Date of Award

January 2015

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Jay D. Humphrey

Second Advisor

Tarek Fahmy

Subject Area(s)

Biomedical engineering, Materials Science

Abstract

Tissue-engineered vascular grafts (TEVGs) offer tremendous therapeutic potential for congenital cardiovascular malformations, and our computational model of growth and remodeling may help expedite TEVG design by identifying optimal scaffold parameters. To evaluate our model’s assumptions about scaffold physical properties, we measured the effects of in vitro hydrolytic degradation on the compressibility and mechanical behavior of poly(glycolic acid) (PGA) scaffolds. Degradation in neutral PBS at 37°C passed through two stages of first-order decay: the first 50 percent of PGA mass was lost from 5 to 40 days (~1 to 6 weeks) at a rate constant of 0.175/wk, after which the mass degraded with a rate constant of 0.091/wk. The half-life of PGA coincided with a drop in the rate of pH change from 2.5/wk to 1.5/wk at 6 weeks, showing that the remaining mass of polymer influences the creation of acidic degradation byproducts from PGA. Over 25 days, the degrading scaffolds became less stiff (Young’s modulus decreased from 6.45 to 0.12 MPa), underwent a dissipative, non-elastic process during repeated loading-unloading cycles, and exhibited increasing diversity of mechanical behavior that is similar to the phenotypic diversity manifested by 2 year-old TEVG grafts [2]. Incompressibility was maintained until day 25, possibly because by then the scaffolds are heterogeneously fragmented and the load is not transmitted evenly throughout the material. These scaffolds behave in a complex manner as they degrade in vitro, and more complete data are necessary to inform the next generation of computational models and to illustrate clearly the evolving mechanical behavior of TEVGs from implantation to neovessel formation.

Comments

This is an Open Access Thesis.

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