title: Human growth hormone locally released in bone sites by calcium-phosphate biomaterial stimulates ceramic bone substitution without systemic effects: a rabbit study.
abstract: Calcium-phosphate bone replacement biomaterial has been used as a drug carrier for therapeutic agents. This study investigated the efficacy of local administration of human growth hormone (hGH) by macroporous biphasic calcium phosphate (MBCP) implants in improving the bone substitution qualities of ceramics. hGH release from MBCP implants loaded with 1 microg of hGH was rapid during the first 48 h and then sustained for a total of 9 days. Immunolocalization of hGH in vitro and in vivo by transmission electron microscopy showed its presence inside the material, indicating that it was able to penetrate within the porosity of the ceramic during the adsorption process. MBCP cylinders (6 x 6 mm) were loaded with 0.1, 1, and 10 microg of hGH and implanted into rabbit femurs (n = 40). The effects of locally released hGH on bone ingrowth and ceramic resorption were evaluated by scanning electron microscopy and image analysis. The results indicated that hGH increased bone ingrowth (+65%) and ceramic resorption (+140%) significantly in comparison with control implants and that the increase was dose dependent. Biochemical parameters monitored in rabbit plasma and urine, as well as the absence of any significant difference between contralateral implants and the control, indicated that hGH did not produce detectable systemic effects. Thus, the use of MBCP appears to be effective for local delivery of hGH, resulting in improved bone substitution.
authors.affiliation: Laboratoire de recherche sur les matériaux d'intérêt biologique, Faculté de Chirurgie Dentaire, Nantes, France.
authors.forename: J
authors.initials: J
authors.lastname: Guicheux
authors.forename: O
authors.initials: O
authors.lastname: Gauthier
authors.forename: E
authors.initials: E
authors.lastname: Aguado
authors.forename: P
authors.initials: P
authors.lastname: Pilet
authors.forename: S
authors.initials: S
authors.lastname: Couillaud
authors.forename: D
authors.initials: D
authors.lastname: Jegou
authors.forename: G
authors.initials: G
authors.lastname: Daculsi
authors.forename: D
authors.initials: D
authors.lastname: Heymann
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D001862:Bone Resorption; D002130:Calcium Phosphates / Q000008:administration & dosage; D002516:Ceramics; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D005269:Femur / Q000187:drug effects / Q000648:ultrastructure; D006622:Hip Prosthesis; D019382:Human Growth Hormone / Q000008:administration & dosage*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D019736:Prostheses and Implants; D011817:Rabbits; D011863:Radioimmunoassay
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D004343:Drug Implants; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D019382:Human Growth Hormone; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous