Nanoengineered injectable hydrogels for wound healing application

• Published in: Acta biomaterialia 2018-04, Vol.70, p.35-47
• Main Authors: Lokhande, Giriraj, Carrow, James K., Thakur, Teena, Xavier, Janet R., Parani, Madasamy, Bayless, Kayla J., Gaharwar, Akhilesh K.
• Format: Article
• Language: English
• Subjects: Blood coagulation; Carrageenan; Carrageenan - chemistry; Carrageenan - pharmacology; Cell adhesion; Cell Adhesion - drug effects; Clotting; Crosslinking; Gels; Hemostasis; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Kappa-carrageenan; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Nanocomposite hydrogels; Nanocomposites; Nanocomposites - chemistry; Platelets; Polysaccharides; Protein adsorption; Proteins; Regeneration; Stiffness; Therapeutic release; Tissue engineering; Two-dimensional nanoparticles; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Wound healing; Wound Healing - drug effects
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2018.01.045

[Display omitted] 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 synthetic two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be injected for minimally invasive approaches. The injectable gels can be physically crosslinked in presence of monovalent ions to form mechanically strong hydrogels. By controlling the ratio between κCA and nanosilicates, compressive stiffness of crosslinked hydrogels can be modulated between 20 and 200 kPa. Despite high mechanical stiffness, nanocomposite hydrogels are highly porous with an interconnected network. The addition of nanosilicates to κCA increases protein adsorption on nanocomposite hydrogels that results in enhance cell adhesion and spreading, increase platelets binding and reduce blood clotting time. Moreover, due to presence of nanosilicates, a range of therapeutic biomacromolecules can be deliver in a sustain manner. The addition of nanosilicates significantly suppresses the release of entrap vascular endothelial growth factor (VEGF) and facilitate in vitro tissue regeneration and wound healing. Thus, this multifunctional nanocomposite hydrogel can be used as an injectable hemostat and an efficient vehicle for therapeutic delivery to facilitate tissue regeneration. Hemorrhage 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.