A major challenge with the in vitro control over growth and differentiation in human primary and stem cells (especially towards forming functional tissues with differentiated structures) is the inability to replicate the complex spatiotemporal chemical gradients that are present in vivo.  Extensive research has been conducted to understand the role other environmental cues such as presence of chemical and biological signals, mechanical properties of scaffold, topography of substrate, and spatial clustering of anchoring sites. Currently only a handful of examples have been developed where spatial and temporal chemical gradients are capable of directing cell growth, migration and differentiation.  These efforts include microfluidic systems capable of pumping biomolecules into a scaffold and thereby establishing gradients or polymeric scaffold with photolabile functional groups capable of releasing signaling molecules in response to light exposure. While insightful, these examples prove cumbersome to implement as routine practices. In order to overcome these challenges, we report on the development of stimuli-responsive capsules capable of releasing biomolecules in response to light exposure providing the ability to create 3-dimensional spatiotemporal gradients within a hydrogel matrix.  The capsules are fabricated from poly(lactic-co-glycolic acid) (PLGA) using an additive manufacturing layer-by-layer approach allowing accurate positioning and patterning of the capsules within the matrix while maintaining highly efficient encapsulation of the active biomolecule.  The capsules are functionalized with gold nanorods to allow for wavelength selective rupture of the PLGA shell.  The use of gold nanorods is advantageous in this application because the longitudinal LSPR peak easily tunable allowing for multiplexed and selective release of biomolecules at different wavelengths.  We have demonstrated this approach with selective release of fluorescently tagged dextrans and horseradish peroxidase in a 3-dimensional gel matrix.

Stimuli-responsive capsules for 3D spatiotemporal biomolecular gradients

248th National Meeting (2014)

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