Abstract:
Cardiovascular disease, including myocardial infarction (MI) and heart failure (HF), remains a major cause of death globally. The irreversible and progressive damage of a failing heart is due to its limited regenerative capacity, and a heart transplant remains the gold-standard treatment for end-stage HF patients. A heart transplant is available to only a few patients due to its risks and its limited compatibility. Our team has recently demonstrated that the transplantation of alginate (Alg) and gelatin (Gel) bioprinted patches represents a promising approach to improve cardiac function in vivo using a murine MI model. Additionally, we showed that CT and MRI scans can be used to generate patient-specific bioprinted patches that can be folded and delivered via a keyhole procedure, which means faster recovery for patients compared to the current open-heart surgery required for a heart transplant. More recently, we demonstrated that the addition of silk fibroin (SF, a natural polymer used for its strength and elastic properties) to Alg/Gel hydrogels can improve the contractile function of in vitro vascularised cardiac spheroids. In this talk, we will present how the addition of SF to Alg/Gel hydrogels could improve the performance of the transplanted patch following MI in vivo, therefore protecting against HF. The transplantation of Alg/Gel/SF patches improved the LVEF% by ~20% compared to that in MI animals.
Histological analyses showed that AlgGelSF patches reduced fibrosis in infarcted animals, while bulk RNAseq analyses demonstrated that they improved the expression of genes regulating tissue-repairing processes, fibrosis, cell proliferation, and tissue homeostasis in MI mice.
Altogether, our findings demonstrate that AlgGelSF hydrogels can be used to protect against the reduction in LVEF% following MI, with the potential to be used as a safer and personalised alternative to heart transplant in HF patients.
Biography:
Associate Professor Carmine Gentile, PharmD/PhD, FAHA, leads the Cardiovascular Regeneration Group working on 3D bioprinting and stem cell technologies at the University of Technology Sydney (UTS) and at the Heart Research Institute (HRI). He is also an Associate Professor within the School of Electrical, Mechanical and Biomedical Engineering (Faculty of Engineering and IT) at UTS. He received his BSc/MSc (Pharmaceutical Chemistry and Technologies) and PharmD at the University of Pisa, Italy, and his PhD in Biomedical Sciences (Cardiovascular) at the Medical University of South Carolina, Charleston, SC, USA, funded by a prestigious American Heart Association Fellowship. Since 2013, Assoc/Prof Gentile has worked in Australia at the Heart Research Institute, the University of Sydney and now at UTS, supported by several awards and grants, working within a multidisciplinary team with scientists, industry partners and clinicians to quickly translate his findings from bench to bedside. Assoc/Prof Gentile is internationally recognised for his studies in 3D bioprinting and stem cell technologies, and his more recent studies focus on novel molecular and cellular approaches to treat cardiovascular disease, including myocardial infarction and heart failure. These studies are based on the use of “mini-hearts” he developed as “bioinks” for human heart tissues. In 2016, he was invited as a Visiting Research Fellow at Harvard Medical School, where he worked towards novel in vitro models using mini-hearts to study human heart physiology.
Links:
https://profiles.uts.edu.au/Carmine.Gentile