Problems with current TEVGs

Meeting the requirements for a functional TEVG for use in a clinical setting is still difficult to achieve. Currently, there are no approaches that are able to physiologically mimic the native vessel. Specifically, there are no constructs that have been developed to have the circumferential alignment of the SMCs, collagen fibers, and elastin lamellae, which is a key feature of the tunica media. Furthermore, elastin fibers that mature (i.e. cross-link with each other) is a significant requirement to provide vessel compliance for the arterial pressure range, yet only the self-assembly approach using fibroblasts were able to achieve sucessful maturation. Overcoming this challenge may provide the critical step that is required for functional TEVGs [L’Heureux et al].

 

Another challenge lies in the endothelialization of current TEVGs. Once the challenge of creating a mature, elastin network within the graft is overcome, the graft would require an endothelium that would not induce a significant immune response by the host and prevent any thrombosis from occurring. In order to accomplish this, the host’s endothelial cells would have to be extracted and grown to cover the useful length. The problem with this is that it can take many weeks for the isolation and expansion of the endothelial cells of the graft. Outsourcing of the endothelial is also not a possibility at this moment because there are no current substitutes for autologous cells that can minimize the immune response.  

 

Some New Considerations

There has been a recent study that published the ability to develop a matured elastin fiber network with the use of neonatal SMCs seeded into fibrin-based constructs, which gradually become remodeled (Isenberg, 2006). There is still much more work on ideas that has yet to be tested in regards to elastogenesis.

 

Since current technologies require highly invasive procedures to monitor the performance or status of grafts, the development of an imaging system that can measure all of the parameters measured by invasive procedures would be very beneficial to research. The ability to monitor performance can provide longer studies, and may open up doors to clinical usage.

 

Creating a set of predictive parameters for optimal tissue growth has the potential to lead to the development of new physical models. The development of these model systems has the potential to ultimately relate the remodeling of the ECM to the mechanical/functional properties. There have been recent developments using continuum mechanics models to understand vascular growth and remodeling (Gleason, 2004).

 

Several techniques have been recently developed to be able to capture the same natural nanometer architecture of the vascular basement membrane of veins. Some of these techniques include colloidal lithography, chemical etching, and electrospinning (Miller, 2007). Furthermore, many groups may start looking into local nanoscale mechanical properties of natural arteries and fabricated grafts. With the rapidly-growing field of nanotechnology, its implementation can significantly enhance the ability to properly characterize the surrounding environment.