Orthopaedic implant failure: aseptic implant loosening–the contribution and future challenges of mouse models in translational research

Abstract

Aseptic loosening as a result of wear debris is considered to be the main cause of long-term implant failure in orthopaedic surgery and improved biomaterials for bearing surfaces decreases significantly the release of micrometric wear particles. Increasingly, in-depth knowledge of osteoimmunology highlights the role of nanoparticles and ions released from some of these new bearing couples, opening up a new era in the comprehension of aseptic loosening. Mouse models have been essential in the progress made in the early comprehension of pathophysiology and in testing new therapeutic agents for particle-induced osteolysis. However, despite this encouraging progress, there is still no valid clinical alternative to revision surgery. The present review provides an update of the most commonly used bearing couples, the current concepts regarding particle-cell interactions and the approaches used to study the biology of periprosthetic osteolysis. It also discusses the contribution and future challenges of mouse models for successful translation of the preclinical progress into clinical applications.

NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases

“…or endogenous (necrotic cells) stimuli. Immune cells recognize the inflammatory stimuli to activate several cellular signaling including nuclear factor-κB (NF-κB) (Cordova et al, 2014). NF-κB is a master transcriptional factor in regulation of the inflammatory response and bone-remodeling process (Lin, Tamaki, et al, 2014; Novack, 2011).…”

Pro‐osteoclastic in vitro effect of Polyethylene‐like nanoparticles: Involvement in the pathogenesis of implant aseptic loosening

“…FPN are internalized by macrophages and are able to promote osteoclast differentiation. An assessment of these two key events described in particle‐induced inflammation and osteolysis will be necessary in preclinical animal models . The first objective of in vivo assessment should be to determine if FPN are able to induce inflammatory and osteolytic changes in a bone site.…”

“…To address this subject, the use of the cost‐effective calvaria mouse model appears very appropriate as a first step. This model allows a quick assessment of both inflammation and osteolysis in an orthotopic site . Our group recently reported inflammatory and osteolytic changes starting at day 7 after surgical microparticle (6 μm) implantation .…”

“…Based on these reports, it may possible to carry out the implantation of these FPN in a bone site by transcutaneous injection. The second step will be an infusion of FPN into the epiphysis of a long bone using the continuous infusion femoral model, the most clinically relevant mouse model in this field …”

Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies

“…This procedure leads to an improvement of pain and joint functionality, and the number of THR and TKR amounts to 1.5 million every year [1,2,3]. Given the increase of the life span and of implants in young active patients, this number is expected to increase even further in the coming years (nearly 5% per year) [3,4] and, in 2030, THR will have increased by 154% worldwide [5]. Although total joint replacement (TJR) still represents the most employed and the most successful surgical orthopedic practice, it can fail despite the advances in surgical techniques and materials used for the prostheses.…”