More than 70% of patients with traumatic brain injury (TBI) reported at least one problematic symptom at one year of follow-up that was new or worse than before injury according to a study published in the Journal of Neurotrauma. Half of the patients reported three or more such symptoms after a year.
Joan Machamer, from the University of Washington, Harborview Medical Center, and colleagues representing the TRACK-TBI Investigators, compared the frequency and persistence of symptoms in patients with TBI to two control groups: patients with orthopedic trauma and friend controls. The groups were evaluated at 2 weeks, and 3, 6, and 12 months after injury.
Physical symptoms such as headache, fatigue, and dizziness tended to occur earlier, according to the researchers, with cognitive symptoms becoming dominant later. While physical symptoms declined noticeably over time, cognitive symptoms remained more constant over time.
“Clinicians should inquire about symptoms in patients who have had a TBI, reassure them that experiencing symptoms is common, and direct them to seek treatment for symptoms that are disrupting their lives,” the researchers said.
Commenting on the study, David L. Brody, MD, PhD, Editor-in-Chief of Journal of Neurotrauma noted that is remarkable for several reasons. “First, it is among the largest studies of its type, with over 2,000 participants. Second, it confirms what many of us who practice brain injury medicine have observed for many years– a wide variety of symptoms can be very persistent and very troubling to our patients even after so-called ‘mild’ TBI. Third, the investigators used the right controls; people with orthopedic injury as well as friends of the patients with TBI. Symptoms in patients with TBI were substantially more common and more severe than in both control groups.”
Researchers at MIT have found the ideal size for injectable nanoparticles that could slow traumatic internal bleeding, buying more time for a patient to reach a hospital for further treatment.
In a rat study, the researchers showed that polymer nanoparticles particles in an intermediate size range, (about 150nm in diameter) were the most effective at stopping bleeding. These particles also were much less likely to travel to the lungs or other off-target sites, which larger particles often do. The results were published in ACS Nano.
“With nano systems, there is always some accumulation in the liver and the spleen, but we’d like more of the active system to accumulate at the wound than at these filtration sites in the body,” said senior author Paula Hammond, Professor at MIT.
Nanoparticles that can stop bleeding, also called haemostatic nanoparticles, can be made in a variety of ways. One of the most commonly used strategies is to create nanoparticles made of a biocompatible polymer conjugated with a protein or peptide that attracts platelets, the blood cells that initiate blood clotting.
In this study, the researchers used a polymer known as PEG-PLGA, conjugated with a peptide called GRGDS, to make their particles. Most of the previous studies of polymeric particles to stop bleeding have focused on particles ranging in size from 300–500nm. However, few, if any studies have systematically analysed how size affects the function of the nanoparticles.
“We were really trying to look at how the size of the nanoparticle affects its interactions with the wound, which is an area that hasn’t been explored with the polymer nanoparticles used as haemostats before,” Hong says.
Studies in animals have shown that larger nanoparticles can help to stop bleeding, but those particles also tend to accumulate in the lungs, which can cause unwanted clotting there. In the new study, the MIT team analysed a range of nanoparticles, including small (< 100nm), intermediate (140–220nm), and large (500–650nm).
They first analysed the nanoparticles in the lab to see how how they interacted with platelets in various conditions, to see how well platelets bound to them. They found that, flowing through a tube, the smallest particles bound best to platelets, while the largest particles stuck best to surfaces coated with platelets. However, in terms of the ratio particles to platelets, the intermediate-sized particles were the lowest.
“If you attract a bunch of nanoparticles and they end up blocking platelet binding because they clump onto each other, that is not very useful. We want platelets to come in,” said lead author, Celestine Hong, an MIT graduate student. “When we did that experiment, we found that the intermediate particle size was the one that ended up with the greatest platelet content.”
The researchers injected the different size classes of nanoparticles into mice to see how long they would circulate for, and where they would end up in the body. As with previous studies, the largest nanoparticles tended accumulated in the lungs or other off-target sites.
The researchers then used a rat model of internal injury to study which particles would be most effective at stopping bleeding. They found that the intermediate-sized particles appeared to work the best, and that those particles also showed the greatest accumulation rate at the wound site.
“This study suggests that the bigger nanoparticles are not necessarily the system that we want to focus on, and I think that was not clear from the previous work. Being able to turn our attention to this medium-size range can open up some new doors,” Prof Hammond said.
The researchers now hope to test these intermediate-sized particles in larger animal models, to get more information on their safety and the most effective doses. They hope that eventually, such particles could be used as a first line of treatment to stop bleeding from traumatic injuries long enough for a patient to reach the hospital.
Having a spinal cord injury increases risk of developing mental health conditions such as depression and anxiety by nearly 80% compared to those without the traumatic injury, a new study shows. However, chronic pain may have an equally large, negative effect on mental health.
The study, published in Spinal Cord, compared private insurance claims from more than 9000 adults with a traumatic spinal cord injury with those of more than 1 million without. Researchers accounted for a range of psychological conditions, from anxiety and mood disorders to insomnia and dementia.
People living with a spinal cord injury had a diagnosis of a mental health condition more often than those without – 59.1% versus 30.9%. While depression and adverse mental health effects are not inevitable consequences of every traumatic spinal injury, previous studies have consistently echoed higher levels of psychological morbidity among this group than the general population without spinal cord injuries.
However, this study found that chronic centralised and neuropathic pain among adults living with a spinal cord injury were robustly associated with post-traumatic stress disorder, substance use disorders and other mental health conditions. In most cases, chronic pain was an even greater influence on these conditions than exposure to living with the injury itself.
The study authors said the findings should prompt physicians to identify mental health conditions when seeing patients with spinal cord injuries and refer them for treatment.
“Improved clinical efforts are needed to facilitate screening of, and early treatment for, both chronic pain and psychological health in this higher-risk population,” said lead author Dr Mark Peterson, associate professor of physical medicine and rehabilitation at Michigan Medicine.
However, researchers note a lack of insurance coverage and limited available services will likely cause the issue to remain largely unaddressed.
“Stakeholders need to work together to lobby for more federal research funding and special policy amendments to ensure adequate and long-term insurance coverage for both physical and mental health to meet the needs of folks living with spinal cord injuries,” Dr Peterson said.
Using metal K-wires (aka ‘pins’) to hold broken wrist bones in place while they heal are no better than a traditional moulded plaster cast, finds a study published by The BMJ.
If the bone fragments in wrist fractures have displaced, they often require manipulation followed either by surgery to insert metal wires or plates, or a moulded cast as a non-surgical alternative, to hold the bones in place while they heal.
Surgery is expensive and carries risk for the patient, whereas a moulded plaster cast is cheaper but may not provide the same functional outcome.
To see which option is superior, researchers tracked the progress of 500 adults, average age of 60 and 83% female. with a displaced wrist fracture. Patients were randomly allocated to receive a cast (255) or surgical fixation with K-wires (245) after manipulation of their fracture. The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months, which included questions about pain, function and disability, and gave an overall score from 0 (best) to 100 (worst).
Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for later surgery.
Of the 79% of patients who completed the follow-up, no statistically significant difference was seen in the PRWE score at three, six or 12 months (average score 21.2 in the cast group compared with 20.7 in the K-wire group). Quality of life was similar.
However, one in eight patients with cast needed later surgery for loss of fracture position in the first six weeks after their injury compared with only one patient in the K-wire group.
Other complications were rare, with no evidence of a difference between the two groups (28 in the cast group compared with 22 in the K-wire group).
Limitations included the fact that neither the treating clinicians nor the participants could be blind to the interventions. Still, the researchers noted this was a large trial involving adults of all ages and the results are based on validated patient reported outcomes, reflecting the care provided across a healthcare system.
As such, they conclude: “Surgical fixation with K-wires did not provide better wrist function at 12 months compared with a moulded cast, indicating that a cast is an acceptable first line treatment following manipulation of a dorsally displaced fracture of the distal radius.”
They added: “Cast treatment avoids the expense and risks of surgical fixation for seven out of eight patients. However, careful follow-up is needed as one in eight patients treated with a cast required subsequent surgical intervention as the fracture reduction could not be maintained.”
Traumatic brain injury can lead to long-term visual impairment, which researchers have found is caused by a dramatic drop in the number of neurons in the visual cortex. Their findings were published in Communications Biology.
Traumatic brain injury (TBI) is associated with mechanical brain damage and a wide range of neuronal abnormalities. Injuries to the posterior occipital cortex are common in humans, and can result in visual impairment. Up to 75% of current or former soldiers live with permanent visual dysfunction or cortical blindness.
The human brain possesses surprising neuroplasticity, which allows other areas of the brain to take over the functions of a damaged area.
Such neuroplasticity is also characteristic of the sensory areas of the visual cortex, which is final component of the visual pathway, responsible for receiving and processing visual impressions. The primary visual cortex (V1) is reached by the nerve fibres of the optic radiation, which carry nerve impulses from the retinas of both eyes.
Until now, scientists knew little about the effects of TBI on long-term visual circuit function. Using mice, a team of researchers examined how neurons respond to visual stimuli two weeks and three months after mild injury to the primary visual cortex (V1). V1 neurons normally show sensitivity to different features of a visual stimulus, such as colour or direction of movement. The preprocessed data is transmitted to subsequent areas of the visual cortex. This study showed that although the primary visual cortex remained largely intact after the brain injury, there was a 35% reduction in the number of neurons. This loss largely affected inhibitory neurons rather than excitatory neurons, which inhibit or stimulate action in the target cells, respectively.
After TBI, fewer than half of the isolated neurons were sensitive to visual stimuli (32% at two weeks after injury; 49% at three months after the event), compared with 90% of V1 cells in the control group. Up to a threefold decrease in neuronal activity was seen after the brain injury, and the cells themselves had worse spatial orientation. The overall results mean that even minor, superficial brain injuries cause long-term impairment in the way visual stimuli are perceived, persisting several months after the event.
Such a deeper understanding of the functional impairments in damaged visual cortex could provide a basis for developing circuit-level therapies for visual cortex damage.
The Achilles tendon can endure a load nearly 8 times body weight during exercise, rendering it vulnerable to injury despite its strength, which can be worsened by a failure to properly heal, forming bone instead of new tendon. A new study found that by inhibiting blood vessel formation, the anomalous bone growth can be prevented.
Due to the unique nature of tendons, failing to consult a doctor soon after an injury can lead to chronic tendon disease, which is characterised by pain, swelling, and movement problems. Tendon heterotopic ossification(HO) is a rare type of chronic tendon disease where new bone grows the tendon, causing even more damage. Famous athletes have had to retire early from sports due to a lack of a radical solution for Achilles tendon injuries.
Using single-cell sequencing technology, a team led by Professor Ouyang Hongwei found that changes in the tissue microenvironment of tendon HO alterations in gene expression and in tendon stem progenitor cells. These findings were published in Bone Research, providing a novel treatment for tendon heterotopic ossification.
The researchers firstly found that the tendon specific transcription factor MKX decreased significantly in heterotopic ossified human tendon, and deletion of MKX led to spontaneous ossification of mouse tendon, suggesting that MKX plays a critical role in tendon HO.
Further studies revealed that MKX knockout mouse tendon cells expressed high levels of genes related to blood vessel formation, resulting in vascular invasion and remodelling of the tendon extracellular matrix. This also resulted in abnormal activation of genes related to bone and cartilage in tendon stem cells. These data indicated that inhibition of blood vessel formation may improve the tendon tissue microenvironment and prevent HO progression.
Armed with this knowledge, Prof Ouyang and his colleagues searched for drugs that can inhibit the angiogenesis process. They found that local injection of a small molecule inhibitor known as BIBF1120 significantly inhibited the neovascularisation of tendon after injury, thus alleviating the progression of tendon HO.
ESA astronaut Matthias Maurer is shown during preflight training for the BioPrint First Aid investigation, which tests a bioprinted tissue patch for enhanced wound healing. Credit: ESA
A suitably advanced piece of wound care technology will be sent into orbit to the space station in the next few days: a prototype for portable bioprinter that can cover a wound area on the skin by applying a tissue-forming bio-ink that acts like a patch, and accelerates the healing process.
While the aim is to provide a effective wound treatment for astronauts millions of kilometres from the nearest hospital, such a personalised wound healing patch would also have a great benefit on Earth. Since the cultured cells are taken from the patient, immune system rejection is unlikely, allowing a safe regenerative and personalised therapy. Other advantages are the possibilities of treatment and greater flexibility regarding wound size and position. In addition, due to its small size and portability, physicians could take the device anywhere to an immobile patient if their cells were cultivated in advance.
“On human space exploration missions, skin injuries need to be treated quickly and effectively,” said project manager Michael Becker from the German Space Agency. “Mobile bioprinting could significantly accelerate the healing process. The personalised and individual bioprinting-based wound treatment could have a great benefit and is an important step for further personalised medicine in space and on Earth.”
The use of bioprinting for skin reconstruction following burns is one growing application for the technology. However, it presently requires large bioprinters that first print the tissue, allow it to mature, before it is implanted onto the patient. By testing it in the gravity-free environment of space, Bioprint FirstAid will help optimise of bioprinting materials and processes. Microgravity-based 3D tissue models are important for greater understanding of the bioengineering and bio-fabrication requirements that are essential to achieve highly viable and functional tissues. Under microgravity conditions, the pressure of different layers containing cells is absent, as well as the potential sedimentation effect of living cell simulants. The stability of the 3D printed tissue patch, and the potentially gravity-dependent (electrolyte to membrane interface) crosslinking process, can be analysed for future applications.
The Bioprint FirstAid prototype contains no cells at this point. The surprisingly simple prototype is a robust, purely mechanical handheld bioprinter consisting of a dosing device in the handle, a print head, support wheels, and an ink cartridge. The cartridge contains a substitution (in total two different substitutions, both without skin cells) and a crosslinker, which serves as a stabilising matrix. To test it out, the simulant will be applied to the arm or leg of a crew member wrapped in foil, or alternatively at any other surface wrapped in foil. On Earth, a printed sample with human cells will be tested, and the distribution pattern will be compared to the cell-free sample that was printed in space.
New research suggests that wound healing could be enhanced by replicating platelet-rich plasma from our blood to create implants introduced into the wound.
Platelet-rich plasma (PRP) is a natural healing substance in our blood. Researchers explored ways of enhancing the wound healing process by extracting PRP from the blood of a patient with a complex skin wound and manipulating it through 3D printing to form an implant for tissue repair which can be used to treat difficult-to-heal skin wounds in a single surgical procedure.
The results, which are reported in Advanced Functional Materials, showed that application of the 3D-printed PRP implant helped to speed up the healing of the wound by enabling efficient vascularisation and inhibiting fibrosis, which are both essential for effective wound healing.
Professor Fergal O’Brien, at RCSI University of Medicine and Health Sciences said: “Existing literature suggests that while the PRP already present in our blood helps to heal wounds, scarring can still occur. By 3D-printing PRP into a biomaterial scaffold, we can increase the formation of blood vessels while also avoiding the formation of scars, leading to more successful wound healing.
“As well as promising results for skin wound healing, this technology can potentially be used to regenerate different tissues, therefore dramatically influencing the ever-growing regenerative medicine, 3D printing and personalised medicine markets.”
Researchers from Japan have discovered the role of interleukin-36 receptor antagonists in healing skin wounds from ischaemia-reperfusion injuries.
Ischaemia is a medical condition in which the blood supply is cut off to different parts of the body. In patients who are bed-ridden, ischemia can manifest as pressure ulcers. Else, it could be the Raynaud’s phenomenon in someone under severe stress. Ischaemia, from the Latin “staunching of blood”, is a condition can be rescued by blood reperfusion to the affected areas. However, ischaemia-reperfusion (I/R) injuries where tissue damage caused by blood returning to tissues after a period of oxygen deprivation, are a risk.
Skin-based I/R injuries can be exacerbated by inherited immunological mechanisms, for instance in patients who are otherwise showing signs of slow wound healing. To understand the immunological mechanisms underlying the development of this condition better, decided to narrow down their investigation to interleukin-36 receptor antagonist (IL-36Ra), a protein that plays a pivotal immunomodulatory role in wound healing.
Lead researcher Mr Yoshihito Tanaka from Fujita Health University School of Medicine explained the motivation behind the research, “We wanted to understand the immunological mechanisms involved in the healing of wounds from cutaneous ischaemia-reperfusion injuries, such as pressure ulcers and Raynaud’s phenomenon, to narrow down possible therapeutic targets. Drawing from experience, IL-36Ra appeared to be a promising candidate for kickstarting our investigation.”
The scientists used mice knocked out for the IL-36Ra receptor, and induced cutaneous I/R injuries in the knockout and control mice. Then, they studied corresponding immunological responses in both groups of animals, including wound healing time, infiltration of neutrophils/macrophages to the site of the wounds, apoptotic skin cells, and activation of other unwanted immunological defense mechanisms. Their findings appear in the Journal of The European Academy of Dermatology and Venereology.
They found that the absence of IL-36Ra, indeed, significantly slows down wound healing in cutaneous I/R injuries, through increased apoptosis, or ‘suicide’ of useful skins cells, excessive recruitment of inflammatory cells, and employment of unnecessary proinflammatory mechanisms.
Additionally, they demonstrated the role of Cl-amidine, a protein-arginine deiminase inhibitor as effective in normalizing exacerbated I/R injury in IL-36Ra mice. Based on these observations, the scientists assert their findings are the first conclusive report of the involvement of IL-36Ra in cutaneous I/R injury.
The researchers believe IL-36Ra is a good therapeutic candidate against cutaneous I/R injuries. As Mr. Tanaka optimistically adds, “Our research may lead to the development of therapeutic agents for wound healing of various other refractory skin diseases too.”
The quest for novel therapeutic targets in skin wound healing might just have been empowered by these findings of the team and the future indeed looks brighter for alleviating the painful burden of cutaneous I/R injuries.
A research team has developed a smart wearable sensor that can conduct real-time, point-of-care assessment of chronic wounds wirelessly via an app. The world-first sensor technology can detect temperature, pH, bacteria type and inflammatory factors specific to chronic wounds within 15 minutes, enabling fast and accurate wound assessment.
More patients are suffering from non-healing wounds such as diabetic foot and chronic venous leg ulcers due to ageing and diabets, with an estimated 2% of the world’s population suffering from chronic wounds. Pain, stress and even amputation can result. Timely care and proper treatment of chronic wounds are needed to speed up wound recovery, but requires multiple clinical visits for lengthy wound assessment and treatment. This new technology can alleviate these problems.
The development of the technology was outlined in the journal Science Advances.
Currently, clinical assessments of wounds rely on visual inspection, or collecting and sending wound fluid for lab tests for biomarkers. This process usually takes about one to two days and may impede medical interventions. Though flexible sensors designed for wound care have been developed, they can only probe a limited set of markers such as acidity, temperature, oxygen, uric acid, and impedance to diagnose wound inflammation.
VeCare is a response to these problems, a point-of-care wound assessment platform consisting of an innovative wound sensing bandage, an electronic chip and a mobile app. The bandage consists of a wound contact layer, a breathable outer barrier, a microfluidic wound fluid collector and a flexible immunosensor. VeCare is the first wound assessment platform that can detect bacteria type and probe inflammatory factors, in addition to measuring acidity and temperature, within a single 15-minute test. The microfluidic wound collector boosts delivery to the immunosensor for analysis.
In addition, the reusable integrated chip transmits data to an app for convenient, real-time wound assessment and analysis onsite.
The VeCare platform and mobile app enable doctors to monitor the condition of patients’ chronic wounds remotely, and complements the patient’s existing medical treatment while facilitating timely medical intervention for wound healing processes.
“Point-of-care devices coupled with telehealth or digital health capability can play a significant role in transforming the healthcare industry and our society, which is catalysed by the COVID-19 pandemic requirements for safe distancing. Our smart bandage technology is the first of its kind designed for chronic wound management to give patients the freedom to perform the test and monitor their wound conditions at home,” said research leader Professor Lim Chwee Teck from the National University of Singapore’s (NUS) Department of Biomedical Engineering.
A small clinical test of VeCare was conducted on patients with chronic venous leg ulcers, successfully demonstrating the platform’s effectiveness. “The VeCare platform is easily scalable and customisable to accommodate different panels of biomarkers to monitor various types of wounds. The aim is to have an effective and easy to use diagnostic and prognostic tool for precise and data-driven clinical management of patients,” commented Prof Lim.
Next steps include a larger randomised trial and scaling up production to bring the device to market.
