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.
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.
Acta Biomater. 2014 Jul;10(7):3307-16. doi: 10.1016/j.actbio.2014.03.025. Epub 2014 Apr 2.
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.
用生物聚合物涂覆的纳米级羟基磷灰石（HA）制成的多孔泡沫状可降解且具有柔韧性，是一种很有前途的骨科植入物候选材料。甲状旁腺激素相关蛋白（PTHrP）的 C 端（107-111）表位具有成骨特性。本研究的主要目的是评估将 PTHrP（107-111）载入明胶-戊二醛生物聚合物涂覆的 HA（HAGlu）支架中是否会产生一种用于组织工程应用的最佳生物材料。将载有和未载 PTHrP（107-111）的 HAGlu 支架植入成年大鼠胫骨远端干骺端的腔隙性缺损中。4 周后处死动物，对骨痂进行组织学、微计算机断层扫描和基因表达分析。此时，只有在含有 PTHrP（107-111）的 HAGlu 植入物存在的情况下，才会发生骨愈合，这与骨体积/组织体积和小梁厚度、皮质厚度以及骨钙素和血管细胞黏附分子 1 的基因表达增加有关，但 Wnt 抑制剂 SOST 和 dickkopf 同源物 1 的基因表达减少。在小鼠和人成骨细胞培养中证实了载有 PTHrP（107-111）的 HAGlu 支架的自主成骨作用。我们的研究结果证明了将 PTHrP（107-111）载入可降解 HAGlu 支架以获得最佳生物材料的优势，这种生物材料有望用于低承重的临床应用。
