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Osteogenic, anti-osteoclastogenic and immunomodulatory properties of a strontium-releasing hybrid scaffold for bone repair

2019; Elsevier BV; Volume: 99; Linguagem: Inglês

10.1016/j.msec.2019.02.053

1873-0191

Ana Henriques Lourenço, A.L. Torres, Daniela P. Vasconcelos, Cláudia Ribeiro-Machado, Judite N. Barbosa, Mário A. Barbosa, Cristina C. Barrias, Cristina Ribeiro,

Graphene and Nanomaterials Applications

Strontium (Sr) is known to stimulate osteogenesis, while inhibiting osteoclastogenesis, thus encouraging research on its application as a therapeutic agent for bone repair/regeneration. It has been suggested that it may possess immunomodulatory properties, which might act synergistically in bone repair/regeneration processes. To further explore this hypothesis we have designed a Sr-hybrid system composed of an in situ forming Sr-crosslinked RGD-alginate hydrogel reinforced with Sr-doped hydroxyapatite (HAp) microspheres and studied its in vitro osteoinductive behaviour and in vivo inflammatory response. The Sr-hybrid scaffold acts as a dual Sr2+ delivery system, showing a cumulative Sr2+ release of ca. 0.3 mM after 15 days. In vitro studies using Sr2+concentrations within this range (0 to 3 mM Sr2+) confirmed its ability to induce osteogenic differentiation of mesenchymal stem/stromal cells (MSC), as well as to reduce osteoclastogenesis and osteoclasts (OC) functionality. In comparison with a similar Sr-free system, the Sr-hybrid system stimulated osteogenic differentiation of MSC, while inhibiting the formation of OC. Implantation in an in vivo model of inflammation, revealed an increase in F4/80+/CD206+ cells, highlighting its ability to modulate the inflammatory response as a pro-resolution mediator, through M2 macrophage polarization. Therefore, the Sr-hybrid system is potentially an appealing biomaterial for future clinical applications.