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Development and Evaluation of Injectable Bioactive Hydrogel Composed of Silk Fibroin, Puerarin and Reduced Graphene Oxide Directed for Post-Myocardial Infarction Therapy

Grant number: 23/17083-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2024
Effective date (End): February 28, 2027
Field of knowledge:Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
Principal Investigator:Eliana Aparecida de Rezende Duek
Grantee:Bruna Vanessa Quevedo Miranda
Host Institution: Faculdade de Ciências Médicas e da Saúde (FCMS). Pontifícia Universidade Católica de São Paulo (PUC-SP). Sorocaba , SP, Brazil

Abstract

Myocardial infarction (MI) is widely recognized as the leading cause of mortality associated with cardiovascular diseases globally. Projections indicate that by 2030, more than 23.6 million deaths will be attributed to this condition. MI results in significant cardiomyocyte death, triggering the formation of fibrous tissue in the myocardial wall. This process leads to an interruption of intrinsic electrical signaling in the myocardium, contributing to the manifestation of cardiac dysfunction and arrhythmias. Currently, available therapeutic interventions do not effectively promote the repair of the affected area. Therefore, injectable bioactive hydrogel formulations with conductive properties have emerged as promising strategies for the treatment of MI. Injectable hydrogels are considered minimally invasive and can overcome clinical and surgical limitations. Faced with this challenging scenario, the present research project proposes an innovative approach to support post-myocardial infarction therapy. This approach involves of the development and evaluation of a unique bioactive semi-interpenetrating hydrogel, composed of silk fibroin (FS) and Puerarin (PUE). FS, recognized for its biocompatibility and remarkable mechanical properties, forms the structural basis of the hydrogel. At the same time, PUE, a flavonoid extracted from the roots of the Chinese plant Pueraria lobata and target of investigation for its gel-forming ability, provides antioxidant and anti-inflammatory effects, expanding the therapeutic capacity of the hydrogel. To attribute conductive properties, the project also aims to introduce reduced graphene oxide (OGr) to the hydrogel. OGr is a two-dimensional nanomaterial with electrical conductivity that can be employed in various biomedical applications, including cardiovascular applications. The inclusion of OGr in the hydrogel facilitates electrophysiological communication among cardiac cells, improving the treatment's effectiveness and aiding in the restoration of heart rhythm. Therefore, the FS/PUE hydrogel associated with OGr has the prospect of exhibiting synergistic and conductive properties essential for post-infarction therapy, with the potential to facilitate the functional integration of the affected tissue. Therefore, the biomaterial developed in this study will be subjected to a comprehensive characterization in physicochemical and biological terms, aiming to obtain promising results that demonstrate its potential effectiveness in the treatment of MI. This project will significantly contribute to the emerging field of biomaterials applied to regenerative medicine, offering a promising perspective to improve the quality of life of patients impacted by cardiovascular diseases. Furthermore, the literature does not report the existence of hydrogels with a semi-interpenetrating network between FS and PUE, contributing to the innovative and unprecedented nature of the research. Considering the bioactivity and gel-forming ability of PUE, its application in hydrogels deserves more attention, potentially making a significant contribution to the development of new promising biomaterials for application in the medical field.

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