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3D printing enables separation of orthogonal functions within a hydrogel particle

  • Ritu Raman
  • Nicholas E. Clay
  • Sanjeet Sen
  • Molly Melhem
  • Ellen Qin
  • Hyunjoon Kong
  • Rashid Bashir
Article

Abstract

Multifunctional particles with distinct physiochemical phases are required by a variety of applications in biomedical engineering, such as diagnostic imaging and targeted drug delivery. This motivates the development of a repeatable, efficient, and customizable approach to manufacturing particles with spatially segregated bioactive moieties. This study demonstrates a stereolithographic 3D printing approach for designing and fabricating large arrays of biphasic poly (ethylene glycol) diacrylate (PEGDA) gel particles. The fabrication parameters governing the physical and biochemical properties of multi-layered particles are thoroughly investigated, yielding a readily tunable approach to manufacturing customizable arrays of multifunctional particles. The advantage in spatially organizing functional epitopes is examined by loading superparamagnetic iron oxide nanoparticles (SPIONs) and bovine serum albumin (BSA) in separate layers of biphasic PEGDA gel particles and examining SPION-induced magnetic resonance (MR) contrast and BSA-release kinetics. Particles with spatial segregation of functional moieties have demonstrably higher MR contrast and BSA release. Overall, this study will contribute significant knowledge to the preparation of multifunctional particles for use as biomedical tools.

Keywords

Hydrogel Polyethylene glycol Stereolithography 3D printing Biomaterial 

Notes

Acknowledgments

We acknowledge Boris Odintsov for his assistance in MR imaging. This work was funded by the National Science Foundation (NSF) Science and Technology Center EBICS (Grant CBET-0939511) and National Institute of Health (1R01 HL109192 to H.K). R.R was funded by an NSF Graduate Research Fellowship (Grant DGE-1144245) and NSF CMMB IGERT at UIUC (Grant 0965918). N.C. was funded by a Dow Graduate Fellowship.

Supplementary material

10544_2016_68_MOESM1_ESM.jpg (268 kb)
Fig. S1 a Example of a 30 % PEGDA 700 g mol−1 disc-shaped hydrogel particle formed by changing the CAD file sent to the stereolithographic 3D printer, showing the versatility and customizability of this rapid fabrication approach. Scale bar corresponds to 500 μm. b Example of a 30 % PEGDA 400 g mol−1 “matchstick” hydrogel particle formed by varying the energy dose applied for each layer during fabrication, resulting in significantly different thicknesses in each of the two layers. Scale bar corresponds to 500 μm. (JPEG 268 kb)
10544_2016_68_MOESM2_ESM.jpg (287 kb)
Fig. S2 a Schematic of cross-linking in pure PEGDA hydrogels. b Schematic of cross-linking in hydrogels containing a mix of PEGDA and alginate methacrylate. (JPEG 287 kb)

References

  1. Annabi, N. et al., 2013. 25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine. Advanced Materials, p.n/a–n/a. Available at: http://doi.wiley.com/10.1002/adma.201303233 [Accessed November 8, 2013].
  2. Arcaute, K., Mann, B.K. & Wicker, R.B., 2011. Practical use of hydrogels in stereolithography for tissue engineering applications. In P. J. Bártolo, ed. Stereolithography: Materials, Processes, and Applications. Boston, MA: Springer US, pp. 299–331. Available at: http://link.springer.com/10.1007/978-0-387-92904-0 [Accessed February 21, 2014].
  3. Bartolo, P.J., 2011. Stereolithographic processes. In P. J. Bártolo, ed. Stereolithography: Materials, Processes and Applications. Boston, MA: Springer US, pp. 1–36. Available at: http://www.springerlink.com/index/10.1007/978-0-387-92904-0 [Accessed February 16, 2013].
  4. S. Bhaskar et al., Towards designer Microparticles: simultaneous control of anisotropy, shape, and size. Small 6(3), 404–411 (2010)CrossRefGoogle Scholar
  5. C. Cha, R. H. Kohman, H. Kong, Biodegradable polymer Crosslinker: independent control of stiffness, toughness, and hydrogel degradation rate. Adv. Funct. Mater. 19(19), 3056–3062 (2009). http://doi.wiley.com/10.1002/adfm.200900865 [Accessed July 1, 2014]Available at:
  6. Chan, V. et al., 2010. Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation. Lab Chip, 10(16), pp. 2062–2070. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20603661 [Accessed February 12, 2013].
  7. Jeong, J.H. et al., 2012. “Living” microvascular stamp for patterning of functional neovessels; Orchestrated control of matrix property and geometry. Adv. Mater., 24(1), pp. 58–63, 1. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22109941 [Accessed February 11, 2013].
  8. M. Lai et al., Bacteria-mimicking nanoparticle surface functionalization with targeting motifs. Nanoscale 7, 6737–6744 (2015)CrossRefGoogle Scholar
  9. B. Li et al., Multifunctional hydrogel Microparticles by polymer-assisted photolithography. ACS Appl. Mater. Interfaces 8, 4158–4164 (2016)CrossRefGoogle Scholar
  10. Melchels, F.P.W., Feijen, J. & Grijpma, D.W., 2010. A review on stereolithography and its applications in biomedical engineering. Biomaterials, 31(24), pp. 6121–6130. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20478613 [Accessed November 18, 2013].
  11. J. A. S. Neiman et al., Photopatterning of hydrogel scaffolds coupled to filter materials using stereolithography for perfused 3D culture of hepatocytes. Biotechnol. Bioeng. 112(4), 777–787 (2015). http://doi.wiley.com/10.1002/bit.25494Available at:CrossRefGoogle Scholar
  12. N. A. Peppas et al., Hydrogels in biology and medicine: from molecular principles to Bionanotechnology. Adv. Mater. 18(11), 1345–1360 (2006). http://doi.wiley.com/10.1002/adma.200501612 [Accessed September 22, 2013]Available at:
  13. Raman, R. et al., 2015. High-Resolution Projection Microstereolithography for Patterning of Neovasculature. Advanced Healthcare Materials, pp. 1–10.Google Scholar
  14. R. Raman, R. Bashir, Stereolithographic 3D Bioprinting for Biomedical Applications. In Essentials 3D Biofabrication Transl, 89–121 (2015)Google Scholar
  15. P. L. Ritger, N. A. Peppas, A simple equation for description of solute release. J. Control. Release 5, 23–36 (1987)CrossRefGoogle Scholar
  16. K. Roh, D. C. Martin, J. Lahann, Biphasic Janus particles with nanoscale anisotropy. Nat. Mater. 4, 759–763 (2005)CrossRefGoogle Scholar
  17. B. R. K. Shah, J. Kim, D. A. Weitz, Janus Supraparticles by induced phase separation of nanoparticles in droplets. Adv. Mater. 729, 1949–1953 (2009)CrossRefGoogle Scholar
  18. E. V. Shevchenko et al., Gold/iron oxide core/hollow-shell nanoparticles. Adv. Mater. 20(22), 4323–4329 (2008)CrossRefGoogle Scholar
  19. Stampfl, J. & Liska, R., 2011. Polymerizable hydrogels for rapid prototyping: chemistry, photolithography, and mechanical properties. In P. J. Bártolo, ed. Stereolithography: Materials, Processes and Applications. Boston, MA: Springer US. Available at: http://www.springerlink.com/index/10.1007/978-0-387-92904-0 [Accessed February 16, 2013].
  20. S. Yang et al., Microfluidic synthesis of multifunctional Janus particles for biomedical applications. Lab Chip 12(12), 2097 (2012)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ritu Raman
    • 1
    • 2
  • Nicholas E. Clay
    • 3
  • Sanjeet Sen
    • 3
  • Molly Melhem
    • 4
  • Ellen Qin
    • 3
  • Hyunjoon Kong
    • 3
  • Rashid Bashir
    • 2
    • 4
  1. 1.Department of Mechanical Science and EngineeringUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Micro and Nanotechnology LaboratoryUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Department of Chemical and Biomolecular EngineeringUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  4. 4.Department of BioengineeringUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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