Study Finds Natural Compound Can Be Used For 3-D Printing Of Medical Implants

Researchers from North Carolina State University, the University of North Carolina at Chapel Hill and Laser Zentrum Hannover have discovered that a naturally-occurring compound can be incorporated into three-dimensional (3-D) printing processes to create medical implants out of non-toxic polymers. The compound is riboflavin, which is better known as vitamin B2.

“This opens the door to a much wider range of biocompatible implant materials, which can be used to develop customized implant designs using 3-D printing technology,” says Dr. Roger Narayan, senior author of a paper describing the work and a professor in the joint biomedical engineering department at NC State and UNC-Chapel Hill.

The researchers in this study focused on a 3-D printing technique called two-photon polymerization, because this technique can be used to create small objects with detailed features – such as scaffolds for tissue engineering, microneedles or other implantable drug-delivery devices.

Two-photon polymerization is a 3-D printing technique for making small-scale solid structures from many types of photoreactive liquid precursors. The liquid precursors contain chemicals that react to light, turning the liquid into a solid polymer. By exposing the liquid precursor to targeted amounts of light, the technique allows users to “print” 3-D objects.

Two-photon polymerization has its drawbacks, however. Most chemicals mixed into the precursors to make them photoreactive are also toxic, which could be problematic if the structures are used in a medical implant or are in direct contact with the body.

But now researchers have determined that riboflavin can be mixed with a precursor material to make it photoreactive. And riboflavin is both nontoxic and biocompatible – it’s a vitamin found in everything from asparagus to cottage cheese.

The paper, “Two-photon polymerization of polyethylene glycol diacrylate scaffolds with riboflavin and triethanolamine used as a water-soluble photoiniator,” is published online in Regenerative Medicine. Lead author of the paper is Alexander Nguyen, a Ph.D. student in NC State and UNC-Chapel Hill’s joint biomedical engineering program. Co-authors include Shaun Gittard, Anastasia Koroleva, Sabrina Schlie, Arune Gaidukeviciute and Boris Chichkov of Laser Zentrum Hannover. The research was supported by National Science Foundation grant 0936110.

The study abstract follows.
“Two-photon polymerization of polyethylene glycol diacrylate scaffolds with riboflavin and triethanolamine used as a water-soluble photoiniator”

Authors: Alexander K. Nguyen and Roger J. Narayan, North Carolina State University and University of North Carolina at Chapel Hill; Shaun D, Gittard, Anastasia Koroleva, Sabrina Schlie, Arune Gaidukeviciute, and Boris N. Chichkov, Laser Zentrum Hannover

Published: Online Oct. 22 in Regenerative Medicine
DOI: 10.2217/rme.13.60

Abstract: Aim: In this study, the suitability of a mixture containing riboflavin (vitamin B2) and triethanolamine (TEOHA) as a novel biocompatible photoinitiator for two-photon polymerization (2PP) processing was investigated. Materials & methods: Polyethylene glycol diacrylate was crosslinked using Irgacure 369, Irgacure 2959 or a riboflavin–TEOHA mixture; biocompatibility of the photopolymer extract solutions was subsequently assessed via endothelial cell proliferation assay, endothelial cell viability assay and single-cell gel electrophoresis (comet) assay. Use of a riboflavin–TEOHA mixture as a photoinitiator for 2PP processing of a tissue engineering scaffold and subsequent seeding of this scaffold with GM-7373 bovine aortic endothelial cells was also demonstrated. Results: The riboflavin–TEOHA mixture was found to produce much more biocompatible scaffolds than those produced with Irgacure 369 or Irgacure 2959.Conclusion: The results suggest that riboflavin is a promising component of photoinitiators for 2PP fabrication of tissue engineering scaffolds and other medically relevant structures (e.g., biomicroelectromechanical systems).