Development and Characterization of Novel Biomaterials for Fabrication of Multilayered Vascular Grafts



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Current synthetic alternatives to autologous grafts have often failed in small diameter applications (<6 mm) due to their thrombogenicity and compliance mismatch of native vasculature. No known synthetic material is capable of providing a non-thrombogenic inner layer that promotes endothelial cell (EC) interactions while also providing sufficient compliance and burst pressure for long term success in vivo. We have developed a multilayer design with an inner thromboresistant poly(ethylene glycol) (PEG) hydrogel based on Scl2-2 proteins designed to promote rapid in situ endothelialization. The bioactive component is reinforced with an electrospun segmented polyurethane (SPU) layer with tunable mechanical properties to withstand physiological loading conditions. The modulating of electrospun parameters to influence graft architecture coupled with the tunability of SPU mechanical performance is expected to give rise to improved graft biomechanical properties. Unfortunately, this advantage was found to be limited to only one property at a time. To this end, we have developed a novel semi-IPN approach to expand the range of possible graft compliance and burst pressures in order to simultaneously achieve biomechanical properties that exceed autologous veins.

In addition to matching biomechanical properties, probability of long term success is also dependent on the grafts retention of perfomance despite cell-mediated attack. Typically, in the case poly(ether urethanes) (PEUs) and poly(carbonate urethanes) (PCUs), oxidative stability is the primary focus in the development of biostable SPUs. We have characterized the biostability of several commercially available polyurethanes while simultaneously evaluating the predictive capabilities of two main in vitro test methods to optimize our graft?s design.

Despite ensured long term performance through optimizing biostability, a permanent scaffold prevents vasoactivity, a key function of vasculature. We have taken a tissue engineering approach to restorate vasoactivity by evaluating a novel aromatic biodegradable poly(ester urethane) (PEsU) for the reinforcing layer of a tissue engineering vascular graft (TEVG). This PEsU was expected to degrade into safe byproducts given its design based on glycolic acid and ethylene glycol. Following characterization, the PEsU was determined to be a strong potential reinforcing layer of a potential TEVG design.

In summary, we have improved small diameter grafts through a multilayer design approach. Our graft demonstrated favorable initial fabrication feasibility, promising in vivo testing, biomechanical properties exceeding autologous veins, and strong oxidative stability. Overall, we have optimized the reinforcing layer through improvement of biomechanical properties via modulated material chemistry, optimized biostability, and identification of a biodegradable component expected to allow for restored vasoactivity.