title: A sustained release of lovastatin from biodegradable, elastomeric polyurethane scaffolds for enhanced bone regeneration.
abstract: Scaffolds prepared from biodegradable polyurethanes (PUR) have been investigated as a supportive matrix and delivery system for skin, cardiovascular, and bone tissue engineering. In this study, we combined reactive two-component PUR scaffolds with lovastatin (LV), which has been reported to have a bone anabolic effect especially when delivered locally, for effective bone tissue regeneration. To incorporate LV into PUR scaffolds, LV was combined with the hardener component before scaffold synthesis. The PUR scaffolds containing LV (PUR/LV) demonstrated a highly porous structure with interconnected pores, which supported in vitro cell attachment and proliferation and in vivo osteoconductive potential. The PUR/LV scaffolds showed sustained release of biologically active LV, as evidenced by the fact that LV releasates significantly enhanced osteogenic differentiation of osteoblastic cells in vitro. A study of bone formation in vivo using a rat plug defect model showed that the PUR/LV scaffolds were biocompatible. Further, locally delivered LV enhanced new bone formation in the PUR scaffolds at week 4, while there were no obvious effects at week 2. These results suggest that the sustained LV delivery system from PUR scaffolds is a potentially safe and effective device for bone regeneration.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yoshii
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Hafeman
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
authors.forename: Javier M
authors.initials: JM
authors.lastname: Esparza
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Dan M
authors.initials: DM
authors.lastname: Spengler
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Mundy
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Gutierrez
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003692:Delayed-Action Preparations; D020724:Elastomers / Q000494:pharmacology*; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects; D011140:Polyurethanes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D020724:Elastomers; D011140:Polyurethanes; D008148:Lovastatin