3D-printable nitric oxide-releasing hybrid hydrogels for the treatment of myocardial infraction

• Grant number: 24/08075-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Agreement: Netherlands Organisation for Scientific Research (NWO)
• Principal Investigator: Marcelo Ganzarolli de Oliveira
• Grantee: Eronildo Alves Pinto Junior
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/14645-2 - Nitric oxide releasing hydrogels and vascular prosthesis for cardiovascular applications, AP.TEM

Abstract

Cardiovascular diseases represent the leading cause of death and disability in the world. Among them, myocardial infarction (MI) has demanded new strategies to facilitate the repair of dysfunctional cardiac tissues. In this scenery, the application of smart and functional hydrogels, both topically and in injectable form, has emerged as a promising strategy capable of both promoting mechanical support during myocardial tissue repair, and serving as a matrix for local drug release. The main objective of this project is the development of nitric oxide (NO) donor hydrogels for 3D printing of cardiac patches to reduce tissue damage resulting from ischemia/reperfusion after acute myocardial infarction. The hydrogels will be obtained through chemical modification reactions of prepolymers that will include non-absorbable synthetic polymers of the Pluronics class and the biopolymers such as hyaluronic acid, gelatin, and pectin. Chitosan and alginate nanoparticles containing NO donors (S-nitrosothiols) will be prepared using inotropic gelation processes, in collaboration with the research group led by Prof. Amedea B. Seabra, at the Federal University of ABC in São Paulo, SP. The hydrogels will be loaded with NO releasing molecule and/or NO-releasing nanoparticles (NPs) and used as topical and injectable NO-releasing matrices in the ex-vivo Langendorff isolated retrograde perfused heart model of ischemia-reperfusion injury. Hydrogels will be injected to the heart tissue external walls, photocured in situ, and the performance of the material ex-vivo will be evaluated in experiments conducted at the Faculty of Medical Sciences at UNICAMP, in collaboration with the research group led by Prof. Andrei Sposito. The main advances expected should result from the combined administration of NO and injectable cell growth factors and/or immunomodulatory agents, with the site-localized release of NO on the heart. In this approach, a synergistic action between growth factors and immunomodulatory agents with the angiogenic action of NO in the infarcted area is expected. Important advances are also expected in the development of stable NO donor hydrogels, whose NO release can be triggered on demand over a wide dose range, to optimize the desired physiological response.