A DARPA-funded research team has created a novel new minimally invasive brain-machine interface and recording device that can be implanted into the brain through blood vessels, reducing the need for invasive surgery and the risks associated with breaching the blood-brain barrier when treating patients for physical disabilities and neurological disorders.

The brain-machine interface consists of a stent-based electrode (stentrode), which is implanted within a blood vessel next to the brain, and records the type of neural activity that has been shown in pre-clinical trials to move limbs through an exoskeleton or to control bionic limbs.

The new device is the size of a small paperclip and will be implanted in the first in-human trial at The Royal Melbourne Hospital in 2017.

The research results, published Monday Feb. 8 in Nature Biotechnology, show the device is capable of recording high-quality signals emitted from the brain’s motor cortex without the need for open brain surgery.

“We have been able to create the world’s only minimally invasive device that is implanted into a blood vessel in the brain via a simple day procedure, avoiding the need for high risk open brain surgery,” said Thomas Oxley, principal author and neurologist at The Royal Melbourne Hospital and Research Fellow at The Florey Institute of Neurosciences and the University of Melbourne.

Stroke and spinal cord injuries are leading causes of disability, affecting 1 in 50 people. There are 20,000 Australians with spinal cord injuries, with the typical patient a 19-year old male, and about 150,000 Australians left severely disabled after stroke.

Implantable stent with electrodes

Co-principal investigator and biomedical engineer at the University of Melbourne, Nicholas Opie, said the concept was similar to an implantable cardiac pacemaker — electrical interaction with tissue using sensors inserted into a vein, but inside the brain.

“The electrode array self-expands to stick to the inside wall of a vein, enabling the researchers to record local brain activity. By extracting the recorded neural signals, we can use these as commands to control wheelchairs, exoskeletons, prosthetic limbs or computers. In our first-in-human trial, that we anticipate will begin within two years, we are hoping to achieve direct brain control of an exoskeleton for three people with paralysis,” he said.

Thought control

“Currently, exoskeletons are controlled by manual manipulation of a joystick to switch between the various elements of walking — stand, start, stop, turn. The stentrode will be the first device that enables direct thought control of these devices.”

Professor Clive May, neurophysiologist at The Florey, said the data from the pre-clinical study highlighted that the implantation of the device was safe for long-term use. “Our study also showed that it was safe and effective to implant the device via angiography, which is minimally invasive compared with the high risks associated with open-brain surgery.

The authors note that “avoiding direct contact with cortical neurons may mitigate brain trauma and chronic local inflammation,” subject to additional evaluation.

In addition to DARPA, the research was supported by Australia’s National Health and Medical Research Council, the U.S. Office of Naval Research Global, The Australian Defence Health Foundation, The Brain Foundation, and The Royal Melbourne Hospital Neuroscience Foundation.

Lighter, more agile exoskeleton helps the paralyzed to walk

Meanwhile, in related research (also based on initial funding from DARPA), SuitX, a spinoff of UC Berkeley’s Robotics and Human Engineering Laboratory robotics lab, introduced last week the Phoenix — a new lighter, more agile and lower-cost manually controlled exoskeleton.

The Phoenix is lightweight and has two motors at the hips and electrically controlled tension settings that tighten when the wearer is standing and swing freely when they’re walking. Users can control the movement of each leg and walk up to 1.1 miles per hour by pushing buttons integrated into a pair of crutches. It’s powered for up to eight hours by a battery pack worn in a backpack.

Developed from the Berkeley Lower Extremity Exoskeleton (BLEEX), the Phoenix is one of the lightest and most accessible exoskeletons available, according to SuitX. It can be adjusted to fit varied weights, heights, and leg sizes and can be used for a range of mobility hindrances. At $40,000, it’s about the half the cost of other exoskeletons that help restore mobility.

Abstract of Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

Just lopped off your ring finger slicing carrots (some time in the future)? No problem. Just speed-read this article while you’re waiting for the dronebulance. …

“Epimorphic regeneration” — growing digits, maybe even limbs, with full 3D structure and functionality —  for the 185,000 people who have limb amputations in the U.S. every year (due to disease or injury) may one day be possible. So say scientists at Tulane University, the University of Washington, and the University of Pittsburgh, writing in a review article just published in Tissue Engineering, Part B, Reviews (open access until March 8).

The process of amphibian epimorphic regeneration may offer hints for humans. After amputation, the wound heals to form an epidermal layer, the underlying tissues undergo matrix remodeling, and cells in the region secrete soluble factors. A heterogeneous cell mass, or blastema, forms from the proliferation and migration of cells from the adjacent tissues. The blastema then gives rise to the various new tissues that are spatially patterned to reconstruct the original limb structure. (credit: Lina M. Quijano et al./Tissue Engineering Part B)

Epimorphic generation occurs in certain animals, such as salamanders and frogs, which are able to regenerate limbs, tails, jaws, and even eye lenses; and in deer antlers and mouse ears.

Turns out there are also rare cases of children and young adults who have had tips of digits regenerated. And there are specific “steps of epimorphic regeneration to promote the partial or complete restoration of a biological digit or limb after amputations,” the scientists believe.

Epimorphic regeneration in the murine (type of mouse) digit is level-specific and provides an opportunity for comparative studies of mammalian epimorphic regeneration. Transection through the P2 element results in the frequent outcome of fibrotic scar tissue formation. Transection through the more distal P3 element instead results in the regeneration of missing tissue. (credit: Lina M. Quijano et al./Tissue Engineering Part B)

Some of those steps are suggested by what’s possible in mice, where the digit tip has been found capable of regrowing multiple structures, including bone, after amputation.

What about humans?

The highly ambitious goal of epimorphic regeneration for humans would require the regrowth of multiple tissues that have been assembled in the proper conformation and patterns to create a fully functional limb, according to the authors.

Epimorphic regeneration has been observed in distal finger tips of children and young adults. Converting such random events into designed clinical outcomes will require altering the default postamputation progression. It may include the transplantation of cells, scaffolds, and/or soluble factors, as well as controlling microenvironmental aspects, such as oxygen concentration, tissue hydration, mechanical, and electrical cues. (credit: Lina M. Quijano et al./Tissue Engineering Part B)

They note that “it may be possible to suture an engineered epithelial layer, much like the present skin grafts, across the injury site. In-depth understanding of the proper soluble factor communication necessary, however, could lead to a more direct approach of delivering growth factors to the region, leveraging drug delivery paradigms that create spatiotemporal gradients.These interventions are intended to mimic the signals that induce a stable cell mass that functions as a blastema [a mass of cells capable of growth and regeneration into organs or body parts].

“Initial studies in mice have already shown the promise of introducing solubilized [extra-cellular matrices, bone morphogenetic proteins,and matrix metalloproteinases, generated by immune cells] in promoting recruitment/mobilization of endogenous cells to proliferate at the transected bone front. Furthermore, the injury response may also be influenced with external bioreactors … that can control parameters, such as hydration, pH, oxygen concentration, and electrical stimulation.”

The research was supported by the National Institutes of Health and the Fulbright Scholars Program.

Abstract of Looking Ahead to Engineering Epimorphic Regeneration of a Human Digit or Limb

Approximately 2 million people have had limb amputations in the United States due to disease or injury, with more than 185,000 new amputations every year. The ability to promote epimorphic regeneration, or the regrowth of a biologically based digit or limb, would radically change the prognosis for amputees. This ambitious goal includes the regrowth of a large number of tissues that need to be properly assembled and patterned to create a fully functional structure. We have yet to even identify, let alone address, all the obstacles along the extended progression that limit epimorphic regeneration in humans. This review aims to present introductory fundamentals in epimorphic regeneration to facilitate design and conduct of research from a tissue engineering and regenerative medicine perspective. We describe the clinical scenario of human digit healing, featuring published reports of regenerative potential. We then broadly delineate the processes of epimorphic regeneration in nonmammalian systems and describe a few mammalian regeneration models. We give particular focus to the murine digit tip, which allows for comparative studies of regeneration-competent and regeneration-incompetent outcomes in the same animal. Finally, we describe a few forward-thinking opportunities for promoting epimorphic regeneration in humans.