Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis
In vitro models of pathological cardiac tissue have attracted interest as predictive platforms for preclinical validation of therapies. However, models reproducing specific pathological features, such as cardiac fibrosis size (i.e., thickness and width) and stage of development are missing. This res...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.983872/full |
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| author | Mattia Spedicati Mattia Spedicati Mattia Spedicati Gerardina Ruocco Gerardina Ruocco Gerardina Ruocco Alice Zoso Alice Zoso Alice Zoso Leonardo Mortati Andrea Lapini Andrea Lapini Andrea Delledonne Carla Divieto Veronica Romano Clotilde Castaldo Franca Di Meglio Daria Nurzynska Irene Carmagnola Irene Carmagnola Irene Carmagnola Valeria Chiono Valeria Chiono Valeria Chiono |
| author_facet | Mattia Spedicati Mattia Spedicati Mattia Spedicati Gerardina Ruocco Gerardina Ruocco Gerardina Ruocco Alice Zoso Alice Zoso Alice Zoso Leonardo Mortati Andrea Lapini Andrea Lapini Andrea Delledonne Carla Divieto Veronica Romano Clotilde Castaldo Franca Di Meglio Daria Nurzynska Irene Carmagnola Irene Carmagnola Irene Carmagnola Valeria Chiono Valeria Chiono Valeria Chiono |
| author_sort | Mattia Spedicati |
| collection | DOAJ |
| description | In vitro models of pathological cardiac tissue have attracted interest as predictive platforms for preclinical validation of therapies. However, models reproducing specific pathological features, such as cardiac fibrosis size (i.e., thickness and width) and stage of development are missing. This research was aimed at engineering 2D and 3D models of early-stage post-infarct fibrotic tissue (i.e., characterized by non-aligned tissue organization) on bioartificial scaffolds with biomimetic composition, design, and surface stiffness. 2D scaffolds with random nanofibrous structure and 3D scaffolds with 150 µm square-meshed architecture were fabricated from polycaprolactone, surface-grafted with gelatin by mussel-inspired approach and coated with cardiac extracellular matrix (ECM) by 3 weeks culture of human cardiac fibroblasts. Scaffold physicochemical properties were thoroughly investigated. AFM analysis of scaffolds in wet state, before cell culture, confirmed their close surface stiffness to human cardiac fibrotic tissue. Following 3 weeks culture, biomimetic biophysical and biochemical scaffold properties triggered the activation of myofibroblast phenotype. Upon decellularization, immunostaining, SEM and two-photon excitation fluorescence microscopy showed homogeneous decoration of both 2D and 3D scaffolds with cardiac ECM. The versatility of the approach was demonstrated by culturing ventricular or atrial cardiac fibroblasts on scaffolds, thus suggesting the possibility to use the same scaffold platforms to model both ventricular and atrial cardiac fibrosis. In the future, herein developed in vitro models of cardiac fibrotic tissue, reproducing specific pathological features, will be exploited for a fine preclinical tuning of therapies. |
| first_indexed | 2024-04-12T07:08:56Z |
| format | Article |
| id | doaj.art-fff9cc539b524ab6bd71edf34a552ce4 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-12T07:08:56Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-fff9cc539b524ab6bd71edf34a552ce42022-12-22T03:42:44ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-11-011010.3389/fbioe.2022.983872983872Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosisMattia Spedicati0Mattia Spedicati1Mattia Spedicati2Gerardina Ruocco3Gerardina Ruocco4Gerardina Ruocco5Alice Zoso6Alice Zoso7Alice Zoso8Leonardo Mortati9Andrea Lapini10Andrea Lapini11Andrea Delledonne12Carla Divieto13Veronica Romano14Clotilde Castaldo15Franca Di Meglio16Daria Nurzynska17Irene Carmagnola18Irene Carmagnola19Irene Carmagnola20Valeria Chiono21Valeria Chiono22Valeria Chiono23Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, ItalyPOLITO Biomedlab, Politecnico di Torino, Torino, ItalyInteruniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, ItalyDepartment of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, ItalyPOLITO Biomedlab, Politecnico di Torino, Torino, ItalyInteruniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, ItalyDepartment of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, ItalyPOLITO Biomedlab, Politecnico di Torino, Torino, ItalyInteruniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, ItalyIstituto Nazionale di Ricerca Metrologica (INRIM), Torino, ItalyIstituto Nazionale di Ricerca Metrologica (INRIM), Torino, ItalyDepartment of Chemistry, Life Science and Environmental Sustainability, University of Parma, Parma, ItalyDepartment of Chemistry, Life Science and Environmental Sustainability, University of Parma, Parma, ItalyIstituto Nazionale di Ricerca Metrologica (INRIM), Torino, ItalyDepartment of Public Health, University of Naples “Federico II”, Napoli, ItalyDepartment of Public Health, University of Naples “Federico II”, Napoli, ItalyDepartment of Public Health, University of Naples “Federico II”, Napoli, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Salerno, ItalyDepartment of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, ItalyPOLITO Biomedlab, Politecnico di Torino, Torino, ItalyInteruniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, ItalyDepartment of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, ItalyPOLITO Biomedlab, Politecnico di Torino, Torino, ItalyInteruniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, ItalyIn vitro models of pathological cardiac tissue have attracted interest as predictive platforms for preclinical validation of therapies. However, models reproducing specific pathological features, such as cardiac fibrosis size (i.e., thickness and width) and stage of development are missing. This research was aimed at engineering 2D and 3D models of early-stage post-infarct fibrotic tissue (i.e., characterized by non-aligned tissue organization) on bioartificial scaffolds with biomimetic composition, design, and surface stiffness. 2D scaffolds with random nanofibrous structure and 3D scaffolds with 150 µm square-meshed architecture were fabricated from polycaprolactone, surface-grafted with gelatin by mussel-inspired approach and coated with cardiac extracellular matrix (ECM) by 3 weeks culture of human cardiac fibroblasts. Scaffold physicochemical properties were thoroughly investigated. AFM analysis of scaffolds in wet state, before cell culture, confirmed their close surface stiffness to human cardiac fibrotic tissue. Following 3 weeks culture, biomimetic biophysical and biochemical scaffold properties triggered the activation of myofibroblast phenotype. Upon decellularization, immunostaining, SEM and two-photon excitation fluorescence microscopy showed homogeneous decoration of both 2D and 3D scaffolds with cardiac ECM. The versatility of the approach was demonstrated by culturing ventricular or atrial cardiac fibroblasts on scaffolds, thus suggesting the possibility to use the same scaffold platforms to model both ventricular and atrial cardiac fibrosis. In the future, herein developed in vitro models of cardiac fibrotic tissue, reproducing specific pathological features, will be exploited for a fine preclinical tuning of therapies.https://www.frontiersin.org/articles/10.3389/fbioe.2022.983872/fullbioartificial scaffoldcardiac fibrosisin vitro modelpoly(caprolactone)gelatinextracellular matrix |
| spellingShingle | Mattia Spedicati Mattia Spedicati Mattia Spedicati Gerardina Ruocco Gerardina Ruocco Gerardina Ruocco Alice Zoso Alice Zoso Alice Zoso Leonardo Mortati Andrea Lapini Andrea Lapini Andrea Delledonne Carla Divieto Veronica Romano Clotilde Castaldo Franca Di Meglio Daria Nurzynska Irene Carmagnola Irene Carmagnola Irene Carmagnola Valeria Chiono Valeria Chiono Valeria Chiono Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis Frontiers in Bioengineering and Biotechnology bioartificial scaffold cardiac fibrosis in vitro model poly(caprolactone) gelatin extracellular matrix |
| title | Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis |
| title_full | Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis |
| title_fullStr | Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis |
| title_full_unstemmed | Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis |
| title_short | Biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis |
| title_sort | biomimetic design of bioartificial scaffolds for the in vitro modelling of human cardiac fibrosis |
| topic | bioartificial scaffold cardiac fibrosis in vitro model poly(caprolactone) gelatin extracellular matrix |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.983872/full |
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