TY - JOUR

T1 - Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for myocardial tissue engineering

AU - Dahlmann, Julia

AU - Krause, Andreas

AU - Möller, Lena

AU - Kensah, George

AU - Möwes, Markus

AU - Diekmann, Astrid

AU - Martin, Ulrich

AU - Kirschning, Andreas

AU - Gruh, Ina

AU - Dräger, Gerald

N1 - Funding information: We thank Ingrid Schmidt-Richter and Tibor Horvarth for excellent technical assistance. This work was funded by the Cluster of Excellence REBIRTH ( DFG EXC 62/1 ).

PY - 2012/11/6

Y1 - 2012/11/6

N2 - Despite recent major advances including reprogramming and directed cardiac differentiation of human cells, therapeutic application of in vitro engineered myocardial tissue is still not feasible due to the inability to construct functional large vascularized contractile tissue patches based on clinically applicable and fully defined matrix components. Typical matrices with preformed porous 3D structure cannot be applied due to the obvious lack of migratory capacity of cardiomyocytes (CM). We have therefore developed a fully defined in situ hydrogelation system based on alginate (Alg) and hyaluronic acid (HyA), in which their aldehyde and hydrazide-derivatives enable covalent hydrazone cross-linking of polysaccharides in the presence of viable myocytes. By varying degrees of derivatization, concentrations and composition of blends in a modular system, mechanophysical properties of the resulting hydrogels are easily adjustable. The hydrogel allowed for the generation of contractile bioartificial cardiac tissue from CM-enriched neonatal rat heart cells, which resembles native myocardium. A combination of HyA and highly purified human collagen I led to significantly increased active contraction force compared to collagen, only. Therefore, our in situ cross-linking hydrogels represent a valuable toolbox for the fine-tuning of engineered cardiac tissue's mechanical properties and improved functionality, facilitating clinical translation toward therapeutic heart muscle reconstruction.

AB - Despite recent major advances including reprogramming and directed cardiac differentiation of human cells, therapeutic application of in vitro engineered myocardial tissue is still not feasible due to the inability to construct functional large vascularized contractile tissue patches based on clinically applicable and fully defined matrix components. Typical matrices with preformed porous 3D structure cannot be applied due to the obvious lack of migratory capacity of cardiomyocytes (CM). We have therefore developed a fully defined in situ hydrogelation system based on alginate (Alg) and hyaluronic acid (HyA), in which their aldehyde and hydrazide-derivatives enable covalent hydrazone cross-linking of polysaccharides in the presence of viable myocytes. By varying degrees of derivatization, concentrations and composition of blends in a modular system, mechanophysical properties of the resulting hydrogels are easily adjustable. The hydrogel allowed for the generation of contractile bioartificial cardiac tissue from CM-enriched neonatal rat heart cells, which resembles native myocardium. A combination of HyA and highly purified human collagen I led to significantly increased active contraction force compared to collagen, only. Therefore, our in situ cross-linking hydrogels represent a valuable toolbox for the fine-tuning of engineered cardiac tissue's mechanical properties and improved functionality, facilitating clinical translation toward therapeutic heart muscle reconstruction.

KW - Alginate

KW - Cardiomyocytes

KW - Hyaluronic acid

KW - Hydrazones

KW - Hydrogels

KW - Myocardial tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=84870373723&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2012.10.008

DO - 10.1016/j.biomaterials.2012.10.008

M3 - Article

C2 - 23141898

AN - SCOPUS:84870373723

VL - 34

SP - 940

EP - 951

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 4

ER -