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FRIMEDBIO-Fri med.,helse,biol

Multifunctional tannic acid nanocoatings for bone-anchored implants with reduced infection risk

Alternative title: Multifunksjonelle nanobelegg av garvesyre på beinforankrede implantater for redusert infeksjonsrisiko

Awarded: NOK 8.0 mill.

Bone-anchored implants, such as dental implants and joint replacements, are implants with a direct anchorage between the implant surface and the bone tissue. To fully function, these implants are dependent on an immune response which results in bone cells adhering to the implant surface and forming new bone tissue that anchors the implant into the existing bone. However, the function and long-term stability of these implants can be jeopardised by the presence of bacteria. Bacterial infections around implants are often very persistent and difficult to treat. With the increasing threat of antibiotic resistant bacteria, current treatment strategies for infected implants are likely to be even less effective in the future. Even today, it is often necessary to remove the affected implant entirely to clear the infection in the surrounding tissues, which can obviously be a very painful and disturbing experience for the patient. This interdisciplinary research project focuses on tackling bacterial infections on implant surfaces using plant polyphenols, a group of antioxidant and antibacterial compounds that are found in several plant-based foods, such as tea, chocolate and wine. We will develop thin polyphenolic coatings on the implant surface and evaluate their ability to prevent bacterial infections and inflammation around bone-anchored implants. Our main aim is to understand the reaction mechanisms resulting in the coating formation and how the reaction conditions affect the physical and chemical properties of the polyphenolic coatings. By studying the coating formation in different chemical environments, a new and efficient route for coating titanium implant surfaces with tannic acid, which is a common plant polyphenol, was developed. Crosslinking the tannic acid molecules with silicic acid allowed for continuous coating formation process and improved control over the coating thickness. The developed polyphenolic coatings altered the physical and chemical surface properties of titanium implants and changed the way proteins interact with the implant surface. The polyphenolic coatings can also release active polyphenolic molecules to the surrounding tissues. As the biological effect of the polyphenols is strongly dependent on their chemistry, thorough understanding of the chemical properties of the formed coatings is essential for designing infection-resistant implant surfaces that can promote wound healing and bone formation around the implant, while simultaneously reducing bacterial colonisation on the implant surface.

For bone-anchored implants, such as dental implants and joint replacements, formation of direct anchorage between the prosthetic material and bone tissue is essential for functionality and long-term stability of the implant. Implant integration is dependent on the appropriate immune response towards the foreign material, resulting in cell-adhesion and regeneration of vital bone tissue surrounding the implant. However, implant integration can be jeopardised by the presence of bacteria, which can cause persistent biomaterial-associated infections that are particularly difficult to treat and often require removal of the implant. Current strategies to control and treat such infections are insufficient and their effectiveness is likely to diminish even further in the imminent era of antibiotic resistance. In this interdisciplinary research project, we focus on developing and thoroughly characterising a bioinspired surface modification strategy based on substrate-independent surface polymerisation of tannic acid, an antioxidant and antibacterial plant polyphenol, to tackle biomaterial-associated infections. We aim to yield fundamental understanding of 1) the reaction mechanism of the in situ surface polymerisation reaction of tannic acid, 2) role of reaction conditions on physical and chemical coating properties, and 3) structure-property relationship involved in governing the biological response towards tannic acid nanocoatings formed under varying reaction conditions. Building on this knowledge, we aim to provide important insight into designing clinically feasible infection-resistant polyphenol-coated implant surfaces that can modulate the wound healing response elicited by the host tissue upon implant placement while simultaneously preventing bacterial colonisation on the implant surface, and thus, reduce the need for prophylactic antibiotics in connection with surgical implantation of biomedical devices.

Funding scheme:

FRIMEDBIO-Fri med.,helse,biol