Breakthrough 3D Printed Neural Scaffold Could Help Patients with Spinal Cord Injuries Regain Some Functions

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Right now, 285,000 people in the US suffer from spinal cord injuries, with roughly 17,000 new injuries each year. 3D printed spinal implants have been shown to help patients recover more easily, and a team of engineers and medical researchers from the University of Minnesota (UMN) have spent the last two years developing an innovative new 3D printed medical device that could help long-term spinal cord injury patients regain some function in the future.

“This is a very exciting first step in developing a treatment to help people with spinal cord injuries. Currently, there aren’t any good, precise treatments for those with long-term spinal cord injuries,” said Ann Parr, MD, PhD, a UMN Medical School Assistant Professor in the Department of Neurosurgery and Stem Cell Institute.

The method involves a 3D printed silicone guide, which acts as a scaffold for special stem cells that are bioprinted directly on top of it. The aim is to surgically implant the guide into the injured part of the spinal cord, and it should act as a bridge between living nerve cells both above and below the area, which could help alleviate pain for patients, in addition to helping them gain control over functions like bladder, bowel, and muscle control again.

“We’ve found that relaying any signals across the injury could improve functions for the patients. There’s a perception that people with spinal cord injuries will only be happy if they can walk again. In reality, most want simple things like bladder control or to be able to stop uncontrollable movements of their legs,” Parr explained. “These simple improvements in function could greatly improve their lives.”

Spinal cord scaffold assembly process: 3D bioprinting cells on silicone scaffolds
allows for in vitro culture of sNPCs and OPCs. (a) Silicone scaffolds are printed with
channels, and (b) cells are dispensed inside the channels. (c) A layer of silicone covers the channels, and (d) scaffolds are placed inside a dish and cultured for 7 days.

The team recently published a paper on their potentially life-changing work, titled “3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds,” in the peer-reviewed scientific journal Advanced Functional Materials.

Fluorescence images of 3D printed cell-laden Matrigel (50%) matrices cultured for 0 (3 hours), 1, and 4 days. Timescale images show (a) sNPCs extending axons, and (b) OPCs exhibiting bi-polar processes.

The abstract reads, “A bioengineered spinal cord is fabricated via extrusion‐based multimaterial 3D bioprinting, in which clusters of induced pluripotent stem cell (iPSC)‐derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) are placed in precise positions within 3D printed biocompatible scaffolds during assembly. The location of a cluster of cells, of a single type or multiple types, is controlled using a point‐dispensing printing method with a 200 µm center‐to‐center spacing within 150 µm wide channels. The bioprinted sNPCs differentiate and extend axons throughout microscale scaffold channels, and the activity of these neuronal networks is confirmed by physiological spontaneous calcium flux studies. Successful bioprinting of OPCs in combination with sNPCs demonstrates a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system (CNS) tissue damage. This platform can be used to prepare novel biomimetic, hydrogel‐based scaffolds modeling complex CNS tissue architecture in vitro and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.”

The process begins with any type of adult stem cell, be it blood or skin, and medical researchers use the latest bioengineering techniques to reprogram these into neuronal stem cells. These cells are then 3D printed onto a silicone guide with a unique extrusion-based technology, which can print both the cells and the guide from the same 3D printer.

Michael McAlpine, PhD, UMN Benjamin Mayhugh Associate Professor of Mechanical Engineering in the University’s College of Science and Engineering, said, “This is the first time anyone has been able to directly 3D print neuronal stem cells derived from adult human cells on a 3D-printed guide and have the cells differentiate into active nerve cells in the lab.”

Photograph of customized 3D bioprinting setup.

The 3D printed silicone guide keeps the stem cells alive, so they can change into neurons.

“Everything came together at the right time. We were able to use the latest cell bioengineering techniques developed in just the last few years and combine that with cutting-edge 3D-printing techniques,” said Parr.

The researchers created a prototype implantable guide to help connect the living cells on each side of a damaged spinal cord area, though this task was not without its difficulties.

“3D printing such delicate cells was very difficult. The hard part is keeping the cells happy and alive,” explained McAlpine. “We tested several different recipes in the printing process. The fact that we were able to keep about 75 percent of the cells alive during the 3D-printing process and then have them turn into healthy neurons is pretty amazing.”

With any luck, the team’s next steps in the process will be successful, which should provide some hope for the future to patients with long-term spinal cord injuries.

Co-authors of the paper are Daeha Joung, Vincent Truong, Colin C. Neitzke, Shuang-Zhuang Guo, Patrick J. Walsh, Joseph R. Monat, Fanben Meng, Sung Hyun Park, James R. Dutton, Parr, and McAlpine.

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