Mouse femoral intramedullary injection model: technique and microCT scan validation.

The murine femoral intramedullary injection model is frequently used to examine the in vivo effects of biomaterials or cancer cells. The surgical technique includes a knee arthrotomy with patellar dislocation for intramedullary access. This study examined a less invasive surgical approach of direct injection of particles via the transpatellar tendon without patellar dislocation. By using polymethylmethacrylate injection and microCT scan, we found that, compared with the traditional technique, this new approach was more reproducible, less time consuming, and achieved identical volumes of intramedullary injections. Animal morbidity and the biomechanics of the joints were also improved as a result of the simplified procedure. Furthermore, our study suggested that an intramedullary volume in excess of 10 microL can lead to major vascular filling and so should be avoided.

microPET-based biodistribution of quantum dots in living mice.

UNLABELLED: This study evaluates the quantitative biodistribution of commercially available CdSe quantum dots (QD) in mice. METHODS: (64)Cu-Labeled 800- or 525-nm emission wavelength QD (21- or 12-nm diameter), with or without 2,000 MW (molecular weight) polyethylene glycol (PEG), were injected intravenously into mice (5.55 MBq/25 pmol QD) and studied using well counting or by serial microPET and region-of-interest analysis. RESULTS: Both methods show rapid uptake by the liver (27.4-38.9 %ID/g) (%ID/g is percentage injected dose per gram tissue) and spleen (8.0-12.4 %ID/g). Size has no influence on biodistribution within the range tested here. Pegylated QD have slightly slower uptake into liver and spleen (6 vs. 2 min) and show additional low-level bone uptake (6.5-6.9 %ID/g). No evidence of clearance from these organs was observed. CONCLUSION: Rapid reticuloendothelial system clearance of QD will require modification of QD for optimal utility in imaging living subjects. Formal quantitative biodistribution/imaging studies will be helpful in studying many types of nanoparticles, including quantum dots.

Systemic trafficking of macrophages induced by bone cement particles in nude mice.

Macrophages play an important role in the biological response to wear particles, which can result in periprosthetic osteolysis and implant loosening. In this study, we demonstrate that polymer particles induce systemic trafficking of macrophages by non-invasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 10% (w/v) Simplex bone cement (BC) suspensions or saline (PBS). Reporter RAW264.7 macrophages which stably expressed the bioluminescent reporter gene fluc, and the fluorescence reporter gene gfp, were injected intravenously. Bioluminescence imaging was performed immediately and periodically at 2-day intervals until day 14. Compared to the non-operated contralateral femora, the bioluminescent signal of femora injected with BC suspension increased 4.7+/-1.6 and 7.8+/-2.9-fold at day 6 and 8, respectively. The same values for PBS group were 1.2+/-0.2 and 1.4+/-0.5, respectively. The increase of bioluminescence of the BC group was significantly greater than the PBS group at day 8 (p<0.05) and day 6 (p<0.1). Histological study confirmed the presence of reporter macrophages within the medullary canal of mice that received cement particles. Modulation of the signaling mechanisms that regulate systemic macrophage trafficking may provide a new strategy for mitigating the chronic inflammatory response and osteolysis associated with wear debris.