Nitric oxide donor biomolecule in the functionalization of biomaterials used in dentistry: study in rat calvaria

• Grant number: 24/09424-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Roberta Okamoto
• Grantee: Bruna Kaori Namba Inoue
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Bone defects can be the result of surgery, trauma, infection, systemic disease or congenital malformations. Currently, the main approaches to correcting bone defects are techniques using diverse types of bone grafts, with autogenous bone grafts being considered the "gold standard". Several types of biomaterials have been synthesized to replace or facilitate this type of procedure, as there are various limitations to their use. Bone substitutes, both natural and synthetic, have proven to be an excellent option due to the wide range of materials available on the market and their osteoconductive capacity, good biocompatibility and bioactive properties to stimulate bone regeneration. To improve their results, we propose the addition of Rutherpy (nitric oxide donor) to their composition, focusing on its vasodilator, antimicrobial, vasodilatory, angiogenic and collagen production stimulating potential. The aim of this study is to evaluate the regenerative potential of bone graft substitutes (BoneCeramic and CeraBone - Straumann® and GelMA) combined with Rutherpy in rat calvarial defects using confocal microscopy, micro-computed tomography (micro-CT), immunohistochemistry and real-time PCR (expression of OPN, COL1, RUNX2, OCN, TRAP, VEGF, iNOS and 4-HNE genes). For this purpose, 144 Wistar rats will undergo surgery to create a calvarial defect and will be randomly divided into groups according to the biomaterial to be implanted in this defect: GelMA (methacryloyl gelatine), GelMA+Rutherpy (GelMA with added Rutherpy compound), BC (BoneCeramic), BC+Rutherpy (BoneCeramic with added Rutherpy), CB (CeraBone) and CB+Rutherpy (CeraBone with added Rutherpy). Animals will be euthanised in 3 rounds at 10-, 28- and 60-days post-surgery and the collected calvaria will be used for RT-PCR, immunohistochemistry and micro-computed tomography and confocal microscopy (20 mg/kg dose of the fluorochromes calcein and alizarin red) analyses. Quantitative data will be subjected to a homoscedasticity test to select the appropriate statistical test (parametric or non-parametric), with a significance level of 5%.