Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment

Table 1

Comparison of different 3D culture approaches.

3D culture systems	Technologies	Advantages	Limitations	Automated production	References
Scaffold-based	Biomaterials	Possibility of modification and activation (physical, chemical, and biological); adaptable scaffold size; mechanical support for damaged tissue	Foreign material (risk of foreign body reaction and overgrowth by fibroblasts and immunogenicity); biocompatibility of degradation products; degradation capacity; invasive implantation; special equipment	No	[1, 3, 5, 11, 17, 24, 26, 32–38, 56, 95, 96, 98, 111, 114]
Scaffold-free	Spinner flasks	Variation of cell density, stirring speed, size, and amount; large-scale production; long-term culture	Cell behavior and viability; constant shear stress; special equipment; high quantities of media	No	[2, 3, 21, 25, 26, 29, 44, 49, 56, 57, 79, 89, 116, 145]
	Microgravity	Constant mixing of cell suspension; minimal shear forces; large-scale production; long-term culture	Variation in size; special equipment (rotary cell culture system); high quantities of media	No	[2, 3, 21, 25, 26, 29, 46, 49, 56, 81, 161]
	Liquid overlay	No special equipment; several available methods	Coating (agarose, agar, poly-HEMA, and poly-D-lysine); variation in size and shape	No	[2, 3, 21, 25, 26, 29, 41, 47–50, 56, 57, 79, 85, 93, 97, 106, 108, 116, 130–133, 152, 156, 160, 161]
	Micromolding	Standardized size, composition, and shape; coculture possibility; defined composition; individual addition of reagents; monitoring and manipulation of single MTs	Media-exchange method; nutrient supply; special equipment (nonadhesive microstructure plates)	Yes	[2, 3, 15, 21, 25, 26, 29, 49, 51]
	Hanging drop	Standardized size, composition, and shape; no external forces; coculture possibility; defined composition; individual addition of reagents; monitoring and manipulation of single MTs	Media-exchange method; nutrient supply; special equipment (for automation)	Yes	[2, 3, 5, 10, 16, 18, 21, 25, 26, 29, 31, 40, 57–60, 80, 93, 96, 99, 102, 105, 110, 117, 120, 122, 123, 167]