title: Tuning the degradation rate of calcium phosphate cements by incorporating mixtures of polylactic-co-glycolic acid microspheres and glucono-delta-lactone microparticles.
abstract: Calcium phosphate cements (CPCs) are frequently used as synthetic bone graft materials in view of their excellent osteocompatibility and clinical handling behavior. Hydroxyapatite-forming CPCs, however, degrade at very low rates, thereby limiting complete bone regeneration. The current study has investigated whether degradation of apatite-forming cements can be tuned by incorporating acid-producing slow-resorbing poly(D,L-lactic-co-glycolic) acid (PLGA) porogens, fast-resorbing glucono-delta-lactone (GDL) porogens, or mixtures thereof. The physicochemical, mechanical, and degradation characteristics of these CPC formulations were systematically analyzed upon soaking in phosphate-buffered saline (PBS). In parallel, various CPC formulations were implanted intramuscularly and orthotopically on top of the transverse process of goats followed by analysis of the soft tissue response and bone ingrowth after 12 weeks. In vitro degradation of GDL was almost completed after 2 weeks, as evidenced by characterization of the release of gluconic acid, while PLGA-containing CPCs released glycolic acid throughout the entire study (12 weeks), resulting in a decrease in compression strength of CPC. Extensive in vitro degradation of the CPC matrix was observed upon simultaneous incorporation of 30% PLGA-10% GDL. Histomorphometrical evaluation of the intramuscularly implanted samples revealed that all CPCs exhibited degradation, accompanied by an increase in capsule thickness. In the in vivo goat transverse process model, incorporation of 43% PLGA, 30% PLGA-5% GDL, and 30% PLGA-10% GDL in CPC significantly increased bone formation and resulted in higher bone height compared with both 10% GDL and 20% GDL-containing CPC samples.
authors.affiliation: 1 Department of Biomaterials, Radboud University Nijmegen Medical Center , Nijmegen, The Netherlands .
authors.forename: Kemal
authors.initials: K
authors.lastname: Sariibrahimoglu
authors.forename: Jie
authors.initials: J
authors.lastname: An
authors.forename: Bart A J A
authors.initials: BA
authors.lastname: van Oirschot
authors.forename: Arnold W G
authors.initials: AW
authors.lastname: Nijhuis
authors.forename: Rhandy M
authors.initials: RM
authors.lastname: Eman
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Alblas
authors.forename: Joop G C
authors.initials: JG
authors.lastname: Wolke
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
authors.forename: Sander C G
authors.initials: SC
authors.lastname: Leeuwenburgh
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001826:Body Fluids / Q000737:chemistry; D001843:Bone Cements / Q000138:chemical synthesis* / Q000627:therapeutic use; D001846:Bone Development / Q000502:physiology*; D018786:Bone Substitutes / Q000737:chemistry* / Q000627:therapeutic use; D002130:Calcium Phosphates / Q000737:chemistry* / Q000627:therapeutic use; D045424:Complex Mixtures / Q000138:chemical synthesis; D019245:Compressive Strength; D006041:Goats; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D010881:Piperidones / Q000737:chemistry* / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D001843:Bone Cements; D018786:Bone Substitutes; D002130:Calcium Phosphates; D045424:Complex Mixtures; D010881:Piperidones; C038504:5-amino-5-deoxygluconic acid delta-lactam; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C020243:calcium phosphate