TABLE 1.

Summary of the main nanostructured calcium-phosphate based materials for bone regeneration, with their respective advantages and disadvantages.

	Advantages	Disadvantages	References
Nanostructured Bioceramics
Nano-bioglasses	Biocompatible	Suboptimal Biodegradation	Vallet-Regí et al., 2003; Izquierdo-Barba et al., 2013; Ducheyne, 2015; Islam et al., 2017; Mancuso et al., 2017
	Enhanced bone integration	Poor mechanical properties
	Improved biodegradation
Hydroxyapatite	High biocompatibility	Poor mechanical properties	Liou et al., 2004; Capuccini et al., 2008; Boanini et al., 2010; Tampieri et al., 2012; Zofková et al., 2013
	Resembles mineral phase of bone
	Can be doped with multiple ions to closely mimic bone mineral	Slow degradation rates in vivo
	Osteoconductive
	Can be used in a plethora of formulations (e.g., powder, solid scaffold, cement, coatings)	Limited osteoinductivity
	High biocompatibility
Tricalcium phosphate	Provides main bulding blocks for new matrix deposition	Poor mechanical properties	Shepherd and Best, 2011; Sadat-Shojai et al., 2013; Vahabzadeh and Bose, 2017; Sergi et al., 2018
	Can be doped with multiple ions to tune bioactivity and degradation
	Osteoconductive
	Can be used in a plethora of formulations (e.g., powder, solid scaffold, cement, coatings)
	Faster in vivo degradation
Nanocomposites
Ceramic/polymer composites (e.g., HA/PLGA, HA/Alginate)	High biocompatibility	May have limited osteoinductivity	Kim et al., 2005; Miao et al., 2005; Tampieri et al., 2005; Heo et al., 2009; Akman et al., 2010; Bernstein et al., 2010; Cruz, 2010; Bhumiratana et al., 2011; Wang Z. et al., 2016; Zhu et al., 2017; Bian et al., 2019
	Ease of fabrication	Fabrication requires organic solvents
	Can be used to prepare scaffolds with complex 3D architecture
	Improved mechanical properties of scaffolds
	Tunable degradation rate
Bio-hybrid composites	High biocompatibility	Poor mechanical properties (not load bearing)	Tampieri et al., 2008; Tampieri et al., 2011; Minardi et al., 2015a; Minardi et al., 2019
	Fabrication not requiring organic solvents
	Highly biomimetic
	Excellent bioactivity