title: Ex vivo degradation of a poly(propylene glycol-fumarate) biodegradable particulate composite bone cement.
abstract: We have developed a biodegradable particulate composite bone cement consisting of a poly(propylene glycolfumarate)-(methylmethacrylate) matrix mixed with calcium carbonate and tricalcium phosphate particulates. Previous ex vivo studies suggest that this system provides sufficient strength for a number of potential clinical applications including structural reinforcement of osseous defects, internal fixation devices for age-related fractures, and delivery of antibiotics to treat osteomyelitis. As a first step toward investigating in vivo responses to this material, we studied the influence of varied concentrations of crosslinker, accelerator, and free radical on the mechanical properties of the cement. We then developed an ex vivo degradation assay and correlated the mechanical properties of degrading cement with the temporal changes in chemical properties of both the cement and the bathing medium. The optimal cement formulation was composed of one-third poly(propylene glycolfumarate)-(methylmethacrylate), one-third calcium carbonate, and one-third tricalcium phosphate, and provided initial compressive strengths of up to 30 MPa and compressive moduli of up to 300 MPa. Degradation rates, measured by a decline in mechanical properties, dissolution of calcium from the cement, and change in pH of the bathing medium, could be controlled by changing the concentration of reactants in the matrix. Specifically, an increase in methylmeth-acrylate or increase in both methylmethacrylate and benzoyl peroxide was inversely proportional to the rate of degradation and directly proportional to the initial mechanical properties. The degradation products and environmental changes appear to be compatible with physiologic remodeling and therefore justify examination of the in vivo response to implantation of this material.
authors.affiliation: Department of Orthopedic Surgery, Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Frazier
authors.forename: V K
authors.initials: VK
authors.lastname: Lathi
authors.forename: T N
authors.initials: TN
authors.lastname: Gerhart
authors.forename: W C
authors.initials: WC
authors.lastname: Hayes
mesh_terms: D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001585:Benzoyl Peroxide; D001673:Biodegradation, Environmental; D001843:Bone Cements; D004337:Drug Carriers; D050723:Fractures, Bone / Q000601:surgery; D006801:Humans; D016268:Internal Fixators; D020366:Methylmethacrylate; D008768:Methylmethacrylates / Q000737:chemistry* / Q000493:pharmacokinetics; D010019:Osteomyelitis / Q000188:drug therapy; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D011409:Propylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D013718:Tensile Strength
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D004337:Drug Carriers; D008768:Methylmethacrylates; D011108:Polymers; D011409:Propylene Glycols; C106431:poly(propylene glycol-fumarate); D020366:Methylmethacrylate; D001585:Benzoyl Peroxide