Reduced graphene oxide-based conductive hydrogels for biomedical engineering applications

Abstract

Conductive biomaterials have been widely used as new types of biomaterials for various biomedical applications, such as bioelectronic devices and electroactive tissue engineering scaffolds. Conventional conductive biomaterials are mostly metal-based (e.g., gold and platinum) as they display excellent electrical properties. However, such, metal-based biomaterials are dry (not hydrated) and mechanically stiff unlike soft living tissues. In particular, mechanical mismatch between rigid implants and soft tissues frequently leads to severe inflammation and thick scar tissue surrounding the implants in the living tissue. The scar tissue surrounding the conductive biomaterial dramatically increases the impedance, hampering electrical signal transduction with the surrounding tissue and resulting in a loss of its function as a conductive material. Hence, this mechanical discrepancy between conductive biomaterials and tissues is a main hurdle to be addressed in fabricating conductive biomaterials. Recently, research on conductive hydrogels has been highlighted as new types of conductive materials. A conductive hydrogel is soft, flexible, and electrical conductive, of which characteristics are similar those of electroactive tissues, such as nerve, heart, and muscle. Conductive hydrogels are typically composed of electrically conductive components and hydrophilic polymers, which play main roles in electrical signal transmission and structural/mechanical support of conductive hydrogels, respectively. Among the various conductive materials, a carbon nanomaterial-based material is an appropriate option because carbon nanomaterials, such as graphene, are highly electrical conductive and flexible, and present large surface area. In my thesis, various functional conductive hydrogels were developed by incorporating reduced graphene oxide (rGO) for various biomedical engineering applications. First, micropatterned conductive hydrogels containing rGO were fabricated to mimic the properties of skeletal muscle with respect to electroactivity, alignment, and softness. The micropatterns were directly created on the conductive hydrogel surface by femtosecond laser ablation. As a result, the micropatterned conductive hydrogel promoted skeletal muscle differentiation and myotube alignment, which could be further enhanced with electrical stimulation. Second, with an aim at developing an effective material for injured peripheral nerve regeneration, electrically conductive hydrogel-based nerve guidance conduits (NGCs) were fabricated by polymerizing GO and methacrylated gelatin and subsequent chemical reduction. NGCs consisting of electrically conductive rGO and biologically active gelatin induced regeneration of peripheral nerves. Interestingly, the conductive NGCs led to regeneration of defected sciatic nerves similar to autograft (a gold standard). Third, to achieve the electrical properties of the conductive hydrogel with a small amount of rGO, a conductive three-dimensional graphene network was created within the hydrogel. To this end, arrangement of graphene was designed. Graphene oxide (GO) flakes presenting different charges were coated onto agarose microbeads by a layer-by-layer method. After assembling the GO-coated agarose microbeads, thermal annealing was performed under the optimized conditions to form connected graphene network within the hydrogel matrix. The resultant graphene-channeled conductive hydrogels were successfully demonstrated to be conductive, biocompatible, and effective for various biomedical applications, including 3D printing, mechanical sensors, and tissue engineering scaffolds. Finally, injectable conductive hydrogels with tunable degradability were developed. Both injectability and tunable degradability are essential in hydrogel applications, including conductive hydrogels. Based on degradability of prepolymers, degradable and non-degradable hydrogel matrices were successfully fabricated. A well-dispersed rGO was synthesized by polymer coating and used together with spontaneously reacting prepolymers via thiol-ene reactions. Stably dispersed graphene flakes in PEG gels allowed for the high conductivity of the fabricated hydrogel. The biodegradability was determined by the hydrolysis potential of the hydrogel matrix polymer. Utilities of the graphene-based injectable conductive hydrogels with different degradability were demonstrated as EMG recording bioelectrode and an injured skeletal muscle patch. In conclusion, this thesis has focused on developing advanced multifunctional conductive hydrogels exhibiting unique characteristics for specific applications. Developed conductive hydrogels have been shown to be beneficial as bioelectrode fors recording biosignals and/or as tissue engineering scaffold for the treatment of electroactive tissues.