title: Long-term biological performance of injectable and degradable calcium phosphate cement.
abstract: Enhancing degradation of poorly degrading injectable calcium phosphate (CaP) cements (CPCs) can be achieved by adding poly(lactic-co-glycolic acid) (PLGA) microparticles, generating porosity after polymer degradation. CPC-PLGA has proven to be biodegradable, although its long-term biological performance is still unknown. Optimization of injectability could be achieved via addition of carboxymethyl cellulose (CMC). Here, we evaluated the long-term in vivo performance of CPC-PLGA with or without the lubricant CMC in comparison to the devitalized bovine bone mineral (DBBM) predicate device Bio-Oss®. Rabbit femoral bone defects were injected with a CPC-formulation or filled with Bio-Oss®granules. Samples were retrieved at 6 and 26 weeks. Material degradation for Bio-Oss®was marginal, starting with 57% material remnants at implantation, 49% at 6 weeks, and 35% at 26 weeks, respectively. In contrast, CPC-PLGA and CPC-PLGA-CMC showed significant material degradation, starting with 100% material remnants at implantation, 56 and 78% at 6 weeks, and 8 and 21% at 26 weeks. Bone formation showed to be rapid for Bio-Oss®, with 24% at 6 weeks, and a similar value (27%) at 26 weeks. Both CPC-PLGA and CPC-PLGA-CMC showed a continuous temporal increase in bone formation, with 13 and 6% at 6 weeks, and 44 and 32% at 26 weeks. This study showed that CPC-PLGA induces favorable bone responses with  >90% degradation and  >40% new bone formation after an implantation period of 26 weeks.
authors.affiliation: Department of Biomaterials, Radboudumc, Nijmegen, the Netherlands.
authors.forename: Eline-Claire
authors.initials: EC
authors.lastname: Grosfeld
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Hoekstra
authors.forename: Ralf-Peter
authors.initials: RP
authors.lastname: Herber
authors.forename: Dietmar J O
authors.initials: DJ
authors.lastname: Ulrich
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001843:Bone Cements; D002130:Calcium Phosphates / Q000737:chemistry*; D002417:Cattle; D005260:Female; D005269:Femur / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D008422:Materials Testing; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011817:Rabbits
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; D002130:Calcium Phosphates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid