The exceptional properties of graphene enable applications in electronics, optoelectronics, energy storage, and structural composites. Here we demonstrate a 3D printable graphene (3DG) composite consisting of majority graphene and minority polylactide-co-glycolide, a biocompatible elastomer, 3D-printed from a liquid ink. This ink can be utilized under ambient conditions via extrusion-based 3D printing to create graphene structures with features as small as 100 μm composed of as few as two layers ( 10 cm thick object). The resulting 3DG material is mechanically robust and flexible while retaining electrical conductivities greater than 800 S/m, an order of magnitude increase over previously reported 3D-printed carbon materials. In vitro experiments in simple growth medium, in the absence of neurogenic stimuli, reveal that 3DG supports human mesenchymal stem cell (hMSC) adhesion, viability, proliferation, and neurogenic differentiation with significant upregulation of glial and neuronal genes. This coincides with hMSCs adopting highly elongated morphologies with features similar to axons and presynaptic terminals. In vivo experiments indicate that 3DG has promising biocompatibility over the course of at least 30 days. Surgical tests using a human cadaver nerve model also illustrate that 3DG has exceptional handling characteristics and can be intraoperatively manipulated and applied to fine surgical procedures. With this unique set of properties, combined with ease of fabrication, 3DG could be applied toward the design and fabrication of a wide range of functional electronic, biological, and bioelectronic medical and nonmedical devices.

Three-dimensional printing of high-content graphene scaffolds for electronic and biomedical applications.

Wound dressings with high flexibility, mechanical strength, and porosity have received increasing attention. Herein, nanocomposite sponges of sodium alginate/graphene oxide (GO)/polyvinyl alcohol were prepared by a freeze-thawing cyclic process and freeze-dried molding. The properties of the sponges were investigated including morphology, mechanical properties, swelling, water vapor permeability, in vitro norfloxacin (NFX) release, antibacterial property, and biocompatibility as well as in vivo wound healing in a mouse model. A GO concentration of 1 wt% resulted in the sponges with a homogeneously porous and interconnected network structure, which exhibited suitable water absorption, breathability, and mechanical properties. Hemolysis tests indicated that the prepared sponges were non-hemolytic material. The CCK-8 assay demonstrated that the presence of an appropriate amount of GO could promote the cell proliferation. The sponges displayed excellent bioavailability of NFX, with a sustained release behavior and a strong inhibitory effect against both Escherichia coli and Staphylococcus aureus. The in vivo evaluations demonstrated that the sponges enhanced wound healing. Therefore, these novel nanocomposite sponges are promising candidates for wound healing applications.

Nanocomposite sponges of sodium alginate/graphene oxide/polyvinyl alcohol as potential wound dressing: In vitro and in vivo evaluation

Injectable hydrogels have received considerable interest in the biomedical field due to their potential applications in minimally invasive local drug delivery, more precise implantation, and site-specific drug delivery into poorly reachable tissue sites and into interface tissues, where wound healing takes a long time. Injectable hydrogels, such as in situ forming and/or shear-thinning hydrogels, can be generated using chemically and/or physically crosslinked hydrogels. Yet, for controlled and local drug delivery applications, the ideal injectable hydrogel should be able to provide controlled and sustained release of drug molecules to the target site when needed and should limit nonspecific drug molecule distribution in healthy tissues. Thus, such hydrogels should sense the environmental changes that arise in disease states and be able to release the optimal amount of drug over the necessary time period to the target region. To address this, researchers have designed stimuli-responsive injectable hydrogels. Stimuli-responsive hydrogels change their shape or volume when they sense environmental stimuli, e.g., pH, temperature, light, electrical signals, or enzymatic changes, and deliver an optimal concentration of drugs to the target site without affecting healthy tissues.

Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

Graphene and graphene oxide (GO) structures and their reduced forms, e.g., GO paper and partially or fully reduced three-dimensional (3D) aerogels, are at the forefront of materials design for extensive biomedical applications that allow for the proliferation and differentiation/maturation of cells, drug delivery, and anticancer therapies. Various viability tests that have been conducted in vitro on human cells and in vivo on mice reveal very promising results, which make graphene-based materials suitable for real-life applications. In this review, we will give an overview of the latest studies that utilize graphene-based structures and their composites in biological applications and show how the biomimetic behavior of these materials can be a step forward in bridging the gap between nature and synthetically designed graphene-based nanomaterials.

/pdf/biomedical-applications-of-graphene-based-structures-1gjrxc8lpt.pdf

Biomedical Applications of Graphene-Based Structures

Cyclodextrin-based host–guest supramolecular hydrogel and its application in biomedical fields

Injectable hydrogels have attracted a lot of attention in drug delivery, however, their capacity to deliver water-insoluble or hydrophobic anti-cancer drugs is limited. Here, we developed injectable graphene oxide/graphene composite supramolecular hydrogels to deliver anti-cancer drugs. Pluronic F-127 was used to stabilize graphene oxide (GO) and reduced graphene oxide (RGO) in solution, which was mixed with α-cyclodextrin (α-CD) solution to form hydrogels. Native hydrogel was used as control. GO or RGO slightly shortened gelation time. The storage and loss moduli of the hydrogels were tracked by dynamic force measurement. The storage modulus of GO or RGO composite hydrogels was larger than that of the native hydrogel. Hydrogels were unstable in solution and eroded gradually. GO or RGO in Pluronic F-127 solution could potentially improve the solubility of the water-insoluble anti-cancer drug camptothecin (CPT), especially with large drug-loaded CPT amount. Drug release behaviors from solutions and hydroge...

Injectable Graphene Oxide/Graphene Composite Supramolecular Hydrogel for Delivery of Anti-Cancer Drugs

Hydrogel contact lenses are ideal drug carriers for ophthalmic drugs delivery. However, some drawbacks of traditional hydrogel restricted their application in the drug delivery field. Herein, we introduced chitosan and β-cyclodextrin (β-CD) into traditional hydrogel in order to improve the properties and control drug release. β-CD functionized and crosslinkable chitosan derivative (CCH) was synthesized and introduced into HEMA/NVP monomers to form HNC tripolymer hydrogel. The introduction of CCH accelerated the polymerization of monomers. Other properties such as equilibrium swelling ratio and oxygen transmissibility of HNC hydrogel were superior to that of HN hydrogel. The capacity of HNC hydrogel to resist the protein absorption was also superior to that of HN hydrogel. Hydrogels exhibited different capacity of drug loading and releasing for different drug.

Synthesis and Characterization of Cyclodextrin-containing Hydrogel for Ophthalmic Drugs Delivery

Graphene as a two-dimensional material is particularly attractive because of its excellent electrical conductivity, mechanical properties, large surface area, low coefficient of thermal expansion and very high aspect ratio. However, the water insoluble property of graphene restricts its application in biomedical fields. Therefore the objective of this reported work is to find an efficient way to synthesise water-soluble and biocompatible graphene for biomedical applications. A stable aqueous graphene oxide (GO) solution was first obtained in the presence of non-ionic Pluronic copolymer. The GO-tripolymer showed good solubility in phosphate buffered saline (PBS) and the same UV absorption peaks as GO. Since a traditional reducing agent such as hydrazine had large toxicity, reduced GO (RGO) obtained by hydrazine reduction has some toxicity. In this work, a non-toxic reducing agent of ascorbic acid, galactose or bovine serum albumin was used as a RGO-tripolymer solution. The RGO-tripolymer exhibited good solubility in PBS. Finally, the cytotoxicity of RGO-tripolymers was investigated. Any RGO-tripolymer showed low cytotoxicity.

Preparation of water-soluble and biocompatible graphene

Considering that conventional hydrogels showed limited capabilities of controlling hydrophobic drug loading and releasing and graphene materials had interactions with hydrophobic drugs, we designed a graphene oxide (GO) composite hydrogel for drug delivery. But GO could not disperse well in monomer solution and agglomerated badly. Thus, water-soluble GO (GO-tripolymer) was first prepared under the stabilization of amphiphilic polymer, Pluronic F-127. The GO-tripolymer showed good solubility in PBS with the increase of polymer concentration. All GO-tripolymer solutions had the same UV absorption peaks as GO. Then, GO composite hydrogels (HNG hydrogels) were formed by the polymerization of hydroxyethyl methacrylate (HEMA), N-Vinyl pyrrolidone (NVP) and GO-tripolymer mixture. The introduction of GO-tripolymer had little effect on the gelation time and equilibrium swelling ratio of hydrogel. The freeze-drying hydrogel showed porous structure. The pore size decreased and the rough surface was detected with the...

Preparation of Biocompatible Graphene Oxide Composite Hydrogel to Deliver Ophthalmic Drugs

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Injectable Graphene Oxide/Graphene Composite Supramolecular Hydrogel for Delivery of Anti-Cancer Drugs

Synthesis and Characterization of Cyclodextrin-containing Hydrogel for Ophthalmic Drugs Delivery

Preparation of water-soluble and biocompatible graphene

Preparation of Biocompatible Graphene Oxide Composite Hydrogel to Deliver Ophthalmic Drugs