Adsorption and release properties of growth factors from biodegradable implants.
The present investigation was performed to study the adsorption behavior of growth factors and their release characteristics from biodegradable implants in an in vitro study. We investigated the stability of growth factors administered on various scaffolds. We used porous tricalcium phosphate ceramics (alpha-TCP), a neutralized glass-ceramics (GB9N), a composite (polylactid/-glycolid/GB9N), and solvent dehydrated human bone as carriers. Block shaped scaffolds (sized: 7 x 7 x 10 mm) were loaded with 5 microg of either bone morphogenetic protein (rxBMP-4), basic fibroblast growth factor (rh-bFGF), or vascular endothelial growth factor (rh-VEGF) solved in 150 microL PBS. The growth factors were labeled with Iodine125 (I-125) for detecting the adsorbed and released amount of growth factors by counting the samples for total I-125 activity. We observed that the adsorption of these growth factors seems to depend on two different parameters: first on the nature of the tested material, and second on the growth factors on their own. The release kinetics of the growth factors from the biodegradable implants can be described as a two phase process-a very rapid release during the first hours by an elution of not adsorbed protein, followed by a specific release, which depends upon the chemical/physical interaction of the material and the growth factor used. Analyzing the eluted proteins on SDS-PAGEs rh-VEGF was degraded into a smaller fragment with a size of around 15 kDa, while rxBMP-4 and rh-bFGF showed a complete degradation into fragments smaller than 3 kDa after more than 3 days. Although this in vitro study suggests that biodegradable implants might be successfully used as carriers for osteogenic growth factors, the different release kinetics as well as the alteration of their molecular structure including loss of biological activity should be considered.
Ziegler
J
J
Orthopaedic Department (RKU), University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Mayr-Wohlfart
U
U
Kessler
S
S
Breitig
D
D
Günther
K-P
KP
D020341:Absorbable Implants / Q000592:standards*; D000327:Adsorption; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000493:pharmacokinetics; D001842:Bone and Bones; D002130:Calcium Phosphates; D002516:Ceramics; D003188:Composite Resins; D004337:Drug Carriers / Q000737:chemistry / Q000592:standards; D004355:Drug Stability; D016228:Endothelial Growth Factors / Q000493:pharmacokinetics; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics; D006133:Growth Substances / Q000493:pharmacokinetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000493:pharmacokinetics; D007700:Kinetics; D008222:Lymphokines / Q000493:pharmacokinetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014982:Xenopus laevis
D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D003188:Composite Resins; D004337:Drug Carriers; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D016222:Fibroblast Growth Factor 2; C485838:calcium phosphate, monobasic, anhydrous; C023506:Glass ceramics; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous