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Cardiomyocytes in vitro adhesion is actively influenced by biomimetic synthetic peptides for cardiac tissue engineering.

ABSTRACT: Scaffolds for tissue engineering must be designed to direct desired events such as cell attachment, growth, and differentiation. The incorporation of extracellular matrix-derived peptides into biomaterials has been proposed to mimic biochemical signals. In this study, three synthetic fragments of fibronectin, vitronectin, and stromal-derived factor-1 were investigated for the first time as potential adhesive sequences for cardiomyocytes (CMs) compared to smooth muscle cells. CMs are responsive to all peptides to differing degrees, demonstrating the existence of diverse adhesion mechanisms. The pretreatment of nontissue culture well surfaces with the (Arginine-Glycine-Aspartic Acid) RGD sequence anticipated the appearance of CMs' contractility compared to the control (fibronectin-coated well) and doubled the length of cell viability. Future prospects are the inclusion of these sequences into biomaterial formulation with the improvement in cell adhesion that could play an important role in cell retention during dynamic cell seeding.

SUBMITTER: Gandaglia A

PROVIDER: S-EPMC3313615 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Cardiomyocytes in vitro adhesion is actively influenced by biomimetic synthetic peptides for cardiac tissue engineering.

Gandaglia Alessandro A Huerta-Cantillo Rocio R Comisso Marina M Danesin Roberta R Ghezzo Francesca F Naso Filippo F Gastaldello Alessandra A Schittullo Eleonora E Buratto Edward E Spina Michele M Gerosa Gino G Dettin Monica M

Tissue engineering. Part A 20111205 7-8

Scaffolds for tissue engineering must be designed to direct desired events such as cell attachment, growth, and differentiation. The incorporation of extracellular matrix-derived peptides into biomaterials has been proposed to mimic biochemical signals. In this study, three synthetic fragments of fibronectin, vitronectin, and stromal-derived factor-1 were investigated for the first time as potential adhesive sequences for cardiomyocytes (CMs) compared to smooth muscle cells. CMs are responsive t ...[more]

PMID: 22011064

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Project description:Natural polymer hydrogels are used ubiquitously as scaffold materials for cardiac tissue engineering as well as for soft tissue engineering more broadly because of FDA approval, minimal immunogenicity, and well-defined physiological clearance pathways. However, the relationships between natural polymer hydrogels and resident cell populations in directing the development of engineered tissues are poorly defined. This interaction is of particular concern for tissues prepared with iPSC-derived cell populations, in which population purity and batch-to-batch variability become additional critical factors to consider. Herein, the design space for a blended fibrin and collagen scaffold is characterized for applications in creating engineered myocardium with human iPSC-derived cardiomyocytes. Stiffness values of the acellular hydrogel formulations approach those of native myocardium in compression, but deviate significantly in tension when compared to rat myocardium in both transverse and longitudinal fiber orientations. A response surface methodology approach to understanding the relationship between collagen concentration, fibrin concentration, seeding density, and cardiac purity found a statistically significant predictive model across three repeated studies that confirms that all of these factors contribute to tissue compaction. In these constructs, increased fibrin concentration and seeding density were each associated with increased compaction, while increased collagen concentration was associated with decreased compaction. Both the lowest (24.4% cTnT+) and highest (60.2% cTnT+) cardiomyocyte purities evaluated were associated with decreased compaction, whereas the greatest compaction was predicted to occur in constructs prepared with a 40-50% cTnT+ population. Constructs prepared with purified cardiomyocytes (≥75.5% cTnT+) compacted and formed syncytia well, although increased fibrin concentration in these groups was associated with decreased compaction, a reversal of the trend observed in unpurified cardiomyocytes. This study demonstrates an analytical approach to understanding cell-scaffold interactions in engineered tissues and provides a foundation for the development of more sophisticated and customized scaffold platforms for human cardiac tissue engineering.

Project description:Joints that connect thermoplastic polymer matrices (TPMs) and metals, which are obtained by comolding, are of growing importance in numerous applications. The overall performance of these constructs is strongly impacted by the TPM-metal interfacial strength, which can be tuned by tailoring the surface chemistry of the metal prior to the comolding process. In the present work, a model TPM-metal system consisting of poly(methyl methacrylate) (PMMA) and titanium is used to prepare comolded joints. The interfacial adhesion is quantified by wire pullout experiments. Pullout tests prior to and following surface modification are performed and analyzed. Unmodified wires show poor interfacial strength, with a work of adhesion (Ga) value of 3.8 J m-2. To enhance interfacial adhesion, a biomimetic polydopamine (PDA) layer is first deposited on titanium followed by a second layer of a poly(methyl methacrylate-co-methacrylic acid) (P(MMA-co-MAA)) copolymer prior to comolding. During processing, the MAA moieties of the copolymer thermally react with PDA, forming amide bonds, while MMA promotes the formation of secondary bonds and molecular interdigitation with the PMMA matrix. Control testing reveals that neither PDA nor the copolymer provides a substantial increase in adhesion. However, when used in combination, a significant increase in adhesion is detected. This observation indicates a pronounced synergistic effect between the two layers that strengthens the PMMA-titanium bonding. Enhanced adhesion is optimized by tuning the MMA-to-MAA ratio of the copolymer, which shows a maximum at a 24% MAA content and a greatly increased Ga value of 155 J m-2; this value corresponds to a 40-fold increase. Further growth in the Ga values at higher MAA contents is hindered by the thermal cross-linking of MAA; MAA contents above 24% restrict the formation of secondary bonds and molecular interdigitation with the PMMA chains. Our results provide new design principles to produce thermoplastic-metal comolded joints with strong interfaces.

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Cardiomyocytes in vitro adhesion is actively influenced by biomimetic synthetic peptides for cardiac tissue engineering.

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Cardiomyocytes in vitro adhesion is actively influenced by biomimetic synthetic peptides for cardiac tissue engineering.

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