Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction
Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium....
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Online Access: | https://hdl.handle.net/10356/81568 http://hdl.handle.net/10220/43492 |
| _version_ | 1826127838141480960 |
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| author | Efraim, Yael Sarig, Hadar Cohen Anavy, Noa Sarig, Udi de Berardinis, Elio Chaw, Su-Yin Krishnamoorthi, Muthukumar Kalifa, Jérôme Bogireddi, Hanumakumar Duc, Thang Vu Kofidis, Theodoros Baruch, Limor Boey, Freddy Yin Chiang Venkatraman, Subbu Subramanian Machluf, Marcelle |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Efraim, Yael Sarig, Hadar Cohen Anavy, Noa Sarig, Udi de Berardinis, Elio Chaw, Su-Yin Krishnamoorthi, Muthukumar Kalifa, Jérôme Bogireddi, Hanumakumar Duc, Thang Vu Kofidis, Theodoros Baruch, Limor Boey, Freddy Yin Chiang Venkatraman, Subbu Subramanian Machluf, Marcelle |
| author_sort | Efraim, Yael |
| collection | NTU |
| description | Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity. Nonetheless, natural biomaterial-based gels may suffer from limited mechanical strength, which often fail to provide the long-term support required by the heart for contraction and relaxation. Here we present newly-developed injectable scaffolds, which are based on solubilized decellularized porcine cardiac extracellular matrix (pcECM) cross-linked with genipin alone or engineered with different amounts of chitosan to better control the gel’s mechanical properties while still leveraging the ECM biological activity. We demonstrate that these new biohybrid materials are naturally remodeled by mesenchymal stem cells, while supporting high viabilities and affecting cell morphology and organization. They exhibit neither in vitro nor in vivo immunogenicity. Most importantly, their application in treating acute and long term chronic MI in rat models clearly demonstrates the significant therapeutic potential of these gels in the long-term (12 weeks post MI). The pcECM-based gels enable not only preservation, but also improvement in cardiac function eight weeks post treatment, as measured using echocardiography as well as hemodynamics. Infiltration of progenitor cells into the gels highlights the possible biological remodeling properties of the ECM-based platform. |
| first_indexed | 2024-10-01T07:15:01Z |
| format | Journal Article |
| id | ntu-10356/81568 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:15:01Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/815682023-07-14T15:56:49Z Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction Efraim, Yael Sarig, Hadar Cohen Anavy, Noa Sarig, Udi de Berardinis, Elio Chaw, Su-Yin Krishnamoorthi, Muthukumar Kalifa, Jérôme Bogireddi, Hanumakumar Duc, Thang Vu Kofidis, Theodoros Baruch, Limor Boey, Freddy Yin Chiang Venkatraman, Subbu Subramanian Machluf, Marcelle School of Materials Science & Engineering Cardiac tissue engineering Injectable scaffold Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity. Nonetheless, natural biomaterial-based gels may suffer from limited mechanical strength, which often fail to provide the long-term support required by the heart for contraction and relaxation. Here we present newly-developed injectable scaffolds, which are based on solubilized decellularized porcine cardiac extracellular matrix (pcECM) cross-linked with genipin alone or engineered with different amounts of chitosan to better control the gel’s mechanical properties while still leveraging the ECM biological activity. We demonstrate that these new biohybrid materials are naturally remodeled by mesenchymal stem cells, while supporting high viabilities and affecting cell morphology and organization. They exhibit neither in vitro nor in vivo immunogenicity. Most importantly, their application in treating acute and long term chronic MI in rat models clearly demonstrates the significant therapeutic potential of these gels in the long-term (12 weeks post MI). The pcECM-based gels enable not only preservation, but also improvement in cardiac function eight weeks post treatment, as measured using echocardiography as well as hemodynamics. Infiltration of progenitor cells into the gels highlights the possible biological remodeling properties of the ECM-based platform. NRF (Natl Research Foundation, S’pore) Accepted version 2017-07-28T04:17:58Z 2019-12-06T14:33:55Z 2017-07-28T04:17:58Z 2019-12-06T14:33:55Z 2016 Journal Article Efraim, Y., Sarig, H., Cohen Anavy, N., Sarig, U., de Berardinis, E., Chaw, S.-Y., et al. (2017). Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction. Acta Biomaterialia, 50, 220-233. 1742-7061 https://hdl.handle.net/10356/81568 http://hdl.handle.net/10220/43492 10.1016/j.actbio.2016.12.015 en Acta Biomaterialia © 2016 Acta Materialia Inc. (published by Elsevier Ltd). This is the author created version of a work that has been peer reviewed and accepted for publication in Acta Biomaterialia, published by Elsevier Ltd on behalf of Acta Materialia Inc. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.actbio.2016.12.015]. 39 p. application/pdf |
| spellingShingle | Cardiac tissue engineering Injectable scaffold Efraim, Yael Sarig, Hadar Cohen Anavy, Noa Sarig, Udi de Berardinis, Elio Chaw, Su-Yin Krishnamoorthi, Muthukumar Kalifa, Jérôme Bogireddi, Hanumakumar Duc, Thang Vu Kofidis, Theodoros Baruch, Limor Boey, Freddy Yin Chiang Venkatraman, Subbu Subramanian Machluf, Marcelle Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction |
| title | Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction |
| title_full | Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction |
| title_fullStr | Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction |
| title_full_unstemmed | Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction |
| title_short | Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction |
| title_sort | biohybrid cardiac ecm based hydrogels improve long term cardiac function post myocardial infarction |
| topic | Cardiac tissue engineering Injectable scaffold |
| url | https://hdl.handle.net/10356/81568 http://hdl.handle.net/10220/43492 |
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