Tag Archives: hyaluronic acid (HA)

“Injectable tissue prosthesis coupled with closed-loop bioelectronic system” for damaged muscle/nerve regeneration and robot-assisted rehabilitation

A fascinating new use for hyaluronic acid (usually discussed in relation to cosmetic wrinkle-reduction) has been found according to a November 1, 2023 news item on ScienceDaily.

In a recent publication in the journal Nature, researchers from the Institute of Basic Science (IBS) in South Korea have made significant strides in biomaterial technology and rehabilitation medicine. They’ve developed a novel approach to healing muscle injury by employing “injectable tissue prosthesis” in the form of conductive hydrogels and combining it with a robot-assisted rehabilitation system.

Let’s imagine you are swimming in the ocean. A giant shark approaches and bites a huge chunk of meat out of your thigh, resulting in a complete loss of motor/sensor function in your leg.

If left untreated, such severe muscle damage would result in permanent loss of function and disability.

How on Earth will you be able to recover from this kind of injury?

Traditional rehabilitation methods for these kinds of muscle injuries have long sought an efficient closed-loop gait rehabilitation system that merges lightweight exoskeletons and wearable/implantable devices.

Such assistive prosthetic system is required to aid the patients through the process of recovering sensory and motor functions linked to nerve and muscle damage.

Unfortunately, the mechanical properties and rigid nature of existing electronic materials render them incompatible with soft tissues.

This leads to friction and potential inflammation, stalling patient rehabilitation.

To overcome these limitations, the IBS researchers turned to a material commonly used as a wrinkle-smoothing filler, called hyaluronic acid.

A November 2, 2023 Institute of Basic Science (IBS) press release (also on EurekAlert but published November 1, 2023), which originated the news item, explains how hyaluronic acid helps in tissue rehabilitation and regeneration,

Using this substance [hyaluronic acid], an injectable hydrogel was developed for “tissue prostheses”, which can temporarily fill the gap of the missing muscle/nerve tissues while it regenerates. The injectable nature of this material gives it a significant advantage over traditional bioelectronic devices, which are unsuitable for narrow, deep, or small areas, and necessitate invasive surgeries.

Thanks to its highly “tissue-like” properties, this hydrogel seamlessly interfaces with biological tissues and can be easily administered to hard-to-reach body areas without surgery. The reversible and irreversible crosslinks within the hydrogel adapt to high shear stress during injection, ensuring excellent mechanical stability. This hydrogel also incorporates gold nanoparticles, which gives it decent electrical properties. Its conductive nature allows for the effective transmission of electrophysiological signals between the two ends of injured tissues. In addition, the hydrogel is biodegrdable, meaning that the patients do not need to get surgery again.

With mechanical properties akin to natural tissues, exceptional tissue adhesion, and injectable characteristics, researchers believe this material offers a novel approach to rehabilitation.

Next, the researchers put this novel idea to the test in rodent models. To simulate volumetric muscle loss injury, a large chunk of muscle has been removed from the hind legs of these animals. By injecting the hydrogel and implanting the two kinds of stretchable tissue-interfacing devices for electrical sensing and stimulation, the researchers were able to improve the gait in the “injured” rodents. The hydrogel prosthetics were combined with robot assistance, guided by muscle electromyography signals. Together, the two helped enhance the animal’s gait without nerve stimulation. Furthermore, muscle tissue regeneration was effectively improved over the long term after the conductive hydrogel was used to fill muscle damage.

The injectable conductive hydrogel developed in this study excels in electrophysiological signal recording and stimulation performance, offering the potential to expand its applications. It presents a fresh approach to the field of bioelectronic devices and holds promise as a soft tissue prosthesis for rehabilitation support.

Emphasizing the significance of the research, Professor SHIN Mikyung notes, “We’ve created an injectable, mechanically tough, and electrically conductive soft tissue prosthesis ideal for addressing severe muscle damage requiring neuromusculoskeletal rehabilitation. The development of this injectable hydrogel, utilizing a novel cross-linking method, is a notable achievement. We believe it will be applicable not only in muscles and peripheral nerves but also in various organs like the brain and heart.”

Professor SON Donghee added, “In this study, the closed-loop gait rehabilitation system entailing tough injectable hydrogel and stretchable and self-healing sensors could significantly enhance the rehabilitation prospects for patients with neurological and musculoskeletal challenges. It could also play a vital role in precise diagnosis and treatment across various organs in the human body.”

The research team is currently pursuing further studies to develop new materials for nerve and muscle tissue regeneration that can be implanted in a minimally invasive manner. They are also exploring the potential for recovery in various tissue damages through the injection of the conductive hydrogel, eliminating the need for open surgery.

Here’s a link to and a citation for the paper,

Injectable tissue prosthesis for instantaneous closed-loop rehabilitation by Subin Jin, Heewon Choi, Duhwan Seong, Chang-Lim You, Jong-Sun Kang, Seunghyok Rho, Won Bo Lee, Donghee Son & Mikyung Shin. Nature volume 623, pages 58–65 (2023) DOI: https://doi.org/10.1038/s41586-023-06628-x Published: 01 November 2023 Issue Date: 02 November 2023

This paper is behind a paywall.

Nanoscale measurements for osteoarthritis biomarker

There’s a new technique for measuring hyaluronic acid (HA), which appears to be associated with osteoarthritis. A March 12, 2018 news item on ScienceDaily makes the announcement,

For the first time, scientists at Wake Forest Baptist Medical Center have been able to measure a specific molecule indicative of osteoarthritis and a number of other inflammatory diseases using a newly developed technology.

This preclinical [emphasis mine] study used a solid-state nanopore sensor as a tool for the analysis of hyaluronic acid (HA).

I looked at the abstract for the paper (citation and link follow at end of this post) and found that it has been tested on ‘equine models’. Presumably they mean horses or, more accurately, members of the horse family. The next step is likely to be testing on humans, i.e., clinical trials.

A March 12, 2018 Wake Forest Baptist Medical Center news release (also on EurekAlert), which originated the news item, provides more details,

HA is a naturally occurring molecule that is involved in tissue hydration, inflammation and joint lubrication in the body. The abundance and size distribution of HA in biological fluids is recognized as an indicator of inflammation, leading to osteoarthritis and other chronic inflammatory diseases. It can also serve as an indicator of how far the disease has progressed.

“Our results established a new, quantitative method for the assessment of a significant molecular biomarker that bridges a gap in the conventional technology,” said lead author Adam R. Hall, Ph.D., assistant professor of biomedical engineering at Wake Forest School of Medicine, part of Wake Forest Baptist.

“The sensitivity, speed and small sample requirements of this approach make it attractive as the basis for a powerful analytic tool with distinct advantages over current assessment technologies.”

The most widely used method is gel electrophoresis, which is slow, messy, semi-quantitative, and requires a lot of starting material, Hall said. Other technologies include mass spectrometry and size-exclusion chromatography, which are expensive and limited in range, and multi-angle light scattering, which is non-quantitative and has limited precision.

The study, which is published in the current issue of Nature Communications, was led by Hall and Elaheh Rahbar, Ph.D., of Wake Forest Baptist, and conducted in collaboration with scientists at Cornell University and the University of Oklahoma.

In the study, Hall, Rahbar and their team first employed synthetic HA polymers to validate the measurement approach. They then used the platform to determine the size distribution of as little as 10 nanograms (one-billionth of a gram) of HA extracted from the synovial fluid of a horse model of osteoarthritis.

The measurement approach consists of a microchip with a single hole or pore in it that is a few nanometers wide – about 5,000 times smaller than a human hair. This is small enough that only individual molecules can pass through the opening, and as they do, each can be detected and analyzed. By applying the approach to HA molecules, the researchers were able to determine their size one-by-one. HA size distribution changes over time in osteoarthritis, so this technology could help better assess disease progression, Hall said.

“By using a minimally invasive procedure to extract a tiny amount of fluid – in this case synovial fluid from the knee – we may be able to identify the disease or determine how far it has progressed, which is valuable information for doctors in determining appropriate treatments,” he said.

Hall, Rahbar and their team hope to conduct their next study in humans, and then extend the technology with other diseases where HA and similar molecules play a role, including traumatic injuries and cancer.

Here’s a link to and a citation for the paper,

Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor by Felipe Rivas, Osama K. Zahid, Heidi L. Reesink, Bridgette T. Peal, Alan J. Nixon, Paul L. DeAngelis, Aleksander Skardal, Elaheh Rahbar, & Adam R. Hall. Nature Communications volume 9, Article number: 1037 (2018) doi:10.1038/s41467-018-03439-x
Published online: 12 March 2018

This paper is open access.