Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

Abstract

ReviewCite this article: Goodman SB et al. 2014 Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. J. R. Soc. Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 ( pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-kB) by delivery of an NF-kB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants.

Probiotics protect mice from CoCrMo particles-induced osteolysis

“…2 Modulation of macrophages from the proinflammatory M1 to the anti-inflammatory M2 phenotype is considered as an important way to mitigate wear particle-induced osteolysis. 1 We next investigated whether L. casei treatment affected the phenotypes of macrophages. The levels of M1 markers TNF-α, IL-6 and iNOS in local tissue were upregulated in the CoPs-treated group compared with the sham group ( Figure 5A).…”

“…The concept of macrophage polarization was recently considered to play a role in the pathological mechanism of aseptic loosening. 1,6,7 M1 proinflammatory macrophages were activated in response to wear debris dominating the M2 antiinflammatory response. M1 macrophages secrete primarily proinflammatory cytokines such as TNF-α, IL-6 and IL-1β, while M2 macrophages produce anti-inflammatory mediators such as IL-4, IL-10 and IL-13.…”

“…[1][2][3] However, wear particle-induced osteolysis and the subsequent aseptic loosening remain the most common causes of arthroplasty failure and revision surgery in the med-to long term. 4 Wear debris that is generated from implant components plays a key role in aseptic loosening.…”

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening

“…38,57 However, these strategies were ineffective in patients and may lead to adverse effects on other organs. The inhibition of TNF may inhibit responses to harmful agents, including bacteria and other infective agents.…”

“…Bisphosphonate, an inhibitor of osteoclast-mediated bone resorption, may result in the impairment of fracture healing, mandibular lesions, pathologic femoral fractures, and other adverse events. 57 Thus, new strategies for treating osteolysis induced by particles are urgently needed. Considering that SIRT1 is a crucial regulator of bone homeostasis and functions as a protective factor against metal nanoparticle-induced inflammatory responses and osteolysis both in vitro and in vivo, SIRT1 may represent a potential therapeutic target in the treatment of aseptic loosening.…”