Researchers have developed a biomaterial that can reduce inflammation and cell damage caused by removing reactive oxygen molecules that are released by the body as a result of traumatic spinal cord injury.

“Spinal cord injury represents a significant global health issue, affecting over 20 million individuals worldwide,” explained Chong Cheng, a professor and head of the Advanced Low-Dimensional Materials Group at Sichuan University, who led the current research.

“Treatment is challenging due to the limited regenerative capacity of nerve cells, which is further hindered by an adverse microenvironment characterized by high levels of reactive oxygen species and inflammation.”

While the research is still at an early stage, results from a study in rats show significant improvements in tissue repair and movement after treatment with this material, suggesting it could be a promising new approach for this type of injury if validated in human studies.

Spinal cord injury, difficult to treat

Traumatic spinal cord injury most commonly occurs after a vehicle accident or a fall and is the second most common cause of paralysis after stroke. It is a difficult injury to treat due to the complexity of the neurological tissue in the spine.

“The difficulty in treating spinal cord injuries arises from the spinal cord’s role as a sophisticated information superhighway, which carries countless important nerve fibers within a limited space,” said Cheng. “Once damage occurs, information transmission is instantly disrupted, making repair extremely challenging. Due to the limited regenerative capacity of nerve cells, this damage is often irreversible.”

There are multiple steps to this type of injury, as after the initial traumatic damage to the area occurs, secondary damage starts to set in. Multiple cellular and molecular changes occur in the tissue starting minutes after the injury and sometimes continuing for months afterwards, resulting in progressive damage and cell death.

For decades, researchers have tried and failed to develop treatments for spinal cord injury. “Surgical treatment aims to restore and maintain spinal stability through internal fixation; however, it does not address existing or progressive injuries,” explained Cheng.

Treating the secondary damage is difficult, however, and no highly effective treatments are currently approved to combat this problem. This is partly due to the complexity of the tissue and the injury. Clinical trials are also difficult and expensive to run for this kind of injury as long time periods are needed to assess the efficacy of treatments due to the slow speed of nerve regeneration.

“Methylprednisolone is the only drug currently recommended in clinical guidelines for [secondary] spinal cord injury treatment,” said Cheng. “Its use, however, remains controversial due to the necessity for early high-dose administration and ongoing treatment, which can lead to significant side effects.”

Reactive oxygen species and how to banish them

The build-up of reactive oxygen species at the site of injury site causes a number of negative effects, including oxidative damage to DNA, oxidation of proteins and lipid peroxidation, all of which push the affected nerve cells towards cell death. In combination with inflammation, this causes significant tissue damage if left unchecked.

“Imagine a spinal cord injury as a sudden forest fire, with reactive oxygen species resembling raging flames engulfing the dense forest of neurons,” said Cheng. “Inflammation acts like smoke, further exacerbating the damage.”

In the current study, Cheng and his colleagues developed a special material, comprised of ruthenium (Ru), a rare metal, and copper hydroxide (Cu(OH)₂) encapsulated in collagen. It is designed to reduce inflammation and additional neuronal cell death after spinal cord injury by removing reactive oxygen species from the injury site. It acts as a scavenger for excess reactive oxygen molecules in the tissue, effectively vacuuming them up.

“Our reactive oxygen species scavenger rapidly eliminates harmful reactive oxygen species, reduces neuronal death, induces macrophages to adopt an anti-inflammatory phenotype, and protects key cells, such as neural stem cells and oligodendrocytes, thereby creating favorable conditions for spinal cord repair,” said Ting Wang, a doctoral student in Cheng’s team.

Other research teams are also looking into using anti-oxidant molecules to treat secondary spinal cord injury, but Cheng believes the new material has advantages over natural antioxidant molecules such as superoxide dismutase, also being tested to treat this type of injury, as it is more stable, easier to deliver, and less likely to provoke an adverse immune reaction in patients.

The team compared their approach with collagen encapsulated Ru/def-Cu(OH)₂ with no intervention, collagen alone, and def-Cu(OH)₂ alone.

In both laboratory and rat studies the researchers showed that their material was able to reduce cell death in neurons caused by excess reactive oxygen species and also reduce inflammation in the area of injury.

Rats treated with the biomaterial had better recovery of spinal cord structure and nerve cell regeneration than controls. “Notably, after 28 days post-injury, these rats showed significant improvements in mobility compared to untreated rats, which exhibited no substantial recovery,” said Wang.

Although these results are promising, this proposed treatment still has some way to go before it can reach patients. “While there are numerous technical and regulatory challenges to address in moving from the lab to clinical trials, we are committed to thoroughly exploring this area to further optimize treatment strategies,” said Cheng.

“Our future plan is to gradually transition this research from the laboratory to clinical applications. We are considering commercialization pathways, such as partnering with biotechnology companies, to accelerate the translation of research findings and benefit more patients. We will also conduct additional research in this field, with the hope of overcoming the clinical challenges of spinal cord repair through continuous innovation and investigation.”

Reference: Jinglun Liu, et al., Constructing Electron-Rich Ru Clusters on Non-Stoichiometric Copper Hydroxide for Superior Biocatalytic ROS Scavenging to Treat Inflammatory Spinal Cord Injury, Advanced Materials (2024). DOI: 10.1002/adma.202411618