Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment

Abstract

The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone. STATEMENT OF SIGNIFICANCE Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with an osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep

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“…Ionic substitutions within the HAP lattice cause changes in the surface structure and local electrical charge, thus increasing the solubility and the ability of the resulting substituted HAPs to participate efficiently in the natural bone remodeling process 15. Although the concentration of ions that are partially substituting the HAP lattice is small,16–20 the major resulting effect of released ions is well known in the bone biochemistry 21–23…”

Surface Modified Techniques and Emerging Functional Coating of Dental Implants

“…In the corresponding in vivo experiment, coating the implant with VEGF significantly increases the activation of osteoblasts and endothelial cells [97]. In a sheep model, a synergistic effect on better ossification, larger bone trabeculae, and higher angiogenesis degree was found in the silicon substituted hydroxyapatite (SiHA)-coated scaffolds combined with VEGF, compared with SiHA or VEGF coated groups, respectively [98].…”

Innovative Options for Bone Metastasis Treatment: An Extensive Analysis on Biomaterials-Based Strategies for Orthopedic Surgeons

“…The incorporation of these ions in the HA structure limits the crystal growth and alters surface properties, thus enhancing its bioactivity and integrability with tissues; additionally, it also helps bone tissue self-healing and regeneration through the stimulation of osteoblasts and bone resident cells to form new bone when released during implant degradation ( Vallet-Regí and Salinas, 2019 ). For all these reasons, HA has been used not only as the pure constituent of implants but also specifically as nano-HA for coatings e.g., in Ti alloys, Ti 6 Al 4 V, and in sol-gel preparations, where bioactive responses and biocompatibility is far higher than pure HA ( Khor et al, 2004 ; Kulpetchdara et al, 2016 ; Sánchez-Salcedo et al, 2016 ; Zhou et al, 2016 ; Domínguez-Trujillo et al, 2018 ; Izquierdo-Barba et al, 2019 ; Lapaj et al, 2019 ; Robertson et al, 2019 ; Vallet-Regí and Salinas, 2019 ; Arcos and Vallet-Regí, 2020 ).…”