title: Biomimetic Polymers for Cardiac Tissue Engineering.
abstract: Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Brisa
authors.initials: B
authors.lastname: Peña
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Mark
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Bosi
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Romano
authors.initials: R
authors.lastname: Lapasin
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Matthew R G
authors.initials: MR
authors.lastname: Taylor
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Carlin S
authors.initials: CS
authors.lastname: Long
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Shandas
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Daewon
authors.initials: D
authors.lastname: Park
authors.affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.|I.C.G.E.B. and ∥ University of Trieste , Trieste Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Mestroni
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D032701:Biomimetics / Q000379:methods*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D007797:Laminin / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D007797:Laminin; D011108:Polymers; D008239:Lysine