TY - JOUR

T1 - Dextran-based scaffolds for in-situ hydrogelation

T2 - Use for next generation of bioartificial cardiac tissues

AU - Banerjee, Samhita

AU - Szepes, Monika

AU - Dibbert, Nick

AU - Rios-Camacho, Julio-Cesar

AU - Kirschning, Andreas

AU - Gruh, Ina

AU - Dräger, Gerald

N1 - Funding Information: This study was funded by the REBIRTH Cluster of Excellence (EXC62, DFG, Germany) and the REBIRTH Research Center for Translational Regenerative Medicine ( ZN3440 , State of Lower Saxony, Ministry of Science and Culture (Nieders. Vorab), Germany).

PY - 2021/6/15

Y1 - 2021/6/15

N2 - In pursuit of a chemically-defined matrix for in vitro cardiac tissue generation, we present dextran (Dex)-derived hydrogels as matrices suitable for bioartificial cardiac tissues (BCT). The dextran hydrogels were generated in situ by using hydrazone formation as the crosslinking reaction. Material properties were flexibly adjusted, by varying the degrees of derivatization and the molecular weight of dextran used. Furthermore, to modulate dextran's bioactivity, cyclic pentapeptide RGD was coupled to its backbone. BCTs were generated by using a blend of modified dextran and human collagen (hColI) in combination with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and fibroblasts. These hColI + Dex blends with or without RGD supported tissue formation and functional maturation of CMs. Contraction forces (hColI + Dex-RGD: 0.27 ± 0.02 mN; hColI + Dex: 0.26 ± 0.01 mN) and frequencies were comparable to published constructs. Thus, we could demonstrate that, independent of the presence of RGD, our covalently linked dextran hydrogels are a promising matrix for building cardiac grafts.

AB - In pursuit of a chemically-defined matrix for in vitro cardiac tissue generation, we present dextran (Dex)-derived hydrogels as matrices suitable for bioartificial cardiac tissues (BCT). The dextran hydrogels were generated in situ by using hydrazone formation as the crosslinking reaction. Material properties were flexibly adjusted, by varying the degrees of derivatization and the molecular weight of dextran used. Furthermore, to modulate dextran's bioactivity, cyclic pentapeptide RGD was coupled to its backbone. BCTs were generated by using a blend of modified dextran and human collagen (hColI) in combination with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and fibroblasts. These hColI + Dex blends with or without RGD supported tissue formation and functional maturation of CMs. Contraction forces (hColI + Dex-RGD: 0.27 ± 0.02 mN; hColI + Dex: 0.26 ± 0.01 mN) and frequencies were comparable to published constructs. Thus, we could demonstrate that, independent of the presence of RGD, our covalently linked dextran hydrogels are a promising matrix for building cardiac grafts.

KW - Cardiac tissue engineering

KW - Cardiomyocytes

KW - Dextran

KW - Human induced pluripotent stem cells

KW - Hydrogel

KW - RGD peptide

UR - http://www.scopus.com/inward/record.url?scp=85102839813&partnerID=8YFLogxK

U2 - 10.1016/j.carbpol.2021.117924

DO - 10.1016/j.carbpol.2021.117924

M3 - Article

C2 - 33838803

AN - SCOPUS:85102839813

VL - 262

JO - Carbohydrate polymers

JF - Carbohydrate polymers

SN - 0144-8617

M1 - 117924

ER -