Abstract
Interconnecting pathways through porous tissue engineering scaffolds play a vital role in determining nutrient supply, cell invasion, and tissue ingrowth. However, the global use of the term “interconnectivity” often fails to describe the transport characteristics of these pathways, giving no clear indication of their potential to support tissue synthesis. This article uses new experimental data to provide a critical analysis of reported methods for the description of scaffold transport pathways, ranging from qualitative image analysis to thorough structural parameterization using X-ray Micro-Computed Tomography. In the collagen scaffolds tested in this study, it was found that the proportion of pore space perceived to be accessible dramatically changed depending on the chosen method of analysis. Measurements of % interconnectivity as defined in this manner varied as a function of direction and connection size, and also showed a dependence on measurement length scale. As an alternative, a method for transport pathway parameterization was investigated, using percolation theory to calculate the diameter of the largest sphere that can travel to infinite distance through a scaffold in a specified direction. As proof of principle, this approach was used to investigate the invasion behavior of primary fibroblasts in response to independent changes in pore wall alignment and pore space accessibility, parameterized using the percolation diameter. The result was that both properties played a distinct role in determining fibroblast invasion efficiency. This example therefore demonstrates the potential of the percolation diameter as a method of transport pathway parameterization, to provide key structural criteria for application-based scaffold design.
Highlights
The physical properties and clinical performance of a tissue engineering scaffold are intimately linked to its porous structure
From the Scanning Electron Microscopy (SEM) images, it is apparent that both structures contain some anisotropy, with pore walls primarily oriented along the z-axis, that is, the direction of solidification during freeze-drying
Dark voids in the pore walls corresponding to inter-pore connections may be seen in all SEM images, but these are most apparent in the scaffold fabricated with acetic acid
Summary
The physical properties and clinical performance of a tissue engineering scaffold are intimately linked to its porous structure. Understanding the characteristics of this structure is crucial for efficient scaffold design and optimization. Some of these characteristics, such as pore size and porosity, are straightforward to measure using microscopic or tomographic imaging techniques.[1,2] The presence of transport pathways through the pore space is vital, for determining permeability,[3] enhancing cell distribution,[4] and facilitating cell–cell interactions similar to those found in vivo.[5] this aspect of the pore structure, commonly termed the ‘‘interconnectivity,’’ is difficult to define, with interpretations in literature ranging from the accessible pore volume to the number of holes in a pore wall.[6]. Apart from testing the applicability of each technique to the complex architecture of collagen scaffolds, we compare the results obtained from each method, identifying the strengths and limitations of each
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