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Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs
Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, an...
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Published in: | Biomaterials science 2024-07, Vol.12 (15), p.3866-3881 |
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creator | Janssen, Jasmijn Chirico, Nino Ainsworth, Madison J Cedillo-Servin, Gerardo Viola, Martina Dokter, Inge Vermonden, Tina Doevendans, Pieter A Serra, Margarida Voets, Ilja K Malda, Jos Castilho, Miguel van Laake, Linda W Sluijter, Joost P. G Sampaio-Pinto, Vasco van Mil, Alain |
description | Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (
i.e.
, a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.
This study is the first to preserve cardiac tissue engineered constructs with encapsulated iPSC-derived cardiomyocytes under hypothermic- and cryogenic conditions. |
doi_str_mv | 10.1039/d3bm01908j |
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i.e.
, a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.
This study is the first to preserve cardiac tissue engineered constructs with encapsulated iPSC-derived cardiomyocytes under hypothermic- and cryogenic conditions.</description><identifier>ISSN: 2047-4830</identifier><identifier>ISSN: 2047-4849</identifier><identifier>EISSN: 2047-4849</identifier><identifier>DOI: 10.1039/d3bm01908j</identifier><identifier>PMID: 38910521</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Availability ; Cardiomyocytes ; Chemistry ; Commercialization ; Construction engineering ; Freezing ; Stem cells ; Tissue engineering ; Viability</subject><ispartof>Biomaterials science, 2024-07, Vol.12 (15), p.3866-3881</ispartof><rights>Copyright Royal Society of Chemistry 2024</rights><rights>This journal is © The Royal Society of Chemistry 2024 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c318t-fb8a24d23824ad357ad6574df8299c85f517f1d16d4637e68b0c4293ec12bd453</cites><orcidid>0000-0002-6047-5900 ; 0000-0003-3543-4821 ; 0000-0001-9906-5047 ; 0000-0002-9241-7676 ; 0000-0002-4269-5889 ; 0000-0002-7768-6392</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38910521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Janssen, Jasmijn</creatorcontrib><creatorcontrib>Chirico, Nino</creatorcontrib><creatorcontrib>Ainsworth, Madison J</creatorcontrib><creatorcontrib>Cedillo-Servin, Gerardo</creatorcontrib><creatorcontrib>Viola, Martina</creatorcontrib><creatorcontrib>Dokter, Inge</creatorcontrib><creatorcontrib>Vermonden, Tina</creatorcontrib><creatorcontrib>Doevendans, Pieter A</creatorcontrib><creatorcontrib>Serra, Margarida</creatorcontrib><creatorcontrib>Voets, Ilja K</creatorcontrib><creatorcontrib>Malda, Jos</creatorcontrib><creatorcontrib>Castilho, Miguel</creatorcontrib><creatorcontrib>van Laake, Linda W</creatorcontrib><creatorcontrib>Sluijter, Joost P. G</creatorcontrib><creatorcontrib>Sampaio-Pinto, Vasco</creatorcontrib><creatorcontrib>van Mil, Alain</creatorcontrib><title>Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs</title><title>Biomaterials science</title><addtitle>Biomater Sci</addtitle><description>Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (
i.e.
, a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.
This study is the first to preserve cardiac tissue engineered constructs with encapsulated iPSC-derived cardiomyocytes under hypothermic- and cryogenic conditions.</description><subject>Availability</subject><subject>Cardiomyocytes</subject><subject>Chemistry</subject><subject>Commercialization</subject><subject>Construction engineering</subject><subject>Freezing</subject><subject>Stem cells</subject><subject>Tissue engineering</subject><subject>Viability</subject><issn>2047-4830</issn><issn>2047-4849</issn><issn>2047-4849</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpdkU1vFDEMhiMEolXphTtoJC6o0kCcj5nkhKAFCipwgXOUSTzbrHaSbTJTaf89KVuWD19sy49f2XoJeQr0FVCuX3s-TBQ0VesH5JhR0bdCCf3wUHN6RE5LWdMafa9pB4_JEVcaqGRwTL5e7rZpvsY8BdfY6BuXd2mFsXbbjAXzrZ1Dik0aG2ezD9Y1cyhlwRbjKkTEjHUnxTLnxc3lCXk02k3B0_t8Qn58eP_9_LK9-vbx0_nbq9ZxUHM7Dsoy4RlXTFjPZW99J3vhR8W0dkqOEvoRPHRedLzHTg3UCaY5OmCDF5KfkDd73e0yTOgdxjnbjdnmMNm8M8kG8-8khmuzSrcGgHVSdqIqvLxXyOlmwTKbKRSHm42NmJZiOO1BAqf8Dn3xH7pOS471v0op3gnNFVTqbE-5nErJOB6uAWrurDIX_N2XX1Z9rvDzv-8_oL-NqcCzPZCLO0z_eM1_AoI4mSU</recordid><startdate>20240723</startdate><enddate>20240723</enddate><creator>Janssen, Jasmijn</creator><creator>Chirico, Nino</creator><creator>Ainsworth, Madison J</creator><creator>Cedillo-Servin, Gerardo</creator><creator>Viola, Martina</creator><creator>Dokter, Inge</creator><creator>Vermonden, Tina</creator><creator>Doevendans, Pieter A</creator><creator>Serra, Margarida</creator><creator>Voets, Ilja K</creator><creator>Malda, Jos</creator><creator>Castilho, Miguel</creator><creator>van Laake, Linda W</creator><creator>Sluijter, Joost P. G</creator><creator>Sampaio-Pinto, Vasco</creator><creator>van Mil, Alain</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6047-5900</orcidid><orcidid>https://orcid.org/0000-0003-3543-4821</orcidid><orcidid>https://orcid.org/0000-0001-9906-5047</orcidid><orcidid>https://orcid.org/0000-0002-9241-7676</orcidid><orcidid>https://orcid.org/0000-0002-4269-5889</orcidid><orcidid>https://orcid.org/0000-0002-7768-6392</orcidid></search><sort><creationdate>20240723</creationdate><title>Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs</title><author>Janssen, Jasmijn ; Chirico, Nino ; Ainsworth, Madison J ; Cedillo-Servin, Gerardo ; Viola, Martina ; Dokter, Inge ; Vermonden, Tina ; Doevendans, Pieter A ; Serra, Margarida ; Voets, Ilja K ; Malda, Jos ; Castilho, Miguel ; van Laake, Linda W ; Sluijter, Joost P. G ; Sampaio-Pinto, Vasco ; van Mil, Alain</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c318t-fb8a24d23824ad357ad6574df8299c85f517f1d16d4637e68b0c4293ec12bd453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Availability</topic><topic>Cardiomyocytes</topic><topic>Chemistry</topic><topic>Commercialization</topic><topic>Construction engineering</topic><topic>Freezing</topic><topic>Stem cells</topic><topic>Tissue engineering</topic><topic>Viability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Janssen, Jasmijn</creatorcontrib><creatorcontrib>Chirico, Nino</creatorcontrib><creatorcontrib>Ainsworth, Madison J</creatorcontrib><creatorcontrib>Cedillo-Servin, Gerardo</creatorcontrib><creatorcontrib>Viola, Martina</creatorcontrib><creatorcontrib>Dokter, Inge</creatorcontrib><creatorcontrib>Vermonden, Tina</creatorcontrib><creatorcontrib>Doevendans, Pieter A</creatorcontrib><creatorcontrib>Serra, Margarida</creatorcontrib><creatorcontrib>Voets, Ilja K</creatorcontrib><creatorcontrib>Malda, Jos</creatorcontrib><creatorcontrib>Castilho, Miguel</creatorcontrib><creatorcontrib>van Laake, Linda W</creatorcontrib><creatorcontrib>Sluijter, Joost P. G</creatorcontrib><creatorcontrib>Sampaio-Pinto, Vasco</creatorcontrib><creatorcontrib>van Mil, Alain</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Janssen, Jasmijn</au><au>Chirico, Nino</au><au>Ainsworth, Madison J</au><au>Cedillo-Servin, Gerardo</au><au>Viola, Martina</au><au>Dokter, Inge</au><au>Vermonden, Tina</au><au>Doevendans, Pieter A</au><au>Serra, Margarida</au><au>Voets, Ilja K</au><au>Malda, Jos</au><au>Castilho, Miguel</au><au>van Laake, Linda W</au><au>Sluijter, Joost P. G</au><au>Sampaio-Pinto, Vasco</au><au>van Mil, Alain</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs</atitle><jtitle>Biomaterials science</jtitle><addtitle>Biomater Sci</addtitle><date>2024-07-23</date><risdate>2024</risdate><volume>12</volume><issue>15</issue><spage>3866</spage><epage>3881</epage><pages>3866-3881</pages><issn>2047-4830</issn><issn>2047-4849</issn><eissn>2047-4849</eissn><abstract>Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (
i.e.
, a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.
This study is the first to preserve cardiac tissue engineered constructs with encapsulated iPSC-derived cardiomyocytes under hypothermic- and cryogenic conditions.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>38910521</pmid><doi>10.1039/d3bm01908j</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-6047-5900</orcidid><orcidid>https://orcid.org/0000-0003-3543-4821</orcidid><orcidid>https://orcid.org/0000-0001-9906-5047</orcidid><orcidid>https://orcid.org/0000-0002-9241-7676</orcidid><orcidid>https://orcid.org/0000-0002-4269-5889</orcidid><orcidid>https://orcid.org/0000-0002-7768-6392</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Availability Cardiomyocytes Chemistry Commercialization Construction engineering Freezing Stem cells Tissue engineering Viability |
title | Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs |
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