Table 2.

Major scaffolds and fabrication technologies used in bone engineering

Type of scaffold			Fabrication techniques
Biologically inspired	Decellularized bone [282–284]	Pros: mimicking bone microenvironment; interconnected porosity for vasculature introduction; osteoinduction and osteoconduction; biomechanical properties	Conventional techniques	Solvent casting/particulate leaching, gas foaming [285, 286]	Pros: ability to generate interconnected porous scaffolds; porosity and pore size can be controlled by altering particle concentration and size or gas concentration
		Cons: difficulty to obtain clinically relevant volumes; specialized perfused apparatus for decellularization; challenge of generating specific anatomical shapes			Cons: inability to produce thick constructs; pore shape and interconnection cannot be controlled
	Extracellular matrix [287–289]	Pros: promote the migration and proliferation of progenitor cells; provide molecules for cell–matrix interactions; provide a structure for mechanotransduction signals		Phase separation [285, 286]	Pros: incorporation of biomolecules within the structure due to mild processing conditions; scaffold customization by altering material and concentration, phase transitions, and/or solvents
		Cons: challenge to minimally disturb biochemical and mechanical properties of the ECM during decellularization; inhomogeneous distribution during cell seeding			Cons: limited material selection and inadequate resolution
Natural/synthetic materials-based scaffolds	Natural polymers [134]	Pros: inherent biocompatibility and bioactivity; can be modified to provide a wide variety of original features; renewability	Additive manufacturing	Selective laser sintering, 3D printing [290, 291]	Pros: control over scaffold internal and external morphology; high production rate; ability to produce large-size scaffolds
		Cons: insufficient mechanical properties; challenge in generating specific morphologies due to poor processing conditions			Cons: laser intensity can induce scaffold degradation; generally low mechanical properties; limited and high-cost materials; high roughness of scaffold’s surface; trapped material inside the scaffold
	Natural ceramics (β-TCP, HA, bioactive glass) [292–294]	Pros: capability to form direct bonds with living bone; osteoinduction and osteoconduction		Fused deposition modeling, computer-aided wet-spinning [157, 158, 165]	Pros: control over scaffold internal and external morphology, pore size, distribution, and interconnection; good mechanical properties; no material trapped in the scaffold
		Cons: brittleness, difficulty of shaping
	Synthetic polymers [135, 295]	Pros: high versatility regarding control over physical–chemical properties and morphology; easy processability; batch-to-batch reproducibility			Cons: relative regular structures; resolution dependent on the utilized machine
		Cons: lack of important biomolecules aiding cell attachment; may degrade into unfavorable products, such as acids	Bioprinting [296, 297]		Pros: geometry and dimension of the cell-laden construct can be controlled by automated process; nonelevated temperatures required
					Cons: careful attention to cell viability, densities, and ratios during and after printing; printability of the selected bioink material

ECM extracellular matrix, TCP tricalcium phosphate, HA hydroxyapatite