Monday, November 9, 2015: 9:50 AM
251A (Salt Palace Convention Center)
Hydrogels are an important class of biomaterials that have received significant attention for controlled drug-delivery applications on account of their highly tunable mechanical properties and similarity to soft biological tissue.1 Shear-thinning hydrogels are water-swollen dynamically cross-linked polymer networks exhibiting viscous flow under shear stress (shear-thinning) and rapid recovery of mechanical properties when the applied stress is relaxed (self-healing).2 These properties afford minimally invasive implantation in vivo through direct injection or catheter delivery to tissues, contributing to a rapid gain in interest in their application for drug delivery and tissue engineering.3 Herein, we report the preparation and application of shear-thinning, injectable hydrogels driven by non-covalent interactions between hydrophobically-modified biopolymers (BPs) and drug-loaded biodegradable nanoparticles (NPs) comprised of poly(ethylene glycol)-block-poly(lactic acid) (PEG-block-PLA). This materials approach builds upon the recent paradigm of NPs as molecular binders in polymeric systems.4 The transient and reversible interactions between BPs and NPs enable flow under applied shear stress, followed by rapid self-healing when the stress is relaxed, demonstrating the shear-thinning and injectable nature of the material.5 The inclusion of PEG-block-PLA NPs facilitates a high-loading content of hydrophobic molecules within the hydrogel, while a second, hydrophilic molecule, can be loaded simultaneously into the aqueous phase of the gel. Delivery of the hydrophilic molecule is controlled by Fickian diffusion through the gel whereas erosion-based release from the gel surface governs delivery of the hydrophobic molecule. In this manner, multiple therapeutic compounds can be delivered with differential release curves. Additionally, the biocompatible, shear-thinning hydrogels can be implanted for short- and long-term controlled release of therapeutics in vivo or as a cell carrier for regenerative medicine applications. The fabrication of PNP gels is highly scalable and further materials development has extended the use of PNP hydrogels to industrial applications. Overall, this presentation will demonstrate the facile synthesis of a shear-thinning and self-healing hydrogel system predicated upon specific and reversible polymer-nanoparticle interactions for a range of applications.
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- Appel EA*, Tibbitt MW*, et al. Nature Communications 6 (2015) 6295