TY - JOUR
T1 - Non-invasive screening method for simultaneous evaluation of in vivo growth factor release profiles from multiple ectopic bone tissue engineering implants
AU - Kempen, Diederik H.R.
AU - Lu, Lichun
AU - Classic, Kelly L.
AU - Hefferan, Theresa E.
AU - Creemers, Laura B.
AU - Maran, Avudaiappan
AU - Dhert, Wouter J.A.
AU - Yaszemski, Michael J.
N1 - Funding Information:
The authors gratefully acknowledge the National Institutes of Health (R01 AR45871 and R01 EB03060) and The Netherlands Organization for Health Research and Development ZonMW (Agiko 920-03-325) and Stichting Anna Fonds for the financial support. The authors thank Dr. Shanfeng Wang and Mr. James Greutzmacher from the Tissue Engineering and Biomaterials laboratory and Mr. Rodney Landsworth and Mr. Al Amundson from Radiation Safety at Mayo Clinic for their contributions to this work.
PY - 2008/8/25
Y1 - 2008/8/25
N2 - The purpose of this study was to develop and validate a screening method based on scintillation probes for the simultaneous evaluation of in vivo growth factor release profiles of multiple implants in the same animal. First, we characterized the scintillation probes in a series of in vitro experiments to optimize the accuracy of the measurement setup. The scintillation probes were found to have a strong geometric dependence and experience saturation effects at high activities. In vitro simulation of 4 subcutaneous limb implants in a rat showed minimal interference of surrounding implants on local measurements at close to parallel positioning of the probes. These characteristics were taken into consideration for the design of the probe setup and in vivo experiment. The measurement setup was then validated in a rat subcutaneous implantation model using 4 different sustained release carriers loaded with 125I-BMP-2 per animal. The implants were removed after 42 or 84 days of implantation, for comparison of the non-invasive method to ex vivo radioisotope counting. The non-invasive method demonstrated a good correlation with the ex vivo counting method at both time-points of all 4 carriers. Overall, this study showed that scintillation probes could be successfully used for paired measurement of 4 release profiles with minimal interference of the surrounding implants, and may find use as non-invasive screening tools for various drug delivery applications.
AB - The purpose of this study was to develop and validate a screening method based on scintillation probes for the simultaneous evaluation of in vivo growth factor release profiles of multiple implants in the same animal. First, we characterized the scintillation probes in a series of in vitro experiments to optimize the accuracy of the measurement setup. The scintillation probes were found to have a strong geometric dependence and experience saturation effects at high activities. In vitro simulation of 4 subcutaneous limb implants in a rat showed minimal interference of surrounding implants on local measurements at close to parallel positioning of the probes. These characteristics were taken into consideration for the design of the probe setup and in vivo experiment. The measurement setup was then validated in a rat subcutaneous implantation model using 4 different sustained release carriers loaded with 125I-BMP-2 per animal. The implants were removed after 42 or 84 days of implantation, for comparison of the non-invasive method to ex vivo radioisotope counting. The non-invasive method demonstrated a good correlation with the ex vivo counting method at both time-points of all 4 carriers. Overall, this study showed that scintillation probes could be successfully used for paired measurement of 4 release profiles with minimal interference of the surrounding implants, and may find use as non-invasive screening tools for various drug delivery applications.
KW - Controlled drug delivery
KW - Method validation
KW - Non-invasive screening
KW - Radiolabelled growth factor
KW - Scintillation detector
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U2 - 10.1016/j.jconrel.2008.05.004
DO - 10.1016/j.jconrel.2008.05.004
M3 - Article
C2 - 18554743
AN - SCOPUS:48749096787
SN - 0168-3659
VL - 130
SP - 15
EP - 21
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -