Targeting regulation of stem cell exosomes: Exploring novel strategies for aseptic loosening of joint prosthesis

Abstract

Periprosthetic osteolysis is a major long-term complication of total joint replacement. A series of biological reactions caused by the interaction of wear particles at the prosthesis bone interface and surrounding bone tissue cells after artificial joint replacement are vital reasons for aseptic loosening. Disorder of bone metabolism and aseptic inflammation induced by wear particles are involved in the occurrence and development of aseptic loosening of the prosthesis. Promoting osteogenesis and angiogenesis and mediating osteoclasts and inflammation may be beneficial in preventing the aseptic loosening of the prosthesis. Current research about the prevention and treatment of aseptic loosening of the prosthesis focuses on drug, gene, and stem cell therapy and has not yet achieved satisfactory clinical efficacy or has not been used in clinical practice. Exosomes are a kind of typical extracellular vehicle. In recent years, stem cell exosomes (Exos) have been widely used to regulate bone metabolism, block inflammation, and have broad application prospects in tissue repair and cell therapy.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty

“…New studies have also shown that MSCs can inhibit osteoclasts, and stem cell exosomes can block osteoclast activation or differentiate into osteoblasts to regulate bone remodeling. BMSC derived exosomes have been demonstrated to activate osteogenesis and downregulate osteoclastogenesis through multiple pathways ( Ma et al., 2022 ).…”

Roles of inflammatory cell infiltrate in periprosthetic osteolysis

“…Consequently, accumulating particle debris activates macrophages CD68 + (45, 88, 98-100). The activation of macrophages at the implant-tissue interface can occur by "failed phagocytosis" of indigestible wear particles to become foreign body giant cells (4,24,76,98,101) or by cell contact through toll-like receptors (TLRs) 2 and 4, CD11b, and CD14 (4,22,38,102). In aseptic loosening, the immune reaction was usually observed in synovial membrane-line interface tissues by co-localizing polymeric particles and macrophages (97, 98, 103).…”

“…The macrophage activation results in the release of inflammatory cytokines, chemokines, reactive oxygen species (ROS), tumor necrosis factor-a (TNF-a), interleukin (IL)-1b, IL-6, IL-17, and interferon-g (IFN-g), which are potent contributors to bone resorption (2,4,22,102,(104)(105)(106)(107)(108). TLRs and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) can recognize exogenous pathogenassociated molecular patterns (PAMPs) and endogenous molecules created during inflammation and tissue remodeling.…”

“…There is strong evidence that osteoclasts play a significant role in particle-induced periprosthetic osteolysis. Regardless of the biological mechanisms leading to osteolysis, osteoclasts are the central bone-resorbing cells (149), and the intensity depends on the number, activity, and survival of osteoclasts (38,102).…”

Titanium particles inhibit bone marrow mesenchymal stem cell osteogenic differentiation through the MAPK signaling pathway

“…The mechanical strength of metal materials is closer to that of human bones, which makes metal materials ideal for the reconstruction of human mechanics. At present, after many years of clinical application of orthopedic metal materials for medical use, there are still many problems, such as autoimmune reaction after material implantation, mismatch between elastic modulus and host bone, nonfusion between bone and interface, as well as the impact of metal corrosion and wear [ 4 , 5 ].…”