Pulmonary valve tissue engineering strategies in large animal models

PLoS One. 2021 Oct 5;16(10):e0258046. doi: 10.1371/journal.pone.0258046. eCollection 2021.

Abstract

In the last 25 years, numerous tissue engineered heart valve (TEHV) strategies have been studied in large animal models. To evaluate, qualify and summarize all available publications, we conducted a systematic review and meta-analysis. We identified 80 reports that studied TEHVs of synthetic or natural scaffolds in pulmonary position (n = 693 animals). We identified substantial heterogeneity in study designs, methods and outcomes. Most importantly, the quality assessment showed poor reporting in randomization and blinding strategies. Meta-analysis showed no differences in mortality and rate of valve regurgitation between different scaffolds or strategies. However, it revealed a higher transvalvular pressure gradient in synthetic scaffolds (11.6 mmHg; 95% CI, [7.31-15.89]) compared to natural scaffolds (4,67 mmHg; 95% CI, [3,94-5.39]; p = 0.003). These results should be interpreted with caution due to lack of a standardized control group, substantial study heterogeneity, and relatively low number of comparable studies in subgroup analyses. Based on this review, the most adequate scaffold model is still undefined. This review endorses that, to move the TEHV field forward and enable reliable comparisons, it is essential to define standardized methods and ways of reporting. This would greatly enhance the value of individual large animal studies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Heart Valve Prosthesis / adverse effects*
  • Models, Animal
  • Pulmonary Valve / transplantation*
  • Tissue Engineering / methods*

Grants and funding

This work was funded by ZonMW, more knowledge with fewer animals (Projectnumber 114024134, 40-42600-98-433). C.R. Hooijmans is employee of SYRCLE. M. Uiterwijk is support from the Netherlands Cardiovascular Research Initiative (CVON 2012-01): The Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences. D.C. van der Valk is supported by the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organization for Scientific Research (024.003.013).