Sep 18, 2015 | By Benedict

As the vital relationship between 3D printing and medical science continues to flourish, potentially life-altering developments continue to be made. A national team of researchers has developed a first-of-its-kind, 3D-printed guide that helps regrow both the sensory and motor functions of complex nerves after injury. The groundbreaking research, undertaken in Minnesota, has the potential to help more than 200,000 people annually who experience nerve injuries or disease.

Image from University of Minnesota College of Science and Engineering

Nerve regeneration is a complex process. Because of this complexity, regrowth of nerves after injury or disease is very rare, according to the Mayo Clinic. Nerve damage is often permanent. While the peripheral nervous system has an intrinsic ability for repair and regeneration, the central nervous system is, for the most part, incapable of self-repair and regeneration. At the present moment, no treatment exists for recovering human nerve function after injury to the central nervous system. Furthermore, although the peripheral nervous system has the capability for regeneration, much research still needs to be conducted in order to optimize the environment for the most effective regrowth potential. Advanced 3D printing methods may now offer one solution to the problem.

In a new study, published today in the journal Advanced Functional Materials, researchers used a combination of 3D imaging and 3D printing techniques to create a custom silicone guide implanted with biochemical cues to help nerve regeneration. The 3D-printed guide's effectiveness was tested in the lab using rats.

To achieve their results, researchers used a 3D scanner to reverse engineer the structure of a rat's sciatic nerve. After being placed on a motorized stage (CR1/M-Z7E, ThorLabs), the rat’s tissue could be imaged from various vantage points over a full rotational angle, using a single camera-projector SLS system (SLS-1, David).

Researchers then used a specialized, custom-built 3D printer to print a guide for regeneration. Incorporated into the guide were 3D-printed chemical cues to promote both motor and sensory nerve regeneration. Scans from the SLS-1 system were aligned and assembled using 3D mesh processing software (MeshLab) and 3D printing software (Netfabb, FIT GmbH), which produced a 3D model of the imaged nerve. Individual scans were aligned and assembled using reverse engineering software (Geomagic Design X, 3DSystems) and additive manufacturing software (Magics, Materialise) using software-provided alignment and assembly algorithms. Once errors were removed from the models, they were exported to 3D CAD software (SolidWorks) for final optimization. These final models were validated using a commercially available plastic 3D printer (Dimension Elite, Alleghaney Ed. Systems). Following validation, the 3D models were converted to printer path information using model slicer software (KISSlicer). Devices were then printed using a custom microextrusion-based 3D printing system. 

According to the team’s report, Printing speeds ranged from ≈0.1–1 mm/s−1. The 3D-printed materials were composed of alginate (alginic acid sodium salt from brown algae, medium viscosity, Sigma), calcium chloride (Sigma), poly(lactic-co-glycolic acid) (75:25, Mw ≈ 76 000–115 000; Sigma), polycaprolactone (average Mn ≈ 10 000; average Mn ≈ 80 000; Sigma), silicone (Superfl ex Clear RTV, Loctite), and gelatin methacrylate hydrogel.

Once produced, the 3D-printed guide was implanted into the rat by surgically grafting it to the cut ends of the nerve. To the great satisfaction of the research team, the rat’s ability to walk again was improved after around 10-12 weeks.

"This represents an important proof of concept of the 3D printing of custom nerve guides for the regeneration of complex nerve injuries," said Michael McAlpine, University of Minnesota mechanical engineering professor and the study's lead researcher. "Someday we hope that we could have a 3D scanner and printer right at the hospital to create custom nerve guides right on site to restore nerve function."

3D scanning and 3D printing such a 3D-printed guide takes about an hour, but the body needs several weeks to regrow the nerves. McAlpine said previous studies have shown regrowth of linear nerves, but this is the first time a study has shown the creation of a custom guide for regrowth of a complex nerve like the Y-shaped sciatic nerve that has both sensory and motor branches.

"The exciting next step would be to implant these guides in humans rather than rats," McAlpine said. There are, however, potential problem cases. Instances where the nerve cannot be scanned would appear to present a much greater challenge for 3D-printing an accurate guide. Luckily, McAlpine has an idea regarding this problem. He says that there could someday be a "library" of scanned nerves from other people or cadavers that hospitals could use to create closely matched 3D-printed guides for patients.

In addition to McAlpine, major contributors to the research team include Blake N. Johnson, Virginia Tech; Xiaofeng Jia, University of Maryland and Johns Hopkins University; and Karen Z. Lancaster, Esteban Engel, and Lynn W. Enquist, Princeton University. The research was funded by grants from the National Institutes of Health, the Defense Advanced Research Projects Agency, the Maryland Stem Cell Research Fund, and the Grand Challenges Program at Princeton University.

 

 

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