A Visible Light-Cross-Linkable, Fibrin–Gelatin-Based Bioprinted Construct with Human Cardiomyocytes and Fibroblasts

In this study, fibrin was added to a photopolymerizable gelatin-based bioink mixture to fabricate cardiac cell-laden constructs seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) or CM cell lines with cardiac fibroblasts (CF). The extensive use of platelet-rich fibrin, i...

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Bibliographic Details
Published in:	ACS biomaterials science & engineering Vol. 5; no. 9; pp. 4551 - 4563
Main Authors:	Anil Kumar, Shweta, Alonzo, Matthew, Allen, Shane C, Abelseth, Laila, Thakur, Vikram, Akimoto, Jun, Ito, Yoshihiro, Willerth, Stephanie M, Suggs, Laura, Chattopadhyay, Munmun, Joddar, Binata
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 09-09-2019
Subjects:	biofabrication 3D bioprinting thrombin fibrinogen furfuryl−gelatin cardiac tissue furfuryl–gelatin
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Summary:	In this study, fibrin was added to a photopolymerizable gelatin-based bioink mixture to fabricate cardiac cell-laden constructs seeded with human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) or CM cell lines with cardiac fibroblasts (CF). The extensive use of platelet-rich fibrin, its capacity to offer patient specificity, and the similarity in composition to surgical glue prompted us to include fibrin in the existing bioink composition. The cell-laden bioprinted constructs were cross-linked to retain a herringbone pattern via a two-step procedure including the visible light cross-linking of furfuryl–gelatin followed by the chemical cross-linking of fibrinogen via thrombin and calcium chloride. The printed constructs revealed an extremely porous, networked structure that afforded long-term in vitro stability. Cardiomyocytes printed within the sheet structure showed excellent viability, proliferation, and expression of the troponin I cardiac marker. We extended the utility of this fibrin–gelatin bioink toward coculturing and coupling of CM and cardiac fibroblasts (CF), the interaction of which is extremely important for maintenance of normal physiology of the cardiac wall in vivo. This enhanced “cardiac construct” can be used for drug cytotoxicity screening or unraveling triggers for heart diseases in vitro.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 S.A.K. and M.A. share equal contribution as first authors in this manuscript. S.A.K. and M.A. performed the experiments repeatedly and collected and analyzed the data. L.A. and S.W. prepared and provided the fibrinogen solutions in varying concentrations and provided technical inputs. S.A.K., M.A., and B.J. wrote the manuscript and prepared all the figures. S.C.A. and L.S. performed rheology and analyzed the resultant data. V.T. and M.C. facilitated the CM and CF cultures, cell coupling experiments, and their microscopic imaging along with images and writing of relevant sections in the manuscript. J.A. and Y.I. provided the furfuryl–gelatin and performed cytotoxicity assay for Rose Bengal. All authors reviewed the manuscript and provided their consent for publication. The manuscript was written through individual contributions of all authors. All authors have given approval to the final version of the manuscript.
ISSN:	2373-9878 2373-9878
DOI:	10.1021/acsbiomaterials.9b00505