Porosity parameters are one of the structural properties of the extracellular microenvironment that have been shown to have a great impact on the cellular phenotype and various biological activities such as diffusion of fluid, initial protein adsorption, permeability, cell penetration and migration, ECM deposition, angiogenesis, and rate and pattern of new tissue formation. The heterogeneity of the study protocols and research methodologies do not allow reliable meta-analysis for definite findings. As such, despite the huge available literature, no generally accepted consensus is defined for the porosity requirements of specific tissue engineering applications. However, based on the biomimetic approach, the biological substitutes should replicate the 3D local microenvironment of the recipient site with matching porosity parameters to best support local cells during tissue regeneration. Ideally, the porosity of biomaterials should mimic the porosity of the substituting natural tissue and match the clinical requirements. Careful analysis of the impact of architectures (i.e., porosity) on biophysical, biochemical, and biological behaviors will support designing smart biomaterials with customized architectural and functional properties that are patient and defect site-specific.
Connected pores like tunnels that are accessible by gas, liquid, and particulate suspensions.
Close pore
Isolated pores with no connection to the scaffold surface and not contributing to the cell microenvironment but affecting the mechanical properties of the scaffold.
Close porosity
Close pore volume/bulk volume.
Open porosity
Open pore volume/bulk volume.
Total porosity
Total pore volume/bulk volume.
Pore interconnectivity
Pore channel that connects different pores and determines the permeability by controlling fluid circulation in the scaffold.
Pore geometry
Architectural configuration of pore including its morphology and pore wall.
Pore dimension
The mean pore size or diameter.
Pore distribution
The spatial arrangement of pore within the scaffold involving pore orientation or alignment.
Pore throat
Entrance or the first part of the pore that may act as pore interconnection.
Pore stomach
Belly or second part of the pore.
Tab.1
Fig.2
Technique
Using
Advantages
Limitations
Porogen leaching
Particulates, fibers, meshes, salt (NaCl), sugar, paraffin, gelatin, ice crystals
The amount and size of the porogen can modify the pore size and porosity; a minimal amount of polymer is required.
Gas generation (i.e., CO2), surface active agents (i.e., tween)
No need for leaching step; reduce overall fabrication time.
Low initial strength; poor reproducibility; risk of embolism; difficult control of pore connectivity and pore sizes.
Emulsion
Oil-water mixtures
Allow modification of pore size and percentage.
May require a cleaning step; risk of embolism.
Freeze-drying
Water freezing+ sublimation
Porosity and pore size can be modified by controlling the porosity parameters, polymer/water ratio, and freezing temperature; no need for a further rinsing step.
Energy and time-consuming; the parameters need to be controlled to increase scaffold homogeneity.
Porosity is determined by the porosity of the template.
Very low strength; residuals from the firing step; crystal changes from the firing step; limited pore connectivity; problems with residual solvents.
3D printing
Direct rapid prototyping
Allows fabrication of a more complex 3D structure with a controlled internal structure.
Micro-architecture limited by the particle’s size; applicable to a limited number of polymers due to high temperatures; ceramic scaffold requires sintering to improve on the brittle toughness.
Selective laser sintering
Layer-by-layer fusion of a powder bed by laser beam
Allows fabrication of complex scaffolds geometries; fast, cost-effective, and does not require the use of any organic solvents.
High energy consumed; chance of degradation and decomposition of materials due to heat generation.
Electrospinning
A potential difference between a polymeric solution and a collector
Simple and cost-effective; generate high surface area and high porosity; possibility to control the diameter of each electrospun fiber.
Involvement of toxic organic solvents during fabrication.
Encapsulation
Cell entrapment during scaffold gellation
Ability to provide immunoshielding for cells; possibility of fabricating injectable forms.
The gelation process and encapsulating materials should be biocompatible; difficulty in control of diffusion coefficient to/from cells; lack of internal porous structure.
Tab.2
Pore size/µm
Cell type
Refs.
100–150
human fibroblast
[82–83]
100–200, 370–400
chondrogenic differentiation
[62,84–85]
200–450
osteogenic differentiation
[44,69,86–87]
75–750 (elongated pores)
peripheral axon regeneration
[88]
20–50
glial and axonal growth
[89]
100
transplantation and differentiation of neural stem cells
[90]
50–200
smooth muscle cells
[91]
<38
microvascular epithelial cells
[40]
Tab.3
Fig.3
Fig.4
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