Development of anisotropic polymeric substrates for tendon tissue engineering

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Date
2015-09-11Author
English, Andrew
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Abstract
Tendon injuries and degenerative conditions constitute an unmet clinical need with
pharmacological strategies and tissue grafts failing to recapitulate native tendon
function. Advancements in bioengineering have enabled the development of various
scaffold fabrication technologies, using natural or synthetic in origin polymers that
closely imitate the native tendon anisotropic architecture. Anisotropic collagen
sponges, extruded collagen fibres, isoelectric focused collagen fibres, electro-spun
polymeric fibres and imprinted polymeric substrates are at the forefront of scientific
and technological research and innovation. Herein, we ventured to assess whether onestep
functionalisation of electro-spun fibres with nano / micro particles is possible and
whether anisotropic imprinted substrates can maintain tenogenic phenotype in vitro
and promote functional neotissue formation in vivo.
Starting with electro-spinning, mechanical evaluation demonstrated that aligned
orientated electro-spun fibres exhibited significant higher stress at break values than
their random aligned counterparts and random orientated electro-spun fibres exhibited
significant higher strain at break values than the aligned orientated scaffolds. While
maintaining fibre structure, a co-deposition method of spraying and electro-spinning
was developed that enabled the incorporation of microspheres within the threedimensional
structure of the scaffold. Of significant importance is that bovine
tenocytes aligned perpendicular to the fibre orientation, possibly due to the absence of
mechanical tension.
With respect to imprinting, it is still unclear whether surface topography can be
translated into a clinically functional response in vivo at the tissue / device interface.
Herein, we demonstrated that anisotropic substrates with groove depth of ~317 nm
and ~1988 nm promoted human tenocyte alignment parallel to underlined topography
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in vitro. However, none of the topographies assessed (~37 nm, ~317 nm and ~1988
nm groove depth) induced parallel to the substrate cellular orientation in a
subcutaneous model and none of the topographies promoted directional tenogenesis
in vivo. Further, the rigid poly(lactic-co-glycolic acid) substrate used induced transdifferentiation
towards chondrogenic / osteogenic lineage, as evidenced by gene
analysis. Collectively, these data indicate that two-dimensional imprinting
technologies are useful tools for in vitro cell phenotype maintenance, rather than for
directional neotissue formation, should multifactorial approaches that consider both
surface topography and substrate rigidity are established.
Overall, both electro-spinning and imprinting technologies show great promise for
tendon repair and regeneration. Imprinting could be the ideal technology for cell
phenotype maintenance in vitro, as we can closely control architectural features.
Although it was not investigated here, electro-spinning is the ideal technology for in
vivo positive outcomes, as the three-dimensional architecture would allow directional
tissue formation within the fibrous construct.
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