Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering.

A novel sol-gel chemistry approach was developed to enable the simple integration of a cast-in-place, ambiently-dried insulation into high temperature applications. The insulation was silica-based and synthesized using methyltrimethoxysilane (MTMS) as the precursor. MTMS created a unique silica microstructure that was mechanically robust, macroporous, and superhydrophobic. To allow for casting into and around small, orthogonal features, zirconia fibers were added to increase stiffness and minimize contraction that could otherwise cause cracking during drying. Nano-sized titania powder was incorporated as an opacifier to reduce radiative heat transport. To assess relevance to high temperature thermoelectric generator technology, a comprehensive set of materials characterization experiments were conducted. The silica gel was thermally stable, retained superhydrophobicity with a water contact angle >150 degrees, and showed a high electrical resistance >1 G Omega, regardless of heating temperature (up to 600 degrees C in Ar for 4 h). In addition, The silica-based thermal insulation exhibited a Young's modulus similar to 3.7 MPa and a low thermal conductivity <0.08 Wi(m.K) at room temperature before and after heat treatment (up to 600 degrees C in Ar for 4 h). Thus, based on the simplicity of the manufacturing process and the optimized Material properties, we believe this technology can act as an effective cast-in-place thermal insulation (CTI) for thermoelectric generators and myriad other applications requiring improved thermal efficiency. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Delivery of nucleic acids with polymeric nanomaterials is an ongoing area of research that has great potential to treat diseases for which cures have remained mostly elusive. These technologies can be used for stem cell gene modification, overexpression of therapeutics, precise control over cell fate and differentiation to specific lineages. In addition, integrating such advanced nanomaterials with tissue engineering platforms enhances modified stem cell survival, proliferation, and regenerative capacity. Overall, this chapter seeks to describe the current types of nanomaterials, including viruses, and nucleic acids and evaluate their use in combination with stem cells. The chapter also underscores the recent developments pertaining to their characterisations and applications in tissue engineering and regenerative medicine.

Event Abstract Back to Event Local delivery of stem cell growth factors with injectable hydrogels for myocardial therapy Renae Waters1, 2, Settimio Pacelli1, Ryan Maloney1, 2 and Arghya Paul1, 2 1 University of Kansas, Chemical and Petroleum Engineering, United States 2 School of Engineering, University of Kansas, Bioengineering Graduate Program, United States Introduction: Stem cell therapy offers a promising approach to regenerate damaged cardiac tissue after acute myocardial infarction. Recent evidences have attributed such improvement to the broad repertoire of angiogenic paracrine factors (growth factors, chemokines and exosomes) secreted by the stem cells, known as secretome[1]. Here, we intend (i) to efficiently bio-manufacture cell secretome from 3D stem cell aggregates using a microfluidic system and (ii) efficiently deliver the harnessed secretome for cardiac repair and revascularization applications using a hydrogel-based injectable delivery system. Experiments and Results: As a first step, a microfluidic device consisting of deep concave microwell arrays was fabricated using soft lithography microscale techniques. Results demonstrate that bone marrow derived human mesenchymal stem cell (hMSC) suspensions, injected to the microfluidic chip through inlet port, form uniformly sized aggregates (~220μm diameter) within 2 days. Computational analysis confirmed rapid oxygen diffusion in the microwells. 3 days post-incubation, hMSC secretome (4.5-9 times increase in angiogenic protein concentrations compared to 2D culture including VEGF, FGF, Angiogenin) was collected, leaving behind the hMSC aggregates at the bottom of the well. As a next step, a physically cross-linked injectable nanocomposite hydrogel, comprising of silicate nanoplatelets and gelatin, was formulated to deliver the harnessed hMSC secretome to the target site. In vitro studies confirmed controlled release of bioactive hMSC growth factors from the hydrogel which induced proliferation of human endothelial cells (HUVEC). For in vivo studies rat model with acute myocardial infarction (n=5) was used. The secretome carrying hydrogel was injected intramyocardially at the per-infarct region of the heart, post infarction as mentioned in earlier work[2]. After 3 weeks, the animals were sacrificed and the injected tissue regions were examined for histological analysis. Masson’s Trichome staining confirmed reduced scar area in the treated Secretome+ group (3D cell aggregates) compared to control group (secretome from 2D cell culture). Immunostaining with CD31 antibodies also confirmed significantly high local myocardial angiogenesis at the injected site in Secretome+ group. These data confirms the angiogenic therapeutic potential of the developed hydrogel in vitro and in vivo. Conclusion: Take together, this study reports a novel strategy to utilize cell secretome, as an alternate to traditional cell therapy, for myocardial regeneration therapy. The strategy can also be used for other biomedical applications, such as wound healing and vascular tissue engineering. Arghya Paul likes to acknowledge the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences, National Institutes of Health (NIH), under Award Number P20GM103638.References:[1] Burdon TJ, Paul A, Noiseux N, Prakash S, Shum-Tim D (2011). Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential. Bone Marrow Res. 2011:207326.[2] Paul A et al (2014). Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair. ACS Nano; 8(8):8050-62. Keywords: Hydrogel, stem cell, growth factor, Bioactivity Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Biomimetic materials Citation: Waters R, Pacelli S, Maloney R and Paul A (2016). Local delivery of stem cell growth factors with injectable hydrogels for myocardial therapy. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00063 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul Google Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul Google Scholar Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul PubMed Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A nanocomposite hydrogel with photocrosslinkable micro-porous networks and a nanoclay component was successfully prepared to control the release of growth factor-rich stem cell secretome. The proven pro-angiogenic and cardioprotective potential of this new bioactive system provides a valuable therapeutic platform for cardiac tissue repair and regeneration.

Event Abstract Back to Event Gelatin-based nanocomposite hydrogel as a platform for stem cell tissue engineering Ryan Maloney1, 2, Vijayan Manoharan2, Flavia Castanho2, Settimio Pacelli2 and Arghya Paul1, 2 1 University of Kansas, Bioengineering Graduate Program, United States 2 University of Kansas, Chemical and Petroleum Engineering, United States Introduction: Bioactive hydrogels show great promise in tissue engineering and clinical applications. Collagen-based hydrogels, such as gelatin methacrylate (GelMA), contain amino acid sequences that mimic portions of native extracellular matrix and thus display excellent biocompatibility. As a photocrosslinkable polymer, GelMA also enables the study of cells in three dimensional culture[1]. Nanodiamonds (NDs), carbon-based nanoparticles displaying low cytotoxicity, have been used to bind small molecules, proteins, and DNA for drug delivery or gene therapy purposes[2]. Combining nanodiamonds with gelatin methacrylate to form a photocrosslinkable nanocomposite creates a flexible tissue engineering and drug delivery platform enabling investigation of ND/drug complexes in 3D culture. The goal of this study was to create GelMA/ND nanocomposites and characterize their structural properties and biocompatibility in vitro with human adipose stem cells (hASC) for regenerative medicine applications. Materials and Methods: Gelatin methacrylate was synthesized by addition of methacrylic anhydride to a solution of 10% gelatin from porcine skin, which was then dialyzed for 5 days with 10 water changes, then frozen and lyophilized. Nanodiamonds at concentrations of 0.5, 1, and 2 mg/mL were dispersed by sonication in GelMA solutions for 30 minutes. Addition of .5% photoinitiator (Irgacure 2959) followed by 30 minutes of UV exposure resulted in nanocomposite gelation. Structural and porosity analysis of the resulting gels was performed using scanning electron microscopy and ImageJ. Mechanical studies to determine elastic modulus were performed using dynamic mechanical analysis. Swelling ratio was determined at 1, 3, 5, 24, and 48 hours. For cell studies, hASCs were seeded on the resulting gels for metabolic activity quantification by MTT, F-actin staining with phalloidin, and nucleus staining with DAPI. Cell area analysis was performed after 24 hours. Results and Discussion: Mechanical analysis showed similar elastic moduli between GelMA, 0.5, and 1 mg/mL gels, while 2 mg/mL ND gels had significantly higher elastic moduli (Fig 1) while 4 mg/mL gels showed significant reduction in mechanical properties (not shown), meaning NDs show some potential for modulating GelMA mechanical properties. ImageJ Analysis of SEM samples (Fig 1) showed an average porosity of 44 ± 2% for GelMA/ND gels and 59 ± 6% for GelMA controls. Determination of the swelling ratio of 0.5, 1, and 2 mg/mL gels suggests that NDs do not significantly the diffusive properties of the GelMA. The MTT assay revealed no significant difference in cytocompatibility between GelMA and GelMA with 1 mg/mL ND, emphasizing the biocompatibility of NDs with the hASCs. Cell area analysis showed similar cell stretching between the GelMA and 1 mg/mL ND groups, further confirming cytocompatibility. These results suggest that NDs have the potential to manipulate mechanical properties with changing concentration and can be used as a drug delivery vehicle. Conclusion: Nanocomposites comprised of GelMA and NDs were successfully synthesized and characterized for mechanical properties, structure, and biocompatibility. This system can thus be used as a tissue engineering platform to study cell-nanomaterial, cell-drug, and cell-hydrogel interactions in a 2D and 3D environment. Arghya Paul likes to acknowledge the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences, National Institutes of Health (NIH), under Award Number P20GM103638.References:[1] Mochalin VN, Shenderova O, Ho D, Gogotsi Y (2011). The properties and applications of nanodiamonds. Nat Nanotechnol. 7(1):11-23.[2] Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010). Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials. (21):5536-44. Keywords: Hydrogel, Tissue Engineering, stem cell, nanocomposite Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Regenerative medicine: biomaterials for control of tissue induction Citation: Maloney R, Manoharan V, Castanho F, Pacelli S and Paul A (2016). Gelatin-based nanocomposite hydrogel as a platform for stem cell tissue engineering. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00585 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ryan Maloney Vijayan Manoharan Flavia Castanho Settimio Pacelli Arghya Paul Google Ryan Maloney Vijayan Manoharan Flavia Castanho Settimio Pacelli Arghya Paul Google Scholar Ryan Maloney Vijayan Manoharan Flavia Castanho Settimio Pacelli Arghya Paul PubMed Ryan Maloney Vijayan Manoharan Flavia Castanho Settimio Pacelli Arghya Paul Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The promising crystallinity and tunable redox capabilities of naphthalene diimides make them attractive candidates as electroactive materials for organic-based lithium-ion batteries. In this study, a family of naphthalene diimide derivates was synthesized and their redox properties explored with the intent of unveiling structures with reduction potentials that are higher than those encountered in previous organic redox processes. Changes in the electronic characteristics of the aryl substituents resulted in materials with discharge potentials that vary from 2.3 to 2.9 V vs Li/Li+, with discharge capacities as high as 121 mAh/g.

Herein we report on the hydrothermal synthesis of niobium pentoxide on carbide-derived carbon (Nb2O5/CDC) with a layered structure. The presence of phenylphosphonic acid guides the deposition during preparation, leading to the formation of amorphous Nb2O5 particles which are 4-10 nm in diameter and homogeneously distributed on the CDC framework. Electrochemical testing of the Nb2O5/CDC electrode indicated that the highest capacitance and Coulombic efficiency occurred using an electrolyte comprised of 1 M lithium perchlorate in ethylene carbonateldimethyl carbonate. Subsequent heat treatment of Nb2O5/CDC in CO2 environment led to crystallization of the Nb2O5, allowing reversible Li+ intercalation/de-intercalation. For sweep rates corresponding to charging and discharging in under 3 min, a volumetric charge of 180 C cm(-3) and Coulombic efficiency of 99.2% were attained. (C) 2014 Elsevier B.V. All rights reserved.

Recent work demonstrated the efficacy of combining layer-by-layer assembly with hydrogels to provide the controlled delivery of proteins for use in nerve repair scaffolds. In this work, we augmented the protein dose response by controlling and increasing the hydrogel internal surface area. Sucrose was added to agarose during gelation to homogenize the nanopore morphology, resulting in increased surface area per unit volume of hydrogel. The surface area of a range of compositions (1.5-5.0 wt% agarose and 0, 50 and 65 wt% sucrose) was measured. Gels were supercritically dried to preserve porosity enabling detailed pore morphology measurements using nitrogen adsorption and high resolution scanning electron microscopy. The resulting surface area, normalized by superficial gel volume, ranged between 6m(2)/cm(3)gel and 56 m(2)/cm(3)gel. Using the layer-by-layer process to load lysozyme, a neurotrophic factor analog, a relationship was observed between surface area and cumulative dose response ranging from 176 to 2556 μg/mL, which is in the range of clinical relevance for the delivery of growth factors. In this work, we demonstrated that the ability to control porosity is key in tuning drug delivery dose response from layer-by-layer modified hydrogels.

The crystalline network of orthorhombic niobium oxide (T-Nb2O5) offers two-dimensional transport pathways for fast intercalation of lithium ions, leading to its high and rate independent intercalation pseudocapacitance. Unlike many other lithium intercalation metal oxides, T-Nb2O5 can be charged in short periods of time, making it suitable as a supercapacitor electrode material. This is due to the fast solid-state diffusion and no structural change of T-Nb2O5 upon intercalation of Li ions. For practical applications of Nb2O5 and other metal oxides in supercapacitors, thick electrodes with large mass loadings are necessary. This, however, will result in ohmic losses and ion transport limitations due the relatively low electrical conductivity of the oxide and limited ion diffusion through the electrode thickness. To address these limitations, we have successfully prepared the layered Nb2O5/carbon hybrid materials through controlled oxidation of layered Nb2C (also called Nb2C-MXene). As-prepared Nb2O5/C well inherited the two dimensional structure of the precursor with Nb2O5 nanocrystals formed between the MXene layers. A detailed study of oxidation temperatures and durations was conducted to achieve nanostructured of T- Nb2O5 and XRD, SEM and TEM studies show the uniform formation T-phase of Nb2O5 on carbon sheets after oxidation at 850℃. The electrochemical characterization of thick electrodes of synthesized material show very promising performance, with specific capacitance of about 350 F/g in 1M LiClO4 /EC/DMC (1:1 in volume ratio) electrolyte. The performance of developed electrodes is believed to be highly dependent of layered two-dimensional structure of Nb2O5/carbon hybrid materials. Acknowledgements: Authors acknowledge Dr. Mengqiang Zhao for his help with TEM studies. Support from DOE via Sandia National Laboratory is appreciated.

Presently, the only commercially available power generating thermoelectric (TE) modules are based on bismuth telluride (Bi2Te3) alloys and are limited to a hot side temperature of 250 °C due to the melting point of the solder interconnects and/or generally poor power generation performance above this point. For the purposes of demonstrating a TE generator or TEG with higher temperature capability, we selected skutterudite based materials to carry forward with module fabrication because these materials have adequate TE performance and are mechanically robust. We have previously reported the electrical power output for a 32 couple skutterudite TE module, a module that is type identical to ones used in a high temperature capable TEG prototype. The purpose of this previous work was to establish the expected power output of the modules as a function of varying hot and cold side temperatures. Recent upgrades to the TE module measurement system built at the Fraunhofer Institute for Physical Measurement Techniques allow for the assessment of not only the power output, as previously described, but also the thermal to electrical energy conversion efficiency. Here we report the power output and conversion efficiency of a 32 couple, high temperature skutterudite module at varying applied loading pressures and with different interface materials between the module and the heat source and sink of the test system. We demonstrate a 7% conversion efficiency at the module level when a temperature difference of 460 °C is established. Extrapolated values indicate that 7.5% is achievable when proper thermal interfaces and loading pressures are used.

As our society continues to pursue an economic future independent of fossil fuels, it has become increasingly clear that large improvements in energy storage technologies are required. In particular, various aspects of lithium-ion batteries are being researched for concurrent improvements in cost, safety, energyand power-density, and cycle life. While numerous recent advances in high-voltage cathodes, high-capacity alloying anodes, engineered electrode architectures and safer electrolytes have advanced the field greatly, there is as of yet no battery solution which has achieved the combination of properties necessary to significantly displace liquid fuels.

The performance of thermoelectric (TE) materials has improved tremendously over the past decade. The intrinsic thermal and electrical properties of state-of-the-art TE materials demonstrate that the potential for widespread practical TE applications is very large and includes TE generators (TEGs) for automotive waste heat recovery. TE materials for automotive TEG applications must have good intrinsic performance, be thermomechanically compatible, and be chemically stable in the 400 K to 850 K temperature range. Both n-type and p-type varieties must be available at low cost, easily fabricated, and durable. They must also form robust junctions and develop good interfaces with other materials to permit efficient flows of electrical and thermal energy. Among the TE materials of interest for automotive waste heat recovery systems are the skutterudite compounds, which are the antimony-based transition-metal compounds RTE4Sb12, where R can be an alkali metal (e.g., Na, K), alkaline earth (e.g., Ba), or rare earth (e.g., La, Ce, Yb), and TE can be a transition metal (e.g., Co, Fe). We synthesized a considerable quantity of n-type and p-type skutterudites, fabricated TE modules, incorporated these modules into a prototype TEG, and tested the TEG on a production General Motors (GM) vehicle. We discuss our progress on skutterudite TE module fabrication and present module performance data for electrical power output under simulated operating conditions for automotive waste heat recovery systems. We also present preliminary durability results on our skutterudite modules.

With the rising cost of fuel and increasing demand for clean energy, solid-state thermoelectric (TE) devices are an attractive option for reducing fuel consumption and CO2 emissions. Although they are reliable energy converters, there are several barriers that have limited their implementation into wide market acceptance for automotive applications. These barriers include: the unsuitability of conventional thermoelectric materials for the automotive waste heat recovery temperature range; the rarity and toxicity of some otherwise suitable materials; and the limited ability to mass-manufacture thermoelectric devices from certain materials. One class of material that has demonstrated significant promise in the waste heat recovery temperature range is skutterudites. These materials have little toxicity, are relatively abundant, and have been investigated by NASA-JPL for the past twenty years as possible thermoelectric materials for space applications. In a recent collaboration between Michigan State University (MSU) and NASA-JPL, the first skutterudite-based 100W thermoelectric generator (TEG) was constructed. In this paper, we will describe the efforts that have been directed towards: (a) enhancing the technology-readiness level of skutterudites to facilitate mass manufacturing similar to that of Bi2Te3, (b) optimizing skutterudites to improve thermal-to-electric conversion efficiencies for class 8 truck applications, and (c) describing how temperature cycling, oxidation, sublimation, and other barriers to wide market acceptance must be managed. To obtain the maximum performance from these devices, effective heat transfer systems need to be developed for integration of thermoelectric modules into practical generators.