Novel methods to prevent prosthetic joint infection (PJI) – NoMorePJI Lundbeck Foundation  in collaboration with University  of Copenhagen 2021-2023 NCSRD Budget: 20.000 Euros. Scientist in charge: Michael Arkas.

Implants – but without the associated infections

If a knee or hip is worn, the answer may be to have a prosthetic fitted – an implant. This restores mobility in many, but in some cases getting a new hip or knee prosthesis can turn into a long and painful nightmare if the prosthesis and the peri-prosthetic bone tissue gets infected with bacteria. Infections of this kind can potentially destroy the bone tissue intended to bond with the implant. In some cases, the prosthetic device needs to be removed, and the bone damage caused by the infection can complicate insertion of a new implant. Such implant-associated infections are usually difficult to treat with antibiotics. This project aims to develop two new methods that can prevent the development of prosthetic joint infection (PJI).

A new nanomaterial will be developed and coated to the surface of prosthetic joints. The nanomaterial, which can bind and burst release extreme high amount of antibiotics, enabling cure of an incipient infection. will be tested in a new mini-pig PJI animal model. Development of the mini-pig model is a central part of the present project. The new nanomaterial will be investigated with respect to biocompatibility, toxicity, release profile of antimicrobials and antimicrobial efficacy.In this framework the biochemical grounds for known infections associated with implants in humans will also be studied. The bacteria causing prosthetic joint infection will destroy the bone tissue around the prosthesis and a key question of the present project is; what is causing the bone destruction? The common textbook theory, which is based on the RANKL molecule, might be wrong as it builds on too simple study setups in cells and mice. The project hypothesizes that the bone destruction is caused by enzymatic breakdown due to activation of specific inflammatory proteolytic enzymes. The project will study if blocking of enzymatic activity can prevent bacterial distribution in distant tissues and, thereby, increase the effect of local antibiotics.