The purpose of this study is to develop and validate a novel murine model of continuous particle infusion and an intramedullarv orthopaedic implant in order to understand fundamental biological processes involved in particle induced periprosthetic bone loss (osteolvsis).
Specific aim #1. To optimize the number of polystyrene blue microspheres (PS) or clinically relevant polyethylene particles (PE) 0.5 urn in diameter, in different concentrations, delivered by an infusion pump connected to a hollow CP titanium rod and tubing over a 4-week period.
Specific aim #2. To develop and optimize an organ culture model using continuous infusion of PS or PE particles into an explanted mouse femur containing a hollow titanium rod connected to an infusion pump and tubing over a 4-week period.
Specific aim #3. To develop, optimize and validate an in vivo model employing continuous infusion of polyethylene particles into the mouse femur containing a hollow titanium intramedullary rod connected to an infusion pump. Three novel models will be introduced. In the first model, different concentrations of 0.5 urn PS or PE particles will be continuously infused into a gathering vessel over a 4-week period using an Alzet infusion pump, tubing and 10 mm long 23 gauge hollow titanium rod. In the second model, an organ culture system will be maintained, consisting of PS or PE particles continuously infused into the explanted murine femur containing a hollow rod connected to an infusion pump. The number of infused particles will be assessed by quantifying the residual particles in the tubing, in the gathering vessel and in the explanted femur using SEM and histomorphometry at 2-weekly intervals. The in vivo experiment will develop and validate a murine model in which clinically relevant PE particles are continuously infused into the femur containing a 10 mm long 23 gauge hollowed titanium rod using an infusion pump and tubing. The harvested femora will be assessed using radiographs, micro CT and histomorphometric analysis. The above experiments will facilitate future research on a) the biological mechanisms of periprosthetic bone loss (osteolysis) using wild type and genetically altered murine species b) the biological effects of novel materials with different particle characteristics and c) potential pharmacologic interventions to mitigate periprosthetic bone loss due to wear debris.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR053189-02
Application #
7140622
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Panagis, James S
Project Start
2005-09-23
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$201,081
Indirect Cost
Name
Stanford University
Department
Surgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Córdova, Luis A; Loi, Florence; Lin, Tzu-Hua et al. (2017) CCL2, CCL5, and IGF-1 participate in the immunomodulation of osteogenesis during M1/M2 transition in vitro. J Biomed Mater Res A 105:3069-3076
Goodman, Stuart B; Gomez Barrena, Enrique; Takagi, Michiaki et al. (2009) Biocompatibility of total joint replacements: A review. J Biomed Mater Res A 90:603-18
Ma, Ting; Ortiz, Steven G; Huang, Zhinong et al. (2009) In vivo murine model of continuous intramedullary infusion of particles--a preliminary study. J Biomed Mater Res B Appl Biomater 88:250-3
Ortiz, Steven G; Ma, Ting; Epstein, Noah J et al. (2008) Validation and quantification of an in vitro model of continuous infusion of submicron-sized particles. J Biomed Mater Res B Appl Biomater 84:328-33
Ren, Pei-Gen; Lee, Sheen-Woo; Biswal, Sandip et al. (2008) Systemic trafficking of macrophages induced by bone cement particles in nude mice. Biomaterials 29:4760-5
Ma, Ting; Huang, Zhinong; Ren, Pei-Gen et al. (2008) An in vivo murine model of continuous intramedullary infusion of polyethylene particles. Biomaterials 29:3738-42
Goodman, Stuart B (2007) Wear particles, periprosthetic osteolysis and the immune system. Biomaterials 28:5044-8
Goodman, Stuart B; Ma, Ting; Chiu, Richard et al. (2006) Effects of orthopaedic wear particles on osteoprogenitor cells. Biomaterials 27:6096-101