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The media advertizes that soon everybody can manufacture models and parts of all kinds via computer-aided design –computer-aided manufacturing by additive manufacturing (AM) technologies. That can boost the do-it-yourself activities enormously. But it can also revolutionize the industries: Most conventional technologies of manufacture are profitable only in big lots of production. For single specimens and small lots of production, they are too expensive. But with AM, one or a few original or spare parts can be produced at low cost. However, to succeed in the market, the AM products must become competitive. They must have reproducibility of an exact shape, even in tiny details, a perfect surface and, above all, sufficient mechanical strength. This article deals with three-dimensional ink-jet printing with monomer inks and polymer powders. Since powder beds are always porous, the main aim was to fill the pores permanently with high amounts of the ink polymer. A new polymer powder that rapidly dissolves in monomer inks is reported.
Bladder tissue engineering technology has provided an alternative treatment for patients with congenital bladder conditions (e.g. bladder exstrophy) and conditions such as radiation damage, infection, interstitial cystitis, neuropathic small bladder disease, and bladder cancer. To treat these end-stage bladder diseases, a partial or total cystectomy is often performed, followed by the creation of a neobladder or a continent urinary reservoir using intestinal segments to restore bladder capacity. However, using bowel tissue for this purpose may cause many side effects, although a recent study showed that all children with neurogenic bladder disease are at increased risk of bladder cancer regardless of exposure to intestinal tissue in the urinary tract [1]. Therefore, new clinical and surgical techniques are needed in order to allow these patients to live healthier and more normal lives. The authors of a clinical study recently reported that it is possible to engineer neo-bladder tissue using autologous cells seeded on biodegradable scaffolds [2] and that this engineered tissue can be used to enlarge the bladder volume and improve function for patients with neuropathic diseases. Additionally, increasing evidence indicates that the use of patients’ own stem cells provides a promising alternative for patients with end-stage bladder diseases in cases in which healthy autologous bladder cells might not be available.
Induced pluripotent stem cells, or iPS cells, have quite similar characteristics to embryonic stem (ES) cells, such as pluripotency and unlimited self-renewal, yet can be derived from somatic cells without using embryos [1]. “Pluripotency” is defined as the ability to differentiate in response to extrinsic cues into all somatic lineages that comprise the entire body, including the germ line. An unlimited self-renewal capacity allows a large amount of stem cells to be cultured and grown in the laboratory. Such unique cell identities are programmed in the gene-expression patterns and epigenetic modification patterns of ES cells, and are quite different from other somatic cells. However, the somatic cells can be “reprogrammed” to confer ES cell-like pluripotency by introducing a cocktail of genes (so-called reprogramming factors) – typically Oct4, Sox2, Klf4, and c-Myc. Therefore, iPS cells hold great promise not only for basic biological studies of cell-fate decisions, but also for medical applications. In this chapter, we first summarize a number of methodologies developed to derive iPS cells, and later discuss the recent progress and challenges in the clinical application of iPS cells.
Cells of origin
Many different types of somatic cells have been reprogrammed to pluripotency to generate iPS cells (Table 2.1). Fibroblasts were the first cell type to be reprogrammed [2, 3], and are one of the most widely used cell types so far, because of the well-established culture conditions, distinct morphology from ES cells, high susceptibility to retroviral vector transduction, and their innate ability to serve as feeder cells. Some particular cell types, especially somatic stem cells or progenitor cells, express a number of reprogramming factors endogenously, which presumably allows low-level transduction of some exogenous reprogramming factor(s). For example, adult neural stem cells [4] and dermal papilla cells [5] endogenously express Sox2 and c-Myc, which allows iPS cells to be derived using only two reprogramming factors (i.e. Oct4 and Klf4), although the resulting reprogramming efficiency is lower than that obtained for cells reprogrammed using the four factors. Keratinocytes are an attractive cell source because of their higher reprogramming efficiency [6]. However, the cultivation and expansion of keratinocytes is challenging [7]. In the hematopoietic lineage, the differentiation stage of the cells influences the efficiency of their reprogramming. Hematopoietic stem/progenitor cells generate iPS cells better than do terminally differentiated B and T cells [8].
By
Mildred Embree, Columbia University Medical Center,
Chang Hun Lee, Columbia University Medical Center,
Ziming Dong, Zhengzhou University,
Mo Chen, Columbia University Medical Center,
Kimi Kong, Columbia University Medical Center,
Hemin Nie, Columbia University Medical Center,
Avital Mendelson, Columbia University Medical Center,
Bhranti Shah, Columbia University Medical Center,
Shoko Cho, Columbia University Medical Center,
Takahiro Suzuki, Columbia University Medical Center,
Rujing Yang, Columbia University Medical Center,
Nan Jiang, Columbia University Medical Center,
Jeremy J. Mao, Columbia University Medical Center
Edited by
Peter X. Ma, University of Michigan, Ann Arbor
Introduction: stem/progenitor cell recruitment vs. transplantation
The utilization of transplanted stem cells in regenerative medicine has been studied extensively as a potential therapy to repair or replace tissues that are lost due to trauma, congenital deformities, tumor resections, or infectious diseases [1–3]. The current cell transplantation model in regenerative medicine is founded on the principle that the application of transplanted stem cells could repopulate and regenerate damaged or diseased tissues, with restored tissue functions and homeostasis. However, cell transplantation is faced with a multitude of clinical and cell culture complications including the complexity of the multistep surgical procedures, donor-site trauma, immune rejection for allogeneic and xenogeneic cells, cell phenotypic variations due to in-vitro culture techniques, potential tumorigenesis associated with long-term cell expansion, failure of exogenous cell engraftment, and uncertainties and difficulties in the regulatory approval process [4–8]. The difficulties in the clinical application of stem cell transplantation are in strong contrast to the results of multiple experimental studies that demonstrate different levels of efficacy of cell delivery in a number of disease models such as Parkinson’s disease [9, 10], blood cancers and diseases [11, 12], and muscle and spinal disorders/injuries [13, 14].
For a number of regenerative medicine applications, the use of stem cell transplantation might not be competitive with the cost-effectiveness of current clinical treatment modalities in the dental and musculoskeletal fields, including titanium joint replacements, dental implants, and operative dental procedures [15–17]. Alternatively, the concept of endogenous stem/progenitor cell recruitment in regenerative medicine is based on the idea that native stem/progenitor cells that already reside within mature tissue can be stimulated and functionally enhanced to repopulate, repair, and/or regenerate damaged tissues [18]. Relative to stem cell transplantation, the application of endogenous stem cell recruitment in regenerative medicine is still in its infancy. The combination of the use of biological factors, release technology, biomaterials, and bioengineered scaffolds to enhance endogenous stem cell recruitment seems very promising for potential use in translational regenerative medicine. However, further scientific experimentation is warranted, since many scientific questions concerning the mechanistic details remain unresolved and it will be necessary to validate the efficacy of this approach for clinical application.
Transparent 0.67(Pb1−xLax)(Mg1/3Nb2/3)O3–0.33(Pb1−xLax)TiO3 (x = 0–0.05) ceramics were successfully prepared without using a hot-pressing technique. The optical transmittance at the wave length of 400–2000 nm increased with increasing lanthanum (La) content, x from 0 to 0.03. The transmittance at 600–2000 nm further increased (with the highest transmittance of 68% at 2000 nm for ceramics with thickness of 0.5 mm) at x = 0.04 and 0.05, while the transmittance at 400–600 nm decreased. X-ray diffraction patterns suggested that the overall increase in the transmittance with x was associated with a change in the crystal systems from a monoclinic phase to a pseudocubic phase, and the decrease at x = 0.04 and 0.05 was related to the formation of an impurity second phase. Their microstructures and dielectric properties were also studied.
Three-dimensional transmission electron microscopy (3D-TEM) is a powerful technology that provides 3D characterization of the internal details of a material. In this work, for the first time, 3D-TEM was used to characterize a laser-sintered polymer nanocomposite. The dispersion of carbon nanotubes (CNTs) in the laser-sintered polyamide 12 (PA12)-CNT nanocomposite parts was evaluated. At first, to prepare 3D-TEM samples at specific locations, a focused ion beam technique was used. Then, high quality two-dimensional (2D)-TEM images were achieved at various scanning angles for the PA12-CNT laser-sintered sample. After that, 3D-TEM images were reconstructed by combining all the 2D-TEM images. Results revealed that the CNTs were agglomerate-free in the PA12-CNT parts after laser sintering, which helps to explain previously reported improvement in mechanical properties of laser-sintered PA12-CNT parts.
Tendon is one of the important components of the musculoskeletal system, which links muscles to bones, so that the tensile force created by muscles can be transmitted to bone for body movement. Tendon injury and defects are common diseases of the musculoskeletal system. Nevertheless, the treatment of tendon defects remains a major challenge to reconstructive surgery, partly because there is limited availability of autologous tendon grafts.
Regenerative medicine represents the future direction for tendon repair and functional recovery, in which stem cell therapy, tissue engineering, and regenerative materials will play important roles in tendon regeneration. Actually, engineered tendon repair might be the major contributor to tendon regeneration, because it can also integrate stem cells and biomaterials into tendon regeneration, although we are a long way from its ultimate translation to clinical therapy.
Scaffold materials
General requirements on tendon scaffold materials
As the major contributor to tissue regeneration, biomaterial plays a key role in engineered tendon regeneration, because it provides an essential scaffold for extracellular matrix (ECM) production and tissue formation. The main tendon extracellular matrix is type I collagen, which is highly organized in a hierarchy of bundles that are aligned in a parallel fashion. In addition, there are small amounts of other collagens and proteoglycans, such as collagens type III, V, XII, and XIV, decorin, and tenascin. In particular, the small linking proteins play important roles in enabling the structural integrity of tendon and affording it mechanical strength. This unique structure provides the unique biomechanical properties of tendon tissues. Therefore, the parallel alignment structure and mechanical strength should be considered for tendon scaffold design.
Graphene is currently one of the most extensively studied materials because it displays a number of unique structural and electronic properties. A variety of methods are currently available for the growth of graphene; however, few are viable for large scale, cost-effective production of high quality graphene. Here, a novel growth process for few layer graphene using chemical vapor deposition (CVD) and a commercial iron nanopowder catalyst is described. This method is readily scalable so it can be used to produce a large volume of graphene sheets. Graphene sheets made from this process were characterized by Raman spectroscopy, and scanning and transmission electron microscopy. Raman spectroscopy shows that the product consists of few layer graphene sheets. This is the first reported method of utilizing nanoparticles to synthesize graphene by a CVD process, which typically produces multiwalled carbon nanotubes. A possible mechanism for the formation of graphene by this modified CVD process is discussed.
This work describes the use of a piezo-actuated inkjet print head with a nozzle aperture of 50 µm to obtain picoliter drops of different model ionic liquids (ILs). A theoretical analysis of the microdrop generation of three model ILs is confirmed by experiments. The inkjet print process was optimized to enable a stable and reproducible drop ejection in both continuous and drop-on-demand modes by controlling the temperature of the nozzle, as well as the electrical signal sent to the piezo actuator used to generate the drops. Controlled volumes ranging from 43 ± 3 pL to 319 ± 1 pL have been achieved, with a volume control down to 3 pL. The null volatility of ILs yields an extremely high stability of the inkjet process, obtaining drops with very constant volumes during the entire print process. It also avoids the coffee staining effect observed in the deposition of conventional liquid drops. The possibility to deposit controlled volumes in a reproducible way is demonstrated here and applied to a proof-of-concept application with the aim to create dense concave optical lens arrays by replicating the deposited ionic liquid microdrops in poly(dimethylsiloxane) (PDMS).
CoCrMo alloy was deposited on a metallic substrate using laser engineered net shaping (LENS™) – a laser-based additive manufacturing technique. Several samples with five layers of deposit were fabricated at different combinations of laser power, powder feed rate, and scan velocity to study their influence using L4 Orthogonal array. The deposits were evaluated for their microstructure, hardness, wear resistance, and electrochemical performance. Grey relational grade analysis and analysis of variance were applied to identify optimum process parameters. The x-ray diffraction and microstructural analysis of the deposits showed uniform and fine microstructural features. Our experimental results revealed that the coatings fabricated using high laser power (350 W), low powder feed rate (5 g/min), and high scan velocity (20 mm/s) provide the highest hardness (446 ± 2.87 Hv) and wear resistance (1.80 ± 0.0007 mm3/Nm). However, the corrosion resistance was observed to be high for the deposits fabricated using low laser power (200 W), low powder feed rate (5 g/min), and low scan velocity (10 mm/s).
Spherical and conical nanoindentation experiments were performed for the same polymer specimens to compare Young's moduli measured from the elastic loading and unloading curves, and bending experiments. Finite-element simulation was employed to ensure pure elastic deformation during spherical nanoindentation. The moduli measured from the elastic loading curves using Hertz's contact law are very close to the bending moduli, because both measurements were conducted under the same elastic deformation. However, the moduli measured from the elastic unloading curves are up to 60% higher than the bending moduli owing to plastic deformation close to the sharp conical indenter tip.
A number of recent mechanical property studies have sought to validate atomistic and multiscale models with matching experimental volumes. One such property is the ductile–brittle transition temperature (DBTT). Currently no model exists that incorporates both external and internal variables in an analytical model to address both length scales and environment. Using thermally activated parameters for dislocation plasticity, the present study attempts a small piece of this. With activation energy and activation volumes previously determined for single and polycrystalline Fe–3% Si, predictions of DBTT both with and without atmospheric hydrogen are made. These are compared with standard fracture toughness measurements similarly for samples both with and without atmospheric hydrogen. In the hydrogen-free samples, average strain rate varied by four orders of magnitude. DBTT shifts are experimentally found and predicted to increase 100 K or more with either increasing strain rate or exposure to hydrogen.
Adsorbents with high specific surface areas, developed porosities, and sustainable CO2 capture capacity (∼180 mg/g at 25 °C, 1 bar) were prepared by KOH activation of hydrothermally carbonized carboxymethylcellulose (CMC). Condensed aromatic carbon materials (CSc) with particle diameters of 2–3 μm and many oxygen-containing groups on their surfaces can be obtained after hydrothermal treatment of CMC; these materials are similar to glucose-derived hydrothermal carbons. The activation conditions, including activation ratio and activation temperature, significantly influence the structure and morphology of the adsorbents. In turn, the pore structures, specific surface areas, and adsorption conditions significantly affect the adsorption capacities of these new adsorbents. For samples with the same activation ratio, those with higher specific surface areas show higher CO2 capture capacities at 25 °C and 1 bar. Under these conditions, for samples with different activation ratios, the capacity is dominated by the microporosity development and, in particular, the high volume of smaller micropores (d = 0.4–0.9 nm); when the adsorption pressure is decreased to 0.1 bar, the CO2 capture ability becomes closely correlated with the number of ultramicropores (d < 0.7 nm).
A characteristic fluorescent tarnish can be observed on some daguerreotypes under shortwave ultraviolet radiation. The fluorescence can be seen in several distinct patterns: edge tarnish, rings, and continuous films. Dispersive Raman spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD) were applied to characterize and identify the fluorescent compound. Raman spectroscopy identified the characteristic peak for copper cyanide, CuCN, at 2172 cm-1. Elemental k-ratio maps of the SEM analysis indicated an increase in copper, sodium, carbon and nitrogen in the area of fluorescence. XRD confirmed the identification of a copper cyanide compound. Shortwave ultraviolet radiation can be used in a monitoring program of daguerreotypes to further characterize the fluorescent tarnish and its effect on the deterioration of daguerreotypes.
Soap formation in traditional oil paintings occurs when heavy-metal-containing pigments, such as lead white, 2Pb(CO3)2·Pb(OH)2, and lead-tin yellow type I, Pb2SnO4, react with fatty acids in the binding medium. These soaps may form aggregates that can be 100-200 μm in diameter, which swell and protrude through the paint surface, resulting in the degradation of the paint film and damage to the integrity of the artwork. In addition, soap formation has been reported to play a role in the increased transparency of paint films that allows the painting support, the preparatory drawing, and the artists’ alterations to become visible to the naked eye. The factors that trigger soap formation and the mechanism(s) of the process are not yet well understood. To elucidate these issues, chemical and structural information is necessary which can be obtained by solid-state 207Pb, 119Sn, and 13C nuclear magnetic resonance (NMR). In the present study, a combination of 207Pb NMR pulse sequences was used to determine accurately the NMR parameters of lead-containing pigments and lead carboxylates known to be involved in soap formation, such as lead palmitate, lead stearate, and lead azelate. These results show that the local coordination environment of lead azelate is different from lead palmitate or lead stearate and therefore it is unlikely that lead azelate would be incorporated into an ordered structure containing lead palmitate and lead stearate. In addition, the chemical shifts of the pigments obtained are different from those of the soaps, demonstrating that 207Pb NMR is useful in characterizing the components when present in a mixture, such as a paint film. The NMR methods discussed can also be applied to other Pb-containing cultural heritage materials, electronic and optoelectronic materials, superconducting materials, and environmentally contaminated materials.
This paper discusses the effectiveness of hydroxyapatite (HAP) as an inorganic consolidant for physically weathered Indiana Limestone, and as a coupling agent between limestone and a silicate consolidant. A double application is investigated, in which samples are coated with HAP followed by a commercially available silicate-based consolidant (Conservare® OH-100). To artificially weather limestone, a thermal degradation technique was utilized. Diammonium hydrogen phosphate (DAP) salt was reacted with limestone, alone and with cationic precursors, to produce HAP films. The dynamic elastic modulus, water sorptivity and tensile strength of the treated stones were evaluated. HAP was found to be an effective consolidant for weathered Indiana Limestone, and its performance was enhanced by addition of millimolar quantities of calcium chloride. However, HAP was not useful as a coupling agent; a double treatment with DAP is more effective than sequential treatment with DAP and Conservare®.
Non-destructive investigation, chemically fingerprinting, and authentication of ceramic cultural artifacts is a challenging analytical problem. Electron paramagnetic resonance (EPR) spectroscopy is capable of distinguishing between clays based on the paramagnetic metals present, and firing temperature (TF) based on the complexes of these metals formed at different TF values. Unfortunately, the 9 GHz frequency of conventional X-band EPR restricts sample size to a few mm and limits its applicability to small fragments. Low frequency EPR (LFEPR) is based on an EPR spectrometer operating at a few hundred MHz. LFEPR can utilize larger samples on the order of a few cm, but has a lower sensitivity due to the smaller Boltzmann ratio. Additionally, LFEPR may not be capable of detecting a spectral transition if the LFEPR operating frequency is less then the zero-field splitting of the paramagnetic metal complex. We utilized an LFEPR operating at 300 MHz which scans the applied magnetic field between the local Earth’s magnetic field and 26 mT to determine the feasibility of detecting EPR signals from clays, pigments, and glazes. Various clay samples were studied at 100 < TF < 1200 °C. Spectral differences were seen as a function of both clay type and TF. Differences in the LFEPR spectra of Han, Egyptian, and Ultramarine blue support the ability to distinguish among pigments. Paramagnetic impurities in glass may allow distinction between glaze spectra. We have also explored the utility of LFESR by the use of a radio frequency surface coil rather than an enclosed resonator. Although the active volume of the surface coil is ∼1 cm3, objects as large as 20 cm in diameter might be easily characterized with our spectrometer.