<i>In vivo</i> murine model of continuous intramedullary infusion of particles—A preliminary study

Ma, Ting; Ortiz, Steven; Huang, Zhu; Ren, Pei‐Gen; Smith, Robert L.; Goodman, Stuart B.

doi:10.1002/jbm.b.31175

Cited by 20 publications

(7 citation statements)

References 44 publications

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“…Ren et al [49] using in vivo bioluminescent imaging showed systemic trafficking of macrophages to PMMA particles injected into the mouse femoral shaft. Macrophages were also found to migrate to sites with UHMWPE injection: this has been shown using either a single bolus of UHMWPE particles in the femoral shaft [50] or using a continuous infusion of UHMWPE particles through a micro-diffusion pump [22,51,52], a more clinically relevant model. The next step was to link in vivo MCP-1 secretion and macrophage recruitment in the presence of particles.…”

Section: Interfering With Ongoing Migration Ofmentioning

confidence: 97%

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

Goodman

Gibon

Pajarinen

et al. 2014

J. R. Soc. Interface.

120

148

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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.

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Section: Interfering With Ongoing Migration Ofmentioning

confidence: 97%

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

Goodman

Gibon

Pajarinen

et al. 2014

J. R. Soc. Interface.

120

148

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“…Male and female BALB/cByJ mice (8–12 weeks old) were used for the continuous femoral intramedullary polyethylene particle infusion model as previously described ( Figure 1A ) ( Ma et al, 2009 ; Lin et al, 2016 ; Pajarinen et al, 2017 ). Briefly, the mouse was administered with preoperative analgesia (0.1 mg/kg of buprenorphine, subcutaneously) and inhalation anesthesia (2% isoflurane in 100% oxygen, 1 L/min) on a warm animal surgery station.…”

Section: Methodsmentioning

confidence: 99%

Sex differences in the therapeutic effect of unaltered versus NFκB sensing IL-4 over-expressing mesenchymal stromal cells in a murine model of chronic inflammatory bone loss

Shen

Kushioka

Toya

et al. 2022

Front. Bioeng. Biotechnol.

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Wear particles from joint arthroplasties induce chronic inflammation associated with prolonged upregulation of nuclear factor kappa-B (NF-κB) signaling in macrophages and osteoclasts, which leads to osteolysis and implant loosening. Mesenchymal stromal cell (MSC)-based therapy showed great potential for immunomodulation and mitigation of osteolysis in vivo, especially in the chronic phase of inflammation. We previously generated genetically modified MSCs that secrete the anti-inflammatory cytokine interleukin 4 (IL-4) in response to NF-κB activation (NFκB-IL-4 MSCs). However, whether the impact of sexual difference in the internal environment can alter the therapeutic effects of IL-4 over-secreting MSCs that simultaneously mitigate prolonged inflammation and enhance bone formation remains unknown. This study investigated the therapeutic effects of unaltered MSCs versus NFκB-IL-4 MSCs in mitigating chronic inflammation and enhancing bone formation in male and female mice. The murine model was established by continuous infusion of polyethylene particles contaminated with lipopolysaccharide (cPE) into the medullary cavity of the distal femur for 6 weeks to induce chronic inflammation. Unaltered MSCs or NFκB-IL-4 MSCs were infused into the femoral intramedullary cavity in sex-matched groups beginning 3 weeks after primary surgery. Femurs were harvested at 6 weeks, and bone marrow density was measured with micro-computational tomography. Numbers of osteoclast-like cells, osteoblasts, and macrophages were evaluated with histochemical and immunofluorescence staining. cPE infusion resulted in severe bone loss at the surgery site, increased tartrate-resistant acid phosphatase positive osteoclasts and M1 pro-inflammatory macrophages, and decreased alkaline phosphatase expression. MSC-based therapy effectively decreased local bone loss and polarized M1 macrophages into an M2 anti-inflammatory phenotype. In females, unaltered MSCs demonstrated a larger impact in enhancing the osteogenesis, but they demonstrated similar anti-inflammatory effects compared to NFκB-IL-4 MSCs. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments in a sexually dimorphic manner, which could be an efficacious therapeutic strategy for treatment of periprosthetic osteolysis in both genders.

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“…The animals were kept in a room at 24℃, 50% humidity, and with a 12 h light/dark cycle (light from AM 7:00 to PM 7:00). The animals were randomly separated into four groups: (1) sham group (n = 8) (underwent surgery only) (2) vehicle group (n = 8) (implanted with PS particles) [36][37][38], (3) WDL 4w (n = 8, implanted with PS particles and treated with WDL for 4 weeks. 7 animals remained at the end of the experiment) and (4) WDL 8w (n = 8, treatment for 8 weeks).…”

Section: Establishing the Calvarial Particle-induced Osteolysis Modelmentioning

confidence: 99%

“…However, considerable time was spent preparing enough wear debris for these animal models, while polystyrene (PS) particles are readily available and are widely used both commercially and for biomedical research [59,60]. PS particles have been used in many animal studies to create particle-induced osteolysis animal models [36][37][38]. Furthermore, given that the size distribution and shape of PS particles are easier to control, this study used PS particles for the animal model.…”

Section: Et Al Also Indicated That Traditional Mixed Extracts Of Medi...mentioning

confidence: 99%

The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study

Chang

Lin

et al. 2022

J Orthop Surg Res

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Background Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. Methods Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. Results The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. Conclusions Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.

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In vivo murine model of continuous intramedullary infusion of particles—A preliminary study

Cited by 20 publications

References 44 publications

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

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

Sex differences in the therapeutic effect of unaltered versus NFκB sensing IL-4 over-expressing mesenchymal stromal cells in a murine model of chronic inflammatory bone loss

The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study

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