholar 

  • Ovsianikov A, Deiwick A, Van Vlierberghe S et al (2011b) Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for applications in tissue engineering. Biomacromolecules 12:851–858

    Article  Google Scholar 

  • Ovsianikov A, Malinauskas M, Schlie S et al (2011c) Three-dimensional laser micro-and nano-structuring of acrylated poly (ethylene glycol) materials and evaluation of their cytoxicity for tissue engineering applications. Acta Biomater 7:967–974

    Article  Google Scholar 

  • Ovsianikov A, MĂĽhleder S, Torgersen J et al (2013) Laser photofabrication of cell-containing hydrogel constructs. Langmuir 30:3787–3794

    Article  Google Scholar 

  • Park S-H, Yang D-Y, Lee K-S (2009) Two-photon stereolithography for realizing ultraprecise three-dimensional nano/microdevices. Laser Photonics Rev 3:1–11

    Article  ADS  Google Scholar 

  • Pitts JD, Campagnola PJ, Epling GA, Goodman SL (2000) Submicron multiphoton free-form fabrication of proteins and polymers: studies of reaction efficiencies and applications in sustained release. Macromolecules 33:1514–1523

    Article  ADS  Google Scholar 

  • Raimondi MT, Eaton SM, Nava MM et al (2012) Two-photon laser polymerization: from fundamentals to biomedical application in tissue engineering and regenerative medicine. J Appl Biomater Biomech 10:55–65

    Google Scholar 

  • Schade R, Weiss T, Berg A et al (2010) Two-photon techniques in tissue engineering. Int J Artif Organs 33:219–227

    Article  Google Scholar 

  • Schafer KJ, Hales JM, Balu M et al (2004) Two-photon absorption cross-sections of common photoinitiators. J Photochem Photobiol A Chem 162:497–502

    Article  Google Scholar 

  • Seidlits SK, Schmidt CE, Shear JB (2009) High-resolution patterning of hydrogels in three dimensions using direct-write photofabrication for cell guidance. Adv Funct Mater 19:3543–3551

    Article  Google Scholar 

  • Selimis A, Mironov V, Farsari M (2015) Direct laser writing: principles and materials for scaffold 3D printing. Microelectron Eng 132:83–89

    Article  Google Scholar 

  • Slaughter BV, Khurshid SS, Fisher OZ et al (2009) Hydrogels in regenerative medicine. Adv Mater 21:3307–3329

    Article  Google Scholar 

  • Spivey EC, Ritschdorff ET, Connell JL et al (2013) Multiphoton lithography of unconstrained three-dimensional protein microstructures. Adv Funct Mater 23:333–339

    Article  Google Scholar 

  • Stevens KR, Ungrin MD, Schwartz RE et al (2013) InVERT molding for scalable control of tissue microarchitecture. Nat Commun 4:1847

    Article  ADS  Google Scholar 

  • Sun H-B, Kawata S (2004) Two-photon photopolymerization and 3D lithographic microfabrication. Adv Polym Sci 170:169–274

    Article  Google Scholar 

  • Tayalia P, Mendonca CR, Baldacchini T et al (2008) 3D cell-migration studies using two-photon engineered polymer scaffolds. Adv Mater 20:4494–4498. https://doi.org/10.1002/adma.200801319

    Article  Google Scholar 

  • Tomatsu I, Peng K, Kros A (2011) Photoresponsive hydrogels for biomedical applications. Adv Drug Deliv Rev 63:1257–1266

    Article  Google Scholar 

  • Torgersen J, Ovsianikov A, Mironov V et al (2012) Photo-sensitive hydrogels for three-dimensional laser microfabrication in the presence of whole organisms. J Biomed Opt 17:105008–105008

    Article  Google Scholar 

  • Torgersen J, Qin X-H, Li Z et al (2013) Hydrogels for two-photon polymerization: a toolbox for mimicking the extracellular matrix. Adv Funct Mater 23:4542–4554

    Article  Google Scholar 

  • Watanabe T, Akiyama M, Totani K et al (2002) Photoresponsive hydrogel microstructure fabricated by two-photon initiated polymerization. Adv Funct Mater 12:611–614

    Article  Google Scholar 

  • Weiss T, Schade R, Laube T et al (2011) Two-photon polymerization of biocompatible photopolymers for microstructured 3D biointerfaces. Adv Eng Mater 13:B264–B273

    Article  Google Scholar 

  • Witzgall G, Vrijen R, Yablonovitch E et al (1998) Single-shot two-photon exposure of commercial photoresist for the production of three-dimensional structures. Opt Lett 23:1745. https://doi.org/10.1364/OL.23.001745

    Article  ADS  Google Scholar 

  • Xing J, Liu L, Song X et al (2015) 3D hydrogels with high resolution fabricated by two-photon polymerization with sensitive water soluble initiators. J Mater Chem B 3:8486–8491

    Article  Google Scholar 

  • Xiong Z, Zheng M-L, Dong X-Z et al (2011) Asymmetric microstructure of hydrogel: two-photon microfabrication and stimuli-responsive behavior. Soft Matter 7:10353–10359

    Article  ADS  Google Scholar 

  • Yang L, El-Tamer A, Hinze U et al (2014) Two-photon polymerization of cylinder microstructures by femtosecond Bessel beams. Appl Phys Lett 105:041110

    Article  ADS  Google Scholar 

  • Yang L, El-Tamer A, Hinze U et al (2015) Parallel direct laser writing of micro-optical and photonic structures using spatial light modulator. Opt Lasers Eng 70:26–32

    Article  Google Scholar 

  • You S, Li J, Zhu W et al (2018) Nanoscale 3D printing of hydrogels for cellular tissue engineering. J Mater Chem B 6:2187–2197. https://doi.org/10.1039/C8TB00301G

    Article  Google Scholar 

  • Yu X, Zhou J, Liang H et al (2018) Mechanical metamaterials associated with stiffness, rigidity and compressibility: a brief review. Prog Mater Sci 94:114–173. https://doi.org/10.1016/j.pmatsci.2017.12.003

    Article  Google Scholar 

  • Zhang W, Chen S (2011) Femtosecond laser nanofabrication of hydrogel biomaterial. MRS Bull 36:1028–1033

    Article  Google Scholar 

  • Zhang W, Soman P, Meggs K et al (2013) Tuning the Poisson’s ratio of biomaterials for investigating cellular response. Adv Funct Mater 23:3226–3232. https://doi.org/10.1002/adfm.201202666

    Article  Google Scholar 

  • Zhang C, Hu Y, Li J et al (2014) An improved multi-exposure approach for high quality holographic femtosecond laser patterning. Appl Phys Lett 105:221104. https://doi.org/10.1063/1.4902925

    Article  ADS  Google Scholar 

  • Zhu W, Ma X, Gou M et al (2016) 3D printing of functional biomaterials for tissue engineering. Curr Opin Biotechnol 40:103–112. https://doi.org/10.1016/j.copbio.2016.03.014

    Article  Google Scholar 

  • Zhu W, Qu X, Zhu J et al (2017) Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials 124:106–115. https://doi.org/10.1016/j.biomaterials.2017.01.042

    Article  ADS  Google Scholar 

  • Zipfel WR, Williams RM, Webb WW (2003) Nonlinear magic: multiphoton microscopy in the biosciences. Nat Biotechnol 21:1369–1377

    Article  Google Scholar 

Download references

Acknowledgments

The work was supported in part by grants from the National Institutes of Health (R01EB021857, R33HD090662) and National Science Foundation (1937653, 1903933).

Author information

Authors and Affiliations

  1. Department of NanoEngineering, University of California, San Diego, La Jolla, CA, USA

    Jiawen Li, Shangting You & Shaochen Chen

  2. Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, China

    Jiawen Li

Authors
  1. Jiawen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shangting You
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaochen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaochen Chen .

Editor information

Editors and Affiliations

  1. RIKEN-SIOM Joint Research Unit, RIKEN Center for Advanced Photonics RIKEN-SIOM Joint Research Unit, Wako, Saitama, Japan

    Koji Sugioka

Section Editor information

  1. Department of Electrical and Computer Engineering, University of Nebraska Lincoln, Lincoln, NE, USA

    Yongfeng Lu

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Li, J., You, S., Chen, S. (2021). Femtosecond Laser-Assisted Nanoscale 3D Printing of Hydrogels. In: Sugioka, K. (eds) Handbook of Laser Micro- and Nano-Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-69537-2_43-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-69537-2_43-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-69537-2

  • Online ISBN: 978-3-319-69537-2

  • eBook Packages: Springer Reference Physics and AstronomyReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation