title: Oxidatively Degradable Poly(thioketal urethane)/Ceramic Composite Bone Cements with Bone-Like Strength.
abstract: Synthetic bone cements are commonly used in orthopaedic procedures to aid in bone regeneration following trauma or disease. Polymeric cements like PMMA provide the mechanical strength necessary for orthopaedic applications, but they are not resorbable and do not integrate with host bone. Ceramic cements have a chemical composition similar to that of bone, but their brittle mechanical properties limit their use in weight-bearing applications. In this study, we designed oxidatively degradable, polymeric bone cements with mechanical properties suitable for bone tissue engineering applications. We synthesized a novel thioketal (TK) diol, which was crosslinked with a lysine triisocyanate (LTI) prepolymer to create hydrolytically stable poly(thioketal urethane)s (PTKUR) that degrade in the oxidative environment associated with bone defects. PTKUR films were hydrolytically stable for up to 6 months, but degraded rapidly (<1 week) under simulated oxidative conditionsin vitro.When combined with ceramic micro- or nanoparticles, PTKUR cements exhibited working times comparable to calcium phosphate cements and strengths exceeding those of trabecular bone. PTKUR/ceramic composite cements supported appositional bone growth and integrated with host bone near the bone-cement interface at 6 and 12 weeks post-implantation in rabbit femoral condyle plug defects. Histological evidence of osteoclast-mediated resorption of the cements was observed at 6 and 12 weeks. These findings demonstrate that a PTKUR bone cement with bone-like strength can be selectively resorbed by cells involved in bone remodeling, and thus represent an important initial step toward the development of resorbable bone cements for weight-bearing applications.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Madison A P
authors.initials: MA
authors.lastname: McEnery
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Sichang
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Gupta
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Zienkiewicz
authors.affiliation: U.S. Army Institute of Surgical Research, San Antonio, TX, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
authors.affiliation: Medtronic Spinal and Biologics, Memphis, TN, USA.
authors.forename: Kerem N
authors.initials: KN
authors.lastname: Kalpakci
authors.affiliation: Medtronic Spinal and Biologics, Memphis, TN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Shimko
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Duvall
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher