Development of a biosynthetic cellulose material for transcatheter deliverable heart valves

Chaid Daniel Schwarz

doi:10.25820/etd.006654

Transcatheter heart valve repair has the potential to transform treatment of damaged heart valves. Current devices utilize pericardial membranes similar to surgically implanted tissue valves. These xenografts do not permit modification, such as manipulating thickness and mechanical properties. Furthermore, they are subject to calcification, stiffening, and tearing. Bacterial cellulose (BC) is an attractive candidate material as it has a fibrous microstructure that can be tuned to achieve a range of mechanical properties suitable for prosthetic heart valves. The goal of this project is to develop the process for fabricating bacterial cellulose membranes, investigate various approaches to control membrane thickness and mechanical properties, and to demonstrate their utility by fabricating a transcatheter aortic valve prototype. Methods involve the fabrication of the BC membranes in culture media using a wild-type strain of cellulose producing bacteria which was identified using 16S gene sequencing. The thickness of the membrane may then be reduced without loss of structural mechanical caliber using a process of dehydration. The membrane’s structural content was evaluated and characterized using carbon-nuclear magnetic resonance (13C-NMR) analysis and scanning electron microscopy (SEM). Mechanical test methods to characterize five different mechanical characteristics of the membrane material were developed. The effect of three culture media (tea, Hestrin and Schramm and modified Hestrin and Schramm) and culture time (5-20 days) on the fabricated membrane’s mechanical properties were evaluated. Comparisons were made with fresh bovine pericardium and two commercially available tissues, porcine small intestinal submucosa and chemically treated bovine pericardium. The effect of dehydration cycles on the thickness and mechanical strength of the membrane were documented. The effect of crosslinkers (glyoxal and glutaraldehyde) on the mechanical properties were also investigated. A novel chemical modification using a NaOH/urea solution to produce all-cellulose membranes was also evaluated and its effects on mechanical properties was documented. Finally, an aortic valve prototype was fabricated using the BC membrane utilizing a polyester fabric sutured to the inside of a custom laser cut Nitinol stent. Results indicate that BC membranes may be fabricated with very low thickness (100 microns or less) without loss of mechanical caliber. Compared to porcine small intestinal submucosa, BC membranes have greater tensile strength and delamination resistance, comparable flexure and less in-plane compliance. Compared to chemically treated bovine pericardium, BC membranes have greater flexibility, comparable tensile strength and less delamination resistance and in-plane compliance. Culture media and culture duration affect specific aspects of the fabricated membrane. Crosslinking with glyoxol and gluteraldehyde was not effective in improving mechanical characteristics. Durability testing with prototype valves suggests that the common mode of failure for BC membranes is free edge delamination. The most recent chemically modified all-cellulose constructs were successful in improving delamination resistance at some loss of flexural rigidity. In conclusion, bacterial cellulose membranes with sub-100 micron thickness could be produced using chosen culture media and processing. The fabrication parameters such as culture media, culture duration, chemical and physical processing could be tuned to achieve a wide range of membrane thickness and mechanical properties. While tensile strength and flexibility are desirable, susceptibility to delamination without impacting flexibility is a challenge that remains to be addressed. The study has demonstrated initial proof-of-concept for BC as a viable membrane material candidate for transcatheter heart valves.

Development of a biosynthetic cellulose material for transcatheter deliverable heart valves

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