Mesenchymal stem cells in the aseptic loosening of total joint replacements

Abstract

Peri-prosthetic osteolysis remains as the main long-term complication of total joint replacement surgery. Research over four decades has established implant wear as the main culprit for chronic inflammation in the peri-implant tissues and macrophages as the key cells mediating the host reaction to implant-derived wear particles. Wear debris activated macrophages secrete inflammatory mediators that stimulate bone resorbing osteoclasts; thus bone loss in the peri-implant tissues is increased. However, the balance of bone turnover is not only dictated by osteoclast-mediated bone resorption but also by the formation of new bone by osteoblasts; under physiological conditions these two processes are tightly coupled. Increasing interest has been placed on the effects of wear debris on the cells of the bone-forming lineage. These cells are derived primarily from multipotent mesenchymal stem cells (MSCs) residing in bone marrow and the walls of the microvasculature. Accumulating evidence indicates that wear debris significantly impairs MSC-to-osteoblast differentiation and subsequent bone formation. In this review, we summarize the current understanding of the effects of biomaterial implant wear debris on MSCs. Emerging treatment options to improve initial implant integration and treat developing osteolytic lesions by utilizing or targeting MSCs are also discussed.

Metal‐Specific Biomaterial Accumulation in Human Peri‐Implant Bone and Bone Marrow

“…This adds weight to the clinical relevance of many studies investigating the osteogenic and inflammationinducing potential of osteoblastic cells following Co exposure in vitro and the derived implication on its direct involvement in the pathomechanism of osteolysis. [46][47][48] Furthermore, it must be considered that not only Co and Cr account for the overall metal exposure in peri-implant BM. Particularly in the adjacent BM of stemmed prostheses and multicomponent revision implants, large quantities of particles consisting of Ti, Ta, and Zr were detected both intracellularly and extracellularly in the micron-, submicron-and nanorange.…”

The USP14–NLRC5 pathway inhibits titanium particle–induced osteolysis in mice by suppressing NF-κB and PI3K/AKT activities

“…The biotoxicity, biocompatibility and mechanics properties had been greatly renovated with the regeneration of prosthesis materials, but the aseptic loosening caused by wear particles still remain unsolved [1]. Upon activation by wear particles, macrophages release a series of proinflammatory cytokine like TNF-α, IL-6 and IL-1β which induce the recruitment of macrophage and trigger the activation of osteoclast precursors [4,5]. It's been reported that the interaction between TNF-α and RANKL promotes osteoclast activity associated with wear debris [14].…”

“…Monocyte/macrophage lineage cells play a significant role in immunology, tissue homeostasis, disease pathogenesis and inflammation. Macrophages are the key players in the response to wear particles from prosthesis [5]. Macrophages, upon activation by wear particles, release a series of proinflammatory cytokine such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) which recruit and activate osteoclast precursors and trigger inflammatory bone resorption.…”

TI-6AL-4V alloy and β-tricalcium phosphate-based systems for in vitro study of mesenchymal stem cell functions at implant–tissue interface

“…In arthroplasty and bone tissue engineering, in vitro testing of the interactions between MSC and diverse orthopaedic biomaterials represents an obligatory step [8][9][10]. All biomechanical, biochemical and biological approaches that enhance bone integration and provide MSC with good functional capacity are a step forward in the endeavours to achieve life-long prosthetic replacement [11]. To this end, there is a need for an effective in vitro model for studying MSC functions at implant-tissue interface.…”