Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts
| Autor: | Amelia Khoo, Kareen L.K. Coulombe, Cassady E. Rupert, Rajeev J. Kant, Fabiola Munarin |
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| Rok vydání: | 2020 |
| Předmět: |
Cardiac function curve
Angiogenesis medicine.medical_treatment Biophysics Ischemia Bioengineering 02 engineering and technology Revascularization Article Biomaterials 03 medical and health sciences Tissue engineering Medicine Myocardial infarction 030304 developmental biology 0303 health sciences business.industry 021001 nanoscience & nanotechnology medicine.disease Cell biology Mechanics of Materials Ceramics and Composites Implant 0210 nano-technology business Perfusion |
| Zdroj: | Biomaterials |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2020.120033 |
| Popis: | Heart regeneration after myocardial infarction requires new cardiomyocytes and a supportive vascular network. Here, we evaluate the efficacy of localized delivery of angiogenic factors from biomaterials within the implanted muscle tissue to guide growth of a more dense, organized, and perfused vascular supply into implanted engineered human cardiac tissue on an ischemia/reperfusion injured rat heart. We use large, aligned 3-dimensional engineered tissue with cardiomyocytes derived from human induced pluripotent stem cells in a collagen matrix that contains dispersed alginate microspheres as local protein depots. Release of angiogenic growth factors VEGF and bFGF in combination with morphogen sonic hedgehog from the microspheres into the local microenvironment occurs from the epicardial implant site. Analysis of the 3D vascular network in the engineered tissue via Microfil® perfusion and microCT imaging at 30 days shows increased volumetric network density with a wider distribution of vessel diameters, proportionally increased branching and length, and reduced tortuosity. Global heart function is increased in the angiogenic factor-loaded cardiac implants versus sham. These findings demonstrate for the first time the efficacy of a combined remuscularization and revascularization therapy for heart regeneration after myocardial infarction. |
| Databáze: | OpenAIRE |
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