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Our objective

The main goal of the Cardiovascular Regeneration Group is to examine the underlying mechanisms of cardiovascular diseases (CVD), focusing on key pathophysiological factors such as inflammation, oxidative stress, and cellular dysfunction, using state-of-the-art bioengineered heart tissues created in our laboratory. In this way, we aim to identify specific molecular and cellular pathways involved in cardiovascular pathophysiology to enhance our understanding of disease progression.

Our team has developed advanced bioengineered heart tissues as “mini-hearts” that mimic the behaviour of the heart using miniature replicas composed of the same cells found in the human heart. This is the result of over 15 years of research in biomaterials, scaffold design, and cell sources, which have been optimised to enhance the maturation and functionality of engineered cardiovascular tissues. Our mini-hearts have been demonstrated to be optimal tools to investigate cellular responses, including migration, proliferation, and differentiation of cells within the engineered cardiovascular tissues. We employ them by themselves or together with a 3D bioprinter to print complex tissues that can be transplanted to repair a failing heart or to be used as advanced in vitro models to predict the effects of drugs on the human heart, as well as to model complex diseases, such as a heart attack and heart failure.

Our ultimate goal is to translate our findings from the bench to the bedside, thanks to the support of our multidisciplinary team comprising experts in cardiovascular pathophysiology, tissue engineering and medicine. The team is strategically located at HRI and the University of Technology Sydney, integrating an extensive network of expertise in both industry and academia, fostering the quick translation of findings to the clinic. At HRI, the team focuses on novel strategies to prevent and treat CVDs using mini-hearts from either commercially available or patient-derived stem cells, with a focus on personalised medicine, paving the way for future clinical trials and therapeutic interventions.

These research objectives aim to comprehensively address both the pathophysiological aspects of CVDs and the development of tissue engineering solutions for regeneration.

Our impact

CVD, including myocardial infarction and heart failure, is a global killer, with one new heart attack every ten minutes in Australia. Our research has the potential to impact cardiovascular medicine by advancing our understanding of myocardial infarction and heart failure, informing novel therapeutic approaches, enhancing tissue engineering strategies, fostering translational research, and ultimately improving long-term health outcomes for individuals affected by cardiovascular diseases.

Given the unique features of our mini-hearts at approximating the human heart microenvironment, they can be used to replace current in vitro and in vivo models, both lacking the complex scenario that characterises the cell-cell and cell-matrix interaction of healthy and diseased heart tissues. This prevents the development of unforeseen and undesired secondary effects of therapies, which heavily impact their safety for patients. The ability to create personalised mini-hearts also presents the opportunity to create patient-specific therapies, adapting current knowledge in the best interest for the patient.

The cross-disciplinary nature of this research contributes to the interdisciplinary knowledge between cardiovascular pathophysiology and tissue engineering, with the potential to foster new collaborations between clinicians, bioengineers and scientists from both academia and industry.

Our bioengineered-focused solutions have the potential to reduce morbidity and improve the quality of life for individuals affected by CVDs. Ultimately, the impact of our research extends to improving long-term cardiovascular health outcomes for patients, saving the lives of millions of people that every year would otherwise die from CVD either directly or as a consequence of undesired effects of drugs.

Collaborators

National

  • Prof Gemma Figtree and Assoc Prof Sean Lal (The University of Sydney)
  • Prof Thomas Cox (Garvan Institute)
  • Prof Fiona Wood and Assoc Prof Mark Fear (University of Western Australia)
  • Prof Phil Hansbro (UTS/Centenary Institute)
  • Prof Peter Ralph (UTS)
  • Assoc Prof Xiaowei Wang (Baker IDI)
  • Assoc Prof Lana McClements and Assoc Prof Kristine McGrath (UTS)
  • Assoc Prof Irina Kabakova (UTS)
  • Assoc Prof Jelena Rnjak-Kovacina (UNSW)

International

  • Prof Carlijn Bouten, Eindhoven Technology University
  • Prof Federica del Monte, Medical Univ of South Carolina/Harvard Medical School
  • Prof Mario Moises Alvarez and Dr Grissel Trujillode Santiago, Tecnologico de Monterrey
  • Prof Donatella Paolino (Magna Graecia University)
  • Assist Prof Carlos Domingues Mota, Maastricht University
  • Assist Prof Sasitorn Rungarunlert, Mahidol University
  • Dr Kai-Hei TSE, Hong Kong University
  • Assist Prof Tiziano Serra, AO Research Institute Davos

Industry

  • CELLINK, Sweden
  • Hoffmann-La Roche, Switzerland
  • Regemat 3D, Spain
  • BIO-INX, Belgium

Selected publications

Gentile, C., Polonchuk, L., Kruszynski, C., “Vascularized cardiac spheroids for drug testing” Wiley Analytical Science, 2023 (4) https://analyticalscience.wiley.com/do/10.1002/was.0019000123

Roche, C., … Gentile, C., “3D bioprinted alginate-gelatin hydrogel patches containing cardiac spheroids recover heart function in a mouse model of myocardial infarction” Bioprinting, 2023 30, e00263

Sharma, P., … Gentile, C., “In vitro modeling of myocardial ischemia/reperfusion injury with murine or human 3D cardiac spheroids” STAR Protocols, 2022 3 (4), 101751

Matthews, N., …, Gentile, C., “Taking It Personally: 3D Bioprinting a Patient-Specific Cardiac Patch for the Treatment of Heart Failure” Bioengineering, 2022 9 (3), 93

Roche, C., … Gentile, C., “Cardiac Patch Transplantation Instruments for Robotic Minimally Invasive Cardiac Surgery: Initial Proof-of-concept Designs and Surgery in a Porcine Cadaver” Frontiers in Robotics and AI, 2022, 8, 714356

Sharma, P., … Gentile, C., “Biofabrication of advanced in vitro 3D models to study ischaemic and doxorubicin-induced myocardial damage”, Biofabrication 2022, 14, 025003

Polonchuk, L., … Gentile, C., “Towards engineering heart tissues from bioprinted cardiac spheroids”, Biofabrication, 2021, 13 (4), 045009

Sharma, S., Wang, X., Ming, C.L.C., Vettori, L., Figtree, G., Boyle, A., Gentile, G. “Considerations for the Bioengineering of Advanced Cardiac In Vitro Models of Myocardial Infarction” Invited submission for Special Issue titled Advanced In Vitro Models for Replacement of Animal Experiments, Small, 2021 17 (15), 2170067 https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202170067

Roche, C.D., Brereton, R.J.L., Ashton, A.W., Jackson, C, Gentile, C. “Current challenges in three-dimensional bioprinting heart tissues for cardiac surgery” Eur J Cardiothorac Surg 2020 Sep 1;58(3):500-510.

Polonchuk, L., Chabria, M., Badi, L., Hoflack, J.C., Figtree, G., M., Davies, M.J., Gentile, C. “Cardiac spheroids as promising in vitro models to study the human heart microenvironment”, Scientific Reports 2017 7 (1), 7005.

Visconti RP, Kasyanov V, Gentile C, Zhang J, Markwald RR, Mironov V. “Towards organ printing: engineering an intra-organ branched vascular tree”, Expert Opin Biol Ther. 2010 Mar;10(3):409-20.

The team

Laura Vettori

PhD candidate

Clara Liu Chung Ming

PhD candidate

Wafa Al Shamery

PhD candidate

Niina Matthews

PhD candidate

Milad Sabbagh

PhD candidate

Martine Tarsitano

Visiting PhD candidate

Ilaria Gisone

Visiting PhD candidate

Demi Scheerman

Visiting Master candidate

Linda Dement

Artist in residence

Dana Idais

Research Assistant

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