rhBMP-collagen sponges as osteoinductive devices: effects of in vitro sponge characteristics and protein pI on in vivo rhBMP pharmacokinetics.
Osteoinductive devices, comprised of biodegradable collagen scaffolds and recombinant human Bone Morphogenetic Proteins (rhBMPs), are being currently pursued for local bone induction. To better understand the biological performance of such devices, we have carried out a series of studies to investigate the effects of sponge properties and protein structural features on the pharmacokinetics of implanted rhBMPs. The results indicated little dependence of the rhBMP-2 pharmacokinetics on the in vitro determined sponge properties. The protein isoelectric point (pI), on the other hand, was found to significantly affect the initial implant retention of rhBMPs, but not the subsequent pharmacokinetics. A 100-fold difference in the implant-retained dose could be observed depending on the type of rhBMP implanted. We conclude that protein structural features are important variables controlling in vivo pharmacokinetics of rhBMPs, and possibly the osteoinductive potency of the devices.
Genetics Institute Inc., Andover, Massachusetts 01810, USA. hasan.uludag@ualberta.ca
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H
Uludag
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W
Friess
D
D
Williams
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T
Porter
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Timony
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D'Augusta
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C
Blake
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R
Palmer
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Biron
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Wozney
D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins / Q000493:pharmacokinetics / Q000494:pharmacology*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D004337:Drug Carriers; D006801:Humans; D007526:Isoelectric Point; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011993:Recombinant Fusion Proteins; D003094:Collagen