Thesis Defense - Design, Synthesis, and Characterization of a Tissue Engineered Small Caliber Vascular Graft
Date: February 26, 2003
Time: 3:00 PM
Location: Commonwealth Hall, Room: 610
Dr. Michele Marcolongo, Advisor
Current autologous and synthetic small diameter vascular grafts fail to satisfy the mechanical and biocompatible criteria required to sustain blood flow4. The ideal coronary artery vascular graft must restore blood flow to the heart as well as endure high fatigue cycling and retain patency over time. These requirements may be satisfied through the use of a tissue-engineered construct that gradually replaces synthetic materials with natural tissue, assembling a new vessel native to the individual. This work focused on the construction of a tissue engineered, small caliber vascular graft. The objectives of the project were to design, synthesize and characterize a vascular graft that mimicked the structure of the host coronary artery and reproduce its mechanical behavior.
The design employed biodegradable poly(glycolic acid) (PGA) fibers in a braided construct utilizing an inner and outer layer with fiber orientations, similar to those of the native coronary artery in order to enable matched mechanical performance and cell orientation. The fiber preform was impregnated with a cross-linked, degradable collagen matrix to enhance mechanical performance and aid tissue integration. For mechanical characterization of the construct, the compliance of the vessel was evaluated both initially and over a period of 48 hours of in vitro degradation. Biocompatibility of the construct was assessed using an in vitro cell culture model. The resulting collagen-permeated vessel achieved a multi-layered architecture that mimicked that of natural arterial tissue. The fiber volume fraction was estimated to be 3.94%. Dimensions of the construct were similar to human coronary arteries, which vary from approximately 2-3 mm ID, with wall thicknesses of about 0.75 mm for men and women over age 2039. Over a range from 40-130mmHg, a linear relationship was found for compliance and pressure. Initial pulse compliance from 80-120mmHg was found to be 1.35 ± 0.1 % (n=16), while after 24 and 48 hours of degradation, the pulse compliance increased to 1.84± 0.16 (n=8), and 2.14 ± 0.31% (n=7), respectively. A series of in vitro biocompatibility tests showed that the graft was unable to support adhesion and proliferation of smooth muscle cells.
A resorbable, small diameter vascular graft has been constructed and the time-dependent changes in mechanical properties due to exposure to physiological solutions over 48 hours have been characterized. The vessel fiber architecture closely resembled the smooth muscle cell orientation in natural arterial tissue. Initial compliance values nearly doubled that of conventional synthetic grafts, and increased by almost 60% over a 48 hour period of in vitro degradation, matching the compliance of the saphenous vein, the current gold standard. It would be expected that tissue integration with the scaffold would alter mechanical compliance, with the mechanical properties of the native tissue eventually dominating those of the initial matrix. Biocompatibility testing suggested that processing conditions as well as glutaraldehyde cross-linking could have contributed to the compromised biocompatibility of the scaffolds. Modification of processing conditions and/or fiber materials may offer fine-tuning to reproduce more closely the mechanical behavior of the native vessel, and achieve a biomechanically optimal conduit for arterial blood flow. Finally, the use of bioactive materials in graft manufacture, combined with handling in a controlled environment and a final sterilization step may render the graft an ideal construct for the study of biomaterial-cellular interactions and the regeneration of arterial tissue in vivo.
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