Parathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin-glutaraldehyde biopolymer-coated hydroxyapatite.
Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HAGlu) scaffolds would produce an optimal biomaterial for tissue engineering applications. HAGlu scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HAGlu implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule 1, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HAGlu scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HAGlu scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications.
Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and Instituto de Salud Carlos III-RETICEF, Avenida Reyes Católicos, 2, 28040, Madrid, Spain; Grupo de Investigación de Cirugía Osteo-Articular, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
Daniel
D
Lozano
Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación perteneciente a la Red de Bioingeniería, Biomateriales y Nanomedicina, Zaragoza, Spain.
Sandra
S
Sánchez-Salcedo
Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and Instituto de Salud Carlos III-RETICEF, Avenida Reyes Católicos, 2, 28040, Madrid, Spain.
Sergio
S
Portal-Núñez
Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación perteneciente a la Red de Bioingeniería, Biomateriales y Nanomedicina, Zaragoza, Spain.
Mercedes
M
Vila
Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and Instituto de Salud Carlos III-RETICEF, Avenida Reyes Católicos, 2, 28040, Madrid, Spain.
Ana
A
López-Herradón
Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and Instituto de Salud Carlos III-RETICEF, Avenida Reyes Católicos, 2, 28040, Madrid, Spain.
Juan Antonio
JA
Ardura
Unidad de Imagen Molecular, Centro Nacional de Investigaciones Oncológicas (CNIO), Calle de Melchor Fernandez Almagro3, 28029, Madrid, Spain.
Francisca
F
Mulero
Grupo de Investigación de Cirugía Osteo-Articular, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
Enrique
E
Gómez-Barrena
Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain; Centro de Investigación perteneciente a la Red de Bioingeniería, Biomateriales y Nanomedicina, Zaragoza, Spain. Electronic address: vallet@ucm.es.
María
M
Vallet-Regí
Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz and Instituto de Salud Carlos III-RETICEF, Avenida Reyes Católicos, 2, 28040, Madrid, Spain.
Pedro
P
Esbrit
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001704:Biopolymers / Q000737:chemistry*; D001861:Bone Regeneration / Q000187:drug effects*; D020099:Coated Materials, Biocompatible; D017931:DNA Primers; D017886:Durapatite / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D005976:Glutaral / Q000737:chemistry*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D054457:Tissue Scaffolds
D001704:Biopolymers; D020099:Coated Materials, Biocompatible; D017931:DNA Primers; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C071784:parathyroid hormone-related protein (107-111); D005780:Gelatin; D017886:Durapatite; D005976:Glutaral
Hydroxyapatite; In vivo bone regeneration; Macroporous scaffolds; PTHrP (107-111); Rat