Despite three decades of intense research into small diameter blood vessel tissue engineering, constructs developed to date lack the elastin necessary for long term patency and the prevention of aneurysms. The suboptimal biochemical composition suggests that new biochemical and mechanical culture methods must be developed. In addition, current biomaterials for tissue engineering lack the strength and elasticity needed for a small diameter blood vessel tissue engineering scaffold. Toward that end, work in our laboratory has lead to the development of poly(diol citrates), a novel family of biodegradable elastomers that has shown significant promise for soft tissue engineering. The long-term goal of the proposed research is to utilize biodegradable elastomers such as poly(diol citrates) to examine and optimize the effect of biochemical and mechanical culture conditions on small diameter blood vessel tissue development. However, before this long-term goal can be reached, further work must be done with poly(diol citrates). Additionally, a bioreactor capable of culturing a blood vessel construct under a variety of mechanical conditions must be developed. This dissertation details the initial steps towards a tissue engineered small diameter blood vessel. In the first aim, since the current method of examining the extent of reaction of thermoset elastomers is not appropriate for poly(diol citrates), a new method was developed based on equilibrium swelling and dynamic mechanical analysis. This method was then used to examine the effect of extent of reaction on mechanical properties. Although this method was only used with poly(1,8-octanediol-co-citrate), it should be applicable to other thermoset elastomers in which the current method for determining the extent of reaction may not be appropriate. In the second aim, a novel bioreactor system capable of imparting a range of pulsatile pressure profiles and flow conditions was developed. The system can set any range of flow and pressure conditions independent of each other while in real time non-invasively measure vessel distension to an accuracy of  2m. The system should allow investigation into the effects of mechanical stimulation and vessel compliance on in vitro small diameter blood vessel tissue engineering. Finally, since the mechanical properties of poly(diol citrates) in the wet state are not sufficient for a small diameter blood vessel tissue engineering scaffold, poly(diol citrate) nanocomposites with enhanced mechanical properties were developed. Poly(diol citrates) were reinforced with poly(lactic-co-glycolic acid) nanoparticles or a poly(L-lactic acid) nanofibrous network. For both methods of reinforcement, the mechanical properties increased with the concentration of nanophase or with increased polymerization time and/or temperature. Furthermore, although the nanocomposites showed an increase in mechanical properties, the materials maintained their elasticity and therefore can be used for soft tissue engineering where mechanical stimulation during development has been shown to be beneficial. However, further work must be done to tailor the mechanical properties for a small diameter blood vessel tissue engineering scaffold.

Last modified

• 09/06/2018

Creator

• Antonio Roy Webb

DOI

• https://doi.org/10.21985/N2KT6B

Subject

• Biomedical Engineering

Keyword

• elastomer
• biomaterials
• vascular graft
• tissue engineering
• bioreactor

Date created

• 2008-03-13

Resource type

• Dissertation

Rights statement

• In Copyright