Outlined characteristics of various biomaterials used to fabricate bone tissue engineering scaffolds.

Biomaterials	Characteristics	Advantages	Disadvantages	Ref.
Metal	Suitable mechanical properties of biocompatible metallic scaffolds	Outstanding mechanical properties	Non-biodegradable
		Biocompatible	Corrosion
Tantalum	Bioactive and corrosion resistance	Extensively used as implant biomaterials	Almost no degradation lead to a second surgery for removing the implant	28–32
Magnesium	Good porous and biodegradable implant	Mechanical properties similar to human bone	Toxicity risk caused by metal ion or particle leaching	33–39
		Biodegradable
Titanium and titanium alloys	Durable, biocompatible, highly corrosion resistant and very similar modulus of elasticity for trabecular bone	High bone affinity	Non-biodegradable	40–44
Nickel-titanium alloy (nitinol)	Particular mechanical properties (such as the shape memory and superelastic effects)	Low modulus of elasticity, pseudo-elasticity, and high damping capacity, better match the properties of natural bone better than any other metals	Almost no degradation for nitinol, the relatively high stiffness of titanium can cause stress shielding and implant loosening	45–48
Natural polymer	Similarity to ECM, specific degradation rates and good biological properties	Biocompatible	Low mechanical strength
		Degradation
Collagen	Important part of natural bone organic materials. Excellent biocompatibility	Biodegradable	Disinfection and handling are relatively difficult	49–51
		Various forms of scaffolds (e.g., sheets)
Gelatin	Denaturalized collagen	Forming blends through cross-linking		52–55
Silk fibroin	Silk fibroin with outstanding mechanical properties			56–58
Chitosan	Polysaccharide with positive charge, biocompatibility and resistance to bacteria			59
Alginate	Polysaccharide with negative charge, and can crosslink and print by injection			60–62
Hyaluronic acid	Glycosaminoglycan with negative charge, biocompatibility, forming hydrogel through cross-linking	Ease to chemical functionalization and degradability		58,63–66
Synthetic polymer		Changeable mechanical and physical properties	Possible adverse tissue reactions caused by acidic degradation
PLA, PGA and PLGA	FDA-approved materials for clinical applications	Water solubility and crystallinity tunable by changing hydroxylation degree	Non-hydrophobic and shortage of cell adhesion	67–69
PCL	Excellent crystallinity and mechanical properties	An crosslink in situ and print by injection	Degradation rate in years	70–73
PVA	Hydroxylated synthetic polyvinyl acetate	Ability to manufacture implants with various characteristics such as shape, porosity and degradation rate		74–77
PPF	Has numerous nonsaturable double bonds and the crosslinks may be toxic	Adjustable mechanical strength and rates of degradation		78,79
Polyurethane (PU)	Remarkable mechanical properties			80–82
Bioinert ceramic	Cannot perform medical reactions with living tissue after implantation
Aluminum, e.g., α-aluminum oxide (Al2O3)	Improve mechanical properties; lack of biological activity			83–86
Zirconia	Interconnected structures; lack of chemical bonds and biological reactions between living tissues			87–89
Bioactive ceramic	Can show medical reactions with living tissue after implantation
HA	The main inorganic component of natural bone	Highly biocompatible, non-toxic and osteoconductive		6,85,90,91
Tricalcium phosphate (TCP), e.g., beta-tricalcium phosphate (β-TCP)	The ratio of calcium to phosphorus is close to natural bone tissue	Biocompatibility, no rejection and can provide calcium and phosphorus for new tissue	α-TCP has excessive dissolution and rapid degradation	56,92–95
			Degradation rate and osteogenic speed are inconsistent
Calcium sulfate (CaSO4)	CaSO4 is a good material to choose after tumor resection			96–99
Akermanite (ca, Si, Mg)	Excellent mechanical properties and controllable degradation rate			100–102
	Better osteogenic differentiation and increased gene expression compared to β-TCP
Diopside (MgCaSi2O6)	Low temperature and fast firing and good thermal expansion properties			103–106
Bioactive glasses (BGs)	The main components for Na2O, CaO, SiO2 and P2O5; brittleness			107–113