Engineering Biomaterials and Biomolecules for Vascular Regeneration

Tissue engineering and regenerative medicine is a multidisciplinary field that combines the knowledge and technologies of biology, materials, chemistry and medicine among others. Within the realm of tissue repair and regeneration, vascular reconstruction, in particular, is influenced by both biophysical and biochemical cues and it is critical to fully understand how these cues interact with the physiological microenvironment. In this dissertation, we demonstrated how host vascular regenerative potential can be harnessed by optimizing vascular grafts from both the biomaterial and biochemical perspectives. We utilized and optimized electrospinning technology to create microfibrous vascular grafts. We showed that incorporating a fast degrading polymer into the vascular grafts effectively enhances cell infiltration without majorly compromising its mechanical and structural properties. Our in vivo data suggests that although the optimized vascular graft was able to induce the initiation of vascular regeneration, the process was accelerated and enhanced with the help of biochemical cues presented in the form of stromal cell-derived factor-1α (SDF-1α). In the presence of chemokine SDF-1α, the vascular grafts demonstrated better wall remodeling and long-term patency. This observation again highlights the significance of both biomaterial and biochemical effects. While the vascular grafts in our studies might recruit inflammatory cells, calcification which is a destructive complication typically associated with inflammatory response was not observed. The final part of this dissertation details our efforts in using protein engineering to broaden the biological application of SDF-1α by introducing a free cysteine residue on its C-terminus. We showed that the cysteine-modified SDF-1α exhibits a bioactivity different from its unmodified counterpart, the underlying mechanism of which needs to be elucidated in future studies. Taken together, this work is expected to provide insights into optimization of vascular graft platforms for broad therapeutic applications