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Biofilm with antimicrobial, antifungal properties for implants; nerve-like polymer network uses biological mechanisms

Biofilm with antimicrobial, antifungal properties for implants; nerve-like polymer network uses biological mechanisms

29-Sep-15

The implantation of medical devices is not without risks. Besides occurrence of bacterial or fungal infections, the body's strong immune response may lead to the rejection of the implant. Researchers at Unit 1121 "Biomaterials and Bio-engineering" (Inserm/Strasbourg University) have succeeded in creating a biofilm with antimicrobial, antifungal and anti-inflammatory properties. It may be used to cover titanium implants (orthopaedic prostheses, pacemakers, etc) prevent or control post-operative infections. Other frequently used medical devices that cause numerous infectious problems, such as catheters, may also benefit. These results have been published in the journal Advanced Healthcare Materials. Implantable medical devices (prosthesis/pacemakers) are an ideal interface for micro-organisms, which can easily colonize their surface. As such, bacterial infection may occur and lead to an inflammatory reaction. This may cause the implant to be rejected. These infections are mainly caused by bacteria such as Staphylococcus aureus, originating in the body, and Pseudomonas aeruginosa. These infections may also be fungal or caused by yeasts. The challenge presented by implanting medical devices in the body is preventing the occurrence of these infections, which lead to an immune response that compromises the success of the implant. Antibiotics are currently used during surgery or to coat certain implants. However, the emergence of multi-resistant bacteria now restricts their effectiveness.
It is within this context that researchers have developed a biofilm with antimicrobial and anti-inflammatory properties. Researchers have used a combination of two substances: polyarginine (PAR) and hyaluronic acid (HA), to develop and create a film invisible to the naked eye (between 400 and 600 nm thick) that is made of several layers. As arginine is metabolised by immune cells to fight pathogens, it has been used to communicate with the immune system to obtain the desired anti-inflammatory effect. Hyaluronic acid, a natural component of the body, was also chosen for its biocompatibility and inhibiting effect on bacterial growth. The film is also unique due to the fact that it embeds natural antimicrobial peptides, in particular catestatin, to prevent possible infection around the implant. This is an alternative to the antibiotics that are currently used. As well as having a significant antimicrobial role, these peptides are not toxic to the body that they are secreted into. They are capable of killing bacteria by creating holes in their cellular wall and preventing any counter-attack on their side.
In this study researchers show that poly(arginine), associated with hyaluronic acid, possesses microbial activity against Staphylococcus aureus (S. aureus) for over 24 hours. "In order to prolong this activity, we have placed a silver-coated precursor before applying the film. Silver is an anti-infectious material currently used on catheters and dressings. This strategy allows us to extend antimicrobial activity in the long term" explains Philippe Lavalle, Research Director at Inserm. The results from numerous tests performed on this new film shows that it reduces inflammation and prevents the most common bacterial and fungal infections. On the one hand, researchers demonstrate, through contact with human blood, that the presence of the film on the implant suppresses the activation of inflammatory markers normally produced by immune cells in response to the implant. Moreover, "the film inhibits the growth and long-term proliferation of staphylococcal bacteria (Staphylococcus aureus), yeast strains (Candida albicans) or fungi (Aspegillus fumigatus) that frequently cause implant-related infection" emphasises Philippe Lavalle. Researchers conclude that this film may be used in vivo on implants or medical devices within a few years to control the complex microenvironment surrounding implants and to protect the body from infection. This work received the financial support from Institut Carnot MICA and from European Commission with the "Immodgel" project.

Using a succession of biological mechanisms, Sandia National Laboratories researchers have created linkages of polymer nanotubes that resemble the structure of a nerve, with many out-thrust filaments poised to gather or send electrical impulses. "This is the first demonstration of naturally occurring proteins assembling chemically created polymers into complex structures that modern machinery can't duplicate," said Sandia National Laboratories researcher George Bachand. Currently, rigid electrodes that cause inflammation are used to penetrate nerve tissue trying to communicate with an artificial limb, he explained. Instead, in a future application, the polymer network could be used extend the nerve, providing a gentler prosthetic interface.
Creation of the neural structure, unachievable by normal manufacturing techniques, begins by altering the behavior of kinesin motor proteins — biological machines found in every human cell. These tiny motors normally tote material from one part of a cell to another, carrying them on what, in video graphics, is portrayed as a vertical body with two legs. These stride along protein microtubules that form the cell structure. The purposefulness of the motors resembles that of the spellbound brooms, relentlessly carrying buckets of water up the castle stairs. Turning natures' machinery on its head, the researchers used known techniques to glue the "shoulders" of kinesin motors to a glass substrate. This prevents their bodies from travelling, but their "legs" above them continue their vigorous movements. These pass microtubules above them, like an audience crowdsurfing entertainers on upraised hands. In the next laboratory step, these travelling protein microtubules, microns in length, encounter relatively large polymer spheres, tens of microns in diameter, inserted by the researchers.
"At that point, we have structures that want to do work- the kinesin-powered microtubules - and something they want to do work on-the spheres," Paxton said. The microtubules, pre-coated with a sticky substance, pinch off polymer nanotubes from the sphere that lengthen as the kinesin motors travel on. The process resembles stringy strands of cheese lengthening as a piece of pizza is removed from a pan, said Paxton. As the nanotubes lengthen and crosslink, they form structures complex enough to bring to mind the lights of a city seen at night from an airplane at high altitude. The networks range from hundreds of micrometers to tens of millimeters in total size and are composed of tubes 30 to 50 nanometers in diameter.
The goal of this work is to make an artificial, highly branched neural structure. The next step is, can we wire them together? The answer is, the motors should do it naturally. And two such networks, joined together, would have self-healing built into them. The motors never stop running until they run out of fuel. A neural branch breaks, and then a motor can act on that area to produce a new branch." The insertion of quantum dots also proved stable, which means that light could be used to carry information through the structure as well as electricity.

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