{"id":{"repo_id":"toronto-retro","oai_identifier":"oai:utoronto.scholaris.ca:1807/153324"},"canonical_url":"https://search.dev.ndltd.org/etd/toronto-retro/oai:utoronto.scholaris.ca:1807/153324","repository":{"repo_id":"toronto-retro","name":"University of Toronto","base_url":"https://utoronto.scholaris.ca/server/oai/request"},"display":{"title":"Delivery of hiPSC Derived Cardiomyocytes via an Injectable Nanofibrous Gelatin Polyurethane Composite Scaffold for Heart Tissue Repair","abstract":"Cardiac cell therapy, utilizing contractile human pluripotent stem cell-derived cardiomyocytes, including embryonic stem cell-derived (hESC-CM) and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), has shown promising results in treating ischemic cardiomyopathy and heart failure. However, poor cell retention has been hindering the translation of such therapies. This thesis hypothesized that delivering hiPSC-CM aggregates on an injectable micro-sized nanofibrous carrier would improve cell retention when compared to delivering free cell suspensions. Moving towards testing this hypothesis, we first demonstrated that hiPSC-CMs cultures on a nanofibrous scaffold, made from an in-house elastomeric polyurethane composite exhibited high viability and retained basic CM functionality after 7 days of culture. To enhance the mechanical compliance with cardiac tissue and accelerate degradation of the polyurethane scaffold, a newly formulated composite nanofibrous scaffold containing 55% of gelatin and 45% of the polyurethane composite was generated using a two-spinneret co-electrospinning method. Acclular micro-sized composite scaffolds (300x300 µm2) were produced using laser cutting, and successfully injected into the rat left ventricular (LV) myocardium. In vivo results showed significant and gradual bioresorption of the composite scaffold over 60 days, without impeding the natural wound healing process, as evidenced by the presence of pro-healing immune cells and blood vessels after Day 30. Finally, injectable micro-sized hiPSC-CM cell sheets carried by the micro-sized composite scaffolds were generated in large quantities (approx. 1500 scaffold per batch, each with approx. 120 cells/scaffold) and injected into rat LV myocardium within a Matrigel-free solution. After 14 days, retained hiPSC-CMs were identified in the group receiving micro-sized composite scaffolds pre-seeded with hiPSC-CMs, but not in the control groups receiving Matrigel-free solutions containing either free cells alone or free cells mixed with acellular micro-sized scaffolds. The findings demonstrate the pro-retention benefits of delivering cells pre-adhered to microfibre sheets, and injected on biomaterial carriers, with the ability to provide immediate cell-substrate adhesion and the potential for establishing cell-cell communication, and thereby contributing to cell survival for cardiac cell therapy.","abstract_html":"Cardiac cell therapy, utilizing contractile human pluripotent stem cell-derived cardiomyocytes, including embryonic stem cell-derived (hESC-CM) and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), has shown promising results in treating ischemic cardiomyopathy and heart failure. However, poor cell retention has been hindering the translation of such therapies. This thesis hypothesized that delivering hiPSC-CM aggregates on an injectable micro-sized nanofibrous carrier would improve cell retention when compared to delivering free cell suspensions. Moving towards testing this hypothesis, we first demonstrated that hiPSC-CMs cultures on a nanofibrous scaffold, made from an in-house elastomeric polyurethane composite exhibited high viability and retained basic CM functionality after 7 days of culture. To enhance the mechanical compliance with cardiac tissue and accelerate degradation of the polyurethane scaffold, a newly formulated composite nanofibrous scaffold containing 55% of gelatin and 45% of the polyurethane composite was generated using a two-spinneret co-electrospinning method. Acclular micro-sized composite scaffolds (300x300 µm2) were produced using laser cutting, and successfully injected into the rat left ventricular (LV) myocardium. In vivo results showed significant and gradual bioresorption of the composite scaffold over 60 days, without impeding the natural wound healing process, as evidenced by the presence of pro-healing immune cells and blood vessels after Day 30. Finally, injectable micro-sized hiPSC-CM cell sheets carried by the micro-sized composite scaffolds were generated in large quantities (approx. 1500 scaffold per batch, each with approx. 120 cells/scaffold) and injected into rat LV myocardium within a Matrigel-free solution. After 14 days, retained hiPSC-CMs were identified in the group receiving micro-sized composite scaffolds pre-seeded with hiPSC-CMs, but not in the control groups receiving Matrigel-free solutions containing either free cells alone or free cells mixed with acellular micro-sized scaffolds. The findings demonstrate the pro-retention benefits of delivering cells pre-adhered to microfibre sheets, and injected on biomaterial carriers, with the ability to provide immediate cell-substrate adhesion and the potential for establishing cell-cell communication, and thereby contributing to cell survival for cardiac cell therapy.","abstract_has_math":false,"creators":["Chen, Yizhou"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Biomedical Engineering","school":null,"contributors":[],"advisors":["Santerre, Paul"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-06","date_published":"2025-06","updated_at":"2026-07-27T21:28:13Z","subjects":["Biomaterial","Cardiac cell therapy","cardiomyocyte","Electrospinning","ischemic cardiomyopathy","Polyurethane"],"languages":[],"rights":["Attribution-NonCommercial-ShareAlike 4.0 International"],"rights_urls":["http://creativecommons.org/licenses/by-nc-sa/4.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1807/153324","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Santerre, Paul"]},{"key":"dc:contributor.department","label":"Department","values":["Biomedical Engineering"]},{"key":"dc:creator","label":"Author","values":["Chen, Yizhou"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-06"]},{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-07-01T04:11:04Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-06"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biomaterial","Cardiac cell therapy","cardiomyocyte","Electrospinning","ischemic cardiomyopathy","Polyurethane"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Attribution-NonCommercial-ShareAlike 4.0 International"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-sa/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1807/153324"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Cardiac cell therapy, utilizing contractile human pluripotent stem cell-derived cardiomyocytes, including embryonic stem cell-derived (hESC-CM) and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), has shown promising results in treating ischemic cardiomyopathy and heart failure. However, poor cell retention has been hindering the translation of such therapies. This thesis hypothesized that delivering hiPSC-CM aggregates on an injectable micro-sized nanofibrous carrier would improve cell retention when compared to delivering free cell suspensions. Moving towards testing this hypothesis, we first demonstrated that hiPSC-CMs cultures on a nanofibrous scaffold, made from an in-house elastomeric polyurethane composite exhibited high viability and retained basic CM functionality after 7 days of culture. To enhance the mechanical compliance with cardiac tissue and accelerate degradation of the polyurethane scaffold, a newly formulated composite nanofibrous scaffold containing 55% of gelatin and 45% of the polyurethane composite was generated using a two-spinneret co-electrospinning method. Acclular micro-sized composite scaffolds (300x300 µm2) were produced using laser cutting, and successfully injected into the rat left ventricular (LV) myocardium. In vivo results showed significant and gradual bioresorption of the composite scaffold over 60 days, without impeding the natural wound healing process, as evidenced by the presence of pro-healing immune cells and blood vessels after Day 30. Finally, injectable micro-sized hiPSC-CM cell sheets carried by the micro-sized composite scaffolds were generated in large quantities (approx. 1500 scaffold per batch, each with approx. 120 cells/scaffold) and injected into rat LV myocardium within a Matrigel-free solution. After 14 days, retained hiPSC-CMs were identified in the group receiving micro-sized composite scaffolds pre-seeded with hiPSC-CMs, but not in the control groups receiving Matrigel-free solutions containing either free cells alone or free cells mixed with acellular micro-sized scaffolds. The findings demonstrate the pro-retention benefits of delivering cells pre-adhered to microfibre sheets, and injected on biomaterial carriers, with the ability to provide immediate cell-substrate adhesion and the potential for establishing cell-cell communication, and thereby contributing to cell survival for cardiac cell therapy."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Delivery of hiPSC Derived Cardiomyocytes via an Injectable Nanofibrous Gelatin Polyurethane Composite Scaffold for Heart Tissue Repair"]}]}],"canonical_facts":{"dc:contributor.advisor":["Santerre, Paul"],"dc:contributor.department":["Biomedical Engineering"],"dc:creator":["Chen, Yizhou"],"dc:date":["2025-06"],"dc:date.accessioned":["2026-07-01T04:11:04Z"],"dc:date.issued":["2025-06"],"dc:description.abstract":["Cardiac cell therapy, utilizing contractile human pluripotent stem cell-derived cardiomyocytes, including embryonic stem cell-derived (hESC-CM) and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), has shown promising results in treating ischemic cardiomyopathy and heart failure. However, poor cell retention has been hindering the translation of such therapies. This thesis hypothesized that delivering hiPSC-CM aggregates on an injectable micro-sized nanofibrous carrier would improve cell retention when compared to delivering free cell suspensions. Moving towards testing this hypothesis, we first demonstrated that hiPSC-CMs cultures on a nanofibrous scaffold, made from an in-house elastomeric polyurethane composite exhibited high viability and retained basic CM functionality after 7 days of culture. To enhance the mechanical compliance with cardiac tissue and accelerate degradation of the polyurethane scaffold, a newly formulated composite nanofibrous scaffold containing 55% of gelatin and 45% of the polyurethane composite was generated using a two-spinneret co-electrospinning method. Acclular micro-sized composite scaffolds (300x300 µm2) were produced using laser cutting, and successfully injected into the rat left ventricular (LV) myocardium. In vivo results showed significant and gradual bioresorption of the composite scaffold over 60 days, without impeding the natural wound healing process, as evidenced by the presence of pro-healing immune cells and blood vessels after Day 30. Finally, injectable micro-sized hiPSC-CM cell sheets carried by the micro-sized composite scaffolds were generated in large quantities (approx. 1500 scaffold per batch, each with approx. 120 cells/scaffold) and injected into rat LV myocardium within a Matrigel-free solution. After 14 days, retained hiPSC-CMs were identified in the group receiving micro-sized composite scaffolds pre-seeded with hiPSC-CMs, but not in the control groups receiving Matrigel-free solutions containing either free cells alone or free cells mixed with acellular micro-sized scaffolds. The findings demonstrate the pro-retention benefits of delivering cells pre-adhered to microfibre sheets, and injected on biomaterial carriers, with the ability to provide immediate cell-substrate adhesion and the potential for establishing cell-cell communication, and thereby contributing to cell survival for cardiac cell therapy."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["https://hdl.handle.net/1807/153324"],"dc:rights":["Attribution-NonCommercial-ShareAlike 4.0 International"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-sa/4.0/"],"dc:subject":["Biomaterial","Cardiac cell therapy","cardiomyocyte","Electrospinning","ischemic cardiomyopathy","Polyurethane"],"dc:title":["Delivery of hiPSC Derived Cardiomyocytes via an Injectable Nanofibrous Gelatin Polyurethane Composite Scaffold for Heart Tissue Repair"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:28:13Z"}