TY - JOUR
T1 - Calcification in Pulmonary Heart Valve Tissue Engineering
T2 - A Systematic Review and Meta-Analysis of Large-Animal Studies
AU - van der Valk, Dewy C.
AU - Fomina, Aleksandra
AU - Uiterwijk, Marcelle
AU - Hooijmans, Carlijn R.
AU - Akiva, Anat
AU - Kluin, Jolanda
AU - Bouten, Carlijn V. C.
AU - Smits, Anthal I. P. M.
N1 - Funding Information: The authors would like to thank Dr Fulvia Ortolani, Prof Laura Iop, Dr Michele Gallo, and Dr Jan-Willen van Rijswijk for their quick and informative response to e-mail inquiries, providing added information about their research articles that could be added to the meta-analysis. The authors would like to thank Dr Bente de Kort and Suzanne Koch, MSc, for their discussions on data extraction and meta-analysis. Furthermore, the authors would like to thank Dr Rob de Vries and Dr Judith van Luijk (SYstematic Review Centre for Laboratory animal Experimentation [SYRCLE], Radboudumc, Nijmegen, the Netherlands) for their informative discussions regarding the meta-analysis. Publisher Copyright: © 2023 The Authors
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Tissue-engineered heart valves (TEHVs) are emerging alternatives to current valve prostheses and prospectively a lifelong replacement. Calcification, a pathological complication for biological protheses, has been reported in preclinical TEHV studies. Systematic analysis of its occurrence is missing. This review aims to: 1) systematically review reported calcification of pulmonary TEHVs in large-animal studies; and 2) analyze the influence of engineering methodology (choice of scaffold material, cell preseeding) and animal model (animal species and age) on calcification. Baseline analysis included 80 studies, of which 41 studies containing 108 experimental groups were included in meta-analysis. Inclusion was low because only 55% of studies reported on calcification. Meta-analysis showed an overall average calcification event rate of 35% (95% CI: 28%-43%). Calcification was more prominent (P = 0.023) in the arterial conduit region (34%; 95% CI: 26%-43%) than in the valve leaflets (21%; 95% CI: 17%-27%), and was mostly (42% in leaflets, 60% in conduits) present in a mild form. Time-analysis showed an initial surge within 1 month after implantation, decreased calcification between 1 and 3 months, and then progression over time. There were no significant differences in degree of calcification between TEHV strategy nor animal models. Much variability between individual studies was observed in degree of calcification as well as quality of analysis and reporting thereof, hampering adequate comparisons between studies. These findings underline the need for improved analysis and better reporting standards of calcification in TEHVs. It also necessitates control-based research to further enlighten the risk of calcification for tissue-engineered transplants compared to current options. This can bring the field of heart valve tissue engineering forward toward safe clinical use.
AB - Tissue-engineered heart valves (TEHVs) are emerging alternatives to current valve prostheses and prospectively a lifelong replacement. Calcification, a pathological complication for biological protheses, has been reported in preclinical TEHV studies. Systematic analysis of its occurrence is missing. This review aims to: 1) systematically review reported calcification of pulmonary TEHVs in large-animal studies; and 2) analyze the influence of engineering methodology (choice of scaffold material, cell preseeding) and animal model (animal species and age) on calcification. Baseline analysis included 80 studies, of which 41 studies containing 108 experimental groups were included in meta-analysis. Inclusion was low because only 55% of studies reported on calcification. Meta-analysis showed an overall average calcification event rate of 35% (95% CI: 28%-43%). Calcification was more prominent (P = 0.023) in the arterial conduit region (34%; 95% CI: 26%-43%) than in the valve leaflets (21%; 95% CI: 17%-27%), and was mostly (42% in leaflets, 60% in conduits) present in a mild form. Time-analysis showed an initial surge within 1 month after implantation, decreased calcification between 1 and 3 months, and then progression over time. There were no significant differences in degree of calcification between TEHV strategy nor animal models. Much variability between individual studies was observed in degree of calcification as well as quality of analysis and reporting thereof, hampering adequate comparisons between studies. These findings underline the need for improved analysis and better reporting standards of calcification in TEHVs. It also necessitates control-based research to further enlighten the risk of calcification for tissue-engineered transplants compared to current options. This can bring the field of heart valve tissue engineering forward toward safe clinical use.
KW - biomaterials
KW - cardiac valve prosthesis
KW - mineralization
KW - preclinical
KW - regeneration
KW - scaffold
KW - tissue-engineered heart valve
UR - http://www.scopus.com/inward/record.url?scp=85158026046&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jacbts.2022.09.009
DO - https://doi.org/10.1016/j.jacbts.2022.09.009
M3 - Review article
C2 - 37325410
SN - 2452-302X
VL - 8
SP - 572
EP - 591
JO - JACC. Basic to translational science
JF - JACC. Basic to translational science
IS - 5
ER -