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Table 2 Major scaffolds and fabrication technologies used in bone engineering

From: Engineering in-vitro stem cell-based vascularized bone models for drug screening and predictive toxicology

Type of scaffold

Fabrication techniques

Biologically inspired

Decellularized bone [282,283,284]

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 [287,288,289]

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) [292,293,294]

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

  1. ECM extracellular matrix, TCP tricalcium phosphate, HA hydroxyapatite