Milica Radisic

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

Associate Chair, Research
Principal InvestigatorLaboratory for Functional Tissue Engineering

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

Positions available for graduate and undergraduate students

Awards

E.W.R. Steacie Memorial Fellowship, National Science and Engineering Research Council of Canada, 2014
Queen Elizabeth II Diamond Jubilee Medal, 2013Engineers Canada Young Engineer Award, 2012
McLean Award, University of Toronto, 2012
Canada Research Chair Functional Cardiovascular Tissue Engineering (Tier 2), 2011
Young Engineer Award; Professional Engineers Ontario, 2011
McMaster University Arch Award, 2010
Scientist to Watch; named by the Scientist Magazine, 2010

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

Reis LA, Chiu LL, Liang Y, Hyunh K, Momen A, Radisic M (corresponding author): “A peptide-modified chitosan-collagen hydrogel for cardiac cell culture and delivery” Acta Biomaterialia, 8:1022-36, 2012

Iyer RK, Odedra D, Vunjak-Novakovic G, Radisic M (corresponding author): “VEGF Secretion by Non-Myocytes Modulates Connexin-43 Levels in Cardiac Organoids” Tissue Engineering Part A, 18:1771-83, 2012

Zhang B, Green JV, Murthy SK, Radisic M (corresponding author): “Label-free enrichment of functional cardiomyocytes using microfluidic deterministic lateral flow displacement” PLoS One 2012;7(5):e37619. Epub 2012 May 29.

Leng L, McAllister A, Zhang B, Radisic M, Günther A: “Mosaic hydrogels: One-step formation of multidimensional, multiscale soft materials” Advanced Materials, 24:3650-8, 2012 (cover article)

Al-Haque S, Miklas J, Feric N, Chiu LLY, Chen WLK, Simmons CA, Radisic M (corresponding author): “Substrate stiffness and topography simultaneously influence cardiac fibroblast contact guidance on hydrogels “ Macromolecular Bioscience, 12:1342-53, 2012 (cover article)

Kang K, Sun L, Xiao Y, Li S-H, Wu Y, Yau TM, Weisel RD, Radisic M, Li R-K : “Aged Human Cells Rejuvenated by Cytokine-Enhancement of Biomaterials for Surgical Ventricular Restoration”,  Journal of the American College of Cardiology,  20:2237-49, 2012

Chiu LLY, Montgomery M, Liang Y, Liu H, Radisic M (corresponding author): “Perfusable branching microvessel bed for vascularization of engineered tissues”, Proceedings of the National Academy of Sciences of the United States of America, 109:E3414-23, 2012

Sofla A, Cirkovic B, Hsieh A, Miklas JW, Filipovic N, Radisic M (corresponding author): “Enrichment of live unlabelled cardiomyocytes from heterogeneous cell populations using manipulation of cell settling velocity by magnetic field” Biomicrofluidics 7, 014110, 2013;  http://dx.doi.org/10.1063/1.4791649

Nunes SS, Miklas JW, Xiao Y, Zhang B, Hsieh A, Thavandiran N, Jiang J, Masse S, Ggaliardi M, Laflamme MA, Nanthakumar K, Gross G, Keller G, Radisic M (corresponding author): “Biowire: a platform for maturation of human pluripotent stem cell derived cardiomyocytes” Nature Methods 10:781-787, 2013

Miklas JW, Dallabrida SM, Reis LA, Ismail N, Rupnick M, Radisic M (corresponding author): “QHREDGS enhances tube formation, cell metabolism and cell survival of human umbilical cord endothelial cells in collagen-chitosan hydrogels” PLoS One, 8(8):e72956, 2013 doi:10.1371/journal.pone.0072956

Xiao Yun, Zhang B, Liu H, Miklas JW, Gagliardi M, Pahnke A, Thavandiran N, Sun Y, Simmons CA, Keller G, Radisic M (corresponding author): “Microfabricated perfusable cardiac biowire: a platform that  mimics native cardiac bundle” Lab-on-a-Chip 14:869-82, 2014 (cover article)

Thavandiran N,  Dubois  D, Mikryukov A, Massé S, Beca B, Simmons CA, Deshpande V, McGarry P, Chen CS, Nanthakumar K,  Keller G, Radisic M (co-corresponding author),  Zandstra PW: “Design criteria-quided formulation of pluripotent stem cell-derived cardiac microtissues” Proceedings of the National Academy of Sciences of the United States of America  110(49):E4698-707. doi: 10.1073/pnas.1311120110 , 2013

Liu H, Wen J, Xiao Y, Liu J, Hopyan S, Radisic M, Simmons CA, Sun Y : “In situ mechanical characterization of the cell nucleus by atomic force microscopy”  ACS Nano.  8:3821-8, 2014

Traister A, Li M, Aafaqi S, Lu M, Arab S, Radisic M, Guido F, Sherret J, Verma S,  Slorach C,
Mertens L, Hui W, Hannigan G, Maynes JT, Coles JG: “Rescue of disrupted mechanotransduction as a new therapeutic strategy in human dilated cardiomyopathy” Nature Communications, in press

Dang LT,  Feric N, Laschinger C, Chang WY,  Zhang B, Wood G, Stanford WL, Radisic M (corresponding author):” A biomaterials-based approach to inhibit apoptosis of human induced pluripotent stem cells during expansion in a defined culture using angiopoietin-1 derived peptide QHREDGS”  Biomaterials, 27:7786-99, 2014