Investigation of Systemic Toxicity and Biocompatibility of Biomaterials Incorporated in GelMA Hydrogel in Rats.

• Grant number: 24/13424-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Luciano Tavares Angelo Cintra
• Grantee: Mariana Pagliusi Justo
• Supervisor: Marco Cicero Bottino
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Institution abroad: University of Michigan, United States
• Associated to the scholarship: 22/15097-9 - Systemic toxicity of F18 bioglass. Analysis in hematological, hepatic, renal and cerebral tissues in Wistar rats., BP.DR

Abstract

Regenerative endodontics is advancing modern dentistry by restoring the root canals to a healthy state, allowing for continued development of the root and surrounding tissue. GelMA hydrogels, noted for their tunable mechanical properties and injectability, are ideal for incorporating therapeutic agents like curcumin, which offers anti-inflammatory and antimicrobial benefits. Adding Mineral Trioxide Aggregate (MTA), recognized for its bioactive properties, could further enhance these hydrogels' regenerative potential. Aim: to develop an injectable GelMA hydrogel incorporated with Curcumin and MTA for endodontic procedures to regenerate the pulp-dentin complex. Methods: After conducting cytotoxic screening of curcumin at different concentrations (100%, 75%, 50%, and 25%), the highest non-cytotoxic dose will be incorporated into the GelMA hydrogel, with or without MTA. Their morphological characterization will be done by scanning electron microscopy and energy dispersive spectroscopy, swelling capacity, degradation rate, and analysis of mechanical properties. The osteogenic capacity of the hydrogels will also be assessed through the formation of mineralized nodules and their cytocompatibility through cell adhesion and viability on DPCS cells. Finally, the experimental hydrogels will be tested in vivo in rats subcutaneous tissue for 7 and 30 days. Inflammation will be assessed in tissue sections stained with H&E; mature and immature collagen will be quantified after polarization in sections stained with Picrosirius red; and by immunohistochemical staining for IL-6, TNF-± and OCN. Systemic analysis will be hematological profile (white and red series) and plasma biochemical profile quantifying quantifying ALT, AST, alkaline phosphatase, urea and creatinine levels. Analysis of results: The results will be submitted to statistical tests specific for each case, and a significance level of 5% will be adopted.