Biomolecule Gradient in
Micropatterned Nanofibrous
Scaffold for Spatiotemporal Release
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Abstract
Controlled molecule release from scaffolds can dramatically
increase
the scaffold ability of directing tissue regeneration <i>in vitro</i> and <i>in vivo</i>. Crucial to the regeneration is precise
regulation over release direction and kinetics of multiple molecules
(small genes, peptides, or larger proteins). To this end, we developed
gradient micropatterns of electrospun nanofibers along the scaffold
thickness through programming the deposition of heterogeneous nanofibers
of poly(ε-caprolactone) (PCL) and poly(d,l-lactide-<i>co</i>-glycolide) acid (PLGA). Confocal images of the scaffolds
containing fluorophore-impregnated nanofibers demonstrated close matching
of actual and designed gradient fiber patterns; thermal analyses further
showed their matching in the composition. Using acid-terminated PLGA
(PLGAac) and ester-terminated PLGA (PLGAes) to impregnate molecules
in the PCL-PLGA scaffolds, we demonstrated for the first time their
differences in nanofiber degeneration and molecular weight change
during degradation. PLGAac nanofibers were more stable with gradual
and steady increase in the fiber diameter during degradation, resulting
in more spatially confined molecule delivery from PCL-PLGA scaffolds.
Thus, patterns of PCL-PLGAac nanofibers were used to design versatile
controlled delivery scaffolds. To test the hypothesis that molecule-impregnated
PLGAac in the gradient-patterned PCL-PLGAac scaffolds can program
various modalities of molecule release, model molecules, including
small fluorophores and larger proteins, were respectively used for
time-lapse release studies. Gradient-patterns were used as building
blocks in the scaffolds to program simultaneous release of one or
multiple proteins to one side or, respectively, to the opposite sides
of scaffolds for up to 50 days. Results showed that the separation
efficiency of molecule delivery from all the scaffolds with a thickness
of 200 μm achieved >88% for proteins and >82% for small
molecules.
In addition to versatile spatially controlled delivery, micropatterns
were designed to program sequential release of proteins. The hierarchically
structured materials presented here may enable development of novel
multifunctional scaffolds with defined 3D dynamic microenvironments
for tissue regeneration