The Green Lane Valve: a Novel Decellularised Heart Valve

Background: Valvular prostheses each face some limitations precluding their routine surgical use. Thus, tissue-engineered heart valves have been explored as alternative conduits. Unfortunately, early models have proceeded to clinical use with catastrophic outcomes. The clinical performance of contemporary decellularised heart valves remains unknown. A novel, decellularised scaffold that outperforms standard, glutaraldehyde-treated bioprosthetic valves, in vivo, remains to be developed. Methods: A systematic review and meta-analysis was undertaken of the clinical performance of decellularised heart valves implanted in either outflow tract position, compared with standard tissue conduits. A novel subcutaneous rat model for the assessment of scaffold immunogenicity was developed. Bovine pericardia decellularised using a proprietary protocol were evaluated using the newly-developed model and then compared against standard tissue conduits fixed using an industry-standard glutaraldehyde formula. To evaluate the three-dimensional effects of decellularisation on the bovine pericardial scaffolds, a non-destructive imaging technique was developed using microcomputed tomography. The concentration-dependent effects of detergent-use were then assessed. Along with histological, immunohistochemical, and biomechanical analyses, the subcutaneous rat model and microcomputed tomography imaging methodology were used to evaluate the architectural, biomechanical, and immunogenic effects of decellularisation on bovine pericardial tissue. Results: Systematic review and meta-analysis demonstrated lower postoperative mortality and reoperation rates in patients who received decellularised heart valves. Following subcutaneous implantation in rats, glutaraldehyde-fixed bovine pericardia produced evidence of myofibroblastic activity, chronic M1 inflammation, and calcification. However, with decellularised bovine pericardia, initial CD3 lymphocytosis subsided, and was associated with constructive M2 inflammation and prevention of calcification. Microcomputed tomography produced high-resolution images that displayed the highly organised morphology of collagen. Calcification was observed in glutaraldehyde-treated, but not decellularised, tissue. Compared with native tissue, glutaraldehyde fixation resulted in tissue that was significantly stiffer, whereas decellularised tissue displayed similar biomechanical characteristics. Satisfactory decellularisation, architectural and biomechanical preservation, and the avoidance of calcification, were observed independent of detergent concentration. Conclusion: A novel decellularised bovine pericardial heart valve has been developed using a proprietary protocol. The conduit displays both microarchitectural and biomechanical preservation. Calcification was not seen following subcutaneous implantation in rats, unlike with industry-standard, glutaraldehyde-treated controls. The prosthesis is now ready for evaluation in large animal models.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Medicine

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2023

Author dc:creator

• Waqanivavalagi, Steve Wame Frances Rabonu

Advisor dc:contributor.advisor

• Cornish, Jillian

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/65509

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/65509