Aprotinin extends mechanical integrity time of cell-seeded fibrin sutures

Cell therapy has the potential to treat different pathologies, including myocardial infarctions (heart attacks), although cell engraftment remains elusive with most delivery methods. Biological sutures composed of fibrin have been shown to effectively deliver human mesenchymal stem cell (MSC) to infarcted hearts. However, human MSCs rapidly degrade fibrin making cell seeding and delivery time sensitive. To delay the degradation process, we propose using Aprotinin, a proteolytic enzyme inhibitor that has been shown to slow fibrinolysis. Human MSCs seeded on fibrin sutures and incubated with Aprotinin demonstrated similar cell viability, examined using a LIVE/DEAD stain, to controls. No differences in proliferation, as determined by Ki-67 presence, were observed. Human MSCs incubated in Aprotinin differentiated into adipocytes, osteocytes, and chondrocytes, confirming multipotency. The number of cells adhered to fibrin sutures increased through Aprotinin supplementation at 2, 3, and 5 day time points. Uniaxial tensile testing was used to examine the effect of Aprotinin on suture integrity. Sutures exposed to Aprotinin had higher ultimate tensile strength and modulus when compared to sutures exposed to standard growth media. Fibrin sutures incubated in Aprotinin had larger diameters and less fibrin degradation products compared to the controls, confirming decreased fibrinolysis. These data suggest that Aprotinin can reduce degradation of fibrin sutures without significant effects on MSC function, providing a novel method for extending the implantation window and increasing the number of cells delivered via fibrin sutures. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2271-2279, 2016.