Biofunctional Hydrogel as a Controlled Drug Delivery System with Antimicrobial and Anti-inflammatory Activity for the Treatment of Peri-implant Infections

• Grant number: 25/04497-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Dentistry - Dental Materials
• Principal Investigator: Valentim Adelino Ricardo Barão
• Grantee: Gabriel Pereira Nunes
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Peri-implantitis is characterized by the presence of a dysbiotic pathogenic biofilm around implants, leading to soft tissue inflammation and progressive bone loss in peri-implant areas, representing one of the primary causes of implant failure and loss. The lack of consensus on the ideal treatment reflects the ineffectiveness of traditional approaches, such as mechanical debridement and systemic antibiotics, particularly due to high rates of bacterial resistance. In this context, hydrogels have emerged as promising biomaterials for the local, controlled, and sustained release of drugs, capable of carrying agents with antibacterial and anti-inflammatory properties, thus providing a multifunctional system with therapeutic safety. Therefore, this study aims to develop a new therapeutic approach for controlling peri-implantitis through a light-responsive hydrogel based on methacrylated gelatin (GelMA), which will be loaded with the antibiotic tetracycline (TC) and folic acid (FA), aiming for controlled release and targeted antimicrobial action. Four groups will be evaluated: (1) GelMA (control), (2) GelMA + TC, (3) GelMA + FA, and (4) GelMA + TC + FA. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of tetracycline will be determined, while the concentration of folic acid used will be based on our previous study (Costa et al., 2024), adjusted through a pilot study. Following the synthesis of the hydrogel, its morphology will be assessed by scanning electron microscopy (SEM), interaction and functionality will be evaluated using Fourier-transform infrared spectroscopy (FTIR), critical solution temperature, gelation time, rheological properties, mass distribution by gel permeation chromatography, adhesion, swelling degree, degradation, and release of TC and FA through high-performance liquid chromatography. Antimicrobial activity will be assessed using a polymicrobial biofilm model (microcosm) developed on the surface of dental implants secured in holders to simulate the bone resorption present in peri-implantitis, and the confirmation of these effects in situ with the oral application of the hydrogel on implants placed in palatal devices used by volunteers. Colony-forming units (CFUs), biofilm morphology by SEM, cell viability by confocal laser scanning microscopy (CLSM), and microbial composition by DNA-DNA checkerboard will be evaluated in both in vitro and in situ experiments. Qualitative and quantitative analyses will be carried out to confirm the absence of hydrogel toxicity when in contact with gingival fibroblast cells and MC3T3-E1 pre-osteoblastic cells, by means of CCK-8 analysis, metabolic activity by MTT, cell viability (Live/Dead) and fluorescence microscopy, as well as analysis of the biomaterial's anti-inflammatory response and macrophage polarization through cytokine quantification and assessment of M1 and M2 macrophage markers.The data will be statistically analyzed with a significance level of 0.05.