The objective of this research award is to investigate "vascular wall engineering" (VWE) using a highly synergistic combination of electrospinning, ultrafast femtosecond laser machining and biological integration. These unique, multi-scalar grafts meet the structural and biological requirements normally supplied by human vascular tissues. By studying the fundamental phenomena inherent to each distinct, contributing process, the resulting grafts will be tailorable and can modulate cell adhesion and, ultimately, the clotting response that normally prevents long-term function of synthetic vascular grafts.
VWE that integrates synthetic materials with living cells within biomechanically capable, 3D-structured vascular grafts is desperately needed. The inherent compositional, manufacturing and multiscalar flexibility of this process ultimately allows widespread, rapid reproduction of natural structures. Successful VWE will provide broad treatments for patients having a variety of serious clinical disorders. By studying and integrating two distinct forms of material processing with biomedical engineering, the opportunity exists to create a highly capable platform technology for future manufacturing. This research will support two PhD-level graduate students whose training is essential to the future competitiveness of the US in the domain of biomedical innovation. It also provides a research context continuing the involvement of under-represented minorities at both the high school and undergraduate levels. A presentation entitled ?Tissue Engineering the Human Body? will be developed for use in the Center of Science and Industry?s COSI Academy, a program for aspiring 14 to 18 year-old scientists and engineers.
Coronary vascular disease is the leading cause of death in the US. Coronary bypass grafting is the standard treatment. However, many in the US do not have blood vessels healthy enough for this procedure. About 15% of those patients must use synthetic implants. Thus, a strong need for synthetic, small-diameter vascular grafts exists. In response, our proposal, Laser Machined Vascular Wall Engineering for Blood Vessel Manufacturing, was funded by the Civil, Mechanical and Manufacturing Innovation (CMMI) Division in 2009 and this Project Outcomes Report briefly summarizes progress made since that time. We have been successful in combining very different materials manufacturing techniques to provide the targeted seeding needed to create "vascular wall engineering." Our approach envisions layer-wise construction to integrate three distinct processes demonstrating easily tailored fabrication of vascular grafts. Electrospinning of tubular implants Femtosecond laser ablation Cell seeding on or within these implants (Figure 1) In pursuing these three approaches, we have shown that electrospinning can be combined with localized laser ablation to achieve precise control over the internal physical dimensions of these resorbable structures. We have worked together to design and build the integrated fabrication mechanism and demonstrate that the manufacturing process provides desired internal and external morphologies without compromising either the nanoscaled surface or overall mechanical properties. Integration of representative mammalian cells (Figure 1) was also examined to check and modify the targeted dimensions and demonstrate biological assembly outside the body with unprecedented levels of sophistication. Finally, suture retention strength (SRS) is widely used measure of the ability of sutures to adhere such implants to surrounding tissue. Although broadly employed, the effects of sutures on the microstructure of engineered implants is poorly understood. This is particularly important for broad utilization of electrospun implants in tissue engineering. These implants must retain their initial nanoscale topography while simultaneously preserving clinically critical mechanical properties. Our findings are significant as they allow us to employ new, counterintuitive design criteria for nanofiber-based scaffolds in which reliable mechanical integration with the surrounding tissues via suture-based methods is important. This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
