title: Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for myocardial tissue engineering.
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.
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs, REBIRTH Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Dahlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Krause
authors.forename: Lena
authors.initials: L
authors.lastname: Möller
authors.forename: George
authors.initials: G
authors.lastname: Kensah
authors.forename: Markus
authors.initials: M
authors.lastname: Möwes
authors.forename: Astrid
authors.initials: A
authors.lastname: Diekmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Martin
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirschning
authors.forename: Ina
authors.initials: I
authors.lastname: Gruh
authors.forename: Gerald
authors.initials: G
authors.lastname: Dräger
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000737:chemistry; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D004867:Equipment Design; D020723:Glucuronic Acid / Q000737:chemistry; D006321:Heart / Q000254:growth & development*; D006603:Hexuronic Acids / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D006820:Hyaluronic Acid