Nanoengineered Injectable Hydrogels from kappa-Carrageenan and Two-dimensional Nanosilicates for Wound Healing Application

Publication date: Available online 7 February 2018
Source:Acta Biomaterialia
Author(s): Giriraj Lokhande, James K. Carrow, Teena Thakur, Janet R. Xavier, Madasamy Parani, Kayla J. Bayless, Akhilesh K. Gaharwar
We report injectable nanoengineered hemostats for enhanced wound healing and tissue regeneration. The nanoengineered system consists of the natural polysaccharide, κ-carrageenan (κCA), loaded with bioactive two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be injected for a minimally invasive approach. The hydrogel can be physically crosslinked in presence of monovalent ions and result in mechanically strong hydrogels. By controlling the ratio between κCA and nanosilicates, compressive stiffness of nanoengineered hydrogels can be modulated between 20 to 200kPa. Despite high mechanical stiffness, nanocomposite hydrogels were highly porous with an interconnected network. The addition of nanosilicates to κCA increases protein adsorption on nanocomposite hydrogels that results in enhanced cell adhesion and spreading, platelets binding and reducing the blood clotting time by more than two-fold. Moreover, due to presence of nanosilicates, a range of therapeutic macromolecules could be delivered. The addition of nanosilicates significantly suppressed the release of entrapped vascular endothelial growth factor (VEGF) and facilitated in vitro tissue regeneration and wound healing. Thus, this multifunctional nanocomposite hydrogel could be used as an injectable hemostat and an efficient vehicle for delivery of therapeutics to facilitate tissue regeneration.Statement of SignificanceHemorrhage is a leading cause of death in battlefield wounds, anastomosis hemorrhage and percutaneous intervention. Thus, there is a need for the development of novel bioactive materials to reduce the likelihood of hemorrhagic shock stemming from internal wounds. Here, we introduce an injectable hemostat from kappa-carrageenan and two-dimensional (2D) nanosilicates. Nanosilicates mechanically reinforce the hydrogels, provide enhanced physiological stability and accelerate the clotting time by two-fold. The sustained release of entrapped therapeutics due to presence of nanosilicates promotes enhanced wound healing. The multifunctional nanocomposite hydrogels could be used as an injectable hemostat for penetrating injury and percutaneous intervention during surgery.

Graphical abstract

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