Wesley Hejl

Introduction: Coronary artery disease is a disease involving lipid deposition both intracellularly and extracellularly in the walls of the coronary arteries of the heart¹. This disease is a leading cause of death of death both in the United States and worldwide¹. The disease progression is well researched and results from initial endothelial injury². Current treatments include stenting and bypass grafting with autologous venous grafts. Current grafting techniques face several challenges including compliance mismatching, and clotting³. Developing a small diameter vascular graft via tissue engineering techniques could provide a novel clinical solution. Mechanical forces have been shown to play a major role in developing small diameter arteries similar to those found in vivo. Methods:  Mef2b-Nox1 was explored as a possible signaling pathway of importance in mechanotransduction⁴. The role of cyclic mechanical forces play ion growing patent small diameter vascular grafts was assessed by imposing different mechanical forces on developing grafts in bioreactors. The role of both uniaxial and biaxial forces on graft development were assessed⁵.  The effects of different frequencies of cyclic straining on cytoskeletal rearrangement in smooth muscle cells as well as endothelium was assessed⁶.  Changes in the histological and mechanical properties of grafts due to biaxial vs uniaxial stretch was assessed using light microscopy and various mechanical techniques such as the opening angle⁵.  Augmenting current grafting techniques using electrospinning technology was considered after its success as a short term scaffold⁷. Results: MEF2b-Nox1 was shown to be increased cells experiencing increased mechanical stress similar to that caused by hypertension. The increase in MEF2-Nox1 signaling corresponded with increased reactive oxygen species in the cell⁴. Changing the frequency of mechanical forces on developing grafts showed a frequency dependence on vascular graft remodeling. Increasing the frequency of cyclic force increases the activity of RhoA and Rac1 causing an increase in cytoskeletal rearrangement⁶. In biaxial cyclic stretch, histological studies showed increased mature elastin and collagen deposition. Mechanical studies showed a decreased toe region and compliance similar to those found in native vessels⁵. Electrospun scaffolds show potential for increased cell infiltration shown by graft patency and ECM deposition in implanted scaffolds in the sheep model⁸. Conclusions: The intracellular mechanisms for mechanotransduction of axial and circumferential force are still unclear and remain to be elucidated. Use of cyclic stretch in bioreactors is promising technology that could lead to clinically useful grafts. Pairing with electrospun scaffolds shows possibilities for efficacy.

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