Experimental and computational models for tissue-engineered heart valves: a narrative review
Ge Yan, Yuqi Liu, Minghui Xie, Jiawei Shi, Weihua Qiao, Nianguo Dong
Table 2 Advantages and disadvantages of animal models and bioreactors used in tissue-engineered heart valve studies.
Species & bioreactors Advantages Disadvantages
Small animal model
Mouse Low cost of maintenance, ease of gene-editing and surgical manipulation, multiple types of antibodies Not-suitable for in situ studies for small size and mismatched anatomy and physiology
Rat Low cost of maintenance, ease of surgical approach, access for implantation into the systemic circulation Not-suitable for in situ studies
Rabbit Low cost of upkeep, larger size for larger graft implantation Especially suitable for ectopic studies (subcutaneous implantation)
Large animal model
Sheep The golden standard for translational studies, the similarity of body size to human, easy access for transcatheter replacement of tissue-engineered heart valves, suitable growing speed for growing model Higher cost of purchase and upkeep, special facilities required for housing
Pig Resemblance to humans in terms of cardiovascular anatomy and physiology, access to transgenic models Higher cost of purchase and upkeep, special facilities required for housing, higher risk of post-operation infection, the possibility of chronic arterial occlusion and cardiac death after CPB, unsuitable growing speed compared with sheep
Dog Docile character, thin skin for implantation of catheters and convenient imaging, lower risk of
post-operative infection
Higher cost of purchase and upkeep, special facilities required for housing, difficulty in getting approval
Non-human primate The best model for translational clinical research for anatomical, physiological, genetic, and immune similarity The highest cost of purchase and upkeep, special facilities required for housing and social needs of primates, special equipment, and training required for surgical approach
Bioreactors
Pulse-flow bioreactors The anatomy is more similar to the physiology Generate complex and ill-defined mechanical conditioning, which cannot be readily controlled
Single mechanical stimulus bioreactor The type and size of the mechanical stimulation can be finely adjusted Only single stimulation can be made, a good cultural environment is needed and high cost
Multi-mechanical stimulus bioreactor Know the synergistic effect of different combinations of mechanical stimuli on cells and tissues May exist mutual interference that led to inconsistent results
Computer-regulated bioreactor Predictable, easy to understand hydrodynamic parameters Only mechanical simulations, not chemical and biological ones