Researchers at Lund University, Lund, Sweden, have developed a new hydrogel based on the body’s natural peptide defence, which has been shown to prevent and treat infections in wounds. The formulation kills multi-resistant bacteria, something that is “increasing in importance with antibiotic resistance growing globally”.
“The ability to effectively heal wounds is key for our survival in evolutionary terms. There are peptides in wounds that defend against bacteria and prevent their toxins from causing inflammation. The gel is based on these natural defence mechanisms and has had a dual effect—by both preventing as well as treating wound infections”, says Artur Schmidtchen (Lund University, Lund, Sweden), commenting on the new treatment option.
According to the investigators, including Schmidtchen and colleagues, there is a clinical need for wound treatments that prevent both infection and excessive inflammation, as well as improving wound healing and reducing complications in patients with various types of wounds, such as burns, surgical wounds, or other types of wounds that do not heal easily.
They add that current treatments are primarily directed solely at the bacteria. A patient is treated with antibiotics either preventively or when they get an infection, and various antiseptics are used. However, the extensive use of antibiotics is adding to the issue of antibiotic resistance. Consequently, infections with multi-resistant bacteria are a major global problem today, and they cannot be treated with antibiotics.
“Antibiotics and antiseptics kill the bacteria but do not affect the subsequent harmful inflammatory process. Another problem is that the active substances in today’s antiseptic wound treatment are often toxic and harmful to the environment. We have not seen this with our active substance, and it also kills multi-resistant bacteria”, says Schmidtchen.
The wound gel is not only antibacterial; researchers have previously shown that the peptides in the gel, including the thrombin-derived TCP-25, can inactivate so-called lipopolysaccharides (LPS) that are found in cell walls of bacteria, triggering an inflammatory reaction. This peptide is also said, by Schmidtchen et al, to reduce downstream immune activation. “The reaction is an essential part of our immune system, as we quickly respond to and fight bacteria,” the authors note.
Results of a study evaluating peptide effects and structure—in the presence of different formulation components—showed that “the TCP-25–functionalised hydrogels killed gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa bacteria in vitro, as well as in experimental mouse models of subcutaneous infection”. In terms of the relevance of this investigation, it was stated by researchers that “porcine wound healing studies are considered to have a good translation to the human wound healing situation”.
They added: “The TCP-25 hydrogel also mediated reduction of LPS-induced local inflammatory responses, as demonstrated by analysis of local cytokine production and in vivo bioimaging.” Furthermore, the immunomodulatory action recorded also demonstrated that the effects on inflammation preceded antibacterial effects, while it was found that TCP-25 forms bioactive fragments after degradation that are identical to those found in vivo.
“Severe and uncontrolled inflammation inhibits wound healing, and it is very interesting to see that the gel lowers the inflammatory response within 24 hours of the treatment, and then further reduces the bacterial levels over a period of three to four days,” says Manoj Puthia (Lund University, Lund, Sweden), first author of the study. We have designed a whole new type of treatment that uses nature’s own principles by not only killing bacteria, but also acting as an immune-modulator”, he added.
The researchers are now collaborating with the company in2cure AB, in order to get the gel approved for use in clinical studies involving patients with burn injuries. “We will also look into the possibility of developing new peptide-based drugs for eye infections and infections in other internal organs. It could become a new way of treating both infection and inflammation without using antibiotics”, concludes Schmidtchen.
