title: Effect of varied release kinetics of the osteogenic thrombin peptide TP508 from biodegradable, polymeric scaffolds on bone formation in vivo.
abstract: This study was designed to assess the influence of varied release kinetics of the osteogenic thrombin peptide TP508 from osteoconductive poly(propylene fumarate)-based (PPF) composite scaffolds on bone formation in vivo. Four classes of scaffolds were constructed with different TP508 dosages (200, 100, or 0 microg) and release kinetics (large burst release, minimal burst release, or no release) and implanted in 15.0 mm segmental defects in rabbit radii. The animals were euthanized at 12 weeks and the implants were analyzed by light microscopy, histological scoring analysis, and histomorphometric analysis. Samples from all classes displayed bone growth within the pores of the scaffold near the edges of the defect. In areas where bone was not observed, the pores were filled with mostly fibrous tissue and exhibited minimal inflammatory response for all classes. In contrast to other scaffold classes, scaffolds containing a total dose of 200 microg TP508 and exhibiting a large burst release profile showed statistically more bone formation guided along the surface of the scaffold, with these scaffolds averaging 80% of the defect length bridged with bone compared to 10% or less bridged for the other scaffold classes. These results demonstrate that the extent of in vivo bone formation in response to controlled release from PPF-composite scaffolds is determined by the release kinetics of the incorporated osteogenic peptide.
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892-MS 142, Houston, Texas 77251-1892, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hedberg
authors.forename: Henriette C
authors.initials: HC
authors.lastname: Kroese-Deutman
authors.forename: Charles K
authors.initials: CK
authors.lastname: Shih
authors.forename: Roger S
authors.initials: RS
authors.lastname: Crowther
authors.forename: Darrell H
authors.initials: DH
authors.lastname: Carney
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005650:Fumarates / Q000627:therapeutic use*; D020007:Implants, Experimental; D007700:Kinetics; D010012:Osteogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011126:Polypropylenes / Q000627:therapeutic use*; D011817:Rabbits; D013917:Thrombin / Q000008:administration & dosage / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D005650:Fumarates; D010446:Peptide Fragments; D011126:Polypropylenes; C097850:poly(propylene fumarate); D013917:Thrombin