Development and characterization of new titanium surfaces coated with strontium-doped bio-glasses: in vitro and pre-clinical tests on osteoporotic rats

• Grant number: 24/16854-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Joni Augusto Cirelli
• Grantee: Luan Viana Faria
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Pure titanium (Ti) and its alloys are the most used materials for dental implants due to their excellent corrosion resistance and superior mechanical properties. However, their biological inertness can lead to clinical failures. In parallel, in regenerative medicine, bioactive glasses (BGs) are considered outstanding biomaterials in the field of tissue restoration due to their remarkable biocompatibility. Given the unique properties of these two biomaterials, modifying the titanium surface with BGs can effectively combine the superior mechanical properties of the substrate with the biological characteristics of the coating material. Moreover, certain systemic factors related to the patient, such as osteoporosis, may affect or compromise the longevity of these implant treatments. To address this systemic challenge, bioactive ions can be added to BGs, providing additional osteogenic, angiogenic, and anti-inflammatory effects. Strontium (Sr) is a promising option, as it exerts a dual action on bone metabolism, promoting osteogenesis and inhibiting osteoclastogenesis-the dysregulated process in osteoporosis. Since bone remodeling is the primary target in both osseointegration and osteoporosis, with overlapping mechanisms, modifying implant surfaces with BG and Sr may offer a promising solution to the poor osseointegration observed in osteoporotic bone. In this context, this study aims to develop and evaluate a novel Ti implant surface coated with Sr-modified BG. To this end, an innovative ultrasonic spray deposition technique will be employed to deposit BG nanoparticles, produced via the sol-gel method, onto a commercial nanotopographic dental implant substrate. This chemically treated commercial surface with dual acid etching will be used as the control group (GI -C), and two test groups will be evaluated: a BG coating (G II - BG) and a Sr-doped bioglass coating (G III - BG + Sr). The physicochemical characterization of these new substrates will be conducted (Experimental Phase I) using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), atomic force microscopy (AFM), contact angle measurement, electrochemical assays to assess corrosion resistance and electrochemical stability, ion release profile assays of the coating components, and bioactivity evaluation by the hydroxyapatite induction capacity. Subsequently, in vitro biological tests (Experimental Phase II) with pre-osteoblast cell cultures (MC3T3-E1 lineage), osteoclasts (RAW 264.7 lineage induced), human endothelial cells (HUVEC), and co-culture models of osteoblasts and osteoclasts will be performed to assess the osteogenic, anti-osteoclastic, and angiogenic potential of the substrates. Cell viability, adhesion and morphology assays, gene expression via RT-qPCR, matrix mineralization, TRAP staining, tube formation, cell migration, and immunofluorescence will be conducted during in vitro biological characterization. Subsequently, osseointegration will be evaluated in an in vivo rat tibiae model (Phase III) under two distinct conditions: a healthy animal model and an osteoporotic model induced by ovariectomy. Primary stability, removal torque, bone formation around the implants, micro-computed tomography (micro-CT), histomorphometric analysis of bone-implant contact, and genes of interest related to osteogenesis, angiogenesis, and osteoclastogenesis will be evaluated. The quantitative data will be expressed using appropriate summary measures and confidence intervals.