title: Long-term cell-mediated protein release from calcium phosphate ceramics.
abstract: Efficient delivery of growth factors from carrier biomaterials depends critically on the release kinetics of the proteins that constitute the carrier. Immobilizing growth factors to calcium phosphate ceramics has been attempted by direct adsorption and usually resulted in a rapid and passive release of the superficially adherent proteins. The insufficient retention of growth factors limited their bioavailability and their efficacy in the treatment of bone regeneration. In this study, a coprecipitation technique of proteins and calcium phosphate was employed to modify the delivery of proteins from biphasic calcium phosphate (BCP) ceramics. To this end, tritium-labeled bovine serum albumin ([(3)H]BSA) was utilized as a model protein to analyze the coprecipitation efficacy and the release kinetics of the protein from the carrier material. Conventional adsorption of [(3)H]BSA resulted in a rapid and passive release of the protein from BCP ceramics, whereas the coprecipitation technique effectively prevented the burst release of [(3)H]BSA. Further analysis of the in vitro kinetics demonstrated a sustained, cell-mediated release of coprecipitated [(3)H]BSA from BCP ceramics induced by resorbing osteoclasts. The coprecipitation technique described herein, achieved a physiologic-like protein release, by incorporating [(3)H]BSA into its respective carriers, rendering it a promising tool in growth factor delivery for bone healing.
authors.affiliation: Department of Clinical Research, Group for Bone Biology and Orthopedic Research, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Ellen
authors.initials: E
authors.lastname: Wernike
authors.forename: Willy
authors.initials: W
authors.lastname: Hofstetter
authors.forename: Yuelian
authors.initials: Y
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Sebald
authors.forename: Daniel
authors.initials: D
authors.lastname: Wismeijer
authors.forename: Ernst B
authors.initials: EB
authors.lastname: Hunziker
authors.forename: Klaus-Arno
authors.initials: KA
authors.lastname: Siebenrock
authors.forename: Frank M
authors.initials: FM
authors.lastname: Klenke
mesh_terms: D000135:Acid Phosphatase / Q000737:chemistry; D000327:Adsorption; D000818:Animals; D001562:Benzimidazoles; D001672:Biocompatible Materials / Q000737:chemistry; D001854:Bone Marrow Cells / Q000378:metabolism*; D018786:Bone Substitutes / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry*; D005456:Fluorescent Dyes; D007527:Isoenzymes / Q000737:chemistry; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D000071681:Tartrate-Resistant Acid Phosphatase; D016707:Tissue Fixation; D014316:Tritium
chemical_list: D001562:Benzimidazoles; D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D005456:Fluorescent Dyes; D007527:Isoenzymes; D011506:Proteins; D014316:Tritium; D012710:Serum Albumin, Bovine; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C017807:bisbenzimide ethoxide trihydrochloride