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    Surface functionalization of polyurethane scaffolds mimicking the myocardial microenvironment to support cardiac primitive cells

    Year: 2018

    Journal: PLoS One, Volume 13, JUL 6

    Authors: Boffito, Monica; Di Meglio, Franca; Mozetic, Pamela; Giannitelli, Sara Maria; Carmagnola, Irene; Castaldo, Clotilde; Nurzynska, Daria; Sacco, Anna Maria; Miraglia, Rita; Montagnani, Stefania; Vitale, Nicoletta; Brancaccio, Mara; Tarone, Guido; Basoli, Francesco; Rainer, Alberto; Trombetta, Marcella; Ciardelli, Gianluca; Chiono, Valeria

    Organizations: MIUR-FIRB [RBFR10L0GK]; European Social Fund; European Regional Development Fund [CZ.02.1.01/0.0/0.0/15_003/0000492]

    Scaffolds populated with human cardiac progenitor cells (CPCs) represent a therapeutic opportunity for heart regeneration after myocardial infarction. In this work, square-grid scaffolds are prepared by melt-extrusion additive manufacturing from a polyurethane (PU), further subjected to plasma treatment for acrylic acid surface grafting/polymerization and finally grafted with laminin-1 (PU-LN1) or gelatin (PU-G) by carbodiimide chemistry. LN1 is a cardiac niche extracellular matrix component and plays a key role in heart formation during embryogenesis, while G is a low-cost cell-adhesion protein, here used as a control functionalizing molecule. X-ray photoelectron spectroscopy analysis shows nitrogen percentage increase after functionalization. O1s and C1s core-level spectra and static contact angle measurements show changes associated with successful functionalization. ELISA assay confirms LN1 surface grafting. PU-G and PU-LN1 scaffolds both improve CPC adhesion, but LN1 functionalization is superior in promoting proliferation, protection from apoptosis and expression of differentiation markers for cardiomyocytes, endothelial and smooth muscle cells. PU-LN1 and PU scaffolds are biodegraded into non-cytotoxic residues. Scaffolds subcutaneously implanted in mice evoke weak inflammation and integrate with the host tissue, evidencing a significant blood vessel density around the scaffolds. PU-LN1 scaffolds show their superiority in driving CPC behavior, evidencing their promising role in myocardial regenerative medicine.
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