title: Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats.
abstract: Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and μ-computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016.
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and UAM, Madrid, Spain.|RETICEF-Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Ardura
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and UAM, Madrid, Spain.|RETICEF-Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Portal-Núñez
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and UAM, Madrid, Spain.|RETICEF-Instituto de Salud Carlos III, Madrid, Spain.|Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense, Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lozano
authors.affiliation: Instituto de Salud Carlos III, Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Rojas
authors.affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense, Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sánchez-Salcedo
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and UAM, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: López-Herradón
authors.affiliation: Unidad de Imagen Molecular, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mulero
authors.affiliation: Instituto de Salud Carlos III, Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Villanueva-Peñacarrillo
authors.affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense, Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vallet-Regí
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and UAM, Madrid, Spain.|RETICEF-Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Esbrit
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D021621:Imaging, Three-Dimensional; D020007:Implants, Experimental; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D020099:Coated Materials, Biocompatible; D044162:Parathyroid Hormone-Related Protein; D005780:Gelatin; D017886:Durapatite
keywords: N- and C-terminal PTHrP; aging; bone regeneration; diabetes; gelatin-glutaraldehyde-coated hydroxyapatite