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