Non-invasive screening method for simultaneous evaluation of in vivo growth factor release profiles from multiple ectopic bone tissue engineering implants.
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 (125)I-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.
Tissue Engineering and Biomaterials Laboratory, Departments of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Diederik H R
DH
Kempen
Lichun
L
Lu
Kelly L
KL
Classic
Theresa E
TE
Hefferan
Laura B
LB
Creemers
Avudaiappan
A
Maran
Wouter J A
WJ
Dhert
Michael J
MJ
Yaszemski
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D015902:Gamma Cameras; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta