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Macrogeometry and drug delivery as strategies to improve periimplant repair in osteopenic bone tissue: histological, histometric, biomechanical and ultrastructural analysis of the bone/implant interface

Grant number: 21/06849-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2022
Effective date (End): February 28, 2025
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal Investigator:Roberta Okamoto
Grantee:Ana Cláudia Ervolino da Silva
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil


Osteoporosis is characterized by a decrease in bone mass and an imbalance of bone metabolism, both factors which can impair the success of rehabilitation with osseointegrated implants. This systemic change is classically recognized as a significant health problem in women, due to depletion in estrogen supply in the postmenopausal phase. Although Osteoporosis is not an absolute contraindication for implant installation, some clinical studies show a higher incidence of implant failure in osteoporotic or osteopenic patients. Changes in implant geometry, topography, and surface are promising alternatives that may improve osseointegration in patients with bone compromise, however, a greater understanding of how implant design and local drugs may affect periimplant bone repair is needed. The present project aims to evaluate different strategies that may contribute to the improvement of the periimplant bone repair process in estrogen-deficient rats. To this end, a new model of porous titanium implant manufactured by additive manufacturing that mimics osteopenic bone tissue will be used. These implants will act as a scaffold to deliver drugs or biomolecules to the periimplant compartment with the goal of promoting improved periimplant bone formation responses. We hypothesize that teriparatide, a parathormone-based anti-Osteoporosis drug whose function is to stimulate bone formation, will have positive effects on periimplant repair. Another biomolecule, Wnt3a, which acts by stimulating stem cells and osteoblasts, seems to be a local therapeutic agent that helps bone repair. To evaluate periimplant repair in estrogen-deficient rats, we will use the bilateral ovariectomy model. For this purpose, 288 rats will be divided into two large groups: 1. SHAM (n=144): in which rats will undergo sham surgery; 2. OVX (n=144): in which rats will undergo bilateral ovariectomy. In each large group, porous or conventional (solid) implants will be used, and each implant will be functionalized with teriparatide, Wnt3a or will not be functionalized. After 30 days of ovariectomy, all rats will undergo implant installation according to the surface corresponding to their group. To analyze the periimplant bone, we will take an interdisciplinary methodological approach so that we can characterize the structural, cellular and molecular response. At 14 days after implant installation, the first euthanasia will be performed to collect samples for real-time pcr, reverse torque and immunohistochemistry, using antibodies against runx2, alkaline phosphatase (ALP), osteopontin (OPN), Wnt and beta catenin. At 28 days after implant installation, the tibiae will be collected for high-resolution ultrastructural analysis, evaluating osseointegration at various scales (nano-, and micro-scale) using Plasma-Focused Ion Beam Tomography (PFIB), never used to study osseointegration. At 42 days after implant installation, samples will be collected to perform real-time pcr, removal torque, computed microtomography (BV.TV, Tb.Th, Tb.N, Tb.Sp, I.S. and Conn.Den.) and confocal microscopy to analyze daily mineral apposition (MAR), active mineralization surface and bone dynamics. Quantitative data will be submitted to homoscedasticity test for the selection of the appropriate statistical test (parametric or nonparametric), with a significance level of 5%. (AU)

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