Milica Radisic

Milica RadisicProfessor (BME, ChemE)
B.Eng. McMaster University (1999), Ph.D. MIT (2004), Post-doc Harvard-MIT Division of Health Science and Technology (2005)

Canada Research Chair in Functional Cardiovascular Tissue Engineering

Principal InvestigatorLaboratory for Functional Tissue Engineering

Room: MB317 | Tel.: 416-946-5295 | Email: m.radisic@utoronto.ca

Awards (selected)

2018 E.W.R. Steacie Prize

2018 Fellow of the Tissue Engineering and Regenerative Medicine Society

2018 YWCA Toronto Women of Distinction Award

2017 Fellow of the Royal Society of Canada (RSC), Academy of Science

2016 Fellow of the Canadian Academy of Engineering

2016 Hatch Innovation Award, Canadian Society for Chemical Engineering

2015 Fellow of the American Institute of Medical and Biological Engineers

2014 E.W.R. Steacie Memorial Fellowship, National Science and Engineering Research Council of Canada

2012 Queen Elizabeth II Diamond Jubilee Medal, 2013Engineers Canada Young Engineer Award

2012 McLean Award, University of Toronto

2011 Canada Research Chair Functional Cardiovascular Tissue Engineering (Tier 2)

2011 Young Engineer Award; Professional Engineers Ontario

2010 McMaster University Arch Award

2010 Scientist to Watch; named by the Scientist Magazine

Memberships

  • American Association for the Advancement of Science (AAAS)
  • American Institute of Chemical Engineers (AIChE)
  • Biomedical Engineering Society (BMES)
  • Society for Biological Engineering (SBE)
  • Tissue Engineering and Regenerative Medicine Society International (TERMIS)

Research Interests

Each year nearly 900,000 people in North America alone suffer from myocardial infarction. Tissue engineering may offer alternative treatment options or suitable models for studies of normal and pathological cardiac tissue function in vitro. Conventional tissue engineering approaches are limited by inadequate oxygen supply, lack of physical stimuli and absence of multiple cell types characteristic of the native myocardium.

My research program consists of several different projects that all fall under umbrella of cardiac tissue engineering and regenerative medicine. We are focused on pursuing molecular mechanisms governing the formation of contractile cardiac tissue in vitro as well as on practical strategies for treatment of myocardial infarction and heart failure through development of new biomaterials. We pursue the research programs alone (e.g. advanced bioreactors and cell tri-culture) or in collaboration with other PIs (e.g. microfluidic separation of heart cells).

Tissue Engineering of Cardiac Patches

The key projects in this area are focused on: 1) designing advanced bioreactors for cardiac tissue engineering capable of integrating mechanical and electrical stimuli with perfusion, 2) developing strategies to engineer vascularized myocardium based on the tri-culture of key heart cell types and 3) using the engineered cardiac tissue as a model system for cardiac cell therapy or drug testing.

Injectable Biomaterials

Cell injection into the infracted myocardium can result in functional improvements, but the utility of this procedure in clinical settings is hampered by the massive death and washout of the injected cells (~90%). We are working on the development of injectable hydrogel that will promote survival and localization of the cardiomyocytes injected into the infracted myocardium. The hydrogels are functionalized with specific peptides capable of promoting the survival of cardiomyocytes.

Microfluidic Cell Separation

The existence of resident cardiac progenitor cells was recently reported by several research groups. The main goal of this project is to develop size and adhesion based microfluidic cell separation methods capable of fractionating cells from small samples such as human biopsies. The system would enable fractionation of endothelial cells, cardiomyocytes, fibroblasts, smooth muscle cells and resident progenitors without the need for labeling.

Microfabricated Systems for Cell Culture

In vivo, multiple physical and biochemical stimuli act in concert to determine cell fate and phenotype. In order to engineer functional cardiac patches and develop advanced bioreactors we need to understand interactive effects of multiple physical stimuli. We are currently developing microfabricated cell culture systems with built-in electrodes and precisely defined groove and ridge heights for simultaneous application of field stimulation and contact guidance cues.

Selected publications

Zhao Y et al: “A platform for generation of cardiac tissues with chamber-specific electrophysiological properties” Cell, 176:913-927, 2019 (featured article)

Wang EY et al: “Biowire model of interstitial and focal cardiac fibrosis” ACS Central Science, 571146-1158, 2019 (supplementary cover)

Davenport-Huyer L et al: “One‐Pot Synthesis of Unsaturated Polyester Bioelastomer with Controllable Material Curing for Microscale Designs”, Advanced Healthcare Materials, https://doi.org/10.1002/adhm.201900245, 2019 (cover article)

Mandla S et al:  “Macrophage Polarization with Angiopoietin-1 Peptide QHREDGS” ACS Biomaterials Science & Engineering, https://doi.org/10.1021/acsbiomaterials.9b00483, 2019

Zhang B et al : “Microfabrication of AngioChip”, Nature Protocols, 13:1793-1813, 2018 (cover article)

Zhang B et al: “Advances in organ-on-a-chip engineering”, Nature Reviews Materials, 3: 257-278, 2018

Lai BFL et al “InVADE: Integrated Vasculature for Assessing Dynamic Events”, Advanced Functional Materials, 27, 1703524, 2017 (back cover)

Montgomery M et al: “Flexible Shape-memory Scaffold for Minimally Invasive Delivery of Functional Tissues”, Nature Materials, 16:1038-1046, 2017 (cover article)

Zhang B et al : “Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis”, Nature Materials, 15(6):669-78, 2016 (cover article)

Davenport-Huyer L et al: “A highly elastic and moldable polyester biomaterial for cardiac tissue engineering applications”, ACS Biomaterials Science & Engineering,  2:780–788, 2016

Xiao Y et al: “Diabetic wound regeneration using peptide-modified hydrogels targeting the epithelium”,  PNAS, 113(40):E5792-E5801, 2016

Reis LA et al: “Hydrogels with integrin binding angiopoietin-1 derived peptide QHREDGS for treatment of acute myocardial infarction”, Circulation- Heart Failure, 8:333-41, 2015

Zhang B et al: “Platform technology for scalable assembly of instantaneously functional mosaic tissues.” Science Advances 1(7):e1500423, 2015

Dang LT et al : “Inhibition of apoptosis in human induced pluripotent stem cells during expansion in a defined culture using angiopoietin-1 derived peptide QHREDGS”,  Biomaterials, 35:7786-99, 2014

Nunes SS et al: “Biowire: a platform for maturation of human pluripotent stem cell derived cardiomyocytes”, Nature Methods 10:781-787, 2013

Radisic M et al : “Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds”, PNAS 101:18129-18134, Dec 28, 2004 (cover article)