Controlled Release of Growth Factors from Multilayered Fibrous Scaffold for Functional Recoveries in Crushed Sciatic Nerve

In
this study, we designed and fabricated a multilayered fibrous
scaffold capable of the controlled release of multiple growth factors
for sciatic nerve regeneration in rats. The scaffold consists of three
layers prepared by sequential electrospinning, where the first layer
is fabricated using polycaprolactone (PCL)-aligned electrospun nanofibers
for the attachment and differentiation of cells toward the direction
of the sciatic nerve. The second and third layers are fabricated using
poly­(lactic-co-glycolic acid) 6535 (PLGA 6535) and
8515 (PLGA 8515), respectively. The resultant three nanofiber layers
were stacked and fixed by incorporating hydrogel micropatterns at
both ends of nanofiber scaffold, which also facilitated the surgical
handling of the multilayered scaffolds. The PLGA layers acted as reservoirs
to release growth factors neurotrophin (NT-3), brain-derived neurotrophic
factor (BDNF), and platelet-derived growth factor (PDGF). The different
biodegradation rate of each PLGA layer enabled the controlled release
of multiple growth factors such as NT-3, BDNF, and PDGF with different
patterns. In a rat model, the injured nerve was rolled up with the
multilayered scaffold loading growth factors, and behavior tests were
performed five weeks after surgery. Sciatic functional index (SFI)
and mechanical allodynia analysis revealed that the fast release of
NT-3 and BDNF from PLGA 6535 and subsequent slow release of PDGF from
PLGA 8515 proved to be the greatest aid to neural tissue regeneration.
In addition to the biochemical cues from growth factors, the aligned
PCL layer that directly contacts the injured nerve could provide topographical
stimulation, offering practical assistance to new tissue and cells
for directional growth parallel to the sciatic nerve. This study demonstrated
that our multilayered scaffold performs a function that can be used
to promote locomotor activity and enhance nerve regeneration in combination
with align-patterned topography and the controlled release of growth
factors.