Table 2.

The pros and cons of natural hydrogels

Materials	Advantages	Disadvantages	References
Alginate	Non-thrombogenic, structure is similar to ECM, biocompatible, bio-inert	Limited cell adhesion and needs modification for cell binding, limited stability in vivo	[5, 6, 81]
Chitosan	Good biocompatibility, non-immunogenic, can be conjugated with other molecules, low toxicity	Uncontrollable mechanical properties	[38]
Collagen	Low immunogenicity, good availability, remarkable biocompatibility, biodegradability, provides sufficient mechanical stability, tensile strength can be modified by changing collagen amount and cross-linking, enhances stem cell engraftment and requires fewer cells to be transplanted, easy to change shape, can be 3D-printed	Non-tunable mechanical properties, lack of mechanical robustness, gels with high weight fraction limit cell migration and nutrient diffusion	[8, 13, 82]
Elastin	Antibacterial, good cell–matrix interaction, good elasticity, biocompatibility, soft, stretchable	Formation of aggregates or self-assembly above a specific temperature, insolubility, tendency to calcify, hard to purify, poor mechanical stability	[83, 84]
Fibrin	Good biocompatibility, biodegradability, mechanical properties, bioactivity, easy cross-linking for cells and in vivo experiments, can be injected into tissues in vivo, easily modified into many shapes, good drug delivery system, great extensibility	Stiffness, rapid degradation	[85, 86]
Gelatin	Good biocompatibility, biodegradability, easy for isolation, solubility, thermo-reversible, low processing cost, nontoxic, safe, can be 3D-printed, ideal for drug delivery	Prolonged existence in vivo	[22]
Hyaluronic acid (HA)	Excellent biocompatibility, biodegradable, non-immunogenic, proper viscosity, promotes angiogenesis	Rapid degradation, poor retention of cells, poor survival of cells	[20]
Matrigel	Soluble, good attachment for cells, promotes cellular attachment, proliferation, and differentiation, angiogenesis, thermosensitive, provides many growth factors, cytoprotective, less invasive, myocardial-injectable	Structural weakness, fast transition to solid at 37 °C, adopted for short-term analysis	[29, 30]
Keratin	Low cost, easy and wide availability, renewable, good biocompatibility, good biodegradability, tough biomaterial, high stability, no inflammatory or immunogenic response	Insoluble, chemicals for increasing solubility are toxic	[87]
Silk fibroin	Wide availability from nature, low cost, incredibly robust mechanical and elastic properties, thermal and chemical stability, enzymatic biodegradability, nontoxic, drug stabilization, injectable, can be modified into multiple forms and used as 3D-printed material	Mild immune and inflammatory response, difficult for chemical modification, degradation rate is dependent on processing	[33, 34]

ECM extracellular matrix