Details
| Original language | English |
|---|---|
| Pages (from-to) | 940-951 |
| Number of pages | 12 |
| Journal | Biomaterials |
| Volume | 34 |
| Issue number | 4 |
| Publication status | Published - 6 Nov 2012 |
Abstract
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.
Keywords
- Alginate, Cardiomyocytes, Hyaluronic acid, Hydrazones, Hydrogels, Myocardial tissue engineering
ASJC Scopus subject areas
- Chemical Engineering(all)
- Bioengineering
- Materials Science(all)
- Ceramics and Composites
- Biochemistry, Genetics and Molecular Biology(all)
- Biophysics
- Materials Science(all)
- Biomaterials
- Engineering(all)
- Mechanics of Materials
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In: Biomaterials, Vol. 34, No. 4, 06.11.2012, p. 940-951.
Research output: Contribution to journal › Article › Research › peer review
}
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 -