Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43−. Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.
Graphene oxide (GO), the oxidized form of graphene, holds great potential as a component of biomedical devices, deriving utility from its ability to support a broad range of chemical functionalities and its exceptional mechanical, electronic, and thermal properties. GO composites can be tuned chemically to be biomimetic, and mechanically to be stiff yet strong. These unique properties make GO-based materials promising candidates as a scaffold for bone regeneration. However, questions still exist as to the compatibility and long-term toxicity of nanocarbon materials. Unlike other nanocarbons, GO is meta-stable, water dispersible, and autodegrades in water on the timescale of months to humic acid-like materials, the degradation products of all organic matter. Thus, GO offers better prospects for biological compatibility over other nanocarbons. Recently, many publications have demonstrated enhanced osteogenic performance of GO-containing composites. Ongoing work toward surface modification or coating strategies could be useful to minimize the inflammatory response and improve compatibility of GO as a component of medical devices. Furthermore, biomimetic modifications could offer mechanical and chemical environments that encourage osteogenesis. So long as care is given to assure their safety, GO-based materials may be poised to become the next generation scaffold for bone regeneration. WIREs Nanomed Nanobiotechnol 2017, 9:e1437. doi: 10.1002/wnan.1437 For further resources related to this article, please visit the WIREs website.
Lightweight, flexible, low‐cost, and disposable electronics have transformed modern life and promise to continue to drive a diversity of applications from defense to medicine. For flexible and stretchable devices, the mechanical demands are actually quite great, requiring a material to maintain its ability to undergo elastic deformation, in both tension and compression, through many cycles of deformation. Traditional electronics are fabricated using organic semiconductors, which offer excellent electronic performance, but are often stiff and brittle. Conductive polymers offer potential for electronic materials with high toughness and an ability to deform elastically, making inexpensive, flexible electronics possible in a way no other material can. This paper reports the bulk thermal, electronic, and mechanical properties of a series of conductive polymers based on regioregular poly(3‐alkylthiophenes) (P3ATs) with randomly incorporated polythiophene (PT) in 3:1 (P3AT3‐ran‐PT1) and 1:1 (P3AT1‐ran‐PT1) ratios. These random copolymers are synthesized with no added synthetic complexity with respect to the homopolymer, and reproducibly give polymers with dramatically different mechanical and electronic properties. It is shown that random incorporation of the unsubstituted thiophene results in conductive polymers with excellent electronic properties (conductivities up to 500 S/cm, mobilities up to 0.11 cm2 V−1 s−1) and enhanced toughness (up to 760% improvement).
Synthetic biomaterials are poised to transform medicine; however, current synthetic options have yet to ideally recapitulate the desirable properties of native tissue. Thus, the development of new synthetic biomaterials remains an active challenge. Due to its excellent properties, including electrical conductivity, water dispersibility, and capacity for functionalization, graphene oxide (GO) holds potential for myriads of applications, including biological devices. While many studies have evaluated the compatibility of freshly prepared GO, understanding the compatibility of GO as it ages in an aqueous environment is crucial for its safe implementation in long-term biological applications. This is a critical disconnect, as GO has been shown to undergo an autodegradation pathway in aqueous conditions, dynamically changing its composition and structure while producing degradation products. Thus, the long-term cytocompatibility of GO is investigated by "aging" GO over time in water and accelerating aging and decomposition via sonication. While age affects the composition and size of GO, it has no effect on cellular vitality and does not alter subcellular structures or DNA melting. Overall, GO is cytocompatible throughout the process of aging, beginning to demonstrate that GO may be utilized for long-term in vivo applications such as implanted tissue engineered scaffolds or biosensors.
Bioactive, synthetic materials represent next-generation composites for tissue regeneration. Design of contemporary materials attempts to recapitulate the complexities of native tissue; however, few successfully mimic the order in nature. Recently, graphene oxide (GO) has emerged as a scaffold due to its potential for bioactive functionalization and long-range order instilled by the self-assembly of graphene sheets. Chemical reduction of GO results in a more compatible material with enhanced properties but compromises the ability to functionalize the graphenic backbone. However, using Johnson-Claisen rearrangement chemistry, functionalization is achieved that is not liable to reduction. From reduced Claisen graphene, we polymerized short homopeptides from -amino acid N-carboxyanhydride monomers of glutamate and lysine to result in functionalized graphenes (pGlu-rCG and pLys-rCG) that are cytocompatible, degradable, and bioactive. Exposure to NIH-3T3 fibroblasts and RAW 264.7 macrophages revealed that the materials are cytocompatible and do not alter important sub-cellular compartments. Powders were hot pressed to form mechanically stiff (E ′ : 41 and 49 MPa), strong (UCS: 480 and 140 MPa), and tough (U T : 2898 and 584 J m −3 × 10 4 ) three-dimensional constructs (pGlu-rCG and pLys-rCG, respectively). Overall, we report a robust chemistry and processing strategy for facile bioactive functionalization of compatible, reduced Claisen graphene for three-dimensional biomedical applications.
Chemically functionalized graphene covalently reactsin situwith chondroitin sulfate to form an enhanced, injectable hydrogel for potential cartilage therapy.
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