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Milica Radisic
Dr. Milica Radisic
Born
Serbia
Alma materMcMaster University (B.Eng.)
Massachusetts Institute of Technology (Ph.D.)
Known forFunctional Cardiovascular Tissue Engineering
Scientific career
FieldsTissue Engineering, Biomaterials, Regenerative Medicine, Microfabrication
InstitutionsUniversity of Toronto, IBBME
Toronto General Hospital Research Institute
Thesis Biomimetic Approach to Cardiac Tissue Engineering
Doctoral advisorRobert Langer
WebsiteRadisic Lab website

Milica Radisic is a Professor at the University of Toronto at the Institute of Biomaterials and Biomedical Engineering (IBBME) and the Department of Chemical Engineering and Applied Chemistry.[1][2] She is also a senior scientist at the Toronto General Hospital Research Institute. Radisic is known for creating beating heart tissue in a dish using human-induced pluripotent stem cells. Her research has allowed for the replication of diseased human heart tissue that can be used for drug screening to help create treatment therapies for patients with heart injury.[1]

Biography

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Early Life

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Milica Radisic was born in Serbia in 1976. She attended the University of Novi Sad for her freshman year and transferred to McMaster University in 1996. At McMaster, Radisic read a paper in Scientific American on tissue engineering and was inspired to work as a scientist in the area.[3] She completed her undergraduate thesis on interfacial tension in polymer melts under Andrew Hrymak and graduated with a Bachelor's degree in chemical engineering in 1999. Next, Radisic earned her Ph.D. in chemical engineering at MIT in 2004 and completed a postdoctoral fellowship at Harvard-MIT Division of Health Sciences and Technology in 2005, conducting cardiac tissue engineering research under the supervision of Robert Langer and Gordana Vunjak-Novakovic. Radisic was the first author of a highly cited paper in PNAS,[4] where she successfully generated beating heart tissues from embryonic stem cells via electrical stimulation. Following that, she was named a Top 35 Innovators Under 35 in the MIT Technology Review.[5]

Academic Life

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In 2005, after completing her postdoc at MIT, Radisic joined IBBME at the University of Toronto, where she continued her research on cardiac tissue engineering.[6] Her research focused on using human embryonic stem cells to develop a heart patch that could be used to study the safety and efficacy of new drugs as well as its compatibility with various cell lines. Further, Radisic collaborated with stem cell bioengineer, Peter Zandstra, to study the tissue repair capability of the embryonic stem cells.[6]

In 2008, Radisic worked with Zandstra to engineer heart tissue that mimics the damaged tissue of patients who had a previous heart attack or patients with diabetes. The ultimate research goal is to create new therapies that can treat patients with injured hearts by testing drugs that could help guide the repair of the engineered heart tissues.[7]

In addition to her drug screening research on heart patches, Radisic is also creating novel biomaterials that can guide cellular response in order to repair damaged heart tissue. She is also investigating methods to repair injured heart tissue by making cardiac vasculature and cardiac muscle.[8] In 2014, Radisic was appointed as a Canada Research Chair in Functional Cardiovascular Tissue Engineering (Tier 2) for her research on cardiac regeneration.[2]

Research Topics

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Milica Radisic’s general research focuses on treatments for myocardial infarction and drug cardiotoxicity screening.[9]

Tissue Engineering of Cardiac Patches

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The projects in Radisics's lab focused on: 1) designing advanced bioreactors for cardiac tissue engineering capable of integrating mechanical and electrical stimuli with perfusion,[10] 2) developing strategies to engineer vascularized myocardium based on the tri-culture of key heart cell types[11] and 3) using the engineered cardiac tissue as a model system for cardiac cell therapy or drug testing[12].

Injectable Biomaterials

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Radisic's lab works on the development of injectable hydrogels with specific peptides[13][14] and other biomaterials[15] that will promote survival and localization of the cardiomyocytes injected into the infarcted myocardium.

Injectable Cardiac Patch

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Radisic's lab developed a flexible shape-memory scaffold for minimally invasive delivery of functional tissues. The scaffold utilizes a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) previously developed in the lab, and a microfabricated lattice design to allow its shape memory property. The patch was injected into a rodent model of myocardial infarction and showed significant improvement of cardiac function, compared to untreated controls. The cardiac patch was also successfully delivered to the epicardium, aorta and liver in a large-animal(porcine) model, which is a more physiologically relevant model often used in pre-clinical studies of the cardiovascular system.[16]

Microfabricated Systems for Cell Culture

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Radisic's lab designs 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, in order to understand interactive effects of multiple physical stimuli.

Biowire

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Radisic’s lab developed a microfabricated system for generating 3D, aligned beating cardiac tissue (Biowire) from human pluripotent stem cells (hPSC) derived cardiomyocytes. The system utilized electrical stimulation to increase the maturation of hPSC derived cardiomyocytes. Biowire is the first system combining electrical stimulation with geometry control of 3D tissue assembly to improve the electrical and ultrastructural properties of human cardiac tissue.[17][18] The next generation of the system, Biowire II, achieved engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends and enabled modeling of polygenic left ventricular hypertrophy starting from pateint cells.[19]

AngioChip

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Radisic’s lab developed a technique for fabricating a scaffold (AngioChip) that supports the assembly of parenchymal cells with a perfusable, branched, 3D microchannel network coated with endothelial cells which models an engineered vessel network. The scaffold system incorporates nanopores and micro-holes in the vessel walls to permits intercellular crosstalk and endothelial cells extravasation. AngioChip can be combined with cardiomyocytes culture to generate vascularized cardiac tissue. Radisic’s lab demonstrated that the AngioChip cardiac tissues can be implanted to the femoral vessels of rat hindlimbs to establish immediate blood perfusion.[20]

Industrial Involvement

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TARA Biosystems

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Milica Radisic is the co-founder of TARA Biosystems, focusing on creating model platforms for drug testing on cardiac tissues. She is currently a member of the company’s Board of Advisors as a Scientific Founder.[21] TARA Biosystems currently have an estimated Annual revenue of 2.5 Million US dollars, with 44 employees.[22]

Focus on the development of human relevant cardiac models and platforms for drug testing, products of TARA Biosystems include: The Biowire II platform, used in the generation of healthy or diseased human cardiomyocytes tissues from induced pluripotent cells, allowing more accurate prediction on the various effects of drugs and therapy.[23] Cardiotype.Fo and Cardiotype.Ep, in vitro assays used along side Biowire II to assess cardiac contractility and electrophysiology respectively.[24] Biowire received an award for most innovative invention in 2018[25] and is publishes in 2019.[23][26]

Media Recognition

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In 2016, Milica Radisic gave a TEDxVaughan talk about using stem cells and microfabrication techniques to engineer mature beating heart tissue in a dish. She also gave a talk in the same year at the Engineering Innovations Forum to talk about engineering tissue organs in humans. Dr. Radisic has also given a presentation to the American Heart Association in 2015 to talk about her research on human cardiac biowires.

In addition, Dr. Radisic has appeared in a CTV interview in 2010 to talk about her heart-tissue-regenerative-engineering research.

Social Contributions

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Milica Radisic is recognized as a YWCA Toronto Woman of Distinction in 2018, which honors those who work to improve the lives and opportunities for woman in their communities.[27] Radisic received the Women in Science and Engineering Breaking the Glass Ceiling Award, nominated by her graduate students.[28] As the former Chair of the Membership Committee for the Tissue Engineering and Regenerative Medicine Society (TERMIS) Americas, Radisic advocates for increased gender equality in the selection of key speakers, providing more chances for women researchers and engineers to present their contributions on an international stage.[28] In 2006, Millica Radisic was featured on the cover of the book Changing Our World: True Stories of Women Engineers by Sybil E. Hatch. She is also featured by the Canada Science and Technology Museum as part of the Canadian Women and Innovation website.[28]

Awards & Honours

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Radisic has received numerous awards for her work, including Natural Sciences and Engineering Research Council's E.W.R Steacie Memorial Fellowship (2014) and Engineers Canada Young Engineer Award (2012)[29]. In 2014, Radisic was named as Canada Research Chair in Functional Cardiovascular Tissue Engineering for her cardiovascular regeneration research[29]. The following is a list are some of the awards she received:[2]

  1. E.W.R. Steacie Memorial Fellowship, National Science and Engineering Research Council of Canada, 2014[30]
  2. Queen Elizabeth II Diamond Jubilee Medal, 2013
  3. Engineers Canada Young Engineer Award, 2012
  4. McLean Award, University of Toronto, 2012
  5. Young Engineer Award; Professional Engineers Ontario, 2011
  6. McMaster University Arch Award, 2010
  7. Scientist to Watch; named by the Scientist Magazine, 2010
  8. Frost & Sullivan’s 2018 Technology Innovation Award, 2018[25]

Main Publications

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  • Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds (PNAS, 2004)[31]
  • Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds (Tissue Engineering, 2006)[32]
  • Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells (Acta Biomaterialia, 2008)[33]
  • Biodegradable collagen patch with covalently immobilized VEGF for myocardial repair (Biomaterials, 2011)[34]
  • Biowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes (Nature methods, 2013)[35]
  • Design and formulation of functional pluripotent stem cell-derived cardiac microtissues (PNAS, 2013)[36]
  • Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis (Nature Materials, 2016)[37]
  • Flexible shape-memory scaffold for minimally invasive delivery of functional tissues (Nature Materials, 2017)[38]
  • A platform for generation of chamber-specific cardiac tissues and disease modeling (Cell, 2019)[39]

Memberships

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Radisic is a member of the following academic societies:[2][40]

  1. Royal Society of Canada
  2. American Association for the Advancement of Science (AAAS)
  3. American Institute of Chemical Engineers (AIChE)
  4. Biomedical Engineering Society (BMES)
  5. Society for Biological Engineering (SBE)
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Publications on PubMed

Google Scholar Page

Lab Website

TARA Biosystems

Twitter Handle

References

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  1. ^ a b "Milica Radisic". Institute of Biomaterials and Biomedical Engineering.
  2. ^ a b c d "Milica Radisic". Chemical Engineering & Applied Chemistry. Retrieved 2019-02-08.
  3. ^ "Cardiac researcher Milica Radisic to present keynote address at Libin Institute's Cardiac Research Day". UToday | University of Calgary. 2017-03-14. Retrieved 2019-03-15.
  4. ^ Radisic, Milica; Park, Hyoungshin; Shing, Helen; Consi, Thomas; Schoen, Frederick J.; Langer, Robert; Freed, Lisa E.; Vunjak-Novakovic, Gordana (2004-12-28). "Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds". Proceedings of the National Academy of Sciences of the United States of America. 101 (52): 18129–18134. doi:10.1073/pnas.0407817101. ISSN 0027-8424. PMC 539727. PMID 15604141.
  5. ^ Review, MIT Technology. "Innovator Under 35: Milica Radisic, 32". MIT Technology Review. Retrieved 2019-03-15.
  6. ^ a b "Milica Radisic: Mending broken hearts". The Scientist Magazine®. Retrieved 2019-02-16.
  7. ^ "2010's people to watch: Peter Zandstra & Milica Radisic, bioengineers | The Star". www.thestar.com. Retrieved 2019-02-16.
  8. ^ "Cardiac researcher Milica Radisic to present keynote address at Libin Institute's Cardiac Research Day". UToday | University of Calgary. 2017-03-14. Retrieved 2019-02-16.
  9. ^ "Research « Laboratory for Functional Tissue Engineering". Retrieved 2019-02-12.
  10. ^ Miklas, Jason W; Nunes, Sara S; Sofla, Aarash; Reis, Lewis A; Pahnke, Aric; Xiao, Yun; Laschinger, Carol; Radisic, Milica (2014-05-30). "Bioreactor for modulation of cardiac microtissue phenotype by combined static stretch and electrical stimulation". Biofabrication. 6 (2): 024113. doi:10.1088/1758-5082/6/2/024113. ISSN 1758-5082. PMC 4108215. PMID 24876342.
  11. ^ Iyer, Rohin K.; Odedra, Devang; Chiu, Loraine L.Y.; Vunjak-Novakovic, Gordana; Radisic, Milica (2012-09-18). "Vascular Endothelial Growth Factor Secretion by Nonmyocytes Modulates Connexin-43 Levels in Cardiac Organoids". Tissue Engineering Part A. 18 (17–18): 1771–1783. doi:10.1089/ten.tea.2011.0468. ISSN 1937-3341. PMC 3432907. PMID 22519405.
  12. ^ Zhao, Yimu; Korolj, Anastasia; Feric, Nicole; Radisic, Milica (2016-09-12). "Human pluripotent stem cell-derived cardiomyocyte based models for cardiotoxicity and drug discovery". Expert Opinion on Drug Safety. 15 (11): 1455–1458. doi:10.1080/14740338.2016.1223624. ISSN 1474-0338. PMID 27560951. S2CID 31375083.
  13. ^ Reis, Lewis A.; Chiu, Loraine L.Y.; Wu, Jun; Feric, Nicole; Laschinger, Carol; Momen, Abdul; Li, Ren-Ke; Radisic, Milica (2015-03-08). "Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction". Circulation: Heart Failure. 8 (2): 333–341. doi:10.1161/circheartfailure.114.001881. ISSN 1941-3289. PMID 25632037. S2CID 2180167.
  14. ^ Chiu, Loraine L.Y.; Janic, Katarina; Radisic, Milica (2012-04-13). "Engineering of Oriented Myocardium on Three-Dimensional Micropatterned Collagen-Chitosan Hydrogel". The International Journal of Artificial Organs. 35 (4): 237–250. doi:10.5301/ijao.5000084. ISSN 0391-3988. PMID 22505198. S2CID 28641813.
  15. ^ Ahadian, Samad; Davenport Huyer, Locke; Estili, Mehdi; Yee, Bess; Smith, Nathaniel; Xu, Zhensong; Sun, Yu; Radisic, Milica (2017-04-01). "Moldable elastomeric polyester-carbon nanotube scaffolds for cardiac tissue engineering". Acta Biomaterialia. 52: 81–91. doi:10.1016/j.actbio.2016.12.009. PMID 27940161.
  16. ^ Montgomery, Miles; Ahadian, Samad; Davenport Huyer, Locke; Lo Rito, Mauro; Civitarese, Robert A.; Vanderlaan, Rachel D.; Wu, Jun; Reis, Lewis A.; Momen, Abdul (2017-08-14). "Flexible shape-memory scaffold for minimally invasive delivery of functional tissues". Nature Materials. 16 (10): 1038–1046. doi:10.1038/nmat4956. ISSN 1476-1122. PMID 28805824.
  17. ^ Nunes, Sara S; Miklas, Jason W; Liu, Jie; Aschar-Sobbi, Roozbeh; Xiao, Yun; Zhang, Boyang; Jiang, Jiahua; Massé, Stéphane; Gagliardi, Mark (2013-06-23). "Biowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes". Nature Methods. 10 (8): 781–787. doi:10.1038/nmeth.2524. ISSN 1548-7091. PMC 4071061. PMID 23793239.
  18. ^ Xiao, Yun; Zhang, Boyang; Liu, Haijiao; Miklas, Jason W.; Gagliardi, Mark; Pahnke, Aric; Thavandiran, Nimalan; Sun, Yu; Simmons, Craig (2014). "Microfabricated perfusable cardiac biowire: a platform that mimics native cardiac bundle". Lab Chip. 14 (5): 869–882. doi:10.1039/c3lc51123e. ISSN 1473-0197. PMC 3969269. PMID 24352498.
  19. ^ Zhao, Yimu; Rafatian, Naimeh; Feric, Nicole T.; Cox, Brian J.; Aschar-Sobbi, Roozbeh; Wang, Erika Yan; Aggarwal, Praful; Zhang, Boyang; Conant, Genevieve (2019-02-07). "A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling". Cell. 176 (4): 913–927.e18. doi:10.1016/j.cell.2018.11.042. ISSN 0092-8674. PMC 6456036. PMID 30686581.
  20. ^ Zhang, Boyang; Montgomery, Miles; Chamberlain, M. Dean; Ogawa, Shinichiro; Korolj, Anastasia; Pahnke, Aric; Wells, Laura A.; Massé, Stéphane; Kim, Jihye (2016-03-07). "Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis". Nature Materials. 15 (6): 669–678. doi:10.1038/nmat4570. ISSN 1476-1122. PMC 4879054. PMID 26950595.
  21. ^ "Team – TARA / Innovating predictive cardiac physiology". Retrieved 2019-02-15.
  22. ^ "Tara Biosystems Competitors, Revenue and Employees - Owler Company Profile". Owler. Retrieved 2019-02-15.
  23. ^ a b "TARA Biosystems Biowire™ II Heart-on-a-Chip Platform Published in CELL". www.newswire.com. Retrieved 2019-02-15.
  24. ^ Inc, TARA Biosystems. "TARA Biosystems Announces Launch of Cardiotype.Fo, Best-in-Class In Vitro Assay for Assessment of Cardiac Contractility". www.prnewswire.com. Retrieved 2019-02-15. {{cite web}}: |last= has generic name (help)
  25. ^ a b Sullivan, Frost &. "TARA Biosystems' Groundbreaking Biowire™ II Heart-on-a-Chip Platform Earns Acclaim from Frost & Sullivan". www.prnewswire.com. Retrieved 2019-02-15.
  26. ^ https://www.cell.com/cell/fulltext/S0092-8674(18)31567-8
  27. ^ "Professor Milica Radisic named a YWCA Toronto Woman of Distinction". U of T Engineering News. 2018-03-08. Retrieved 2019-02-15.
  28. ^ a b c "2018 Women of Distinction Award Recipients". www.ywcatoronto.org. Retrieved 2019-02-15.
  29. ^ a b "Milica Radisic". Chemical Engineering & Applied Chemistry. Retrieved 2019-02-08.
  30. ^ "Professor Milica Radisic receives the Steacie Prize". U of T Engineering News. 2017-12-18. Retrieved 2019-02-08.
  31. ^ Radisic, Milica; Park, Hyoungshin; Shing, Helen; Consi, Thomas; Schoen, Frederick J.; Langer, Robert; Freed, Lisa E.; Vunjak-Novakovic, Gordana (2004-12-28). "Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds". Proceedings of the National Academy of Sciences of the United States of America. 101 (52): 18129–18134. doi:10.1073/pnas.0407817101. ISSN 0027-8424. PMC 539727. PMID 15604141.
  32. ^ Radisic, Milica; Park, Hyoungshin; Chen, Fen; Salazar-Lazzaro, Johanna E.; Wang, Yadong; Dennis, Robert; Langer, Robert; Freed, Lisa E.; Vunjak-Novakovic, Gordana (2006-09-12). "Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds". Tissue Engineering. 12 (8): 2077–2091. doi:10.1089/ten.2006.12.2077. ISSN 1076-3279. PMID 16968150.
  33. ^ Shen, Yi Hao; Shoichet, Molly S.; Radisic, Milica (2008-05-01). "Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells". Acta Biomaterialia. 4 (3): 477–489. doi:10.1016/j.actbio.2007.12.011. ISSN 1742-7061. PMID 18328795.
  34. ^ Miyagi, Yasuo; Chiu, Loraine L. Y.; Cimini, Massimo; Weisel, Richard D.; Radisic, Milica; Li, Ren-Ke (2011-02-01). "Biodegradable collagen patch with covalently immobilized VEGF for myocardial repair". Biomaterials. 32 (5): 1280–1290. doi:10.1016/j.biomaterials.2010.10.007. ISSN 1878-5905. PMID 21035179.
  35. ^ Nunes, Sara S.; Miklas, Jason W.; Liu, Jie; Aschar-Sobbi, Roozbeh; Xiao, Yun; Zhang, Boyang; Jiang, Jiahua; Masse, Stephane; Gagliardi, Mark (2013-06-23). "Biowire: a new platform for maturation of human pluripotent stem cell derived cardiomyocytes". Nature Methods. 10 (8): 781–787. doi:10.1038/nmeth.2524. ISSN 1548-7091. PMC 4071061. PMID 23793239.
  36. ^ Thavandiran, Nimalan; Dubois, Nicole; Mikryukov, Alexander; Massé, Stéphane; Beca, Bogdan; Simmons, Craig A.; Deshpande, Vikram S.; McGarry, J. Patrick; Chen, Christopher S. (2013-12-03). "Design and formulation of functional pluripotent stem cell-derived cardiac microtissues". Proceedings of the National Academy of Sciences of the United States of America. 110 (49): E4698–4707. doi:10.1073/pnas.1311120110. ISSN 1091-6490. PMC 3856835. PMID 24255110.
  37. ^ Zhang, Boyang; Montgomery, Miles; Chamberlain, M. Dean; Ogawa, Shinichiro; Korolj, Anastasia; Pahnke, Aric; Wells, Laura A.; Massé, Stéphane; Kim, Jihye (2016-03-07). "Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis". Nature Materials. 15 (6): 669–678. doi:10.1038/nmat4570. ISSN 1476-1122. PMC 4879054. PMID 26950595.
  38. ^ Montgomery, Miles; Ahadian, Samad; Davenport Huyer, Locke; Lo Rito, Mauro; Civitarese, Robert A.; Vanderlaan, Rachel D.; Wu, Jun; Reis, Lewis A.; Momen, Abdul (2017-08-14). "Flexible shape-memory scaffold for minimally invasive delivery of functional tissues". Nature Materials. 16 (10): 1038–1046. doi:10.1038/nmat4956. ISSN 1476-1122. PMID 28805824.
  39. ^ Zhao, Yimu; Rafatian, Naimeh; Feric, Nicole T.; Cox, Brian J.; Aschar-Sobbi, Roozbeh; Wang, Erika Yan; Aggarwal, Praful; Zhang, Boyang; Conant, Genevieve (2019-02-07). "A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling". Cell. 176 (4): 913–927.e18. doi:10.1016/j.cell.2018.11.042. ISSN 1097-4172. PMC 6456036. PMID 30686581.
  40. ^ "Reza Iravani and Milica Radisic named Fellows of the Royal Society of Canada". U of T Engineering News. 2017-09-07. Retrieved 2019-03-15.


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