Tag: chronic wounds

Categories : Injury & Trauma New Compounds and TreatmentsTags :

New Compound Secreted by Bacteria Speeds up Healing

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Photo by Diana Polekhina on Unsplash

Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. A new study published in eClinical Medicine shows that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.

Previously, the researchers had demonstrated accelerated wound healing after topical treatment using lactic acid bacteria (Limosilactobacillus reuteri) genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

Now, in their first clinical study on humans, the researchers established safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

The results show that treatment using ILP100-Topical was safe and well tolerated among all individuals and doses, and neither ILP100 nor CXCL12 could be detected in locations beyond the wounds. A significantly higher proportion of healed wounds (p=0.020) was seen on day 32 using multi-dose ILP100-Topical compared to saline and placebo (76% (73/96) and 59% (57/96) healed wounds respectively) when the results from the multi-dose-treated wounds were pooled. In addition, the time to first recorded healing was reduced by an average of 6 days, and by 10 days at the highest dose. The mechanism of action of ILP100-Topical was also confirmed when the treatment resulted in increased CXCL12-positive cells in the wounds, as well as increased blood flow around the wounds during the healing phase.

“Our study shows that bacteria modified to produce and deliver human protein for local effects can be used as drugs to accelerate the healing of wounds. This is the first time this has been shown in controlled human studies, and it can be expected that the effect is greater in patients with diseases that negatively affect wound healing,” explains Mia Phillipson, Professor at the Department of Medical Cell Biology at Uppsala University.

The favourable safety profile and the beneficial effects on wound healing observed here support further clinical development of ILP100-Topical for the treatment of complex and hard-to-heal wounds in patients, which is already under way.

Many immune-active proteins are inherently unstable and degrade quickly, so supplying them from lactic acid bacteria to the exact site of action is one way to develop them as drugs.

“The potential is really endless when you consider how important a role proteins play in various processes in the body, and how many diseases we currently do not have good enough treatments for. We have already produced another drug candidate to cure and reduce inflammation in the gut of cancer patients – ILP100-Oral – and in the future we will start a research project with another chemokine for the treatment of lung diseases,” concludes Phillipson.

Source: Uppsala University

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Ripping Through Biofilms in Chronic Treatment-resistant Wounds

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Methicillin-resistant-Staphylococcus-aureus-MRSA

Researchers have developed a new method that combines palmitoleic acid, gentamicin, and non-invasive ultrasound to help improve drug delivery in chronic wounds that have been infected with Staphylococcus aureus and protected by thick biofilms. Their results were published in Cell Chemical Biology.

Chronic wounds are notoriously challenging to treat because of bacterial infections like S. aureus, which can also be resistant to antibiotics.

To defend itself from the immune system and other threats, S. aureus can band together, creating a slick, slimy biofilm around itself. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate through and neutralise the harmful bacteria.

Using a new strategy, researchers at the UNC School of Medicine and the UNC-NC State Joint Department of Biomedical Engineering were able to reduce the challenging MRSA infection in the wounds of diabetic mice by 94%. They were able to completely sterilise the wounds in several of the mice, and the rest had significantly reduced bacterial burden.

“When bacteria are not completely cleared from chronic wounds, it puts the patient at high risk for the infection recurring or of developing a secondary infection,” said senior author Sarah Rowe-Conlon, PhD. “This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients. We are excited about the potential of translating this to the clinic, and that’s what we’re exploring right now.”

Biofilms act as a physical barrier to many classes of antibiotics. Virginie Papadopoulou, PhD, was curious to know if non-invasive cavitation-enhanced ultrasound could create enough agitation to form open spaces in the biofilm to facilitate drug-delivery.

Liquid droplets which can be activated by ultrasound, called phase change contrast agent (PCCA), are applied topically to the wound. An ultrasound transducer is focused on the wound and turned on, causing the liquid inside the droplets to expand and turn into microscopic gas-filled microbubbles, when then move rapidly.

The oscillation of these microbubbles agitates the biofilm, both mechanically disrupting it as well as increasing fluid flow. Ultimately, the combination of the biofilm disruption and the increased permeation of the drugs through the biofilm allowed the drugs to come in and kill the bacterial biofilm with very high efficiency.

“Microbubbles and phase change contrast agents act as local amplifiers of ultrasound energy, allowing us to precisely target wounds and areas of the body to achieve therapeutic outcomes not possible with standard ultrasound,” said Dayton. “We hope to be able to use similar technologies to locally delivery chemotherapeutics to stubborn tumours or drive new genetic material into damaged cells as well.”

When the bacterial cells are trapped inside the biofilm, they are left with little access to nutrients and oxygen. To conserve their resources and energy, they transition into a dormant or sleepy state. The bacteria, which are known as persister cells in this state, are extremely resistant to antibiotics.

Researchers chose gentamicin, a topical antibiotic typically ineffective against S. aureus due to widespread antibiotic resistance and poor activity against persister cells. The researchers also introduced a novel antibiotic adjuvant, palmitoleic acid, to their models.

Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body that has strong antibacterial properties. The fatty acid embeds itself into the membrane of bacterial cells, and the authors discovered that it facilitates the antibiotic’s successful entry into S. aureus cells and is able to kill persistent cells and reverse antibiotic resistance.

Overall, the team is enthusiastic about the new topical, non-invasive approach because it may give scientists and doctors more tools to combat antibiotic resistance and to lessen the serious adverse effects of taking oral antibiotics.

“Systemic antibiotics, such as oral or IV, work very well, but there’s often a large risk associated with them such as toxicity, wiping out gut microflora and C. difficile infection,” said Rowe-Conlon. “Using this system, we are able to make topical drugs work and they can be applied to the site of infection at very high concentrations, without the risks associated with systemic delivery.”

Source: University of North Carolina Health Care

Categories : Injury & TraumaTags :

A New Wound Dressing With Built-in Sensors

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Image by Dian Polekhina on Unsplash

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.

Source: National University of Singapore