Self Assembling Peptide Nanofibers for Extracellular Matrix Remodeling in Diabetic Cardiomyopathy
Journal of Bioengineering and Biomedical Sciences
In the diabetic heart, increased collagen accumulation, stiffness and cardiac dysfunction may be linked to the reduced expression and activity of matrix metalloproteinase-2 (MMP-2), suggesting that diabetes-associated cardiac fibrosis may be attenuated through stimulation of native MMP-2 expression or delivery of exogenous MMP-2. Peptide nanofibers were investigated as a microenvironment for cardiac regeneration via endogenous MMP-2 stimulation or exogenous MMP-2 delivery to promote matrix
... promote matrix remodeling by wild type and diabetic cardiac fibroblasts. Cells were isolated from wild type or diabetic rat hearts and embedded in nanofibers, nanofibers with exogenous MMP-2, and Matrigel controls for 1, 6 and 14 days. Responses associated with matrix remodeling were assessed, including cell survival, native MMP-2 expression, ECM deposition and construct stiffness. The results demonstrate that nanofiber scaffolds provide an effective delivery vehicle with gradual MMP-2 release, while supporting long term survival and temporal matrix remodeling by cardiac fibroblasts. Nanofiber scaffolds maintained the balance between cell proliferation and apoptosis, in contrast to increased apoptosis with time in culture in Matrigel. Diabetic and wild type fibroblasts showed different temporal trends for MMP-2 expression, collagen I deposition and scaffold stiffness, indicating increased matrix remodeling by diabetic cells in the nanofiber microenvironment. The data suggest that stimulation of native MMP expression by the NFs alone may be the more Suitable strategy to improve reparative matrix remodeling. Overall, the results suggest that peptide nanofibers may be uniquely suited to increase local MMP-2 concentration in the diabetic heart and may be promising for applications focused on therapeutic matrix remodeling and cardiac regeneration.