Stefanie A. Sydlik

In Vivo Compatibility of Graphene Oxide with Differing Oxidation States

Graphene oxide (GO) is suggested to have great potential as a component of biomedical devices. Although this nanomaterial has been demonstrated to be cytocompatible in vitro, its compatibility in vivo in tissue sites relevant for biomedical device application is yet to be fully understood. Here, we evaluate the compatibility of GO with two different oxidation levels following implantation in subcutaneous and intraperitoneal tissue sites, which are of broad relevance for application to medical devices. We demonstrate GO to be moderately compatible in vivo in both tissue sites, with the inflammatory reaction in response to implantation consistent with a typical foreign body reaction. A reduction in the degree of GO oxidation results in faster immune cell infiltration, uptake, and clearance following both subcutaneous and peritoneal implantation. Future work toward surface modification or coating strategies could be useful to reduce the inflammatory response and improve compatibility of GO as a component of medical devices.

Modular Functionalization of Carbon Nanotubes and Fullerenes

A series of highly efficient, modular zwitterion-mediated transformations have been developed which enable diverse functionalization of carbon nanotubes (CNTs, both single-walled and multi-walled) and fullerenes. Three functionalization strategies are demonstrated. (1) Trapping the charged zwitterion intermediate with added nucleophiles allows a variety of functional groups to be installed on the fullerenes and carbon nanotubes in a one-pot reaction. (2) Varying the electrophile from dimethyl acetylenedicarboxylate to other disubstituted esters provides CNTs functionalized with chloroethyl, allyl, and propargyl groups, which can further undergo S(N)2 substitution, thiol addition, or 1,3-dipolar cycloaddition reactions. (3) Postfunctionalization transformations on the cyclopentenones (e.g., demethylation and saponification) of the CNTs lead to demethylated or hydrolyzed products, with high solubility in water (1.2 mg/mL for MWCNTs). CNT aqueous dispersions of the latter derivatives are stable for months and have been successfully utilized in preparation of CNT-poly(ethylene oxide) nanocomposite via electrospinning. Large-scale MWCNT (10 g) functionalization has also been demonstrated to show the scalability of the zwitterion reaction. In total we present a detailed account of diverse CNT functionalization under mild conditions (60 degrees C, no strong acids/bases, or high pressure) and with high efficiency (1 functional group per 10 carbon atoms for SWCNTs), which expand the utility of these materials.

A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering

Scaffolds have been broadly applied within tissue engineering and regenerative medicine to regenerate, replace, or augment diseased or damaged tissue. For a scaffold to perform optimally, several design considerations must be addressed, with an eye toward the eventual form, function, and tissue site. The chemical and mechanical properties of the scaffold must be tuned to optimize the interaction with cells and surrounding tissues. For complex tissue engineering, mass transport limitations, vascularization, and host tissue integration are important considerations. As the tissue architecture to be replaced becomes more complex and hierarchical, scaffold design must also match this complexity to recapitulate a functioning tissue. We outline these design constraints and highlight creative and emerging strategies to overcome limitations and modulate scaffold properties for optimal regeneration. We also highlight some of the most advanced strategies that have seen clinical application and discuss the hurdles that must be overcome for clinical use and commercialization of tissue engineering technologies. Finally, we provide a perspective on the future of scaffolds as a functional contributor to advancing tissue engineering and regenerative medicine.

Well-defined, high molecular weight poly(3-alkylthiophene)s in thin-film transistors: side chain invariance in field-effect mobility

In this paper, the effect of side chain length on transistor performance was analyzed by using a series of well-defined, regioregular poly(3-alkylthiophene) (P3AT) samples (with PDI values as low as 1.1). Both untreated and octyltrichlorosilane-treated (OTS) SiO2 transistor dielectric layers were compared for all samples. On untreated SiO2, P3AT with hexyl side chains showed the best mobility, with mobilities as high as 0.1 cm2 V−1 s−1, and mobility values then decreased slightly with longer side-chain length. When using OTS-8 treated SiO2, on the other hand, mobility values remained high even with polymers of longer side-chain length, obtaining mobilities as high as 0.2 cm2 V−1 s−1 for hexyl, octyl and dodecyl side chains, which were much higher than previously reported values. Carrier mobilities of P3ATs with longer side chains were seen to be more sensitive to surface chemistry than for P3ATs with shorter side chains. Using morphological and GIXS studies, we found that for longer side chains, self-assembly is governed by two competing processes—backbone packing (π-stacking) and side-chain packing—that resulted in polymorphic behavior and disorder. On an OTS-treated surface, interactions between dielectric surface and side chains were reduced, resulting in better order at the interface and higher mobility.

Phosphate functionalized graphene with tunable mechanical properties.

The synthesis of a covalently modified graphene oxide derivative with exceptional and tunable compressive strength is reported. Treatment of graphene oxide with triethyl phosphite in the presence of LiBr produces monolithic structures comprised of lithium phosphate oligomers tethered to graphene through covalent phosphonate linkages. Variation of the both phosphate content and associated cation produces materials of various compressive strengths and elasticity.

Graphene oxide as a scaffold for bone regeneration

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.

Functional Graphenic Materials, Graphene Oxide, and Graphene as Scaffolds for Bone Regeneration

AbstractInsufficient bone regeneration is a complex problem affecting millions, and treatment would benefit from a complex material that recapitulates the properties of native bone. No current tissue-engineered scaffold can capture all of the properties of healthy bone. Graphene, graphene oxide (GO), and functional graphenic materials (FGMs) have a variety of interesting properties that make them promising foundations on which to craft sophisticated, biomimetic, osteoinductive, synthetic scaffolds for bone regeneration. GO has shown promise in the osteoinduction of stem cells, especially when coupled with growth factors. Additionally, FGMs have tunable surface chemistry and mechanical properties, as well as periodic long-range order, making this class of materials a promising candidate for regeneration of hard tissues. Strategies for controlling and modifying the surface chemistry of graphenic materials have become increasingly sophisticated in recent years, providing access to new FGMs with distinct implications in biomaterials and medicine. In this review, we discuss promising emerging strategies for the use of graphenic materials in bone regeneration, with a focus on biomimetic and bioinstructive FGMs.Lay SummaryThe regeneration of bone is an interdisciplinary medical, scientific, and engineering challenge. While small fractures heal spontaneously into adulthood, larger injuries and deformities require surgical correction. Currently, grafts or metallic prosthetics are the standard of care, but both suffer limitations. Graphene, graphene oxide, and functional graphenic materials comprise a class of materials that can be derived from graphite (pencil lead) and offer a plethora of promising properties including long-range order, mechanical stability, and autodegradability that make them promising scaffold materials for bone regeneration. Graphical Abstractᅟ

Covalently-controlled drug delivery via therapeutic methacrylic tissue adhesives

Medical cyanoacrylate adhesives have the potential to eliminate the need for sutures but face challenges to widespread implementation due to their brittleness and release of formaldehyde upon degradation. To overcome these limitations, we used molecular design to create therapeutic methacrylic (TMA) monomers to impart tunable mechanical properties, decreased formaldehyde release, and covalently-controlled bioactivity to commercial cyanoacrylate adhesives. The small molecule therapeutics ibuprofen, acetaminophen, and benzocaine were covalently tethered to the carbonyl of methacrylate using anhydride, ester, and amide bonds. When these TMAs were incorporated into n-butyl cyanoacrylate (BCA) tissue adhesives, the resulting TMA-BCA materials provided release of the therapeutics across a range of time scales according to the reactivity of the tether bond to hydrolysis. The anhydride-tether TMA-BCA adhesive delivered ibuprofen on the same order of magnitude and time scale as topical medications (12 ± 6 mg per g adhesive after 3.4 h). TMA-BCA adhesives also produced less formaldehyde than standard BCA adhesive, showed promising cytocompatibility, and adhered effectively to porcine skin. Further, the anhydride, ester, and amide tether TMA-BCA adhesives exhibited a range of shear moduli, with those containing rigid aromatic amide groups being stiffer, and those with flexible alkyl segments being less stiff, which could enable these adhesives to be tailored to match the mechanical properties of target tissues. The amide-tether TMA-BCA adhesive also showed a 219% increase in toughness compared to BCA. Overall, TMAs represent a platform technology that can be used to build adaptable and bioactive tissue adhesives.