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Sample records for engine regenerator matrices

  1. Engineered matrices for bone regeneration

    NASA Astrophysics Data System (ADS)

    Winn, Shelley R.; Hu, Yunhua; Pugh, Amy; Brown, Leanna; Nguyen, Jesse T.; Hollinger, Jeffrey O.

    2000-06-01

    Traditional therapies of autografts and allogeneic banked bone can promote reasonable clinical outcome to repair damaged bone. However, under certain conditions the success of these traditional approaches plummets, providing the incentive for researchers to develop clinical alternatives. The evolving field of tissue engineering in the musculoskeletal system attempts to mimic many of the components from the intact, healthy subject. Those components consist of a biologic scaffold, cells, extracellular matrix, and signaling molecules. The bone biomimetic, i.e., an engineered matrix, provides a porous structural architecture for the regeneration and ingrowth of osseous tissue at the site of injury. To further enhance the regenerative cascade, our strategy has involved porous biodegradable scaffolds containing and releasing signaling molecules and providing a suitable environment for cell attachment, growth and differentiation. In addition, the inclusion of genetically modified osteogenic precursor cells has brought the technology closer to developing a tissue-engineered equivalent. The presentation will describe various formulations and the methods utilized to evaluate the clinical utility of these biomimetics.

  2. Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices

    PubMed Central

    Fisher, James N.; Peretti, Giuseppe M.; Scotti, Celeste

    2016-01-01

    Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates. PMID:26997959

  3. Chemically modified RNA activated matrices enhance bone regeneration.

    PubMed

    Elangovan, Satheesh; Khorsand, Behnoush; Do, Anh-Vu; Hong, Liu; Dewerth, Alexander; Kormann, Michael; Ross, Ryan D; Sumner, D Rick; Allamargot, Chantal; Salem, Aliasger K

    2015-11-28

    There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation. PMID:26415855

  4. Evaluation of ceramic packed-rod regenerator matrices

    NASA Technical Reports Server (NTRS)

    Lawless, W. N.; Arenz, R. W.

    1981-01-01

    An extensive evaluation of a modified cryocooler with various regenerator matrices is reported. The matrices examined are 0.015 in. diam. Pb spheres and 0.008, 0.015, and 0.030 in. diam. rods of a 0.2% SnCl2 doped ceramic labelled LS-8A. Specific heat and thermal conductivity data on these rod materials are also reported. The chronic pulverization/dusting problem common to Pb spheres was investigated. During a 1000 hr life test with 0.0008 in. diam. rods there was no degradation of the refrigerator performance, and a subsequent examination of the rods themselves revealed no evidence of breakage or pulverization. The load temperature characteristics for the rod packed regenerators were inferior to that for the Pb spheres, the effect being to shift the Pb spheres load curve up in temperature. This temperature shift was 5.0, 7.4, and 11.6K for the 0.0008, 0.015, and 0.030 in. diam. rods, respectively.

  5. Elucidation of differential mineralisation on native and regenerated silk matrices.

    PubMed

    Midha, Swati; Tripathi, Rohit; Geng, Hua; Lee, Peter D; Ghosh, Sourabh

    2016-11-01

    Bone mineralisation is a well-orchestrated procedure triggered by a protein-based template inducing the nucleation of hydroxyapatite (HA) nanocrystals on the matrix. In an attempt to fabricate superior nanocomposites from silk fibroin, textile braided structures made of natively spun fibres of Bombyx mori silkworm were compared against regenerated fibroin (lyophilized and films) underpinning the influence of intrinsic properties of fibroin matrices on HA nucleation. We found that native braids could bind Ca(2+) ions through electrostatic attraction, which initiated the nucleation and deposition of HA, as evidenced by discrete shift in amide peaks via ATR-FTIR. This phenomenon also suggests the involvement of amide linkages in promoting HA nucleation on fibroin. Moreover, CaCl2-SBF immersion of native braids resulted in preferential growth of HA along the c-axis, forming needle-like nanocrystals and possessing Ca/P ratio comparable to commercial HA. Though regenerated lyophilized matrix also witnessed prominent peak shift in amide linkages, HA growth was restricted to (211) plane only, albeit at a significantly lower intensity than braids. Regenerated films, on the other hand, provided no crystallographic evidence of HA deposition within 7days of SBF immersion. The present work sheds light on the primary fibroin structure of B. mori which probably plays a crucial role in regulating template-induced biomineralisation on the matrix. We also found that intrinsic material properties such as surface roughness, geometry, specific surface area, tortuosity and secondary conformation exert influence in modulating the extent of mineralisation. Thus our work generates useful insights and warrants future studies to further investigate the potential of bone mimetic, silk/mineral nanocomposite matrices for orthopaedic applications. PMID:27524066

  6. Elucidation of differential mineralisation on native and regenerated silk matrices.

    PubMed

    Midha, Swati; Tripathi, Rohit; Geng, Hua; Lee, Peter D; Ghosh, Sourabh

    2016-11-01

    Bone mineralisation is a well-orchestrated procedure triggered by a protein-based template inducing the nucleation of hydroxyapatite (HA) nanocrystals on the matrix. In an attempt to fabricate superior nanocomposites from silk fibroin, textile braided structures made of natively spun fibres of Bombyx mori silkworm were compared against regenerated fibroin (lyophilized and films) underpinning the influence of intrinsic properties of fibroin matrices on HA nucleation. We found that native braids could bind Ca(2+) ions through electrostatic attraction, which initiated the nucleation and deposition of HA, as evidenced by discrete shift in amide peaks via ATR-FTIR. This phenomenon also suggests the involvement of amide linkages in promoting HA nucleation on fibroin. Moreover, CaCl2-SBF immersion of native braids resulted in preferential growth of HA along the c-axis, forming needle-like nanocrystals and possessing Ca/P ratio comparable to commercial HA. Though regenerated lyophilized matrix also witnessed prominent peak shift in amide linkages, HA growth was restricted to (211) plane only, albeit at a significantly lower intensity than braids. Regenerated films, on the other hand, provided no crystallographic evidence of HA deposition within 7days of SBF immersion. The present work sheds light on the primary fibroin structure of B. mori which probably plays a crucial role in regulating template-induced biomineralisation on the matrix. We also found that intrinsic material properties such as surface roughness, geometry, specific surface area, tortuosity and secondary conformation exert influence in modulating the extent of mineralisation. Thus our work generates useful insights and warrants future studies to further investigate the potential of bone mimetic, silk/mineral nanocomposite matrices for orthopaedic applications.

  7. Decellularized matrices for cardiovascular tissue engineering.

    PubMed

    Moroni, Francesco; Mirabella, Teodelinda

    2014-01-01

    Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950's. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to "biointegration". Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption.

  8. Decellularized matrices for cardiovascular tissue engineering

    PubMed Central

    Moroni, Francesco; Mirabella, Teodelinda

    2014-01-01

    Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950’s. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to “biointegration”. Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption. PMID:24660110

  9. Regenerator for gas turbine engine

    DOEpatents

    Lewakowski, John J.

    1979-01-01

    A rotary disc-type counterflow regenerator for a gas turbine engine includes a disc-shaped ceramic core surrounded by a metal rim which carries a coaxial annular ring gear. Bonding of the metal rim to the ceramic core is accomplished by constructing the metal rim in three integral portions: a driving portion disposed adjacent the ceramic core which carries the ring gear, a bonding portion disposed further away from the ceramic core and which is bonded thereto by elastomeric pads, and a connecting portion connecting the bonding portion to the driving portion. The elastomeric pads are bonded to radially flexible mounts formed as part of the metal rim by circumferential slots in the transition portion and lateral slots extending from one end of the circumferential slots across the bonding portion of the rim.

  10. Heat engine regenerators: Research status and needs

    SciTech Connect

    Hutchinson, R.A.

    1987-08-01

    The rapidly oscillating, variable density flows of regenerative heat engines provide a class of poorly understood unsteady flow and heat transfer problems. These problems are not currently amenable to direct experimental resolution. Experiences in engine development and test programs and efforts to develop analysis tools point to the regenerator as a key area of insufficient understanding. Focusing on flow and heat transfer in regenerators, this report discusses similarity parameters for the flows and reviews the experimental data currently available for Stirling analysis. Then a number of experimental results are presented from recent fundamental fluid mechanical and thermal investigations that shed additional light on the functioning of heat engine regenerators. Suggestions are made for approaches for further measurement and analysis efforts.

  11. Composite Matrix Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Knowles, Timothy R.

    1997-01-01

    This project concerns the design, fabrication and testing of carbon regenerators for use in Stirling power convertors. Radial fiber design with nonmetallic components offers a number of potential advantages over conventional steel regenerators: reduced conduction and pressure drop losses, and the capability for higher temperature, higher frequency operation. Diverse composite fabrication methods are explored and lessons learned are summarized. A pulsed single-blow test rig has been developed that has been used for generating thermal effectiveness data for different flow velocities. Carbon regenerators have been fabricated by carbon vapor infiltration of electroflocked preforms. Performance data in a small Stirling engine are obtained. Prototype regenerators designed for the BP-1000 power convertor were fabricated and delivered to NASA-Lewis.

  12. Effects of sudden expansion and contraction flow on pressure drops in the Stirling engine regenerator

    SciTech Connect

    Hamaguchi, K.; Yamashita, I.; Hirata, K.

    1998-07-01

    The flow losses in the regenerators greatly influence the performance of the Stirling engine. The losses mainly depend on fluid friction through the regenerator matrix, but are also generated in sudden expansion and contraction flow at the regenerator ends. The latter losses can't be neglected in the case of small area ratio (entrance area/cross-sectional area in regenerator). The pressure drops in regenerators are usually estimated assuming a uniform velocity distribution of working gas in the matrices. The estimation results, however, are generally smaller than practical data. The cross-sectional flow areas of the heater and cooler of typical Stirling engines are smaller than the cross- sectional area of the regenerator. The effects of the small flow passage on the velocity distribution of working fluid in the matrix, that is, a flow transition from tubes or channels to a regenerator matrix, can be often confirmed by the discolored matrix. Especially, the lack of a uniform distribution of velocity in the matrix causes increased flow loss and decreased thermal performance. So, it is necessary to understand the quantitative effects of the sudden change in flow area at the regenerator ends on the velocity distribution and pressure drop. In this paper, using matrices made of stacks of wire screens, the effects of the entrance and exit areas and the length of the regenerator on pressure drops are examined by an unidirectional steady flow apparatus. The experimental data are arranged in an empirical equation. The lack of a uniformity of velocity distribution is visualized using smoke-wire methods. The empirical equation presented is applied to the estimation of pressure loss in an actual engine regenerator. The applicability of the equation is examined by comparison of estimated value with engine data in pressure loss.

  13. Engineering approaches for regeneration of T lymphopoiesis.

    PubMed

    Roh, Kyung-Ho; Roy, Krishnendu

    2016-01-01

    T cells play a central role in immune-homeostasis; specifically in the induction of antigen-specific adaptive immunity against pathogens and mutated self with immunological memory. The thymus is the unique organ where T cells are generated. In this review, first the complex structures and functions of various thymic microcompartments are briefly discussed to identify critical engineering targets for regeneration of thymic functions in vitro and in vivo. Then the biomimetic regenerative engineering approaches are reviewed in three categories: 1) reconstruction of 3-D thymic architecture, 2) cellular engineering, and 3) biomaterials-based artificial presentation of critical biomolecules. For each engineering approach, remaining challenges and clinical opportunities are also identified and discussed. PMID:27358746

  14. Thermal Expansion Behavior of Hot-Pressed Engineered Matrices

    NASA Technical Reports Server (NTRS)

    Raj, S. V.

    2016-01-01

    Advanced engineered matrix composites (EMCs) require that the coefficient of thermal expansion (CTE) of the engineered matrix (EM) matches those of the fiber reinforcements as closely as possible in order to reduce thermal compatibility strains during heating and cooling of the composites. The present paper proposes a general concept for designing suitable matrices for long fiber reinforced composites using a rule of mixtures (ROM) approach to minimize the global differences in the thermal expansion mismatches between the fibers and the engineered matrix. Proof-of-concept studies were conducted to demonstrate the validity of the concept.

  15. Tissue engineering strategies for bone regeneration.

    PubMed

    Mistry, Amit S; Mikos, Antonios G

    2005-01-01

    Bone loss due to trauma or disease is an increasingly serious health problem. Current clinical treatments for critical-sized defects are problematic and often yield poor healing due to the complicated anatomy and physiology of bone tissue, as well as the limitations of medical technology. Bone tissue engineering offers a promising alternative strategy of healing severe bone injuries by utilizing the body's natural biological response to tissue damage in conjunction with engineering principles. Osteogenic cells, growth factors, and biomaterial scaffolds form the foundation of the many bone tissue engineering strategies employed to achieve repair and restoration of damaged tissue. An ideal biomaterial scaffold will provide mechanical support to an injured site and also deliver growth factors and cells into a defect to encourage tissue growth. Additionally, this biomaterial should degrade in a controlled manner without causing a significant inflammatory response. The following chapter highlights multiple strategies and the most recent advances in various areas of research for bone tissue regeneration.

  16. Tissue engineering and ureter regeneration: is it possible?

    PubMed

    Kloskowski, Tomasz; Kowalczyk, Tomasz; Nowacki, Maciej; Drewa, Tomasz

    2013-06-25

    Large ureter damages are difficult to reconstruct. Current techniques are complicated, difficult to perform, and often associated with failures. The ureter has never been regenerated thus far. Therefore the use of tissue engineering techniques for ureter reconstruction and regeneration seems to be a promising way to resolve these problems. For proper ureter regeneration the following problems must be considered: the physiological aspects of the tissue, the type and shape of the scaffold, the type of cells, and the specific environment (urine). 
This review presents tissue engineering achievements in the field of ureter regeneration focusing on the scaffold, the cells, and ureter healing.

  17. Ultrasound-mediated gene transfer (sonoporation) in fibrin-based matrices: potential for use in tissue regeneration.

    PubMed

    Nomikou, Nikolitsa; Feichtinger, Georg A; Redl, Heinz; McHale, Anthony P

    2016-01-01

    It has been suggested that gene transfer into donor cells is an efficient and practical means of locally supplying requisite growth factors for applications in tissue regeneration. Here we describe, for the first time, an ultrasound-mediated system that can non-invasively facilitate gene transfer into cells entrapped within fibrin-based matrices. Since ultrasound-mediated gene transfer is enhanced using microbubbles, we compared the efficacy of neutral and cationic forms of these reagents on the ultrasound-stimulated gene transfer process in gel matrices. In doing so we demonstrated the beneficial effects associated with the use of cationic microbubble preparations that interact directly with cells and nucleic acid within matrices. In some cases, gene expression was increased two-fold in gel matrices when cationic microbubbles were compared with neutral microbubbles. In addition, incorporating collagen into fibrin gels yielded a 25-fold increase in gene expression after application of ultrasound to microbubble-containing matrices. We suggest that this novel system may facilitate non-invasive temporal and spatial control of gene transfer in gel-based matrices for the purposes of tissue regeneration.

  18. Hierarchically engineered fibrous scaffolds for bone regeneration

    PubMed Central

    Sachot, Nadège; Castaño, Oscar; Mateos-Timoneda, Miguel A.; Engel, Elisabeth; Planell, Josep A.

    2013-01-01

    Surface properties of biomaterials play a major role in the governing of cell functionalities. It is well known that mechanical, chemical and nanotopographic cues, for example, influence cell proliferation and differentiation. Here, we present a novel coating protocol to produce hierarchically engineered fibrous scaffolds with tailorable surface characteristics, which mimic bone extracellular matrix. Based on the sol–gel method and a succession of surface treatments, hollow electrospun polylactic acid fibres were coated with a silicon–calcium–phosphate bioactive organic–inorganic glass. Compared with pure polymeric fibres that showed a completely smooth surface, the coated fibres exhibited a nanostructured topography and greater roughness. They also showed improved hydrophilic properties and a Young's modulus sixfold higher than non-coated ones, while remaining fully flexible and easy to handle. Rat mesenchymal stem cells cultured on these fibres showed great cellular spreading and interactions with the material. This protocol can be transferred to other structures and glasses, allowing the fabrication of various materials with well-defined features. This novel approach represents therefore a valuable improvement in the production of artificial matrices able to direct stem cell fate through physical and chemical interactions. PMID:23985738

  19. Tissue engineering in periodontal regeneration: A brief review.

    PubMed

    Dabra, Sarita; Chhina, Kamalpreet; Soni, Nitin; Bhatnagar, Rakhi

    2012-11-01

    Periodontal disease is a major public health issue and the development of effective therapies to treat the disease and regenerate periodontal tissue is an important goal of today's medicine. Regeneration of periodontal tissue is perhaps one of the most complex process to occur in the body. Langer and colleagues proposed tissue engineering as a possible technique for regenerating the lost periodontal tissues. Tissue engineering is a multidisciplinary field, which involves the application of the principles and methods of engineering and life sciences to help in the development of biological substitutes to restore, maintain or improve the function of damaged tissues and organs. A Google/Medline search was conducted and relevant literature evaluating the potential role of the tissue engineering in periodontal regeneration, which included histological studies and controlled clinical trials, was reviewed. A comprehensive search was designed. The articles were independently screened for eligibility. Articles with authentic controls and proper randomization and pertaining specifically to their role in periodontal regeneration were included. The available literature was analyzed and compiled. The analysis indicate tissue engineering to be a promising, as well as an effective novel approach to reconstruct and engineer the periodontal apparatus. Here, we represent several articles, as well as recent texts that make up a special and an in-depth review on the subject. The purpose behind writing this brief review has been to integrate the evidence of research related to tissue engineering so as to implement them in our daily practice. PMID:23559940

  20. Matrices and Scaffolds for DNA Delivery in Tissue Engineering

    PubMed Central

    De Laporte, Laura; Shea, Lonnie D.

    2007-01-01

    Regenerative medicine aims to create functional tissue replacements, typically through creating a controlled environment that promotes and directs the differentiation of stem or progenitor cells, either endogenous or transplanted. Scaffolds serve a central role in many strategies by providing the means to control the local environment. Gene delivery from the scaffold represents a versatile approach to manipulating the local environment for directing cell function. Research at the interface of biomaterials, gene therapy, and drug delivery has identified several design parameters for the vector and the biomaterial scaffold that must be satisfied. Progress has been made towards achieving gene delivery within a tissue engineering scaffold, though the design principles for the materials and vectors that produce efficient delivery require further development. Nevertheless, these advances in obtaining transgene expression with the scaffold have created opportunities to develop greater control of either delivery or expression and to identify the best practices for promoting tissue formation. Strategies to achieve controlled localized expression within the tissue engineering scaffold will have broad application to the regeneration of many tissues, with great promise for clinical therapies. PMID:17512630

  1. Mechanical regulation of vascular network formation in engineered matrices.

    PubMed

    Lesman, Ayelet; Rosenfeld, Dekel; Landau, Shira; Levenberg, Shulamit

    2016-01-15

    Generation of vessel networks within engineered tissues is critical for integration and perfusion of the implanted tissue in vivo. The effect of mechanical cues in guiding and stabilizing the vessels has begun to attract marked interest. This review surveys the impact of mechanical cues on formation of vascular networks in 2D and 3D gel matrices. We give less emphasis to regulation of endothelial monolayers and single endothelial cells. Several vascularization models have consistently found that the stress generated in the gel, and encountered by embedded cells, control various aspects of vascular network formation, including sprouting, branching, alignment, and vessel maturation. This internal stress is generated by cell contractile forces, and is balanced by gel stiffness and boundary constrains imposed on the gel. Actin and myosin II are key molecular players in controlling initiation of vessel sprouting and branching morphogenesis. Additionally, the impact of external mechanical cues on tissue vascularization, and studies supporting the notion that mechanical forces regulate vascularization in the live animal are reviewed.

  2. Ceramic regenerator systems development program. [for automobile gas turbine engines

    NASA Technical Reports Server (NTRS)

    Cook, J. A.; Fucinari, C. A.; Lingscheit, J. N.; Rahnke, C. J.

    1977-01-01

    Ceramic regenerator cores are considered that can be used in passenger car gas turbine engines, Stirling engines, and industrial/truck gas turbine engines. Improved materials and design concepts aimed at reducing or eliminating chemical attack were placed on durability test in Ford 707 industrial gas turbine engines. The results of 19,600 hours of turbine engine durability testing are described. Two materials, aluminum silicate and magnesium aluminum silicate, continue to show promise toward achieving the durability objectives of this program. A regenerator core made from aluminum silicate showed minimal evidence of chemical attack damage after 6935 hours of engine test at 800 C and another showed little distress after 3510 hours at 982 C. Results obtained in ceramic material screening tests, aerothermodynamic performance tests, stress analysis, cost studies, and material specifications are also included.

  3. The Quest toward limb regeneration: a regenerative engineering approach

    PubMed Central

    Laurencin, Cato T.; Nair, Lakshmi S.

    2016-01-01

    The Holy Grail to address the clinical grand challenge of human limb loss is to develop innovative strategies to regrow the amputated limb. The remarkable advances in the scientific understanding of regeneration, stem cell science, material science and engineering, physics and novel surgical approaches in the past few decades have provided a regenerative tool box to face this grand challenge and address the limitations of human wound healing. Here we discuss the convergence approach put forward by the field of Regenerative Engineering to use the regenerative tool box to design and develop novel translational strategies to limb regeneration. PMID:27047679

  4. Dynamic Stabilization of Expressed Proteins in Engineered Diatom Biosilica Matrices.

    PubMed

    Xiong, Yijia; Ford, Nicole R; Hecht, Karen A; Roesijadi, Guritno; Squier, Thomas C

    2016-05-18

    Self-assembly of recombinant proteins within the biosilica of living diatoms represents a means to construct functional materials in a reproducible and scalable manner that will enable applications that harness the inherent specificities of proteins to sense and respond to environmental cues. Here we describe the use of a silaffin-derived lysine-rich 39-amino-acid targeting sequence (Sil3T8) that directs a single chain fragment variable (scFv) antibody or an enhanced green fluorescent protein (EGFP) to assemble within the biosilica frustule, resulting in abundance of >200 000 proteins per frustule. Using either a fluorescent ligand bound to the scFv or the intrinsic fluorescence of EGFP, we monitored protein conformational dynamics, accessibility to external quenchers, binding affinity, and conformational stability. Like proteins in solution, proteins within isolated frustules undergo isotropic rotational motion, but with 2-fold increases in rotational correlation times that are indicative of weak macromolecular associations within the biosilica. Solvent accessibilities and high-affinity (pM) binding are comparable to those in solution. In contrast to solution conditions, scFv antibodies within the biosilica matrix retain their binding affinity in the presence of chaotropic agents (i.e., 8 M urea). Together, these results argue that dramatic increases in protein conformational stability within the biosilica matrices arise through molecular crowding, acting to retain native protein folds and associated functionality with the potential to allow the utility of engineered proteins under a range of harsh environmental conditions associated with environmental sensing and industrial catalytic transformations.

  5. Microfabricated Segmented-Involute-Foil Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gedeon, David; Qiu, Songgang; Wood, Gary; Kelly, Kevin; McLean, Jeffrey

    2010-01-01

    An involute-foil regenerator was designed, microfabricated, and tested in an oscillating-flow test rig. The concept consists of stacked involute-foil nickel disks (see figure) microfabricated via a lithographic process. Test results yielded a performance of about twice that of the 90-percent random-fiber currently used in small Stirling converters. The segmented nature of the involute- foil in both the axial and radial directions increases the strength of the structure relative to wrapped foils. In addition, relative to random-fiber regenerators, the involute-foil has a reduced pressure drop, and is expected to be less susceptible to the release of metal fragments into the working space, thus increasing reliability. The prototype nickel involute-foil regenerator was adequate for testing in an engine with a 650 C hot-end temperature. This is lower than that required by larger engines, and high-temperature alloys are not suited for the lithographic microfabrication approach.

  6. Tissue engineering strategies to study cartilage development, degeneration and regeneration.

    PubMed

    Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

    2015-04-01

    Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm.

  7. Heart Regeneration with Engineered Myocardial Tissue

    PubMed Central

    Bajpai, Vivek K.; Andreadis, Stelios T.; Murry, Charles E.

    2014-01-01

    Heart disease is the leading cause of morbidity and mortality worldwide, and regenerative therapies that replace damaged myocardium could benefit millions of patients annually. The many cell types in the heart, including cardiomyocytes, endothelial cells, vascular smooth muscle cells, pericytes, and cardiac fibroblasts, communicate via intercellular signaling and modulate each other’s function. Although much progress has been made in generating cells of the cardiovascular lineage from human pluripotent stem cells, a major challenge now is creating the tissue architecture to integrate a microvascular circulation and afferent arterioles into such an engineered tissue. Recent advances in cardiac and vascular tissue engineering will move us closer to the goal of generating functionally mature tissue. Using the biology of the myocardium as the foundation for designing engineered tissue and addressing the challenges to implantation and integration, we can bridge the gap from bench to bedside for a clinically tractable engineered cardiac tissue. PMID:24819474

  8. Gelatin Nanofiber Matrices Derived from Schiff Base Derivative for Tissue Engineering Applications.

    PubMed

    Jaiswal, Devina; James, Roshan; Shelke, Namdev B; Harmon, Matthew D; Brown, Justin L; Hussain, Fazle; Kumbar, Sangamesh G

    2015-11-01

    Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of 2-nitrobenzyl-gelatin (N-Gelatin)--a novel gelatin Schiff base derivative--and the resulting electrospun nanofiber matrices. The 2-nitrobenzyl group is a photoactivatable-caged compound and can be cleaved from the gelatin nanofiber matrices following UV exposure. Such hydrophobic modification allowed the fabrication of gelatin and blend nanofibers with poly(caprolactone) (PCL) having significantly improved tensile properties. Neat gelatin and their PCL blend nanofiber matrices showed a modulus of 9.08 ± 1.5 MPa and 27.61 ± 4.3 MPa, respectively while the modified gelatin and their blends showed 15.63 ± 2.8 MPa and 24.47 ± 8.7 MPa, respectively. The characteristic infrared spectroscopy band for gelatin Schiff base derivative at 1560 cm(-1) disappeared following exposure to UV light indicating the regeneration of free NH2 group and gelatin. These nanofiber matrices supported cell attachment and proliferation with a well spread morphology as evidenced through cell proliferation assay and microscopic techniques. Modified gelatin fiber matrices showed a 73% enhanced cell attachment and proliferation rate compared to pure gelatin. This polymer modification methodology may offer a promising way to fabricate electrospun nanofiber matrices using a variety of proteins and peptides without loss of bioactivity and mechanical strength.

  9. Biological approaches toward dental pulp regeneration by tissue engineering.

    PubMed

    Sun, Hai-Hua; Jin, Tao; Yu, Qing; Chen, Fa-Ming

    2011-04-01

    Root canal therapy has been the predominant approach in endodontic treatment, wherein the entire pulp is cleaned out and replaced with a gutta-percha filling. However, living pulp is critical for the maintenance of tooth homeostasis and essential for tooth longevity. An ideal form of therapy, therefore, might consist of regenerative approaches in which diseased/necrotic pulp tissues are removed and replaced with regenerated pulp tissues to revitalize the teeth. Dental pulp regeneration presents one of the most challenging issues in regenerative dentistry due to the poor intrinsic ability of pulp tissues for self-healing and regrowth. With the advent of modern tissue engineering and the discovery of dental stem cells, biological therapies have paved the way to utilize stem cells, delivered or internally recruited, to generate dental pulp tissues, where growth factors and a series of dentine extracellular matrix molecules are key mediators that regulate the complex cascade of regeneration events to be faithfully fulfilled.

  10. A Microfabricated Involute-Foil Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Tew, Roy; Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gedeon, David; Kelly, Kevin; McLean, Jeffrey; Qiu, Songgang

    2007-01-01

    A segmented involute-foil regenerator has been designed, microfabricated and tested in an oscillating-flow rig with excellent results. During the Phase I effort, several approximations of parallel-plate regenerator geometry were chosen as potential candidates for a new microfabrication concept. Potential manufacturers and processes were surveyed. The selected concept consisted of stacked segmented-involute-foil disks (or annular portions of disks), originally to be microfabricated from stainless-steel via the LiGA (lithography, electroplating, and molding) process and EDM. During Phase II, re-planning of the effort led to test plans based on nickel disks, microfabricated via the LiGA process, only. A stack of nickel segmented-involute-foil disks was tested in an oscillating-flow test rig. These test results yielded a performance figure of merit (roughly the ratio of heat transfer to pressure drop) of about twice that of the 90 percent random fiber currently used in small approx.100 W Stirling space-power convertors-in the Reynolds Number range of interest (50 to 100). A Phase III effort is now underway to fabricate and test a segmented-involute-foil regenerator in a Stirling convertor. Though funding limitations prevent optimization of the Stirling engine geometry for use with this regenerator, the Sage computer code will be used to help evaluate the engine test results. Previous Sage Stirling model projections have indicated that a segmented-involute-foil regenerator is capable of improving the performance of an optimized involute-foil engine by 6 to 9 percent; it is also anticipated that such involute-foil geometries will be more reliable and easier to manufacture with tight-tolerance characteristics, than random-fiber or wire-screen regenerators. Beyond the near-term Phase III regenerator fabrication and engine testing, other goals are (1) fabrication from a material suitable for high temperature Stirling operation (up to 850 C for current engines; up to 1200 C

  11. A Microfabricated Involute-Foil Regenerator for Stirling Engines

    NASA Technical Reports Server (NTRS)

    Tew, Roy; Ibrahim, Mounir; Danila, Daniel; Simon, Terry; Mantell, Susan; Sun, Liyong; Gedeon, David; Kelly, Kevin; McLean, Jeffrey; Wood, Gary; Qiu, Songgang

    2007-01-01

    A segmented involute-foil regenerator has been designed, microfabricated and tested in an oscillating-flow rig with excellent results. During the Phase I effort, several approximations of parallel-plate regenerator geometry were chosen as potential candidates for a new microfabrication concept. Potential manufacturers and processes were surveyed. The selected concept consisted of stacked segmented-involute-foil disks (or annular portions of disks), originally to be microfabricated from stainless-steel via the LiGA (lithography, electroplating, and molding) process and EDM (electric discharge machining). During Phase II, re-planning of the effort led to test plans based on nickel disks, microfabricated via the LiGA process, only. A stack of nickel segmented-involute-foil disks was tested in an oscillating-flow test rig. These test results yielded a performance figure of merit (roughly the ratio of heat transfer to pressure drop) of about twice that of the 90% random fiber currently used in small 100 W Stirling space-power convertors in the Reynolds Number range of interest (50-100). A Phase III effort is now underway to fabricate and test a segmented-involute-foil regenerator in a Stirling convertor. Though funding limitations prevent optimization of the Stirling engine geometry for use with this regenerator, the Sage computer code will be used to help evaluate the engine test results. Previous Sage Stirling model projections have indicated that a segmented-involute-foil regenerator is capable of improving the performance of an optimized involute-foil engine by 6-9%; it is also anticipated that such involute-foil geometries will be more reliable and easier to manufacture with tight-tolerance characteristics, than random-fiber or wire-screen regenerators. Beyond the near-term Phase III regenerator fabrication and engine testing, other goals are (1) fabrication from a material suitable for high temperature Stirling operation (up to 850 C for current engines; up to

  12. Lean Gasoline Engine Reductant Chemistry During Lean NOx Trap Regeneration

    SciTech Connect

    Choi, Jae-Soon; Prikhodko, Vitaly Y; Partridge Jr, William P; Parks, II, James E; Norman, Kevin M; Huff, Shean P; Chambon, Paul H; Thomas, John F

    2010-01-01

    Lean NOx Trap (LNT) catalysts can effectively reduce NOx from lean engine exhaust. Significant research for LNTs in diesel engine applications has been performed and has led to commercialization of the technology. For lean gasoline engine applications, advanced direct injection engines have led to a renewed interest in the potential for lean gasoline vehicles and, thereby, a renewed demand for lean NOx control. To understand the gasoline-based reductant chemistry during regeneration, a BMW lean gasoline vehicle has been studied on a chassis dynamometer. Exhaust samples were collected and analyzed for key reductant species such as H2, CO, NH3, and hydrocarbons during transient drive cycles. The relation of the reductant species to LNT performance will be discussed. Furthermore, the challenges of NOx storage in the lean gasoline application are reviewed.

  13. Tissue engineering strategies for the regeneration of orthopedic interfaces.

    PubMed

    Lu, Helen H; Subramony, Siddarth D; Boushell, Margaret K; Zhang, Xinzhi

    2010-06-01

    A major focus in the field of orthopedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), necessitates a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone, or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality.

  14. Tissue Engineering Strategies for the Regeneration of Orthopaedic Interfaces

    PubMed Central

    Lu, Helen H.; Subramony, Siddarth D.; Boushell, Margaret K.; Zhang, Xinzhi

    2013-01-01

    A major focus in the field of orthopaedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), requires a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties that mimics that of the multi-tissue transition between bone and soft tissues. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality. PMID:20422291

  15. Strategies to minimize hypertrophy in cartilage engineering and regeneration

    PubMed Central

    Chen, Song; Fu, Peiliang; Cong, Ruijun; Wu, HaiShan; Pei, Ming

    2015-01-01

    Due to a blood supply shortage, articular cartilage has a limited capacity for self-healing once damaged. Articular chondrocytes, cartilage progenitor cells, embryonic stem cells, and mesenchymal stem cells are candidate cells for cartilage regeneration. Significant current attention is paid to improving chondrogenic differentiation capacity; unfortunately, the potential chondrogenic hypertrophy of differentiated cells is largely overlooked. Consequently, the engineered tissue is actually a transient cartilage rather than a permanent one. The development of hypertrophic cartilage ends with the onset of endochondral bone formation which has inferior mechanical properties. In this review, current strategies for inhibition of chondrogenic hypertrophy are comprehensively summarized; the impact of cell source options is discussed; and potential mechanisms underlying these strategies are also categorized. This paper aims to provide guidelines for the prevention of hypertrophy in the regeneration of cartilage tissue. This knowledge may also facilitate the retardation of osteophytes in the treatment of osteoarthritis. PMID:26000333

  16. Three Conceptions of Thermodynamics: Technical Matrices in Science and Engineering

    ERIC Educational Resources Information Center

    Christiansen, Frederik V.; Rump, Camilla

    2008-01-01

    Introductory thermodynamics is a topic which is covered in a wide variety of science and engineering educations. However, very different teaching traditions have evolved within different scientific specialties. In this study we examine three courses in introductory thermodynamics within three different scientific specialties: physics, chemical…

  17. Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration.

    PubMed

    Chávez, Myra Noemi; Schenck, Thilo Ludwig; Hopfner, Ursula; Centeno-Cerdas, Carolina; Somlai-Schweiger, Ian; Schwarz, Christian; Machens, Hans-Günther; Heikenwalder, Mathias; Bono, María Rosa; Allende, Miguel L; Nickelsen, Jörg; Egaña, José Tomás

    2016-01-01

    The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy. PMID:26474040

  18. Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration.

    PubMed

    Chávez, Myra Noemi; Schenck, Thilo Ludwig; Hopfner, Ursula; Centeno-Cerdas, Carolina; Somlai-Schweiger, Ian; Schwarz, Christian; Machens, Hans-Günther; Heikenwalder, Mathias; Bono, María Rosa; Allende, Miguel L; Nickelsen, Jörg; Egaña, José Tomás

    2016-01-01

    The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy.

  19. Material-based engineering strategies for cardiac regeneration.

    PubMed

    Marion, Mieke H van; Bax, Noortje A M; Spreeuwel, Ariane C C van; van der Schaft, Daisy W J; Bouten, Carlijn V C

    2014-01-01

    Cardiac tissue is composed of muscle and non-muscle cells, surrounded by extracellular matrix (ECM) and spatially organized into a complex three-dimensional (3D) architecture to allow for coordinated contraction and electrical pulse propagation. Despite emerging evidence for cardiomyocyte turnover in mammalian hearts, the regenerative capacity of human cardiac tissue is insufficient to recover from damage, e.g. resulting from myocardial infarction (MI). Instead, the heart 'repairs' lost or injured tissue by ongoing synthesis and remodeling of scar tissue. Conventional therapies and timely (stem) cell delivery to the injured tissue markedly improve short-term function and remodeling, but do not attenuate later stage adverse remodeling, leading to functional deterioration and eventually failure of the heart. Material-based therapies have been successfully used to mechanically support and constrain the post-MI failing heart, preventing it from further remodeling and dilation. When designed to deliver the right microenvironment for endogenous or exogenous cells, as well as the mechanical and topological cues to guide neo-tissue formation, material-based therapies may even reverse remodeling and boost cardiac regeneration. This paper reviews the up-to-date status of material-based cardiac regeneration with special emphasis on 1) the use of bare biomaterials to deliver passive constraints that unload the heart, 2) the use of materials and cells to create engineered cardiac constructs for replacement, support, or regeneration of damaged myocardium, and 3) the development of bio-inspired and bioactive materials that aim to enhance the endogenous regenerative capacity of the heart. As the therapies should function in the infarcted heart, the damaged host environment and engineered in vitro test systems that mimic this environment, are reviewed as well.

  20. Neural tissue engineering options for peripheral nerve regeneration.

    PubMed

    Gu, Xiaosong; Ding, Fei; Williams, David F

    2014-08-01

    Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system.

  1. Stem Cell Sources for Vascular Tissue Engineering and Regeneration

    PubMed Central

    Bajpai, Vivek K.

    2012-01-01

    This review focuses on the stem cell sources with the potential to be used in vascular tissue engineering and to promote vascular regeneration. The first clinical studies using tissue-engineered vascular grafts are already under way, supporting the potential of this technology in the treatment of cardiovascular and other diseases. Despite progress in engineering biomaterials with the appropriate mechanical properties and biological cues as well as bioreactors for generating the correct tissue microenvironment, the source of cells that make up the vascular tissues remains a major challenge for tissue engineers and physicians. Mature cells from the tissue of origin may be difficult to obtain and suffer from limited proliferative capacity, which may further decline as a function of donor age. On the other hand, multipotent and pluripotent stem cells have great potential to provide large numbers of autologous cells with a great differentiation capacity. Here, we discuss the adult multipotent as well as embryonic and induced pluripotent stem cells, their differentiation potential toward vascular lineages, and their use in engineering functional and implantable vascular tissues. We also discuss the associated challenges that need to be addressed in order to facilitate the transition of this technology from the bench to the bedside. PMID:22571595

  2. Engineering Pre-vascularized Scaffolds for Bone Regeneration.

    PubMed

    Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

    2015-01-01

    Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering. PMID:26545745

  3. Engineering Pre-vascularized Scaffolds for Bone Regeneration.

    PubMed

    Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

    2015-01-01

    Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.

  4. Role of morphogenetic proteins in skeletal tissue engineering and regeneration.

    PubMed

    Reddi, A H

    1998-03-01

    Morphogenesis is the developmental cascade of pattern formation and body plan establishment, culminating in the adult form. It has formed the basis for the emerging discipline of tissue engineering, which uses principles of molecular developmental biology and morphogenesis gleaned through studies on inductive signals, responding stem cells, and the extracellular matrix to design and construct spare parts that restore function to the human body. Among the many organs in the body, bone has considerable powers for regeneration and is a prototype model for tissue engineering. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and has permitted the isolation of bone morphogens, such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are also involved in the morphogenesis of organs other than bone. The symbiosis of the mechanisms underlying bone induction and differentiation is critical for tissue engineering and is governed by both biomechanics (physical forces) and context (microenvironment/extracellular matrix), which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue architecture elucidated in bone morphogenesis may provide insights into tissue engineering and be universally applicable for all organs/tissues, including bones and joints. PMID:9528003

  5. Statistical model for the mechanical behavior of the tissue engineering non-woven fibrous matrices under large deformation.

    PubMed

    Rizvi, Mohd Suhail; Pal, Anupam

    2014-09-01

    The fibrous matrices are widely used as scaffolds for the regeneration of load-bearing tissues due to their structural and mechanical similarities with the fibrous components of the extracellular matrix. These scaffolds not only provide the appropriate microenvironment for the residing cells but also act as medium for the transmission of the mechanical stimuli, essential for the tissue regeneration, from macroscopic scale of the scaffolds to the microscopic scale of cells. The requirement of the mechanical loading for the tissue regeneration requires the fibrous scaffolds to be able to sustain the complex three-dimensional mechanical loading conditions. In order to gain insight into the mechanical behavior of the fibrous matrices under large amount of elongation as well as shear, a statistical model has been formulated to study the macroscopic mechanical behavior of the electrospun fibrous matrix and the transmission of the mechanical stimuli from scaffolds to the cells via the constituting fibers. The study establishes the load-deformation relationships for the fibrous matrices for different structural parameters. It also quantifies the changes in the fiber arrangement and tension generated in the fibers with the deformation of the matrix. The model reveals that the tension generated in the fibers on matrix deformation is not homogeneous and hence the cells located in different regions of the fibrous scaffold might experience different mechanical stimuli. The mechanical response of fibrous matrices was also found to be dependent on the aspect ratio of the matrix. Therefore, the model establishes a structure-mechanics interdependence of the fibrous matrices under large deformation, which can be utilized in identifying the appropriate structure and external mechanical loading conditions for the regeneration of load-bearing tissues.

  6. Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering

    PubMed Central

    Nau, Thomas; Teuschl, Andreas

    2015-01-01

    Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon. PMID:25621217

  7. Engineering Tendon: Scaffolds, Bioreactors, and Models of Regeneration.

    PubMed

    Youngstrom, Daniel W; Barrett, Jennifer G

    2016-01-01

    Tendons bridge muscle and bone, translating forces to the skeleton and increasing the safety and efficiency of locomotion. When tendons fail or degenerate, there are no effective pharmacological interventions. The lack of available options to treat damaged tendons has created a need to better understand and improve the repair process, particularly when suitable autologous donor tissue is unavailable for transplantation. Cells within tendon dynamically react to loading conditions and undergo phenotypic changes in response to mechanobiological stimuli. Tenocytes respond to ultrastructural topography and mechanical deformation via a complex set of behaviors involving force-sensitive membrane receptor activity, changes in cytoskeletal contractility, and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell-matrix forces with high fidelity. While early bioreactor designs have greatly expanded our knowledge of mechanotransduction, traditional scaffolds do not fully model the topography, composition, and mechanical properties of native tendon. Decellularized tendon is an ideal scaffold for cultivating replacement tissue and modeling tendon regeneration. Decellularized tendon scaffolds (DTS) possess high clinical relevance, faithfully translate forces to the cellular scale, and have bulk material properties that match natural tissue. This review summarizes progress in tendon tissue engineering, with a focus on DTS and bioreactor systems. PMID:26839559

  8. Engineering Tendon: Scaffolds, Bioreactors, and Models of Regeneration

    PubMed Central

    Youngstrom, Daniel W.; Barrett, Jennifer G.

    2016-01-01

    Tendons bridge muscle and bone, translating forces to the skeleton and increasing the safety and efficiency of locomotion. When tendons fail or degenerate, there are no effective pharmacological interventions. The lack of available options to treat damaged tendons has created a need to better understand and improve the repair process, particularly when suitable autologous donor tissue is unavailable for transplantation. Cells within tendon dynamically react to loading conditions and undergo phenotypic changes in response to mechanobiological stimuli. Tenocytes respond to ultrastructural topography and mechanical deformation via a complex set of behaviors involving force-sensitive membrane receptor activity, changes in cytoskeletal contractility, and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell-matrix forces with high fidelity. While early bioreactor designs have greatly expanded our knowledge of mechanotransduction, traditional scaffolds do not fully model the topography, composition, and mechanical properties of native tendon. Decellularized tendon is an ideal scaffold for cultivating replacement tissue and modeling tendon regeneration. Decellularized tendon scaffolds (DTS) possess high clinical relevance, faithfully translate forces to the cellular scale, and have bulk material properties that match natural tissue. This review summarizes progress in tendon tissue engineering, with a focus on DTS and bioreactor systems. PMID:26839559

  9. Engineering Tendon: Scaffolds, Bioreactors, and Models of Regeneration.

    PubMed

    Youngstrom, Daniel W; Barrett, Jennifer G

    2016-01-01

    Tendons bridge muscle and bone, translating forces to the skeleton and increasing the safety and efficiency of locomotion. When tendons fail or degenerate, there are no effective pharmacological interventions. The lack of available options to treat damaged tendons has created a need to better understand and improve the repair process, particularly when suitable autologous donor tissue is unavailable for transplantation. Cells within tendon dynamically react to loading conditions and undergo phenotypic changes in response to mechanobiological stimuli. Tenocytes respond to ultrastructural topography and mechanical deformation via a complex set of behaviors involving force-sensitive membrane receptor activity, changes in cytoskeletal contractility, and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell-matrix forces with high fidelity. While early bioreactor designs have greatly expanded our knowledge of mechanotransduction, traditional scaffolds do not fully model the topography, composition, and mechanical properties of native tendon. Decellularized tendon is an ideal scaffold for cultivating replacement tissue and modeling tendon regeneration. Decellularized tendon scaffolds (DTS) possess high clinical relevance, faithfully translate forces to the cellular scale, and have bulk material properties that match natural tissue. This review summarizes progress in tendon tissue engineering, with a focus on DTS and bioreactor systems.

  10. A Microfabricated Segmented-Involute-Foil Regenerator for Enhancing Reliability and Performance of Stirling Engines

    NASA Technical Reports Server (NTRS)

    Ibrahim, Mounir; Danila, Daniel; Simon, Terrence; Mantell, Susan; Sun, Liyong; Gadeon, David; Qiu, Songgang; Wood, Gary; Kelly, Kevin; McLean, Jeffrey

    2007-01-01

    An actual-size microfabricated regenerator comprised of a stack of 42 disks, 19 mm diameter and 0.25 mm thick, with layers of microscopic, segmented, involute-shaped flow channels was fabricated and tested. The geometry resembles layers of uniformly-spaced segmented-parallel-plates, except the plates are curved. Each disk was made from electro-plated nickel using the LiGA process. This regenerator had feature sizes close to those required for an actual Stirling engine but the overall regenerator dimensions were sized for the NASA/Sunpower oscillating-flow regenerator test rig. Testing in the oscillating-flow test rig showed the regenerator performed extremely well, significantly better than currently used random-fiber material, producing the highest figures of merit ever recorded for any regenerator tested in that rig over its approximately 20 years of use.

  11. Failure Analysis and Regeneration Performances Evaluation on Engine Lubricating Oil

    NASA Astrophysics Data System (ADS)

    Wang, X. L.; Zhang, G. N.; Zhang, J. Y.; Yin, Y. L.; Xu, Y.

    To investigate the behavior of failure and recycling of lubricating oils, three sorts of typical 10w-40 lubricating oils used in heavy-load vehicle including the new oil, waste oil and regeneration oil regenerated by self-researched green regeneration technology were selected. The tribology properties were tested by four-ball friction wear tester as well. The results indicated that the performance of anti-extreme pressure of regeneration oil increase by 34.1% compared with the waste one and its load- carrying ability is close to the new oil; the feature of wear spot are better than those of the waste oil and frictional coefficient almost reach the level of the new oil's. As a result, the performance of anti-wear and friction reducing are getting better obviously.

  12. Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

    PubMed

    Decaris, Martin L; Leach, J Kent

    2011-04-01

    The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.

  13. Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering

    PubMed Central

    Cheng, Christina W.; Solorio, Loran D.; Alsberg, Eben

    2014-01-01

    The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. PMID:24417915

  14. The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

    PubMed Central

    Zhang, Lijie; Hu, Jerry; Athanasiou, Kyriacos A.

    2011-01-01

    Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed. PMID:20201770

  15. The application of cell sheet engineering in the vascularization of tissue regeneration.

    PubMed

    Moschouris, Kathryn; Firoozi, Negar; Kang, Yunqing

    2016-09-01

    Scaffold-free cell sheet engineering (CSE) is a new technology to regenerate injured or damaged tissues, which has shown promising potential in tissue regeneration. CSE uses a thermosensitive surface to form a dense cell sheet that can be detached when temperature decreases. The detached cell sheet can be stacked on top of one another according to the thickness of cell sheet for the specific tissue regeneration application. One of the key challenges of tissue engineering is vascularization. CSE technique provides excellent microenvironment for vascularization since the technique can maintain the intact cell matrix that is crucial for angiogenesis. In this review paper, we will highlight the principle technique of CSE and its application in tissue regeneration.

  16. The application of cell sheet engineering in the vascularization of tissue regeneration.

    PubMed

    Moschouris, Kathryn; Firoozi, Negar; Kang, Yunqing

    2016-09-01

    Scaffold-free cell sheet engineering (CSE) is a new technology to regenerate injured or damaged tissues, which has shown promising potential in tissue regeneration. CSE uses a thermosensitive surface to form a dense cell sheet that can be detached when temperature decreases. The detached cell sheet can be stacked on top of one another according to the thickness of cell sheet for the specific tissue regeneration application. One of the key challenges of tissue engineering is vascularization. CSE technique provides excellent microenvironment for vascularization since the technique can maintain the intact cell matrix that is crucial for angiogenesis. In this review paper, we will highlight the principle technique of CSE and its application in tissue regeneration. PMID:27527673

  17. Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates

    PubMed Central

    Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

    2015-01-01

    Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions. PMID:26347862

  18. DYGABCD: A program for calculating linear A, B, C, and D matrices from a nonlinear dynamic engine simulation

    NASA Technical Reports Server (NTRS)

    Geyser, L. C.

    1978-01-01

    A digital computer program, DYGABCD, was developed that generates linearized, dynamic models of simulated turbofan and turbojet engines. DYGABCD is based on an earlier computer program, DYNGEN, that is capable of calculating simulated nonlinear steady-state and transient performance of one- and two-spool turbojet engines or two- and three-spool turbofan engines. Most control design techniques require linear system descriptions. For multiple-input/multiple-output systems such as turbine engines, state space matrix descriptions of the system are often desirable. DYGABCD computes the state space matrices commonly referred to as the A, B, C, and D matrices required for a linear system description. The report discusses the analytical approach and provides a users manual, FORTRAN listings, and a sample case.

  19. Experimental performance of the regenerator for the Chrysler upgraded automotive gas turbine engine

    NASA Technical Reports Server (NTRS)

    Winter, J. M.; Nussle, R. C.

    1982-01-01

    Automobile gas turbine engine regenerator performance was studied in a regenerator test facility that provided a satisfactory simulation of the actual engine operating environment but with independent control of airflow and gas flow. Velocity and temperature distributions were measured immediately downstream of both the core high-pressure-side outlet and the core low-pressure-side outlet. For the original engine housing, the regenerator temperature effectiveness was 1 to 2 percent higher than the design value, and the heat transfer effectiveness was 2 to 4 percent lower than the design value over the range of test conditions simulating 50 to 100 percent of gas generator speed. Recalculating the design values to account for seal leakage decreased the design heat transfer effectiveness to values consistent with those measured herein. A baffle installed in the engine housing high-pressure-side inlet provided more uniform velocities out of the regenerator but did not improve the effectiveness. A housing designed to provide more uniform axial flow to the regenerator was also tested. Although temperature uniformity was improved, the effectiveness values were not improved. Neither did 50-percent flow blockage (90 degree segment) applied to the high-pressure-side inlet change the effectiveness significantly.

  20. Reduced contraction of skin equivalent engineered using cell sheets cultured in 3D matrices.

    PubMed

    Ng, Kee Woei; Hutmacher, Dietmar Werner

    2006-09-01

    In order to alleviate their extensive contraction, human fibroblast sheets were cultured in combination with three-dimensional matrices (knitted poly(lactic-co-glycolic acid) (PLGA) mesh and collagen-hyaluronic acid (CHA) sponge) to form contiguous dermal constructs for tissue engineering a bilayered skin equivalent. The resulting constructs were viable, and supported the development of bilayered skin equivalents which did not contract over the 4-week culture period. When implanted into full-thickness wounds in nude rats, cultured skin equivalents based on PLGA meshes registered a take rate of 100% and showed an extent of wound contraction that was statistically similar to autografts, while wounds grafted with PLGA meshes without cell sheets contracted more than autografts. On the other hand, skin equivalents based on CHA sponges were all sloughed off within 2 weeks of transplantation. In all cell sheet-incorporated specimens, cells from the constructs infiltrated and produced extracellular matrix within the neo-dermis, shown by positive human leukocyte antigen and collagen I expression. This technique offers an alternative approach for scaffold-based tissue engineering to produce mechanically stable grafts with matured neo-tissue.

  1. Craniofacial defect regeneration using engineered bone marrow mesenchymal stromal cells.

    PubMed

    Yang, Yi; Hallgrimsson, Benedikt; Putnins, Edward E

    2011-10-01

    Large craniofacial bony defects remain a significant clinical challenge. Bone marrow mesenchymal stromal cells (BM-MSCs) constitute a multipotent population. Previously, we developed a novel approach for BM-MSC expansion on 3D CultiSpher-S gelatin microcarrier beads in spin culture with preservation of their multipotentiality, reduction of apoptosis, and enhancement of bone formation in vivo. Here, we hypothesized that such cultured BM-MSCs without exogenous growth factors would respond to the orthopedic microenvironment, thus promoting craniofacial defect regeneration. BM-MSCs isolated from green fluorescent protein (GFP) transgenic rats were ex vivo expanded and transplanted into critical-sized (5-mm diameter) rat calvaria defects. Gelatin beads or defect alone served as controls. By 28 and 42 days, rats were sacrificed for microcomputed tomography (microCT), histologic, and immunohistochemistry examination. MicroCT results demonstrated that BM-MSCs were a statistically significant factor contributing to new bone volume regeneration. Histologic assessment showed that the BM-MSCs group produced more and higher quality new bone compared with beads or defect-alone groups in both osteoinductive and osteoconductive manners. Specifically, immunohistochemical staining identified GFP(+) cells residing in new bone lacunae in conjunction with non-GFP(+) cells. Therefore, ex vivo expanded BM-MSCs at least in part regenerated critical-sized calvaria defects by osteogenic differentiation in vivo.

  2. A new era in periodontal and periimplant regeneration: use of growth-factor enhanced matrices incorporating rhPDGF.

    PubMed

    Lynch, Samuel E; Wisner-Lynch, Leslie; Nevins, Myron; Nevins, Marc L

    2006-12-01

    A new, powerful off-the-shelf wound healing and bone regeneration technology termed growth-factor enhanced matrix (GEM) has recently become available for clinical use. This graft material consists of a concentrated solution of pure recombinant human platelet-derived growth factor (rhPDGF-BB), the synthetic form of the body's key natural wound healing stimulator PDGF-BB, and an osteoconductive (bone scaffold) matrix. This is the first available purified, recombinant (synthetic) growth factor product and is the result of over a decade of extensive research. Clinical and animal study results with this graft material demonstrate that it is capable of simultaneously promoting wound healing, regeneration of bone, and acceleration of gingival attach-plent gain in challenging periodontal and periimplant defects. PMID:17191649

  3. Layer-by-layer heparinization of decellularized liver matrices to reduce thrombogenicity of tissue engineered grafts

    PubMed Central

    Bruinsma, Bote G; Kim, Yeonhee; Berendsen, Tim A; Ozer, Sinan; Yarmush, Martin L; Uygun, Basak E

    2015-01-01

    Background Tissue-engineered liver grafts may offer a viable alternative to orthotopic liver transplantation and help overcome the donor organ shortage. Decellularized liver matrices (DLM) have a preserved vasculature and sustain hepatocellular function in culture, but graft survival after transplantation remains limited due to thrombogenicity of the matrix. Aim To evaluate the effect of heparin immobilization on DLM thrombogenicity. Methods Heparin was immobilized on DLMs by means of layer-by-layer deposition. Grafts with 4 or 8 bilayers and 2 or 4 g/L of heparin were recellularized with primary rat hepatocytes and maintained in culture for 5 days. Hemocompatibility of the graft was assessed by ex vivo diluted whole-blood perfusion and heterotopic transplantation. Results Heparin was deposited throughout the matrix and the heparin content in the graft was higher with increasing number of bilayers and concentration of heparin. Recellularization and in vitro albumin and urea production were unaffected by heparinization. Resistance to blood flow during ex vivo perfusion was lower with increased heparinization and, macroscopically, no clots were visible in grafts with 8 bilayers. Following transplantation, flow through the graft was limited in all groups. Histological evidence of thrombosis was lower in heparinized DLMs, but transplantation of DLM grafts was not improved. Conclusions Layer-by-layer deposition of heparin on a DLM is an effective method of immobilizing heparin throughout the graft and does not impede recellularization or hepatocellular function in vitro. Thrombogenicity during ex vivo blood perfusion was reduced in heparinized grafts and optimal with 8 bilayers, but transplantation remained unsuccessful with this method. Relevance for patients Tissue engineered liver grafts may offer a viable solution to dramatic shortages in donor organs PMID:26478914

  4. Fast-regenerable sulfur dioxide adsorbents for diesel engine emission control

    DOEpatents

    Li, Liyu [Richland, WA; King, David L [Richland, WA

    2011-03-15

    Disclosed herein are sorbents and devices for controlling sulfur oxides emissions as well as systems including such sorbents and devices. Also disclosed are methods for making and using the disclosed sorbents, devices and systems. In one embodiment the disclosed sorbents can be conveniently regenerated, such as under normal exhaust stream from a combustion engine, particularly a diesel engine. Accordingly, also disclosed are combustion vehicles equipped with sulfur dioxide emission control devices.

  5. Traceability of fluorescent engineered nanomaterials and their fate in complex liquid waste matrices.

    PubMed

    Part, Florian; Zaba, Christoph; Bixner, Oliver; Zafiu, Christian; Hann, Stephan; Sinner, Eva-Kathrin; Huber-Humer, Marion

    2016-07-01

    The number of products containing engineered nanomaterials (ENMs) has increased due to their high industrial relevance as well as their use in diverse consumer products. At the end of their life cycle ENMs might be released to the environment and therefore concerns arise regarding their environmental impact. In order to track their fate upon disposal, it is crucial to establish methods to trace ENMs in complex environmental samples and to differentiate them from naturally-occurring nanoparticles. The goal of this study was to distinctively trace ENMs by (non-invasive) detection methods. For this, fluorescent ENMs, namely quantum dots (QDs), were distinctively traced in complex aqueous matrices, and were still detectable after a period of two months using fluorescence spectroscopy. In particular, two water-dispersible QD-species, namely CdTe/CdS QDs with N-acetyl-l-cysteine as capping agent (NAC-QDs) and surfactant-stabilized CdSe/ZnS QDs (Brij(®)58-QDs), were synthesized to examine their environmental fate during disposal as well as their potential interaction with naturally-occurring substances present in landfill leachates. When QDs were spiked into a leachate from an old landfill site, alteration processes, such as sorption, aggregation, agglomeration, and interactions with dissolved organic carbon (DOC), led to modifications of the optical properties of QDs. The spectral signatures of NAC-QDs deteriorated depending on residence time and storage temperature, while Brij(®)58-QDs retained their photoluminescence fingerprints, indicating their high colloidal stability. The observed change in photoluminescence intensity was mainly caused by DOC-interaction and association with complexing agents, such as fulvic or humic acids, typically present in mature landfill leachates. For both QD-species, the results also indicated that pH of the leachate had no significant impact on their optical properties. As a result, the unique spectroscopic fingerprints of QDs

  6. Traceability of fluorescent engineered nanomaterials and their fate in complex liquid waste matrices.

    PubMed

    Part, Florian; Zaba, Christoph; Bixner, Oliver; Zafiu, Christian; Hann, Stephan; Sinner, Eva-Kathrin; Huber-Humer, Marion

    2016-07-01

    The number of products containing engineered nanomaterials (ENMs) has increased due to their high industrial relevance as well as their use in diverse consumer products. At the end of their life cycle ENMs might be released to the environment and therefore concerns arise regarding their environmental impact. In order to track their fate upon disposal, it is crucial to establish methods to trace ENMs in complex environmental samples and to differentiate them from naturally-occurring nanoparticles. The goal of this study was to distinctively trace ENMs by (non-invasive) detection methods. For this, fluorescent ENMs, namely quantum dots (QDs), were distinctively traced in complex aqueous matrices, and were still detectable after a period of two months using fluorescence spectroscopy. In particular, two water-dispersible QD-species, namely CdTe/CdS QDs with N-acetyl-l-cysteine as capping agent (NAC-QDs) and surfactant-stabilized CdSe/ZnS QDs (Brij(®)58-QDs), were synthesized to examine their environmental fate during disposal as well as their potential interaction with naturally-occurring substances present in landfill leachates. When QDs were spiked into a leachate from an old landfill site, alteration processes, such as sorption, aggregation, agglomeration, and interactions with dissolved organic carbon (DOC), led to modifications of the optical properties of QDs. The spectral signatures of NAC-QDs deteriorated depending on residence time and storage temperature, while Brij(®)58-QDs retained their photoluminescence fingerprints, indicating their high colloidal stability. The observed change in photoluminescence intensity was mainly caused by DOC-interaction and association with complexing agents, such as fulvic or humic acids, typically present in mature landfill leachates. For both QD-species, the results also indicated that pH of the leachate had no significant impact on their optical properties. As a result, the unique spectroscopic fingerprints of QDs

  7. Dental Pulp and Dentin Tissue Engineering and Regeneration – Advancement and Challenge

    PubMed Central

    Huang, George T.-J.

    2012-01-01

    Hard tissue is difficult to repair especially dental structures. Tooth enamel is incapable of self-repairing whereas dentin and cememtum can regenerate with limited capacity. Enamel and dentin are commonly under the attack by caries. Extensive forms of caries destroy enamel and dentin and can lead to dental pulp infection. Entire pulp amputation followed by the pulp space disinfection and filled with an artificial rubber-like material is employed to treat the infection --commonly known as root canal or endodontic therapy. Regeneration of dentin relies on having vital pulps; however, regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. With the advent of modern tissue engineering concept and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the recent endeavor on pulp and dentin tissue engineering and regeneration. The prospective outcome of the current advancement and challenge in this line of research will be discussed. PMID:21196351

  8. Geomicrobiological Regeneration of Iron Sulfides in Engineered barrier Systems

    NASA Astrophysics Data System (ADS)

    Vannela, R.; Adriaens, P.; Hayes, K. F.

    2005-12-01

    The reactive capacity of iron sulfide-based permeable reactive barriers (PRB) to complex and co-precipitate heavy metal ions from groundwater will depend on the potential for regeneration of reactive FeS during the expected lifetime of the PRB. FeS reactivity may decrease in a PRB in time as the result of the following processes: (i) oxidation of FeS and the formation of ferric iron (Fe(III)) oxide solids in the presence of oxygenated groundwater at the entrance of the PRB, (ii) oxidation of FeS in the presence of redox active metals like As(V) with the formation of ferric solids, (iii) co-precipitation of heavy metals within the PRB with the reactive FeS leading to the formation of insoluble metal sulfides co-precipitates with the concomitant release of ferrous iron and formation of ferrous (Fe(II) oxide, hydroxide, or carbonate solids, (iv) clogging of the PRB structure due to formation of precipitate products from processes (i) - (iii).. We have demonstrated the formation of triolite in the presence of an oxidized form of hydrous ferric oxide (HFO), various sulfate concentrations, and biomass densities for the sulfate reducing bacterium (SRB) Desulfovibrio vulgaris. This result has allowed us to demonstrate the feasibility of regeneration of FeS from the ferric oxide and hydroxide solids that may be produced under scenarios (i) and (ii) above as well as to establish the electron donor and acceptor requirements for this SRB. Using Desulfobacterium autotrophicum, both HFO and soluble complexed forms of ferric iron gave rise to the formation of mackinawite. The latter have been shown to react with As (V) and Cd (II) to form ferric solids. Both organisms will be used to generate FeS solids in the presence of crystalline forms of ferric solids expected to form from scenarios (i) and (ii) (e.g., goethite and the mixed Fe(II)/(Fe(III) magnetite, and green rusts) and ferrous iron solids from scenarios (iii) and (iv) (Fe(II) oxides and siderite). Similar to the study

  9. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

    PubMed Central

    Henkel, Jan; Woodruff, Maria A.; Epari, Devakara R.; Steck, Roland; Glatt, Vaida; Dickinson, Ian C.; Choong, Peter F. M.; Schuetz, Michael A.; Hutmacher, Dietmar W.

    2013-01-01

    The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts. PMID:26273505

  10. The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury

    PubMed Central

    Chung, Yeun Goo; Algarrahi, Khalid; Franck, Debra; Tu, Duong D.; Adam, Rosalyn M.; Kaplan, David L.; Estrada, Carlos R.; Mauney, Joshua R.

    2014-01-01

    Adverse side-effects associated with enterocystoplasty for neurogenic bladder reconstruction have spawned the need for the development of alternative graft substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa (SIS) matrices were investigated for their ability to support bladder tissue regeneration and function in a rat model of spinal cord injury (SCI). Bladder augmentation was performed with each scaffold configuration in SCI animals for 10 wk of implantation and compared to non-augmented control groups (normal and SCI alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18) while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective survival rates of 83% (10/12) and 75% (9/12) over the course of the study period. Histological (Masson’s trichrome analysis) and immunohistochemical (IHC) evaluations demonstrated both implant groups supported de novo formation of smooth muscle layers with contractile protein expression [α-smooth muscle actin (α-SMA) and SM22α] as well as maturation of multi-layer urothelia expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of the level of α-SMA+ smooth muscle bundles present in SCI-alone controls, while similar degrees of CK+ urothelium across all experimental groups were detected. Parallel evaluations showed similar degrees of vascular area and synaptophysin+ boutons in all regenerated tissues compared to SCI-alone controls. In addition, improvements in certain urodynamic parameters in SCI animals, such as decreased peak intravesical pressure, following implantation with both matrix configurations were also observed. The data presented in this study detail the ability of acellular SIS and bi-layer SF scaffolds to support formation of innervated, vascularized smooth muscle and urothelial tissues in a neurogenic bladder model. PMID:24917031

  11. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    PubMed Central

    Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

    2013-01-01

    Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF), and bone morphogenetic protein 7 (BMP7) were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure. PMID:23293519

  12. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

    PubMed Central

    Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

    2014-01-01

    The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

  13. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber.

    PubMed

    Zhan, Weiqing; Chang, Qiang; Xiao, Xiaolian; Dong, Ziqing; Zeng, Zhaowei; Gao, Jianhua; Lu, Feng

    2015-01-01

    The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a tissue engineering chamber consist mostly of connective rather than adipose tissue. Here, we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration.

  14. Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

    PubMed

    Shen, Yue; Yang, Shizhou; Liu, Jianli; Xu, Huazi; Shi, Zhongli; Lin, Zhongqing; Ying, Xiaozhou; Guo, Peng; Lin, Tiao; Yan, Shigui; Huang, Qing; Peng, Lei

    2014-08-13

    Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration. PMID:25033438

  15. Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

    PubMed

    Shen, Yue; Yang, Shizhou; Liu, Jianli; Xu, Huazi; Shi, Zhongli; Lin, Zhongqing; Ying, Xiaozhou; Guo, Peng; Lin, Tiao; Yan, Shigui; Huang, Qing; Peng, Lei

    2014-08-13

    Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.

  16. Potential of non-mulberry silk protein fibroin blended and grafted poly(Є-caprolactone) nanofibrous matrices for in vivo bone regeneration.

    PubMed

    Bhattacharjee, Promita; Naskar, Deboki; Maiti, Tapas K; Bhattacharya, Debasis; Das, Piyali; Nandi, Samit Kumar; Kundu, Subhas C

    2016-07-01

    An in vivo investigation is conducted to evaluate effectiveness of poly(Є-caprolactone) (PCL) nanofibrous matrices, with non-mulberry silk fibroin (NSF) (from Antheraea mylitta) inclusion, for bone tissue engineering. Inclusion is achieved by either blending NSF with PCL prior to electrospinning substrates or by grafting NSF onto electrospun PCL substrates. Proceeding from our previous in vitro results, showing that NSF grafted matrices have an edge when it comes to aiding cellular adhesion and proliferation, animal trials using rabbits are planned. As this is first in vivo trial of nanofibrous scaffolds with silk fibroin from A. mylitta, aim is to both evaluate the grafted and blended scaffolds independently and compare the method of silk fibroin introduction into the nanofibrous structures. The scaffolds are implanted at bone defect site in distal metaphysis region of the rabbits' femur. Host tissue immuno-compatibility of implants is assessed from measurements of IL-2, IL-6 and TNF-α level through 4 weeks after implantation. Barring an initial inflammatory response, IL-2, IL-6 and TNF-α levels fall back at baseline values in 2 or 4 weeks, thus confirming long term compatibility. Substantial interfacial bonding strength between grafts and host bone is evidenced from mechanical push-out test. Formation of bone tissue for both implant varieties is confirmed using histological and radiological examinations along with fluorochrome labelling and scanning electron microscopy. Significantly better bone formation is observed for NSF grafted matrices. The cumulative results from in vivo tests indicate suitability of NSF grafted PCL nanofibrous matrix as an ECM for bone repair and regrowth. PMID:27037780

  17. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  18. Multifaceted signaling regulators of chondrogenesis: Implications in cartilage regeneration and tissue engineering

    PubMed Central

    Green, Jordan D.; Tollemar, Viktor; Dougherty, Mark; Yan, Zhengjian; Yin, Liangjun; Ye, Jixing; Collier, Zachary; Mohammed, Maryam K.; Haydon, Rex C.; Luu, Hue H.; Kang, Richard; Lee, Michael J.; Ho, Sherwin H.; He, Tong-Chuan; Shi, Lewis L.; Athiviraham, Aravind

    2015-01-01

    Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature. Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue. Here, we review the current understanding of the most important biological regulators of chondrogenesis and their interactions, to provide insight into potential applications for cartilage tissue engineering. These include various signaling pathways, including: fibroblast growth factors (FGFs), transforming growth factor β (TGF-β)/bone morphogenic proteins (BMPs), Wnt/β-catenin, Hedgehog, Notch, hypoxia, and angiogenic signaling pathways. Transcriptional and epigenetic regulation of chondrogenesis will also be discussed. Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering. PMID:26835506

  19. Feasibility of silica-hybridized collagen hydrogels as three-dimensional cell matrices for hard tissue engineering.

    PubMed

    Yu, Hye-Sun; Lee, Eun-Jung; Seo, Seog-Jin; Knowles, Jonathan C; Kim, Hae-Won

    2015-09-01

    Exploiting hydrogels for the cultivation of stem cells, aiming to provide them with physico-chemical cues suitable for osteogenesis, is a critical demand for bone engineering. Here, we developed hybrid compositions of collagen and silica into hydrogels via a simple sol-gel process. The physico-chemical and mechanical properties, degradation behavior, and bone-bioactivity were characterized in-depth; furthermore, the in vitro mesenchymal stem cell growth and osteogenic differentiation behaviors within the 3D hybrid gel matrices were communicated for the first time. The hydrolyzed and condensed silica phase enabled chemical links with the collagen fibrils to form networked hybrid gels. The hybrid gels showed improved chemical stability and greater resistance to enzymatic degradation. The in vitro apatite-forming ability was enhanced by the hybrid composition. The viscoelastic mechanical properties of the hybrid gels were significantly improved in terms of the deformation resistance to an applied load and the modulus values under a dynamic oscillation. Mesenchymal stem cells adhered well to the hybrid networks and proliferated actively with substantial cytoskeletal extensions within the gel matrices. Of note, the hybrid gels substantially reduced the cell-mediated gel contraction behaviors, possibly due to the stiffer networks and higher resistance to cell-mediated degradation. Furthermore, the osteogenic differentiation of cells, including the expression of bone-associated genes and protein, was significantly upregulated within the hybrid gel matrices. Together with the physico-chemical and mechanical properties, the cellular behaviors observed within 3D gel matrices, being different from the previous approaches reported on 2D substrates, provide new information on the feasibility and usefulness of the silica-collagen system for stem cell culture and tissue engineering of hard tissues.

  20. Modeling planarian regeneration: a primer for reverse-engineering the worm.

    PubMed

    Lobo, Daniel; Beane, Wendy S; Levin, Michael

    2012-01-01

    A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences-using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an engineering-like style

  1. Modeling Planarian Regeneration: A Primer for Reverse-Engineering the Worm

    PubMed Central

    Lobo, Daniel; Beane, Wendy S.; Levin, Michael

    2012-01-01

    A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences—using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an engineering

  2. Cardiac tissue engineering and regeneration using cell-based therapy

    PubMed Central

    Alrefai, Mohammad T; Murali, Divya; Paul, Arghya; Ridwan, Khalid M; Connell, John M; Shum-Tim, Dominique

    2015-01-01

    Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. PMID:25999743

  3. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    PubMed Central

    2009-01-01

    Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves. PMID:19939265

  4. Promoting epithelium regeneration for esophageal tissue engineering through basement membrane reconstitution.

    PubMed

    Lv, Jingjing; Chen, Ling; Zhu, Yabin; Hou, Lei; Liu, Yuxin

    2014-04-01

    Scaffolds mimicking hierarchical features of native extracellular matrices may facilitate cell growth and anatomical tissue regeneration. In our previous study, esophageal basement membrane (BM) was shown to be composed of interwoven fibers with mean diameter of 66 ± 24 nm (range 28-165 nm) and with abundant pores of unequal sizes. The main extracellular matrix (ECM) contents found in porcine esophageal BM were collagen IV, laminin, entactin, and proteoglycans. In this work, biodegradable polycaprolactone (PCL) and silk fibroin (SF) were spun with electrospinning technology, both individually and in combination, to fabricate fibrous scaffolds with diameters between 64 and 200 nm. The surface morphologies of PCL, PCL/SF, and SF scaffolds were observed under scanning electron microscopy. Their mechanical properties were tested and the cytocompatibility was evaluated in vitro via culture of primary epithelial cells (ECs). The SF or PCL/SF scaffold favorably promoted epithelial cell attachment and proliferation comparing with PCL scaffold. However, mitochondrial activity of epithelial cells was greatly promoted when major BM proteins were coated onto the electrospun scaffold to provide an ECM-like structure. Results from in vivo tests revealed that the electrospun scaffolds coated with BM protein possess good biocompatibility and capability to promote epithelium regeneration.

  5. Biocomposite cryogels as tissue-engineered biomaterials for regeneration of critical-sized cranial bone defects.

    PubMed

    Mishra, Ruchi; Goel, Sudhir Kumar; Gupta, Kailash Chand; Kumar, Ashok

    2014-02-01

    Analysis of the in vivo regeneration capability of any tissue-engineered biomaterial is necessary once it shows potential characteristics during in vitro studies. Thus, we applied polyvinyl alcohol-tetraethylorthosilicate-alginate-calcium oxide (PTAC) biocomposite cryogel on critical-sized cranial bone defects in wistar rats for examining the comparative bone regeneration of cryogel-treated and nontreated defects over a period of 4 weeks. An in-depth analysis was performed from macroscopic level till the gene level. Bone regeneration in cryogel-treated defects was clearly evident from the results, whereas the nontreated group did not show any defect healing except at few peripheral areas. At the macroscopic level, micro-computed tomography analysis revealed new bone formation. This was further confirmed at the cellular level, wherein, new bone formation was demonstrated by hematoxylin and eosin staining. Osteoblastic differentiation was further validated by immunohistological staining of runt-related transcription factor-2 (Runx-2) protein and via calcium-phosphate crystal formation after 2 weeks through scanning electron microscopy and energy dispersive X-ray spectroscopy. Finally, at the gene level, real-time PCR analysis confirmed the mRNA expression of osteoblastic markers, that is, runx-2, collagen type I (Col I), alkaline phosphatase (ALP), and osteocalcin (OCN). Therefore, the results of in vivo cranial defect model studies suggest that PTAC biocomposite cryogels can show suitable potential for human bone regeneration. PMID:24147880

  6. Biocomposite cryogels as tissue-engineered biomaterials for regeneration of critical-sized cranial bone defects.

    PubMed

    Mishra, Ruchi; Goel, Sudhir Kumar; Gupta, Kailash Chand; Kumar, Ashok

    2014-02-01

    Analysis of the in vivo regeneration capability of any tissue-engineered biomaterial is necessary once it shows potential characteristics during in vitro studies. Thus, we applied polyvinyl alcohol-tetraethylorthosilicate-alginate-calcium oxide (PTAC) biocomposite cryogel on critical-sized cranial bone defects in wistar rats for examining the comparative bone regeneration of cryogel-treated and nontreated defects over a period of 4 weeks. An in-depth analysis was performed from macroscopic level till the gene level. Bone regeneration in cryogel-treated defects was clearly evident from the results, whereas the nontreated group did not show any defect healing except at few peripheral areas. At the macroscopic level, micro-computed tomography analysis revealed new bone formation. This was further confirmed at the cellular level, wherein, new bone formation was demonstrated by hematoxylin and eosin staining. Osteoblastic differentiation was further validated by immunohistological staining of runt-related transcription factor-2 (Runx-2) protein and via calcium-phosphate crystal formation after 2 weeks through scanning electron microscopy and energy dispersive X-ray spectroscopy. Finally, at the gene level, real-time PCR analysis confirmed the mRNA expression of osteoblastic markers, that is, runx-2, collagen type I (Col I), alkaline phosphatase (ALP), and osteocalcin (OCN). Therefore, the results of in vivo cranial defect model studies suggest that PTAC biocomposite cryogels can show suitable potential for human bone regeneration.

  7. Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Di Martino, Alberto; Denaro, Vincenzo

    2015-06-01

    Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials-based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self-renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell-based therapies and tissue-engineering strategies for disc regeneration.

  8. Vascularization strategies of engineered tissues and their application in cardiac regeneration.

    PubMed

    Sun, Xuetao; Altalhi, Wafa; Nunes, Sara S

    2016-01-15

    The primary function of vascular networks is to transport blood and deliver oxygen and nutrients to tissues, which occurs at the interface of the microvasculature. Therefore, the formation of the vessels at the microcirculatory level, or angiogenesis, is critical for tissue regeneration and repair. Current strategies for vascularization of engineered tissues have incorporated multi-disciplinary approaches including engineered biomaterials, cells and angiogenic factors. Pre-vascularization of scaffolds composed of native matrix, synthetic polymers, or other biological materials can be achieved through the use of single cells in mono or co-culture, in combination or not with angiogenic factors or by the use of isolated vessels. The advance of these methods, together with a growing understanding of the biology behind vascularization, has facilitated the development of vascularization strategies for engineered tissues with therapeutic potential for tissue regeneration and repair. Here, we review the different cell-based strategies utilized to pre-vascularize engineered tissues and in making more complex vascularized cardiac tissues for regenerative medicine applications.

  9. Should we use cells, biomaterials, or tissue engineering for cartilage regeneration?

    PubMed

    Bernhard, Jonathan C; Vunjak-Novakovic, Gordana

    2016-01-01

    For a long time, cartilage has been a major focus of the whole field of tissue engineering, both because of the constantly growing need for more effective options for joint repair and the expectation that this apparently simple tissue will be easy to engineer. After several decades, cartilage regeneration has proven to be anything but easy. With gratifying progress in our understanding of the factors governing cartilage development and function, and cell therapy being successfully used for several decades, there is still a lot to do. We lack reliable methods to generate durable articular cartilage that would resemble the original tissue lost to injury or disease. The question posed here is whether the answer would come from the methods using cells, biomaterials, or tissue engineering. We present a concise review of some of the most meritorious efforts in each area, and propose that the solution will most likely emerge from the ongoing attempts to recapitulate certain aspects of native cartilage development. While an ideal recipe for cartilage regeneration is yet to be formulated, we believe that it will contain cell, biomaterial, and tissue engineering approaches, blended into an effective method for seamless repair of articular cartilage. PMID:27089917

  10. Engineering Redox Cofactor Regeneration for Improved Pentose Fermentation in Saccharomyces cerevisiae

    PubMed Central

    Verho, Ritva; Londesborough, John; Penttilä, Merja; Richard, Peter

    2003-01-01

    Pentose fermentation to ethanol with recombinant Saccharomyces cerevisiae is slow and has a low yield. A likely reason for this is that the catabolism of the pentoses d-xylose and l-arabinose through the corresponding fungal pathways creates an imbalance of redox cofactors. The process, although redox neutral, requires NADPH and NAD+, which have to be regenerated in separate processes. NADPH is normally generated through the oxidative part of the pentose phosphate pathway by the action of glucose-6-phosphate dehydrogenase (ZWF1). To facilitate NADPH regeneration, we expressed the recently discovered gene GDP1, which codes for a fungal NADP+-dependent d-glyceraldehyde-3-phosphate dehydrogenase (NADP-GAPDH) (EC 1.2.1.13), in an S. cerevisiae strain with the d-xylose pathway. NADPH regeneration through an NADP-GAPDH is not linked to CO2 production. The resulting strain fermented d-xylose to ethanol with a higher rate and yield than the corresponding strain without GDP1; i.e., the levels of the unwanted side products xylitol and CO2 were lowered. The oxidative part of the pentose phosphate pathway is the main natural path for NADPH regeneration. However, use of this pathway causes wasteful CO2 production and creates a redox imbalance on the path of anaerobic pentose fermentation to ethanol because it does not regenerate NAD+. The deletion of the gene ZWF1 (which codes for glucose-6-phosphate dehydrogenase), in combination with overexpression of GDP1 further stimulated d-xylose fermentation with respect to rate and yield. Through genetic engineering of the redox reactions, the yeast strain was converted from a strain that produced mainly xylitol and CO2 from d-xylose to a strain that produced mainly ethanol under anaerobic conditions. PMID:14532041

  11. Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model.

    PubMed

    Lu, Zijing; Yuan, Yi; Gao, Jianhua; Lu, Feng

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation.

  12. Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice

    PubMed Central

    Itaba, Noriko; Matsumi, Yoshiaki; Okinaka, Kaori; Ashla, An Afida; Kono, Yohei; Osaki, Mitsuhiko; Morimoto, Minoru; Sugiyama, Naoyuki; Ohashi, Kazuo; Okano, Teruo; Shiota, Goshi

    2015-01-01

    Mesenchymal stem cells (MSCs) are an attractive cell source for cell therapy. Based on our hypothesis that suppression of Wnt/β-catenin signal enhances hepatic differentiation of human MSCs, we developed human mesenchymal stem cell-engineered hepatic cell sheets by a small molecule compound. Screening of 10 small molecule compounds was performed by WST assay, TCF reporter assay, and albumin mRNA expression. Consequently, hexachlorophene suppressed TCF reporter activity in time- and concentration-dependent manner. Hexachlorophene rapidly induced hepatic differentiation of human MSCs judging from expression of liver-specific genes and proteins, PAS staining, and urea production. The effect of orthotopic transplantation of human mesenchymal stem cell-engineered hepatic cell sheets against acute liver injury was examined in one-layered to three-layered cell sheets system. Transplantation of human mesenchymal stem cell-engineered hepatic cell sheets enhanced liver regeneration and suppressed liver injury. The survival rates of the mice were significantly improved. High expression of complement C3 and its downstream signals including C5a, NF-κB, and IL-6/STAT-3 pathway was observed in hepatic cell sheets-grafted tissues. Expression of phosphorylated EGFR and thioredoxin is enhanced, resulting in reduction of oxidative stress. These findings suggest that orthotopic transplantation of hepatic cell sheets manufactured from MSCs accelerates liver regeneration through complement C3, EGFR and thioredoxin. PMID:26553591

  13. Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

    PubMed Central

    Dennis, S. Connor; Berkland, Cory J.; Bonewald, Lynda F.

    2015-01-01

    Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's “ideal” osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the “hard” or “bony” callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures and, thus, can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies which mimic the initial inflammatory or fibrocartilaginous ECM (i.e., “pro-” or “soft” callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (1) native ECM biomaterials and (2) developmental engineering, which will attempt to overcome the technical, business, and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native “raw” materials

  14. Fast-regenerable sulfur dioxide absorbents for lean-burn diesel engine emission control

    SciTech Connect

    Li, Liyu; King, David L.

    2010-01-23

    It is known that sulfur oxides contribute significantly and deleteriously to the overall performance of lean-burn diesel engine aftertreatment systems, especially in the case of NOx traps. A Ag-based, fast regenerable SO2 absorbent has been developed and will be described. Over a temperature range of 300oC to 550oC, it absorbs almost all of the SO2 in the simulated exhaust gases during the lean cycles and can be fully regenerated by the short rich cycles at the same temperature. Its composition has been optimized as 1 wt% Pt-5wt%Ag-SiO2, and the preferred silica source for the supporting material has been identified as inert Cabosil fumed silica. The thermal instability of Ag2O under fuel-lean conditions at 230oC and above makes it possible to fast regenerate the sulfur-loaded absorbent during the following fuel-rich cycles. Pt catalyst helps reducing Ag2SO4 during rich cycles at low temperatures. And the chemically inert fumed SiO2 support gives the absorbent long term stability. This absorbent shows great potential to work under the same lean-rich cycling conditions as those imposed on the NOx traps, and thus, can protect the downstream particulate filter and the NOx trap from sulfur poisoning.

  15. Fatigue failure of regenerator screens in a high frequency Stirling engine

    NASA Technical Reports Server (NTRS)

    Hull, David R.; Alger, Donald L.; Moore, Thomas J.; Scheuermann, Coulson M.

    1987-01-01

    Failure of Stirling Space Power Demonstrator Engine (SPDE) regenerator screens was investigated. After several hours of operation the SPDE was shut down for inspection and on removing the regenerator screens, debris of unknown origin was discovered along with considerable cracking of the screens in localized areas. Metallurgical analysis of the debris determined it to be cracked-off-deformed pieces of the 41 micron thickness Type 304 stainless steel wire screen. Scanning electron microscopy of the cracked screens revealed failures occurring at wire crossovers and fatigue striations on the fracture surface of the wires. Thus, the screen failure can be characterized as a fatigue failure of the wires. The crossovers were determined to contain a 30 percent reduction in wire thickness and a highly worked microstructure occurring from the manufacturing process of the wire screens. Later it was found that reduction in wire thickness occurred because the screen fabricator had subjected it to a light cold-roll process after weaving. Installation of this screen left a clearance in the regenerator allowing the screens to move. The combined effects of the reduction in wire thickness, stress concentration (caused by screen movement), and highly worked microstructure at the wire crossovers led to the fatigue failure of the screens.

  16. Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

    PubMed Central

    Rodriguez, Isaac A.; Growney Kalaf, Emily A.; Bowlin, Gary L.; Sell, Scott A.

    2014-01-01

    Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use. PMID:25050347

  17. Skeletal muscle regeneration via engineered tissue culture over electrospun nanofibrous chitosan/PVA scaffold.

    PubMed

    Kheradmandi, Mahsa; Vasheghani-Farahani, Ebrahim; Ghiaseddin, Ali; Ganji, Fariba

    2016-07-01

    Skeletal muscle tissue shows a remarkable potential in regeneration of injured tissue. However, in some of chronic and volumetric muscle damages, the native tissue is incapable to repair and remodeling the trauma. In the same condition, stem-cell therapy increased regeneration in situations of deficient muscle repair, but the major problem seems to be the lack of ability to attachment and survive of injected cells on the exact location. In this study, chitosan/poly(vinyl alcohol) nanofibrous scaffold was studied to promote cell attachment and provide mechanical support during regeneration. Scaffold was characterized using scanning electron microscope, X-ray diffraction, and tensile test. Degradation and swelling behavior of scaffold were studied for 20 days. The cell-scaffold interaction was characterized by MTT assay for 10 days and in vivo biocompatibility of scaffold in a rabbit model was evaluated. Results showed that cells had a good viability, adhesion, growth, and spread on the scaffold, which make this mat a desirable engineered muscular graft. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1720-1727, 2016.

  18. Biodiesel Impact on Engine Lubricant Dilution During Active Regeneration of Aftertreatment Systems

    SciTech Connect

    He, X.; Williams, A.; Christensen, E.; Burton, J.; McCormick, R.

    2011-12-01

    Experiments were conducted with ultra low sulfur diesel (ULSD) and 20% biodiesel blends (B20) to compare lube oil dilution levels and lubricant properties for systems using late in-cylinder fuel injection for aftertreatment regeneration. Lube oil dilution was measured by gas chromatography (GC) following ASTM method D3524 to measure diesel content, by Fourier transform infrared (FTIR) spectrometry following a modified ASTM method D7371 to measure biodiesel content, and by a newly developed back-flush GC method that simultaneously measures both diesel and biodiesel. Heavy-duty (HD) engine testing was conducted on a 2008 6.7L Cummins ISB equipped with a diesel oxidation catalyst (DOC) and diesel particle filter (DPF). Stage one of engine testing consisted of 10 consecutive repeats of a forced DPF regeneration event. This continuous operation with late in-cylinder fuel injection served as a method to accelerate lube-oil dilution. Stage two consisted of 16 hours of normal engine operation over a transient test cycle, which created an opportunity for any accumulated fuel in the oil sump to evaporate. Light duty (LD) vehicle testing was conducted on a 2010 VW Jetta equipped with DOC, DPF and a NOx storage catalyst (NSC). Vehicle testing comprised approximately 4,000 miles of operation on a mileage-accumulation dynamometer (MAD) using the U.S. Environmental Protection Agency's Highway Fuel Economy Cycle because of the relatively low engine oil and exhaust temperatures, and high DPF regeneration frequency of this cycle relative to other cycles examined. Comparison of the lube oil dilution analysis methods suggests that D3524 does not measure dilution by biodiesel. The new back-flush GC method provided analysis for both diesel and biodiesel, in a shorter time and with lower detection limit. Thus all lube oil dilution results in this paper are based on this method. Analysis of the HD lube-oil samples showed only 1.5% to 1.6% fuel dilution for both fuels during continuous

  19. A comparative study of zwitterionic ligands-mediated mineralization and the potential of mineralized zwitterionic matrices for bone tissue engineering

    PubMed Central

    Liu, Pingsheng; Emmons, Erin

    2014-01-01

    Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering. PMID:25558374

  20. Epidermal stem cells and skin tissue engineering in hair follicle regeneration.

    PubMed

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-05-26

    The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge still pending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide three-dimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This

  1. Epidermal stem cells and skin tissue engineering in hair follicle regeneration

    PubMed Central

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-01-01

    The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge still pending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients’ psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide three-dimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This

  2. Epidermal stem cells and skin tissue engineering in hair follicle regeneration.

    PubMed

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-05-26

    The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge still pending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide three-dimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This

  3. Fetal and adult fibroblasts display intrinsic differences in tendon tissue engineering and regeneration

    PubMed Central

    Tang, Qiao-Mei; Chen, Jia Lin; Shen, Wei Liang; Yin, Zi; Liu, Huan Huan; Fang, Zhi; Heng, Boon Chin; Ouyang, Hong Wei; Chen, Xiao

    2014-01-01

    Injured adult tendons do not exhibit optimal healing through a regenerative process, whereas fetal tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered tendons. Our results demonstrated that FFs had more potential for tendon tissue engineering, as shown by higher levels of tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult tendon healing. This may assist in the development of future strategies to treat tendon injuries. PMID:24992450

  4. Fetal and adult fibroblasts display intrinsic differences in tendon tissue engineering and regeneration.

    PubMed

    Tang, Qiao-Mei; Chen, Jia Lin; Shen, Wei Liang; Yin, Zi; Liu, Huan Huan; Fang, Zhi; Heng, Boon Chin; Ouyang, Hong Wei; Chen, Xiao

    2014-07-03

    Injured adult tendons do not exhibit optimal healing through a regenerative process, whereas fetal tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered tendons. Our results demonstrated that FFs had more potential for tendon tissue engineering, as shown by higher levels of tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult tendon healing. This may assist in the development of future strategies to treat tendon injuries.

  5. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

    NASA Astrophysics Data System (ADS)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

  6. Liver regeneration.

    PubMed

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  7. Liver Regeneration

    PubMed Central

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-01-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review will provide an overview of the models of study currently utilized in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus will be placed on clinical applications of current knowledge in liver regeneration including small for size liver transplant. Furthermore, cutting edge topics in liver regeneration including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a three dimensional scaffold for liver repopulation will be proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration. PMID:24495569

  8. Fractals in tissue engineering: toward biomimetic cell-culture matrices, microsystems and microstructured implants.

    PubMed

    Díaz Lantada, Andrés; Pareja Sánchez, Beatriz; Gómez Murillo, Cristina; Urbieta Sotillo, Javier

    2013-09-01

    Tissue engineering is a rapidly evolving field in which the complexity of biomaterials and biostructures, with typically non-Euclidean or fractal-like geometries, has to be adequately taken into account for the promotion of enhanced and even personalized diagnostic and therapeutic solutions. This study covers the main applications of fractals in the field of tissue engineering, including their advantages for modeling biological processes and cell-culture procedures, but specially focusing on their benefits for describing the complex geometries and structures of biomaterials (both natural and synthetic), many of which have potential uses for the development of cell culture microsystems, scaffolds for tissue repair and implants for tissue repair in general. We also explore the main supporting design, simulation and manufacturing technologies, as well as the most remarkable difficulties and limitations linked to the generalized use of fractals in engineering design, and also detail some current solution proposals and future directions.

  9. Calculating linear A, B, C, and D matrices from a nonlinear dynamic engine simulation

    NASA Technical Reports Server (NTRS)

    Geyser, L. C.

    1981-01-01

    Digital program DYGABCD generates linear state-space models for simulating turbofan and turbojet engines over complete range of power settings and flight conditions. Program is written in FORTRAN IV for batch execution and is implemented on IBM 360-series computer.

  10. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration.

    PubMed

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-01-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed "lock and key" moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use. PMID:27572698

  11. Fatigue failure of regenerator screens in a high frequency Stirling engine

    NASA Technical Reports Server (NTRS)

    Hull, David R.; Alger, Donald L.; Moore, Thomas J.; Scheuermann, Coulson M.

    1988-01-01

    Failure of Stirling Space Power Demonstrator Engine (SPDE) regenerator screens was investigated. After several hours of operation the SPDE was shut down for inspection and on removing the regenator screens, debris of unknown origin was discovered along with considerable cracking of the screens in localized areas. Metallurgical analysis of the debris determined it to be cracked-off-deformed pieces of the 41 micron thickness Type 304 stainless steel wire screen. Scanning electron microscopy of the cracked screens revealed failures occurring at wire crossovers and fatigue striations on the fracture surface of the wires. Thus, the screen failure can be characterized as a fatigue failure of the wires. The crossovers were determined to contain 30 percent reduction in wire thickness and a highly worked microstructure occurring from the manufacturing process of the wire screens. Later it was found that reduction in wire thickness occurred because the screen fabricator had subjected it to a light cold-roll process after weaving. Installation of this screen left a clearance in the regenerator allowing the screens to move. The combined effects of the reduction in wire thickness, stress concentration (caused by screen movement), and highly worked microstructure at the wire crossovers led to the fatigue failure of the screens.

  12. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

    PubMed Central

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-01-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use. PMID:27572698

  13. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration.

    PubMed

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-01-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed "lock and key" moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use.

  14. Advances and Prospects in Tissue-Engineered Meniscal Scaffolds for Meniscus Regeneration

    PubMed Central

    Guo, Weimin; Liu, Shuyun; Zhu, Yun; Yu, Changlong; Lu, Shibi; Yuan, Mei; Gao, Yue; Huang, Jingxiang; Yuan, Zhiguo; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Chen, Jifeng; Zhang, Li; Sui, Xiang; Xu, Wenjing; Guo, Quanyi

    2015-01-01

    The meniscus plays a crucial role in maintaining knee joint homoeostasis. Meniscal lesions are relatively common in the knee joint and are typically categorized into various types. However, it is difficult for inner avascular meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal extrusions in the long-term and gradually trigger the development of knee osteoarthritis (OA). The relationship between meniscal lesions and knee OA is complex. Partial meniscectomy, which is the primary method to treat a meniscal injury, only relieves short-term pain; however, it does not prevent the development of knee OA. Similarly, other current therapeutic strategies have intrinsic limitations in clinical practice. Tissue engineering technology will probably address this challenge by reconstructing a meniscus possessing an integrated configuration with competent biomechanical capacity. This review describes normal structure and biomechanical characteristics of the meniscus, discusses the relationship between meniscal lesions and knee OA, and summarizes the classifications and corresponding treatment strategies for meniscal lesions to understand meniscal regeneration from physiological and pathological perspectives. Last, we present current advances in meniscal scaffolds and provide a number of prospects that will potentially benefit the development of meniscal regeneration methods. PMID:26199629

  15. CFD modeling and experimental verification of a single-stage coaxial Stirling-type pulse tube cryocooler without either double-inlet or multi-bypass operating at 30-35 K using mixed stainless steel mesh regenerator matrices

    NASA Astrophysics Data System (ADS)

    Dang, Haizheng; Zhao, Yibo

    2016-09-01

    This paper presents the CFD modeling and experimental verifications of a single-stage inertance tube coaxial Stirling-type pulse tube cryocooler operating at 30-35 K using mixed stainless steel mesh regenerator matrices without either double-inlet or multi-bypass. A two-dimensional axis-symmetric CFD model with the thermal non-equilibrium mode is developed to simulate the internal process, and the underlying mechanism of significantly reducing the regenerator losses with mixed matrices is discussed in detail based on the given six cases. The modeling also indicates that the combination of the given different mesh segments can be optimized to achieve the highest cooling efficiency or the largest exergy ratio, and then the verification experiments are conducted in which the satisfactory agreements between simulated and tested results are observed. The experiments achieve a no-load temperature of 27.2 K and the cooling power of 0.78 W at 35 K, or 0.29 W at 30 K, with an input electric power of 220 W and a reject temperature of 300 K.

  16. New Directions in Nanofibrous Scaffolds for Soft Tissue Engineering and Regeneration

    PubMed Central

    Baker, Brendon M.; Handorf, Andrew M.; Ionescu, Lara C.; Li, Wan-Ju; Mauck, Robert L.

    2010-01-01

    This review focuses on the role of nano-structure and nano-scale materials for tissue engineering applications. We detail a scaffold production method (electrospinning) for the production of nanofiber-based scaffolds that can approximate many critical features of the normal cellular microenvironment, and so foster and direct tissue formation. Further, we describe new and emerging methods to increase the applicability of these scaffolds for in vitro and in vivo application. This discussion includes a focus on methods to further functionalize scaffolds to promote cell infiltration, methods to tune scaffold mechanics to meet in vivo demands, and methods to control the release of pharmaceuticals and other biologic agents to modulate the wound environment and foster tissue regeneration. This review provides a perspective in the state-of-the-art of the production, application, and functionalization of these unique nanofibrous structures, and outlines future directions in this growing field. PMID:19751124

  17. Jet Penetration into a Scaled Microfabricated Stirling Cycle Regenerator

    NASA Technical Reports Server (NTRS)

    Sun, Liyong; Simon, Terrence W.; Mantell, Susan; Ibrahim, Mournir; Gedeon, David; Tew, Roy

    2008-01-01

    The cooler and heater adjacent to the regenerator of a Stirling cycle engine have tubes or channels which form jets that pass into the regenerator while diffusing within the matrix. An inactive part of the matrix, beyond the cores of these jets, does not participate fully in the heat transfer between the flow of working fluid and the regenerator matrix material, weakening the regenerator s ability to exchange heat with the working fluid. The objective of the present program is to document this effect on the performance of the regenerator and to develop a model for generalizing the results. However, the small scales of actual Stirling regenerator matrices (on the order of tens of microns) make direct measurements of this effect very difficult. As a result, jet spreading within a regenerator matrix has not been characterized well and is poorly understood. Also, modeling is lacking experimental verification. To address this, a large-scale mockup of thirty times actual scale was constructed and operated under conditions that are dynamically similar to the engine operation. Jet penetration with round jets and slot jets into the microfabricated regenerator geometry are then measured by conventional means. The results are compared with those from a study of spreading of round jets within woven screen regenerator for further documentation of the comparative performance of the microfabricated regenerator geometry.

  18. Tissue Engineered Scaffolds for an Effective Healing and Regeneration: Reviewing Orthotopic Studies

    PubMed Central

    2014-01-01

    It is commonly stated that tissue engineering is the most promising approach to treat or replace failing tissues/organs. For this aim, a specific strategy should be planned including proper selection of biomaterials, fabrication techniques, cell lines, and signaling cues. A great effort has been pursued to develop suitable scaffolds for the restoration of a variety of tissues and a huge number of protocols ranging from in vitro to in vivo studies, the latter further differentiating into several procedures depending on the type of implantation (i.e., subcutaneous or orthotopic) and the model adopted (i.e., animal or human), have been developed. All together, the published reports demonstrate that the proposed tissue engineering approaches spread toward multiple directions. The critical review of this scenario might suggest, at the same time, that a limited number of studies gave a real improvement to the field, especially referring to in vivo investigations. In this regard, the present paper aims to review the results of in vivo tissue engineering experimentations, focusing on the role of the scaffold and its specificity with respect to the tissue to be regenerated, in order to verify whether an extracellular matrix-like device, as usually stated, could promote an expected positive outcome. PMID:25250319

  19. [Application of silk-based tissue engineering scaffold for tendon / ligament regeneration].

    PubMed

    Hu, Yejun; Le, Huihui; Jin, Zhangchu; Chen, Xiao; Yin, Zi; Shen, Weiliang; Ouyang, Hongwei

    2016-03-01

    Tendon/ligament injury is one of the most common impairments in sports medicine. The traditional treatments of damaged tissue repair are unsatisfactory, especially for athletes, due to lack of donor and immune rejection. The strategy of tissue engineering may break through these limitations, and bring new hopes to tendon/ligament repair, even regeneration. Silk is a kind of natural biomaterials, which has good biocompatibility, wide range of mechanical properties and tunable physical structures; so it could be applied as tendon/ligament tissue engineering scaffolds. The silk-based scaffold has robust mechanical properties; combined with other biological ingredients, it could increase the surface area, promote more cell adhesion and improve the biocompatibility. The potential clinical application of silk-based scaffold has been confirmed by in vivo studies on tendon/ligament repairing, such as anterior cruciate ligament, medial collateral ligament, achilles tendon and rotator cuff. To develop novel biomechanically stable and host integrated tissue engineered tendon/ligament needs more further micro and macro studies, combined with product development and clinical application, which will give new hope to patients with tendon/ligament injury.

  20. Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

    PubMed

    Boominathan, Vijay P; Ferreira, Tracie L

    2012-12-01

    Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise. PMID:23244692

  1. Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

    PubMed

    Boominathan, Vijay P; Ferreira, Tracie L

    2012-12-01

    Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise.

  2. Synthetic Bone Substitute Engineered with Amniotic Epithelial Cells Enhances Bone Regeneration after Maxillary Sinus Augmentation

    PubMed Central

    Barboni, Barbara; Mangano, Carlo; Valbonetti, Luca; Marruchella, Giuseppe; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mauro, Annunziata; Bedini, Rossella; Turriani, Maura; Pecci, Raffaella; Nardinocchi, Delia; Zizzari, Vincenzo Luca; Tetè, Stefano; Piattelli, Adriano; Mattioli, Mauro

    2013-01-01

    Background Evidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined. Aim In the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC), loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT) technique, was evaluated in an animal study. Material And Methods Two blocks of synthetic bone substitute (∼0.14 cm3), alone or engineered with 1×106 ovine AEC (oAEC), were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.). Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT), morphological, morphometric and biochemical analyses. Results And Conclusions The obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation), data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their ability to switch

  3. Controlled growth factor release from synthetic extracellular matrices

    NASA Astrophysics Data System (ADS)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  4. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    PubMed

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

  5. Tissue engineering chamber promotes adipose tissue regeneration in adipose tissue engineering models through induced aseptic inflammation.

    PubMed

    Peng, Zhangsong; Dong, Ziqing; Chang, Qiang; Zhan, Weiqing; Zeng, Zhaowei; Zhang, Shengchang; Lu, Feng

    2014-11-01

    Tissue engineering chamber (TEC) makes it possible to generate significant amounts of mature, vascularized, stable, and transferable adipose tissue. However, little is known about the role of the chamber in tissue engineering. Therefore, to investigate the role of inflammatory response and the change in mechanotransduction started by TEC after implantation, we placed a unique TEC model on the surface of the groin fat pads in rats to study the expression of cytokines and tissue development in the TEC. The number of infiltrating cells was counted, and vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) expression levels in the chamber at multiple time points postimplantation were analyzed by enzyme-linked immunosorbent assay. Tissue samples were collected at various time points and labeled for specific cell populations. The result showed that new adipose tissue formed in the chamber at day 60. Also, the expression of MCP-1 and VEGF in the chamber decreased slightly from an early stage as well as the number of the infiltrating cells. A large number of CD34+/perilipin- perivascular cells could be detected at day 30. Also, the CD34+/perilipin+ adipose precursor cell numbers increased sharply by day 45 and then decreased by day 60. CD34-/perilipin+ mature adipocytes were hard to detect in the chamber content at day 30, but their number increased and then peaked at day 60. Ki67-positive cells could be found near blood vessels and their number decreased sharply over time. Masson's trichrome showed that collagen was the dominant component of the chamber content at early stage and was replaced by newly formed small adipocytes over time. Our findings suggested that the TEC implantation could promote the proliferation of adipose precursor cells derived from local adipose tissue, increase angiogenesis, and finally lead to spontaneous adipogenesis by inducing aseptic inflammation and changing local mechanotransduction.

  6. Experimental study on filtration and continuous regeneration of a particulate filter system for heavy-duty diesel engines.

    PubMed

    Tang, Tao; Zhang, Jun; Cao, Dongxiao; Shuai, Shijin; Zhao, Yanguang

    2014-12-01

    This study investigated the filtration and continuous regeneration of a particulate filter system on an engine test bench, consisting of a diesel oxidation catalyst (DOC) and a catalyzed diesel particulate filter (CDPF). Both the DOC and the CDPF led to a high conversion of NO to NO2 for continuous regeneration. The filtration efficiency on solid particle number (SPN) was close to 100%. The post-CDPF particles were mainly in accumulation mode. The downstream SPN was sensitively influenced by the variation of the soot loading. This phenomenon provides a method for determining the balance point temperature by measuring the trend of SPN concentration.

  7. Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration.

    PubMed

    Emmert, Maximilian Y; Hitchcock, Robert W; Hoerstrup, Simon P

    2014-04-01

    Ischemic Heart Disease (IHD) still represents the "Number One Killer" worldwide accounting for the death of numerous patients. However the capacity for self-regeneration of the adult heart is very limited and the loss of cardiomyocytes in the infarcted heart leads to continuous adverse cardiac-remodeling which often leads to heart-failure (HF). The concept of regenerative medicine comprising cell-based therapies, bio-engineering technologies and hybrid solutions has been proposed as a promising next-generation approach to address IHD and HF. Numerous strategies are under investigation evaluating the potential of regenerative medicine on the failing myocardium including classical cell-therapy concepts, three-dimensional culture techniques and tissue-engineering approaches. While most of these regenerative strategies have shown great potential in experimental studies, the translation into a clinical setting has either been limited or too rapid leaving many key questions unanswered. This review summarizes the current state-of-the-art, important challenges and future research directions as to regenerative approaches addressing IHD and resulting HF.

  8. Characterization of Decellularized Heart Matrices as Biomaterials for Regular and Whole Organ Tissue Engineering and Initial In-vitro Recellularization with Ips Cells

    PubMed Central

    Carvalho, Juliana L; de Carvalho, Pablo Herthel; Gomes, Dawidson A; Goes, Alfredo M

    2013-01-01

    Tissue engineering strategies, based on solid/porous scaffolds, suffer from several limitations, such as ineffective vascularization, poor cell distribution and organization within scaffold, in addition to low final cell density, among others. Therefore, the search for other tissue engineering approaches constitutes an active area of investigation. Decellularized matrices (DM) present major advantages compared to solid scaffolds, such as ideal chemical composition, the preservation of vascularization structure and perfect three-dimensional structure. In the present study, we aimed to characterize and investigate murine heart decellularized matrices as biomaterials for regular and whole organ tissue engineering. Heart decellularized matrices were characterized according to: 1. DNA content, through DNA quantificationo and PCR of isolated genomic DNA; 2. Histological structure, assessed after Hematoxylin and Eosin, as well as Masson’s Trichrome stainings; 3. Surface nanostructure analysis, performed, using SEM. Those essays allowed us to conclude that DM was indeed decellularized, with preserved extracellular matrix structure. Following characterization, decellularized heart slices were seeded with induced Pluripotent Stem cells (iPS). As expected, but – to the best of our knowledge - never shown before, decellularization of murine heart matrices maintained matrix biocompatibility, as iPS cells rapidly attached to the surface of the material and proliferated. Strikingly though, heart DM presented a differentiation induction effect over those cells, which lost their pluripotency markers after 7 days of culture in the DM. Such loss of differentiation markers was observed, even though bFGF containing media mTSR was used during such period. Gene expression of iPS cells cultured on DM will be further analyzed, in order to assess the effects of culturing pluripotent stem cells in decellularized heart matrices. PMID:26207188

  9. Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation

    PubMed Central

    Tan, S.J.; Fang, J.Y.; Wu, Y.; Yang, Z.; Liang, G.; Han, B.

    2015-01-01

    Efficiency of cell-based tissue engineering and regenerative medicine has been limited by inadequate cellular responses to injury because of aging and poor controllability of cellular interactions. Since cell progression is under a tight epigenetic regulation, epigenetic modulators such as 5-azacytidine (5-Aza-CR) have been utilized to facilitate reprogramming and development of somatic cells in 2-dimensional (2-D) settings. Nonetheless, progression of a specific tissue lineage toward the terminal phenotype is dependent not only on the genomic potential, but also on the microenvironment cues that are beyond the capability of 2-D approaches. In this study, we investigated the combined effects of matrices of variable rigidities and the treatment with the epigenetic modulator 5-Aza-CR on reprogramming adipose-derived stromal cells (ADSCs) into myoblast-like cells by utilizing tunable transglutaminase cross-linked gelatin (Col-Tgel) in vitro and in vivo. Our experiments demonstrated that cellular plasticity and trans-differentiation were significantly enhanced when ADSCs were treated with an effective dose of 5-Aza-CR (1.25 to 12.5 ng) in the optimal myogenic matrix (15 ± 5 kPa Col-Tgel). Our findings suggest that both physical signals and chemical milieu are critical for the regulation of cellular responses. PMID:26548559

  10. Targeting the hypoxic response in bone tissue engineering: A balance between supply and consumption to improve bone regeneration.

    PubMed

    Stiers, Pieter-Jan; van Gastel, Nick; Carmeliet, Geert

    2016-09-01

    Bone tissue engineering is a promising therapeutic alternative for bone grafting of large skeletal defects. It generally comprises an ex vivo engineered combination of a carrier structure, stem/progenitor cells and growth factors. However, the success of these regenerative implants largely depends on how well implanted cells will adapt to the hostile and hypoxic host environment they encounter after implantation. In this review, we will discuss how hypoxia signalling may be used to improve bone regeneration in a tissue-engineered construct. First, hypoxia signalling induces angiogenesis which increases the survival of the implanted cells as well as stimulates bone formation. Second, hypoxia signalling has also angiogenesis-independent effects on mesenchymal cells in vitro, offering exciting new possibilities to improve tissue-engineered bone regeneration in vivo. In addition, studies in other fields have shown that benefits of modulating hypoxia signalling include enhanced cell survival, proliferation and differentiation, culminating in a more potent regenerative implant. Finally, the stimulation of endochondral bone formation as a physiological pathway to circumvent the harmful effects of hypoxia will be briefly touched upon. Thus, angiogenic dependent and independent processes may counteract the deleterious hypoxic effects and we will discuss several therapeutic strategies that may be combined to withstand the hypoxia upon implantation and improve bone regeneration. PMID:26768117

  11. Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration.

    PubMed

    Mardones, Rodrigo; Jofré, Claudio M; Minguell, José J

    2015-05-01

    Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an 'in situ' cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed. PMID:26019754

  12. Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration

    PubMed Central

    Mardones, Rodrigo; Jofré, Claudio M.; Minguell, José J.

    2015-01-01

    Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an ‘in situ’ cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed. PMID:26019754

  13. Engineering of cofactor regeneration enhances (2S,3S)-2,3-butanediol production from diacetyl

    PubMed Central

    Wang, Yu; Li, Lixiang; Ma, Cuiqing; Gao, Chao; Tao, Fei; Xu, Ping

    2013-01-01

    (2S,3S)-2,3-Butanediol ((2S,3S)-2,3-BD) is a potentially valuable liquid fuel and an excellent building block in asymmetric synthesis. In this study, cofactor engineering was applied to improve the efficiency of (2S,3S)-2,3-BD production and simplify the product purification. Two NADH regeneration enzymes, glucose dehydrogenase and formate dehydrogenase (FDH), were introduced into Escherichia coli with 2,3-BD dehydrogenase, respectively. Introduction of FDH resulted in higher (2S,3S)-2,3-BD concentration, productivity and yield from diacetyl, and large increase in the intracellular NADH concentration. In fed-batch bioconversion, the final titer, productivity and yield of (2S,3S)-2,3-BD on diacetyl reached 31.7 g/L, 2.3 g/(L·h) and 89.8%, the highest level of (2S,3S)-2,3-BD production thus far. Moreover, cosubstrate formate was almost totally converted to carbon dioxide and no organic acids were produced. The biocatalytic process presented should be a promising route for biotechnological production of NADH-dependent microbial metabolites. PMID:24025762

  14. Tissue-engineered nerve constructs under a microgravity system for peripheral nerve regeneration.

    PubMed

    Luo, Hailang; Zhu, Bin; Zhang, Yongjie; Jin, Yan

    2015-01-01

    Mesenchymal stem cells (MSCs) seeded in a 3D scaffold often present characteristics of low proliferation and migration, which affect the microstructure of tissue-engineered nerves (TENs) and impair the therapeutic effects of nerve defects. By promoting MSC differentiation and mass/nutrient transport, rotary cell culture systems (RCCSs) display potential for advancing the construction of MSC-based TENs. Thus, in this study, we attempted to construct a TEN composed of adipose-derived mesenchymal stem cells (ADSCs) and acellular nerve graft (ANG) utilizing an RCCS. Compared to TENs prepared in a static 3D approach, MTT and cell count results displayed an increased number of ADSCs for TENs in an RCCS. The similarity in cell cycle states and high rates of apoptosis in the static 3D culture demonstrated that the higher proliferation in the RCCS was not due to microgravity regulation but a result of preferential mass/nutrient transport. Quantitative PCR and ELISA indicated that the RCCS promoted the expression of ADSC neural differentiation-associated genes compared to the static 3D culture. Furthermore, this difference was eliminated by adding the Notch1 signaling pathway inhibitor DAPT to the 3D static culture. TEM, axon immunostaining, and retrograde labeling analysis after sciatic nerve transplantation indicated that the TENs prepared in the RCCS exhibited more regenerative characteristics for repairing peripheral nerves than those prepared in a static 3D approach. Therefore, these findings suggest that the RCCS can modulate the construction, morphology, and function of engineered nerves as a promising alternative for nerve regeneration. PMID:25088840

  15. Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

    PubMed Central

    Fukahori, Mioko; Chitose, Shun-ichi; Sato, Kiminori; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito; Monden, Yu; Yamakawa, Ryoji

    2016-01-01

    Objectives Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. Study Design Animal experiment using eight beagles (including three controls). Methods A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. Results A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. Conclusion The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds. PMID:26730600

  16. Therapeutic strategy for hair regeneration: Hair cycle activation, niche environment modulation, wound-induced follicle neogenesis and stem cell engineering

    PubMed Central

    Chueh, Shan-Chang; Lin, Sung-Jan; Chen, Chih-Chiang; Lei, Mingxing; Wang, Ling Mei; Widelitz, Randall B.; Hughes, Michael W.; Jiang, Ting-Xing; Chuong, Cheng Ming

    2013-01-01

    Introduction There are major new advancements in the fields of stem cell biology, developmental biology, regenerative hair cycling, and tissue engineering. The time is ripe to integrate, translate and apply these findings to tissue engineering and regenerative medicine. Readers will learn about new progress in cellular and molecular aspects of hair follicle development, regeneration and potential therapeutic opportunities these advances may offer. Areas covered Here we use hair follicle formation to illustrate this progress and to identify targets for potential strategies in therapeutics. Hair regeneration is discussed in four different categories. (1) Intra-follicle regeneration (or renewal) is the basic production of hair fibers from hair stem cells and dermal papillae in existing follicles. (2) Chimeric follicles via epithelial-mesenchymal recombination to identify stem cells and signaling centers. (3) Extra-follicular factors including local dermal and systemic factors can modulate the regenerative behavior of hair follicles, and may be relatively easy therapeutic targets. (4) Follicular neogenesis means the de novo formation of new follicles. In addition, scientists are working to engineer hair follicles, which require hair forming competent epidermal cells and hair inducing dermal cells. Expert opinion Ideally self-organizing processes similar to those occurring during embryonic development should be elicited with some help from biomaterials. PMID:23289545

  17. Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

    PubMed

    Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

    2015-12-01

    In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering.

  18. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone

    PubMed Central

    Muzzarelli, Riccardo A. A.; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-01-01

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience. PMID:26690453

  19. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone.

    PubMed

    Muzzarelli, Riccardo A A; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-12-11

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010-2015 have met the expectations of an interdisciplinary audience.

  20. Stability of engineered nanomaterials in complex aqueous matrices: Settling behaviour of CeO2 nanoparticles in natural surface waters.

    PubMed

    Van Koetsem, Frederik; Verstraete, Simon; Van der Meeren, Paul; Du Laing, Gijs

    2015-10-01

    The stability of engineered nanoparticles (ENPs) in complex aqueous matrices is a key determinant of their fate and potential toxicity towards the aquatic environment and human health. Metal oxide nanoparticles, such as CeO2 ENPs, are increasingly being incorporated into a wide range of industrial and commercial applications, which will undoubtedly result in their (unintentional) release into the environment. Hereby, the behaviour and fate of CeO2 ENPs could potentially serve as model for other nanoparticles that possess similar characteristics. The present study examined the stability and settling of CeO2 ENPs (7.3±1.4 nm) as well as Ce(3+) ions in 10 distinct natural surface waters during 7d, under stagnant and isothermal experimental conditions. Natural water samples were collected throughout Flanders (Belgium) and were thoroughly characterized. For the majority of the surface waters, a substantial depletion (>95%) of the initially added CeO2 ENPs was observed just below the liquid surface of the water samples after 7d. In all cases, the reduction was considerably higher for CeO2 ENPs than for Ce(3+) ions (<68%). A first-order kinetics model was able to describe the observed time-dependant removal of both CeO2 ENPs (R(2)≥0.998) and Ce(3+) ions (R(2)≥0.812) from the water column, at least in case notable sedimentation occurred over time. Solution-pH appeared to be a prime parameter governing nanoparticle colloidal stability. Moreover, the suspended solids (TSS) content also seemed to be an important factor affecting the settling rate and residual fraction of CeO2 ENPs as well as Ce(3+) ions in natural surface waters. Correlation results also suggest potential association and co-precipitation of CeO2 ENPs with aluminium- and iron-containing natural colloidal material. The CeO2 ENPs remained stable in dispersion in surface water characterized by a low pH, ionic strength (IS), and TSS content, indicating the eventual stability and settling behaviour of the

  1. Collagen for bone tissue regeneration.

    PubMed

    Ferreira, Ana Marina; Gentile, Piergiorgio; Chiono, Valeria; Ciardelli, Gianluca

    2012-09-01

    In the last decades, increased knowledge about the organization, structure and properties of collagen (particularly concerning interactions between cells and collagen-based materials) has inspired scientists and engineers to design innovative collagen-based biomaterials and to develop novel tissue-engineering products. The design of resorbable collagen-based medical implants requires understanding the tissue/organ anatomy and biological function as well as the role of collagen's physicochemical properties and structure in tissue/organ regeneration. Bone is a complex tissue that plays a critical role in diverse metabolic processes mediated by calcium delivery as well as in hematopoiesis whilst maintaining skeleton strength. A wide variety of collagen-based scaffolds have been proposed for different tissue engineering applications. These scaffolds are designed to promote a biological response, such as cell interaction, and to work as artificial biomimetic extracellular matrices that guide tissue regeneration. This paper critically reviews the current understanding of the complex hierarchical structure and properties of native collagen molecules, and describes the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of innovative techniques for scaffold and material manufacturing that are currently opening the way to the preparation of biomimetic substrates that modulate cell interaction for improved substitution, restoration, retention or enhancement of bone tissue function. PMID:22705634

  2. A tissue engineering approach to anterior cruciate ligament regeneration using novel shaped capillary channel polymer fibers

    NASA Astrophysics Data System (ADS)

    Sinclair, Kristofer D.

    2009-12-01

    Ruptures of the anterior cruciate ligament (ACL) are the most frequent of injuries to the knee due to its role in preventing anterior translation of the tibia. It is estimated that as many as 200,000 Americans per year will suffer from a ruptured ACL, resulting in management costs on the order of 5 billion dollars. Without treatment these patients are unable to return to normal activity, as a consequence of the joint instability found within the ACL deficient knee. Over the last thirty years, a variety of non-degradable, synthetic fibers have been evaluated for their use in ACL reconstruction; however, a widely accepted prosthesis has been unattainable due to differences in mechanical properties of the synthetic graft relative to the native tissue. Tissue engineering is an interdisciplinary field charged with the task of developing therapeutic solutions for tissue and organ failure by enhancing the natural wound healing process through the use of cellular transplants, biomaterials, and the delivery of bioactive molecules. The capillary channel polymer (CC-P) fibers used in this research were fabricated by melt extrusion from polyethylene terephthalate and polybutylene terephthalate. These fibers possess aligned micrometer scale surface channels that may serve as physical templates for tissue growth and regeneration. This inherent surface topography offers a unique and industrially viable approach for cellular contact guidance on three dimensional constructs. In this fundamental research the ability of these fiber channels to support the adhesion, alignment, and organization of fibroblasts was demonstrated and found to be superior to round fiber controls. The results demonstrated greater uniformity of seeding and accelerated formation of multi-layered three-dimensional biomass for the CC-P fibers relative to those with a circular cross-section. Furthermore, the CC-P geometry induced nuclear elongation consistent with that observed in native ACL tissue. Through the

  3. Analysis of regenerated single-shaft ceramic gas-turbine engines and resulting fuel economy in a compact car

    NASA Technical Reports Server (NTRS)

    Klann, J. L.; Tew, R. C., Jr.

    1977-01-01

    Ranges in design and off-design operating conditions of an advanced gas turbine and their effects on fuel economy were analyzed. The assumed engine incorporated a single stage radial flow turbine and compressor with fixed geometry. Fuel economies were calculated over the composite driving cycle with gasoline as the fuel. At a constant turbine-inlet temperature, with a regenerator sized for a full power effectiveness the best fuel economies ranged from 11.1 to 10.2 km/liter (26.2 to 22.5 mpg) for full power turbine tip speeds of 770 to 488m/sec (2530 to 1600ft/sec), respectively.

  4. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

    PubMed

    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  5. Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering☆

    PubMed Central

    Moioli, Eduardo K.; Clark, Paul A.; Xin, Xuejun; Lal, Shan; Mao, Jeremy J.

    2010-01-01

    Current treatments for diseases and trauma of dental, oral and craniofacial (DOC) structures rely on durable materials such as amalgam and synthetic materials, or autologous tissue grafts. A paradigm shift has taken place to utilize tissue engineering and drug delivery approaches towards the regeneration of these structures. Several prototypes of DOC structures have been regenerated such as temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and periodontium components. However, many challenges remain when taking in consideration the high demand for esthetics of DOC structures, the complex environment and yet minimal scar formation in the oral cavity, and the need for accommodating multiple tissue phenotypes. This review highlights recent advances in the regeneration of DOC structures, including the tooth, periodontium, TMJ, cranial sutures and implant dentistry, with specific emphasis on controlled release of signaling cues for stem cells, biomaterial matrices and scaffolds, and integrated tissue engineering approaches. PMID:17499385

  6. An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair.

    PubMed

    Tajdaran, Kasra; Gordon, Tessa; Wood, Mathew D; Shoichet, Molly S; Borschel, Gregory H

    2016-02-01

    Localized drug delivery strategies could greatly benefit patients with peripheral nerve injury and could be easy for surgeons to implement. We developed a local drug delivery system (DDS) using drug-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) embedded in a fibrin gel. In an in vitro study, we investigated the biocompatibility of this DDS by performing a toxicity assay in which we incubated PC-12 cells with the medium released from the DDS in vitro. In an in vivo study, this DDS was applied at the rat common peroneal (CP) nerve injury site to deliver exogenous glial cell line-derived neurotrophic factor (GDNF) to the regenerating axons after delayed nerve repair. In vitro, PC-12 cells incubated with released media samples from the DDS had similar viability to control cells cultured with normal media, demonstrating that the DDS was not toxic. In vivo, the numbers of motor and sensory neurons that regenerated their axons with empty MS treatment were the same as when there was no MS treatment. The DDS increased the numbers of regenerating motor- and sensory neurons to levels indistinguishable from those observed with immediate nerve repair. The DDS increased neuron regeneration to levels double those observed with negative control groups. This biocompatible, nontoxic, fibrin gel-based DDS enhances outcomes following severe peripheral nerve injuries.

  7. Tissue Engineering and Cellular Regeneration at NASA Report to Regenetech SAB

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.

    2004-01-01

    A project overview describing three dimensional tissue models is shown. The topics include: 1) cellular regeneration; 2) haemopoietic replacement; 3) novel vaccine development; 4) pharmacology and toxicology interventions; 5) development of synthetic viruses; and 6) molecular genetics and proteomics of recapitulated models.

  8. Glottic Regeneration with Tissue Engineering Technique Using Acellular Extracellular Matrix Scaffold in Canine Model

    PubMed Central

    Kitamura, Morimasa; Hirano, Shigeru; Kanemaru, Shin-ichi; Kitani, Yoshiharu; Ohno, Satoshi; Kojima, Tsuyoshi; Nakamura, Tatsuo; Ito, Juichi; Rosen, Clark A.; Gilbert, Thomas W.

    2014-01-01

    Acellular extracellular matrix scaffold derived from porcine urinary bladder (UBM) is decellularized material that has shown success for constructive remodeling of various tissues and organs. The regenerative effects of UBM were reported for the tympanic membrane, esophagus, trachea, larynx, pleura, and pericardium in animal studies with promising results. The aim of this study was to investigate regenerative effects of UBM to regenerate hemilarynx using a canine model. A left partial hemilaryngectomy was performed, and the surgical defects were reconstructed by insertion of UBM scaffold. Although local infection was observed in one dog in a week after implantation of the scaffold, all dogs showed good re-epithelialization with minimum complication in one month. The effect of regeneration of the larynx was evaluated 6 months after the operation. The excised larynx experiments were performed to measure phonation threshold pressure (PTP), normalized mucosal wave amplitude (NMWA), and normalized glottal gap (NGG). The results of the measurements showed that PTP was normal or near normal in 2 cases, NMWA was within normal range in 3 cases, although there were individual variations. Histologic examination was completed to evaluate structural changes of the scaffold with appearance of new cartilaginous structure. However the regenerated vocal fold mucosa is mostly scarred. The UBM scaffold has shown to be biocompatible, biodegradable, and useful for tissue regeneration of the hemilarynx with possible restoration of the vocal fold function. The vocal fold mucosa was scarred, which is the next challenge to improve. PMID:24403099

  9. Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration.

    PubMed

    Masumoto, Hidetoshi; Ikuno, Takeshi; Takeda, Masafumi; Fukushima, Hiroyuki; Marui, Akira; Katayama, Shiori; Shimizu, Tatsuya; Ikeda, Tadashi; Okano, Teruo; Sakata, Ryuzo; Yamashita, Jun K

    2014-01-01

    To realize cardiac regeneration using human induced pluripotent stem cells (hiPSCs), strategies for cell preparation, tissue engineering and transplantation must be explored. Here we report a new protocol for the simultaneous induction of cardiomyocytes (CMs) and vascular cells [endothelial cells (ECs)/vascular mural cells (MCs)], and generate entirely hiPSC-engineered cardiovascular cell sheets, which showed advantageous therapeutic effects in infarcted hearts. The protocol adds to a previous differentiation protocol of CMs by using stage-specific supplementation of vascular endothelial cell growth factor for the additional induction of vascular cells. Using this cell sheet technology, we successfully generated physically integrated cardiac tissue sheets (hiPSC-CTSs). HiPSC-CTS transplantation to rat infarcted hearts significantly improved cardiac function. In addition to neovascularization, we confirmed that engrafted human cells mainly consisted of CMs in >40% of transplanted rats four weeks after transplantation. Thus, our HiPSC-CTSs show promise for cardiac regenerative therapy.

  10. BMP2 Genetically Engineered MSCs and EPCs Promote Vascularized Bone Regeneration in Rat Critical-Sized Calvarial Bone Defects

    PubMed Central

    He, Xiaoning; Dziak, Rosemary; Yuan, Xue; Mao, Keya; Genco, Robert; Swihart, Mark; Sarkar, Debanjan; Li, Chunyi; Wang, Changdong; Lu, Li; Andreadis, Stelios; Yang, Shuying

    2013-01-01

    Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2) gene-modified MSCs and endothelial progenitor cells (EPCs) could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone) and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm) caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs. PMID:23565253

  11. Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration

    PubMed Central

    Lobo, Daniel; Levin, Michael

    2015-01-01

    Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method provides an automated

  12. Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds☆

    PubMed Central

    Madigan, Nicolas N.; McMahon, Siobhan; O’Brien, Timothy; Yaszemski, Michael J.; Windebank, Anthony J.

    2010-01-01

    This review highlights current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury. The concept of developing 3-dimensional polymer scaffolds for placement into a spinal cord transection model has recently been more extensively explored as a solution for restoring neurologic function after injury. Given the patient morbidity associated with respiratory compromise, the discrete tracts in the spinal cord conveying innervation for breathing represent an important and achievable therapeutic target. The aim is to derive new neuronal tissue from the surrounding, healthy cord that will be guided by the polymer implant through the injured area to make functional reconnections. A variety of naturally derived and synthetic biomaterial polymers have been developed for placement in the injured spinal cord. Axonal growth is supported by inherent properties of the selected polymer, the architecture of the scaffold, permissive microstructures such as pores, grooves or polymer fibres, and surface modifications to provide improved adherence and growth directionality. Structural support of axonal regeneration is combined with integrated polymeric and cellular delivery systems for therapeutic drugs and for neurotrophic molecules to regionalize growth of specific nerve populations. PMID:19737633

  13. Bridging the lesion—engineering a permissive substrate for nerve regeneration

    PubMed Central

    Pires, Liliana R.; Pêgo, Ana P.

    2015-01-01

    Biomaterial-based strategies to restore connectivity after lesion at the spinal cord are focused on bridging the lesion and providing an favourable substrate and a path for axonal re-growth. Following spinal cord injury (SCI) a hostile environment for neuronal cell growth is established by the activation of multiple inhibitory mechanisms that hamper regeneration to occur. Implantable scaffolds can provide mechanical support and physical guidance for axon re-growth and, at the same time, contribute to alleviate the hostile environment by the in situ delivery of therapeutic molecules and/or relevant cells. Basic research on SCI has been contributing with the description of inhibitory mechanisms for regeneration as well as identifying drugs/molecules that can target inhibition. This knowledge is the background for the development of combined strategies with biomaterials. Additionally, scaffold design is significantly evolving. From the early simple hollow conduits, scaffolds with complex architectures that can modulate cell fate are currently being tested. A number of promising pre-clinical studies combining scaffolds, cells, drugs and/or nucleic acids are reported in the open literature. Overall, it is considered that to address the multi-factorial inhibitory environment of a SCI, a multifaceted therapeutic approach is imperative. The progress in the identification of molecules that target inhibition after SCI and its combination with scaffolds and/or cells are described and discussed in this review. PMID:26816642

  14. Regenerating cartilages by engineered ASCs: prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure.

    PubMed

    Lu, Chia-Hsin; Yeh, Tsung-Szu; Yeh, Chia-Lin; Fang, Yu-Hua Dean; Sung, Li-Yu; Lin, Shih-Yeh; Yen, Tzu-Chen; Chang, Yu-Han; Hu, Yu-Chen

    2014-01-01

    Adipose-derived stem cells (ASCs) hold promise for cartilage regeneration but their chondrogenesis potential is inferior. Here, we used a baculovirus (BV) system that exploited FLPo/Frt-mediated transgene recombination and episomal minicircle formation to genetically engineer rabbit ASCs (rASCs). The BV system conferred prolonged and robust TGF-β3/BMP-6 expression in rASCs cultured in porous scaffolds, which critically augmented rASCs chondrogenesis and suppressed osteogenesis/hypertrophy, leading to the formation of cartilaginous constructs with improved maturity and mechanical properties in 2-week culture. Twelve weeks after implantation into full-thickness articular cartilage defects in rabbits, these engineered constructs regenerated neocartilages that resembled native hyaline cartilages in cell morphology, matrix composition and mechanical properties. The neocartilages also displayed cartilage-specific zonal structures without signs of hypertrophy and degeneration, and eventually integrated with host cartilages. In contrast, rASCs that transiently expressed TGF-β3/BMP-6 underwent osteogenesis/hypertrophy and resulted in the formation of inferior cartilaginous constructs, which after implantation regenerated fibrocartilages. These data underscored the crucial role of TGF-β3/BMP-6 expression level and duration in rASCs in the cell differentiation, constructs properties and in vivo repair. The BV-engineered rASCs that persistently express TGF-β3/BMP-6 improved the chondrogenesis, in vitro cartilaginous constructs production and in vivo hyaline cartilage regeneration, thus representing a remarkable advance in cartilage engineering. PMID:23851345

  15. Molecular engineering by light emitting diode parameters on the base of methoxy-pyrazoloquinoline dyes in polysilane matrices

    NASA Astrophysics Data System (ADS)

    Gondek, E.; Kityk, I. V.; Danel, A.

    2007-05-01

    Complex current-voltage and electroluminescence (EL) investigations were performed for the single layered light emitting diodes on the base of the methoxy-modified pyrazoloquinoline (PQ) incorporated into polysilane matrices. The quantum chemical simulations performed for the isolated PQ chromophore molecule as well as for the complexes consisting of molecules and surrounding polymers show a principal role of dipole-dipole interactions for the appearance of the trapping levels substantially modifying carrier kinetics and the observed current-voltage and electroluminescent-current features. In particular, a significant change of the power index in the EL-current dependences versus the state dipole moments of the PQ chromophore determining chromophore-polymer chain interactions was established. The performed current-voltage investigations have shown that different power dependences at different voltages may indicate the inclusion of different carriers, which originate not only from the Shottky barrier jumps but also substantially due to trapping by the polaron and localized exciton states. The latter may also change the exciton kinetics and the diffusion lengths determining the power index of electroluminescent-current kinetics.

  16. Nanofiber–microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design

    PubMed Central

    Nelson, Clarke; Khan, Yusuf; Laurencin, Cato T.

    2014-01-01

    Bone is an essential organ for health and quality of life. Due to current shortfalls in therapy for bone tissue engineering, scientists have sought the application of synthetic materials as bone graft substitutes. As a composite organic/inorganic material with significant extra cellular matrix (ECM), one way to improve bone graft substitutes may be to engineer a synthetic matrix that is influenced by the physical appearance of natural ECM networks. In this work, the authors evaluate composite, hybrid scaffolds for bone tissue engineering based on composite ceramic/polymer microsphere scaffolds with synthetic ECM-mimetic networks in their pore spaces. Using thermally induced phase separation, nanoscale fibers were deposited in the pore spaces of structurally sound microsphere-based scaffold with a density proportionate to the initial polymer concentration. Porosimetry and mechanical testing indicated no significant changes in overall pore characteristics or mechanical integrity as a result of the fiber deposition process. These scaffolds displayed adequate mechanical integrity on the scale of human trabecular bone and supported the adhesion and proliferation of cultured mouse calvarial osteoblasts. Drawing from natural cues, these scaffolds may represent a new avenue forward for advanced bone tissue engineering scaffolds. PMID:26816620

  17. Graphene oxide-stimulated myogenic differentiation of C2C12 cells on PLGA/RGD peptide nanofiber matrices

    NASA Astrophysics Data System (ADS)

    Shin, Y. C.; Lee, J. H.; Kim, M. J.; Hong, S. W.; Oh, J.-W.; Kim, C.-S.; Kim, B.; Hyun, J. K.; Kim, Y.-J.; Han, D.-W.

    2015-07-01

    During the last decade, much attention has been paid to graphene-based nanomaterials because they are considered as potential candidates for biomedical applications such as scaffolds for tissue engineering and substrates for the differentiation of stem cells. Until now, electrospun matrices composed of various biodegradable copolymers have been extensively developed for tissue engineering and regeneration; however, their use in combination with graphene oxide (GO) is novel and challenging. In this study, nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 phage with RGD peptide displayed on its surface (RGD peptide-M13 phage) were prepared as extracellular matrix (ECM)-mimicking substrates. RGD peptide is a tripeptide (Arg-Gly-Asp) found on ECM proteins that promotes various cellular behaviors. The physicochemical properties of PLGA and RGD peptide-M13 phage (PLGA/RGD peptide) nanofiber matrices were characterized by atomic force microscopy, Fourier-transform infrared spectroscopy and thermogravimetric analysis. In addition, the growth of C2C12 mouse myoblasts on the PLGA/RGD peptide matrices was examined by measuring the metabolic activity. Moreover, the differentiation of C2C12 mouse myoblasts on the matrices when treated with GO was evaluated. The cellular behaviors, including growth and differentiation of C2C12 mouse myoblasts, were substantially enhanced on the PLGA/RGD peptide nanofiber matrices when treated with GO. Overall, these findings suggest that the PLGA/RGD peptide nanofiber matrices can be used in combination with GO as a novel strategy for skeletal tissue regeneration.

  18. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

    NASA Astrophysics Data System (ADS)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

    2016-08-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

  19. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

    PubMed Central

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard OC

    2016-01-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering. PMID:27577960

  20. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering.

    PubMed

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A; Janeczek, Agnieszka A; Kontouli, Nasia; Kanczler, Janos M; Evans, Nicholas D; Oreffo, Richard Oc

    2016-01-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering. PMID:27577960

  1. Combination of engineered Schwann cell grafts to secrete neurotrophin and chondroitinase promotes axonal regeneration and locomotion after spinal cord injury.

    PubMed

    Kanno, Haruo; Pressman, Yelena; Moody, Alison; Berg, Randall; Muir, Elizabeth M; Rogers, John H; Ozawa, Hiroshi; Itoi, Eiji; Pearse, Damien D; Bunge, Mary Bartlett

    2014-01-29

    Transplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. SCs introduced into lesions support axon regeneration, but because these axons do not exit the transplant, additional approaches with SCs are needed. Here, we transplanted SCs genetically modified to secrete a bifunctional neurotrophin (D15A) and chondroitinase ABC (ChABC) into a subacute contusion injury in rats. We examined the effects of these modifications on graft volume, SC number, degradation of chondroitin sulfate proteoglycans (CSPGs), astrogliosis, SC myelination of axons, propriospinal and supraspinal axon numbers, locomotor outcome (BBB scoring, CatWalk gait analysis), and mechanical and thermal sensitivity on the hind paws. D15A secreted from transplanted SCs increased graft volume and SC number and myelinated axon number. SCs secreting ChABC significantly decreased CSPGs, led to some egress of SCs from the graft, and increased propriospinal and 5-HT-positive axons in the graft. SCs secreting both D15A and ChABC yielded the best responses: (1) the largest number of SC myelinated axons, (2) more propriospinal axons in the graft and host tissue around and caudal to it, (3) more corticospinal axons closer to the graft and around and caudal to it, (4) more brainstem neurons projecting caudal to the transplant, (5) increased 5-HT-positive axons in the graft and caudal to it, (6) significant improvement in aspects of locomotion, and (7) improvement in mechanical and thermal allodynia. This is the first evidence that the combination of SC transplants engineered to secrete neurotrophin and chondroitinase further improves axonal regeneration and locomotor and sensory function.

  2. Combination of Engineered Schwann Cell Grafts to Secrete Neurotrophin and Chondroitinase Promotes Axonal Regeneration and Locomotion after Spinal Cord Injury

    PubMed Central

    Pressman, Yelena; Moody, Alison; Berg, Randall; Muir, Elizabeth M.; Rogers, John H.; Ozawa, Hiroshi; Itoi, Eiji; Pearse, Damien D.; Bunge, Mary Bartlett

    2014-01-01

    Transplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. SCs introduced into lesions support axon regeneration, but because these axons do not exit the transplant, additional approaches with SCs are needed. Here, we transplanted SCs genetically modified to secrete a bifunctional neurotrophin (D15A) and chondroitinase ABC (ChABC) into a subacute contusion injury in rats. We examined the effects of these modifications on graft volume, SC number, degradation of chondroitin sulfate proteoglycans (CSPGs), astrogliosis, SC myelination of axons, propriospinal and supraspinal axon numbers, locomotor outcome (BBB scoring, CatWalk gait analysis), and mechanical and thermal sensitivity on the hind paws. D15A secreted from transplanted SCs increased graft volume and SC number and myelinated axon number. SCs secreting ChABC significantly decreased CSPGs, led to some egress of SCs from the graft, and increased propriospinal and 5-HT-positive axons in the graft. SCs secreting both D15A and ChABC yielded the best responses: (1) the largest number of SC myelinated axons, (2) more propriospinal axons in the graft and host tissue around and caudal to it, (3) more corticospinal axons closer to the graft and around and caudal to it, (4) more brainstem neurons projecting caudal to the transplant, (5) increased 5-HT-positive axons in the graft and caudal to it, (6) significant improvement in aspects of locomotion, and (7) improvement in mechanical and thermal allodynia. This is the first evidence that the combination of SC transplants engineered to secrete neurotrophin and chondroitinase further improves axonal regeneration and locomotor and sensory function. PMID:24478364

  3. Nano-biomimetics for nano/micro tissue regeneration.

    PubMed

    Singh, Dolly; Singh, Deepti; Zo, Sunmi; Han, Sung Soo

    2014-10-01

    Nanostructured biomimetics have recently shown great promise in the field of tissue engineering. They can be used as nanoscaffolds and tailored at the molecular level. The scaffold topography closely resembles the native extracellular matrix in terms of framing, porosity and bio-functionality. This review covers the approaches used for biomimetic fabrication, including soft lithography, the plasmonic nanohybrid matrix method and multilayer self-assembly scaffolds for tissue regeneration. It brings together knowledge from different arenas about the synthesis, characterization and functionalization of matrices to accelerate the tissue regeneration process. Every tissue in the body presents different challenges and requires a specific fabrication process designed to identify and mirror the particular organ. For example, microfluidics systems aim to mimic the extracellular matrix of vascular and cartilage tissue, and these systems have different parts with completely different mechanical strength, cellular adhesion and interplay between matrix and cells. A fully functional nanomatrix designed by a self-assembling methodology for use as a vascular tissue engineering scaffold needs to have intrinsic microvessels that facilitate the transportation of metabolites and nutrients. Similarly, in the case of peripheral nerve regeneration, a scaffold needs to have sufficient mechanical strength to protect the regenerating tissue, yet be biodegradable enough to avoid a possible second surgery. To enhance the functionality of scaffolds, increasing focus has been placed on in vitro and in vivo research to achieve optimal scaffold design. Nanobiomimetics unarguably offer the most suitable physicochemical scaffold properties for tissue regeneration.

  4. Ultra-rapid manufacturing of engineered epicardial substitute to regenerate cardiac tissue following acute ischemic injury.

    PubMed

    Serpooshan, Vahid; Ruiz-Lozano, Pilar

    2014-01-01

    Considering the impaired regenerative capacity of adult mammalian heart tissue, cardiovascular tissue engineering aims to create functional substitutes that can restore the structure and function of the damaged cardiac tissue. The success of cardiac regenerative therapies has been limited mainly due to poor control on the structure and properties of the tissue substitute, lack of vascularization, and immunogenicity. In this study we introduce a new approach to rapidly engineer dense biomimetic scaffolds consisting of type I collagen, to protect the heart against severe ischemic injury. Scaffold biomechanical properties are adjusted to mimic embryonic epicardium which is shown to be optimal to support cardiomyocyte contractile work. Moreover, the designed patch can serve as a delivery device for targeted, controlled release of cells or therapeutic macromolecules into the lesion area.

  5. Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering.

    PubMed

    Gómez-Leduc, Tangni; Hervieu, Magalie; Legendre, Florence; Bouyoucef, Mouloud; Gruchy, Nicolas; Poulain, Laurent; de Vienne, Claire; Herlicoviez, Michel; Demoor, Magali; Galéra, Philippe

    2016-01-01

    Umbilical cord blood (UCB) is a promising alternative source of mesenchymal stem cells (MSCs), because UCB-MSCs are abundant and harvesting them is a painless non-invasive procedure. Potential clinical applications of UCB-MSCs have been identified, but their ability for chondrogenic differentiation has not yet been fully evaluated. The aim of our work was to characterize and determine the chondrogenic differentiation potential of human UCB-MSCs (hUCB-MSCs) for cartilage tissue engineering using an approach combining 3D culture in type I/III collagen sponges and chondrogenic factors. Our results showed that UCB-MSCs have a high proliferative capacity. These cells differentiated easily into an osteoblast lineage but not into an adipocyte lineage. Furthermore, BMP-2 and TGF-β1 potentiated chondrogenic differentiation, as revealed by a strong increase in mature chondrocyte-specific mRNA (COL2A1, COL2B, ACAN) and protein (type II collagen) markers. Although growth factors increased the transcription of hypertrophic chondrocyte markers such as COL10A1 and MMP13, the cells present in the neo-tissue maintained their phenotype and did not progress to terminal differentiation and mineralization of the extracellular matrix after subcutaneous implantation in nude mice. Our study demonstrates that our culture model has efficient chondrogenic differentiation, and that hUCB-MSCs can be a reliable source for cartilage tissue engineering. PMID:27604951

  6. Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering

    PubMed Central

    Gómez-Leduc, Tangni; Hervieu, Magalie; Legendre, Florence; Bouyoucef, Mouloud; Gruchy, Nicolas; Poulain, Laurent; de Vienne, Claire; Herlicoviez, Michel; Demoor, Magali; Galéra, Philippe

    2016-01-01

    Umbilical cord blood (UCB) is a promising alternative source of mesenchymal stem cells (MSCs), because UCB-MSCs are abundant and harvesting them is a painless non-invasive procedure. Potential clinical applications of UCB-MSCs have been identified, but their ability for chondrogenic differentiation has not yet been fully evaluated. The aim of our work was to characterize and determine the chondrogenic differentiation potential of human UCB-MSCs (hUCB-MSCs) for cartilage tissue engineering using an approach combining 3D culture in type I/III collagen sponges and chondrogenic factors. Our results showed that UCB-MSCs have a high proliferative capacity. These cells differentiated easily into an osteoblast lineage but not into an adipocyte lineage. Furthermore, BMP-2 and TGF-β1 potentiated chondrogenic differentiation, as revealed by a strong increase in mature chondrocyte-specific mRNA (COL2A1, COL2B, ACAN) and protein (type II collagen) markers. Although growth factors increased the transcription of hypertrophic chondrocyte markers such as COL10A1 and MMP13, the cells present in the neo-tissue maintained their phenotype and did not progress to terminal differentiation and mineralization of the extracellular matrix after subcutaneous implantation in nude mice. Our study demonstrates that our culture model has efficient chondrogenic differentiation, and that hUCB-MSCs can be a reliable source for cartilage tissue engineering. PMID:27604951

  7. Improved non-invasive Optical Coherence Tomography detection of different engineered nanoparticles in food-mimicking matrices.

    PubMed

    Grombe, Ringo; Kirsten, Lars; Mehner, Mirko; Linsinger, Thomas P J; Koch, Edmund

    2016-12-01

    Food industry and regulators require fast and reliable analytical methods for quality control. This especially counts for the detection of engineered nanomaterials (ENMs) in food products. Respective EU regulation is in force, but the development of appropriate methods is still underway. This paper updates the scope of Optical Coherence Tomography (OCT) for ENM/food matrix analysis. A range of nanomaterials and composites - Au@SiO2, Ag, Ag@SiO2 and SiO2 - in a simplified food matrix was investigated. The earlier finding of linear dependencies between concentration in the dispersion and light responses could be reproduced. Being able to analyse non-invasively for a relevant industrial compound such as SiO2, makes OCT an excellent candidate for screening purposes. PMID:27374569

  8. Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

    PubMed Central

    Duan, Bin; Hockaday, Laura A.; Das, Shoshana; Xu, Charlie

    2015-01-01

    Living tissue-engineered heart valves (TEHV) would be a major benefit for children who require a replacement with the capacity for growth and biological integration. A persistent challenge for TEHV is accessible human cell source(s) that can mimic native valve cell phenotypes and matrix remodeling characteristics that are essential for long-term function. Mesenchymal stem cells derived from bone marrow (BMMSC) or adipose tissue (ADMSC) are intriguing cell sources for TEHV, but they have not been compared with pediatric human aortic valve interstitial cells (pHAVIC) in relevant 3D environments. In this study, we compared the spontaneous and induced multipotency of ADMSC and BMMSC with that of pHAVIC using different induction media within three-dimensional (3D) bioactive hybrid hydrogels with material modulus comparable to that of aortic heart valve leaflets. pHAVIC possessed some multi-lineage differentiation capacity in response to induction media, but limited to the earliest stages and much less potent than either ADMSC or BMMSC. ADMSC expressed cell phenotype markers more similar to pHAVIC when conditioned in basic fibroblast growth factor (bFGF) containing HAVIC growth medium, while BMMSC generally expressed similar extracellular matrix remodeling characteristics to pHAVIC. Finally, we covalently attached bFGF to PEG monoacrylate linkers and further covalently immobilized in the 3D hybrid hydrogels. Immobilized bFGF upregulated vimentin expression and promoted the fibroblastic differentiation of pHAVIC, ADMSC, and BMMSC. These findings suggest that stem cells retain a heightened capacity for osteogenic differentiation in 3D culture, but can be shifted toward fibroblast differentiation through matrix tethering of bFGF. Such a strategy is likely important for utilizing stem cell sources in heart valve tissue engineering applications. PMID:25594437

  9. Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach

    PubMed Central

    Bader, Augustinus; Macchiarini, Paolo

    2010-01-01

    Abstract In June 2008, the world’s first whole tissue-engineered organ – the windpipe – was successfully transplanted into a 31-year-old lady, and about 18 months following surgery she is leading a near normal life without immunosuppression. This outcome has been achieved by employing three groundbreaking technologies of regenerative medicine: (i) a donor trachea first decellularized using a detergent (without denaturing the collagenous matrix), (ii) the two main autologous tracheal cells, namely mesenchymal stem cell derived cartilage-like cells and epithelial respiratory cells and (iii) a specifically designed bioreactor that reseed, before implantation, the in vitro pre-expanded and pre-differentiated autologous cells on the desired surfaces of the decellularized matrix. Given the long-term safety, efficacy and efforts using such a conventional approach and the potential advantages of regenerative implants to make them available for anyone, we have investigated a novel alternative concept how to fully avoid in vitro cell replication, expansion and differentiation, use the human native site as micro-niche, potentiate the human body’s site-specific response by adding boosting, permissive and recruitment impulses in full respect of sociological and regulatory prerequisites. This tissue-engineered approach and ongoing research in airway transplantation is reviewed and presented here. PMID:20406329

  10. Design and Assembly of an Integrated Metabolic Heat Regenerated Temperature Swing Adsorption (MTSA) Subassembly Engineering Development Unit

    NASA Technical Reports Server (NTRS)

    Padilla, Sebastian A.; Powers, Aaron; Iacomini, Christie S.; Bower, Chad E.; Paul, Heather L.

    2012-01-01

    Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed for thermal and carbon dioxide (CO2) control for a Portable Life Support System (PLSS), as well as water recycling. The core of the MTSA technology is a sorbent bed that removes CO2 from the PLSS ventilation loop gas via a temperature swing. A Condensing Icing Heat eXchanger (CIHX) is used to warm the sorbent while also removing water from the ventilation loop gas. A Sublimation Heat eXchanger (SHX) is used to cool the sorbent. Research was performed to explore an MTSA designed for both lunar and Martian operations. Previously the sorbent bed, CIHX, and SHX had been built and tested individually on a scale relevant to PLSS operations, but they had not been done so as an integrated subassembly. Design and analysis of an integrated subassembly was performed based on this prior experience and an updated transient system model. Focus was on optimizing the design for Martian operations, but the design can also be used in lunar operations. An Engineering Development Unit (EDU) of an integrated MTSA subassembly was assembled based on the design. Its fabrication is discussed. Some details on the differences between the as-assembled EDU and the future flight unit are considered.

  11. Immobilization of collagen peptide on dialdehyde bacterial cellulose nanofibers via covalent bonds for tissue engineering and regeneration.

    PubMed

    Wen, Xiaoxiao; Zheng, Yudong; Wu, Jian; Wang, Lu-Ning; Yuan, Zhenya; Peng, Jiang; Meng, Haoye

    2015-01-01

    Bacterial cellulose (BC) is an alternative nanostructured biomaterial to be utilized for a wide range of biomedical applications. Because of its low bioactivity, which restricted its practical application, collagen and collagen hydrolysate were usually composited into BC. It is necessary to develop a new method to generate covalent bonds between collagen and cellulose to improve the immobilization of collagen on BC. This study describes a facile dialdehyde BC/collagen peptide nanocomposite. BC was oxidized into dialdehyde bacterial cellulose (DBC) by regioselective oxidation, and then composited with collagen peptide (Col-p) via covalent bonds to form Schiff's base type compounds, which was demonstrated by the results of microstructures, contact angle, Col-p content, and peptide-binding ratio. The peptide-binding ratio was further affected by the degree of oxidation, pH value, and zeta potential. In vitro desorption measurement of Col-p suggested a controlled release mechanism of the nanocomposite. Cell tests indicated that the prepared DBC/Col-p composite was bioactive and suitable for cell adhesion and attachment. This work demonstrates that the DBC/Col-p composite is a promising material for tissue engineering and regeneration.

  12. Design and Assembly of an Integrated Metabolic Heat Regenerated Temperature Swing Adsorption (MTSA) Subassembly Engineering Development Unit

    NASA Technical Reports Server (NTRS)

    Padilla, Sebastian A.; Powers, Aaron; Iacomini, Christie S.; Paul, Heather L.

    2011-01-01

    Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed for thermal and carbon dioxide (CO2) control for a Portable Life Support System (PLSS), as well as water recycling. The core of the MTSA technology is a sorbent bed that removes CO2 from the PLSS ventilation loop gas via a temperature swing. A Condensing Ice Heat eXchanger (CIHX) is used to warm the sorbent while also removing water from the ventilation loop gas. A Sublimation Heat eXchanger (SHX) is used to cool the sorbent. Research was performed to explore an MTSA designed for both lunar and Martian operations. Previously each the sorbent bed, CIHX, and SHX had been built and tested individually on a scale relevant to PLSS operations, but they had not been done so as an integrated subassembly. Design and analysis of an integrated subassembly was performed based on this prior experience and an updated transient system model. Focus was on optimizing the design for Martian operations, but the design can also be used in lunar operations. An Engineering Development Unit (EDU) of an integrated MTSA subassembly was assembled based on the design. Its fabrication is discussed. Some details on the differences between the as-assembled EDU to the future flight unit are considered.

  13. Immobilization of collagen peptide on dialdehyde bacterial cellulose nanofibers via covalent bonds for tissue engineering and regeneration

    PubMed Central

    Wen, Xiaoxiao; Zheng, Yudong; Wu, Jian; Wang, Lu-Ning; Yuan, Zhenya; Peng, Jiang; Meng, Haoye

    2015-01-01

    Bacterial cellulose (BC) is an alternative nanostructured biomaterial to be utilized for a wide range of biomedical applications. Because of its low bioactivity, which restricted its practical application, collagen and collagen hydrolysate were usually composited into BC. It is necessary to develop a new method to generate covalent bonds between collagen and cellulose to improve the immobilization of collagen on BC. This study describes a facile dialdehyde BC/collagen peptide nanocomposite. BC was oxidized into dialdehyde bacterial cellulose (DBC) by regioselective oxidation, and then composited with collagen peptide (Col-p) via covalent bonds to form Schiff’s base type compounds, which was demonstrated by the results of microstructures, contact angle, Col-p content, and peptide-binding ratio. The peptide-binding ratio was further affected by the degree of oxidation, pH value, and zeta potential. In vitro desorption measurement of Col-p suggested a controlled release mechanism of the nanocomposite. Cell tests indicated that the prepared DBC/Col-p composite was bioactive and suitable for cell adhesion and attachment. This work demonstrates that the DBC/Col-p composite is a promising material for tissue engineering and regeneration. PMID:26229466

  14. Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration

    PubMed Central

    Trachtenberg, Jordan E.; Vo, Tiffany N.; Mikos, Antonios G.

    2014-01-01

    Pre-clinical animal models play a crucial role in the translation of biomedical technologies from the bench top to the bedside. However, there is a need for improved techniques to evaluate implanted biomaterials within the host, including consideration of the care and ethics associated with animal studies, as well as the evaluation of host tissue repair in a clinically relevant manner. This review discusses non-invasive, quantitative, and real-time techniques for evaluating host-materials interactions, quality and rate of neotissue formation, and functional outcomes of implanted biomaterials for bone and cartilage tissue engineering. Specifically, a comparison will be presented for pre-clinical animal models, histological scoring systems, and non-invasive imaging modalities. Additionally, novel technologies to track delivered cells and growth factors will be discussed, including methods to directly correlate their release with tissue growth. PMID:25319726

  15. Design and Use of a Novel Bioreactor for Regeneration of Biaxially Stretched Tissue-Engineered Vessels.

    PubMed

    Huang, Angela Hai; Lee, Yong-Ung; Calle, Elizabeth A; Boyle, Michael; Starcher, Barry C; Humphrey, Jay D; Niklason, Laura E

    2015-08-01

    Conventional bioreactors are used to enhance extracellular matrix (ECM) production and mechanical strength of tissue-engineered vessels (TEVs) by applying circumferential strain, which is uniaxial stretching. However, the resulting TEVs still suffer from inadequate mechanical properties, where rupture strengths and compliance values are still very different from native arteries. The biomechanical milieu of native arteries consists of both circumferential and axial loading. Therefore, to better simulate the physiological stresses acting on native arteries, we built a novel bioreactor system to enable biaxial stretching of engineered arteries during culture. This new bioreactor system allows for independent control of circumferential and axial stretching parameters, such as displacement and beat rate. The assembly and setup processes for this biaxial bioreactor system are reliable with a success rate greater than 75% for completion of long-term sterile culture. This bioreactor also supports side-by-side assessments of TEVs that are cultured under three types of mechanical conditions (static, uniaxial, and biaxial), all within the same biochemical environment. Using this bioreactor, we examined the impact of biaxial stretching on arterial wall remodeling of TEVs. Biaxial TEVs developed the greatest wall thickness compared with static and uniaxial TEVs. Unlike uniaxial loading, biaxial loading led to undulated collagen fibers that are commonly found in native arteries. More importantly, the biaxial TEVs developed the most mature elastin in the ECM, both qualitatively and quantitatively. The presence of mature extracellular elastin along with the undulated collagen fibers may contribute to the observed vascular compliance in the biaxial TEVs. The current work shows that biaxial stretching is a novel and promising means to improve TEV generation. Furthermore, this novel system allows us to optimize biomechanical conditioning by unraveling the interrelationships among the

  16. Design and Use of a Novel Bioreactor for Regeneration of Biaxially Stretched Tissue-Engineered Vessels

    PubMed Central

    Huang, Angela Hai; Lee, Yong-Ung; Calle, Elizabeth A.; Boyle, Michael; Starcher, Barry C.; Humphrey, Jay D.

    2015-01-01

    Conventional bioreactors are used to enhance extracellular matrix (ECM) production and mechanical strength of tissue-engineered vessels (TEVs) by applying circumferential strain, which is uniaxial stretching. However, the resulting TEVs still suffer from inadequate mechanical properties, where rupture strengths and compliance values are still very different from native arteries. The biomechanical milieu of native arteries consists of both circumferential and axial loading. Therefore, to better simulate the physiological stresses acting on native arteries, we built a novel bioreactor system to enable biaxial stretching of engineered arteries during culture. This new bioreactor system allows for independent control of circumferential and axial stretching parameters, such as displacement and beat rate. The assembly and setup processes for this biaxial bioreactor system are reliable with a success rate greater than 75% for completion of long-term sterile culture. This bioreactor also supports side-by-side assessments of TEVs that are cultured under three types of mechanical conditions (static, uniaxial, and biaxial), all within the same biochemical environment. Using this bioreactor, we examined the impact of biaxial stretching on arterial wall remodeling of TEVs. Biaxial TEVs developed the greatest wall thickness compared with static and uniaxial TEVs. Unlike uniaxial loading, biaxial loading led to undulated collagen fibers that are commonly found in native arteries. More importantly, the biaxial TEVs developed the most mature elastin in the ECM, both qualitatively and quantitatively. The presence of mature extracellular elastin along with the undulated collagen fibers may contribute to the observed vascular compliance in the biaxial TEVs. The current work shows that biaxial stretching is a novel and promising means to improve TEV generation. Furthermore, this novel system allows us to optimize biomechanical conditioning by unraveling the interrelationships among the

  17. Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo

    PubMed Central

    Gao, Peng; Zhang, Haoqiang; Liu, Yun; Fan, Bo; Li, Xiaokang; Xiao, Xin; Lan, Pingheng; Li, Minghui; Geng, Lei; Liu, Dong; Yuan, Yulin; Lian, Qin; Lu, Jianxi; Guo, Zheng; Wang, Zhen

    2016-01-01

    The drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable β-tricalcium phosphate (β-TCP) granules for bone regeneration and identify an efficient method to establish β-TCP-based osteo-regenerators. β-TCP granules with diameters of 1 mm and 1–2.5 mm were evaluated in vitro. The β-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1–2.5 mm β-TCP compared with 1-mm granules (P < 0.05). In addition, BMSCs incubated with 1–2.5 mm β-TCP expressed significantly higher levels of the genes for runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 and the osteogenesis-related proteins alkaline phosphatase, collagen type-1 and runt-related transcription factor-2 compared with BMSCs incubated with 1 mm β-TCP (P < 0.05). Fluorochrome labelling, micro-computed tomography and histological staining analyses indicated that the osteo-regenerator with two holes perforating the femur promoted significantly greater bone regeneration compared with the osteo-regenerator with a periosteum incision (P < 0.05). This study provides an alternative to biofunctionalized bioreactors that exhibits improved osteogenesis. PMID:27000963

  18. Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration.

    PubMed

    Li, Linqing; Stiadle, Jeanna M; Lau, Hang K; Zerdoum, Aidan B; Jia, Xinqiao; Thibeault, Susan L; Kiick, Kristi L

    2016-11-01

    Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

  19. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    PubMed

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  20. Evaluating Osteoarthritic Chondrocytes through a Novel 3-Dimensional In Vitro System for Cartilage Tissue Engineering and Regeneration

    PubMed Central

    Li, Hanwei; Davison, Noel; Moroni, Lorenzo; Feng, Felicia; Crist, Joshua; Salter, Erin; Bingham, Clifton O.

    2012-01-01

    Objective: To characterize and evaluate osteoarthritic (OA) chondrocytes, in comparison to normal chondrocytes, through a novel 3-dimensional (3-D) culture system, poly(ethylene-glycol) diacrylate (PEGDA). The cytokine interleukin 1β (IL-1β) was also used to simulate an in vitro OA model. Methods: Normal and OA chondrocytes were cultured in monolayer and analyzed for changes in cartilage-specific gene expressions due to passage number. Then, cells were encapsulated in PEGDA to evaluate phenotype and matrix production capabilities through the in vitro culture system. Characterization was conducted with polymerase chain reaction (PCR), biochemical analyses, and histological staining. 3-D encapsulated chondrocytes (human and bovine) were also treated with IL-1β to characterize how the cytokine affects gene transcription and extracellular matrix (ECM) content. Results: In 2-dimensional monolayer, anabolic genes were down-regulated significantly in both normal and OA chondrocytes. In 3-D culture, OA chondrocytes demonstrated significantly higher expressions of catabolic genes when compared to normal cells. Differentiation medium resulted in significantly more matrix production than growth medium from OA chondrocytes, indicated through histological staining. In addition, normal chondrocytes responded more significantly to exogenous administration of IL-1β than OA chondrocytes. Temporary initial stimulation of IL-1β to OA chondrocytes resulted in comparable gene expressions to untreated cells after 3 weeks of in vitro culture. Conclusions: Our findings demonstrate the use of OA chondrocytes in tissue engineering and their significance for potential future cartilage regeneration research through their matrix production capabilities and the use of a hydrogel culture system. PMID:26069626

  1. Naturally and synthetic smart composite biomaterials for tissue regeneration.

    PubMed

    Pérez, Román A; Won, Jong-Eun; Knowles, Jonathan C; Kim, Hae-Won

    2013-04-01

    The development of smart biomaterials for tissue regeneration has become the focus of intense research interest. More opportunities are available by the composite approach of combining the biomaterials in the form of biopolymers and/or bioceramics either synthetic or natural. Strategies to provide smart capabilities to the composite biomaterials primarily seek to achieve matrices that are instructive/inductive to cells, or that stimulate/trigger target cell responses that are crucial in the tissue regeneration processes. Here, we review in-depth, recent developments concerning smart composite biomaterials available for delivery systems of biofactors and cells and scaffolding matrices in tissue engineering. Smart composite designs are possible by modulating the bulk and surface properties that mimic the native tissues, either in chemical (extracellular matrix molecules) or in physical properties (e.g. stiffness), or by introducing external therapeutic molecules (drugs, proteins and genes) within the structure in a way that allows sustainable and controllable delivery, even time-dependent and sequential delivery of multiple biofactors. Responsiveness to internal or external stimuli, including pH, temperature, ionic strength, and magnetism, is another promising means to improve the multifunctionality in smart scaffolds with on-demand delivery potential. These approaches will provide the next-generation platforms for designing three-dimensional matrices and delivery systems for tissue regenerative applications. PMID:22465488

  2. Tissue Regeneration: A Silk Road.

    PubMed

    Jao, Dave; Mou, Xiaoyang; Hu, Xiao

    2016-01-01

    Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world's best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration.

  3. Tissue Regeneration: A Silk Road.

    PubMed

    Jao, Dave; Mou, Xiaoyang; Hu, Xiao

    2016-01-01

    Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world's best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration. PMID:27527229

  4. Tissue Regeneration: A Silk Road

    PubMed Central

    Jao, Dave; Mou, Xiaoyang; Hu, Xiao

    2016-01-01

    Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world’s best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration. PMID:27527229

  5. A model regenerator for a Stirling cycle

    NASA Astrophysics Data System (ADS)

    Carolan, James

    2001-05-01

    An essential feature of the engine patented by Robert Stirling in 1817 was the careful description of the idea of regeneration. In the standard thermodynamic cycle representation of the engine, regeneration is the storing and the reusing of the thermal energy released in the constant volume cooling part of the cycle. Due to the difficulty in treating regeneration quantitatively, introductory physics texts generally either ignore the concept or assume the regeneration to be perfect. As a result students obtain little or no understanding of regeneration. In addition there seem to be differing views in various texts about the efficiency of Stirling engines. In this work a simple finite element model regenerator is presented with which one can do simple calculations. The model does not accurately represent actual regeneration in a practical engine. But the model might help students gain better insight into Stirling engine efficiency and the idea of regeneration.

  6. Adenosine Signaling Mediates Osteogenic Differentiation of Human Embryonic Stem Cells on Mineralized Matrices

    PubMed Central

    Rao, Vikram; Shih, Yu-Ru V.; Kang, Heemin; Kabra, Harsha; Varghese, Shyni

    2015-01-01

    Human embryonic stem cells (hESCs) are attractive cell sources for tissue engineering and regenerative medicine due to their self-renewal and differentiation ability. Design of biomaterials with an intrinsic ability that promotes hESC differentiation to the targeted cell type boasts significant advantages for tissue regeneration. We have previously developed biomineralized calcium phosphate (CaP) matrices that inherently direct osteogenic differentiation of hESCs without the need of osteogenic-inducing chemicals or growth factors. Here, we show that CaP matrix-driven osteogenic differentiation of hESCs occurs through A2b adenosine receptor (A2bR). The inhibition of the receptor with an A2bR-specific antagonist attenuated mineralized matrix-mediated osteogenic differentiation of hESCs. In addition, when cultured on matrices in an environment deficient of CaP minerals, exogenous adenosine promoted osteogenic differentiation of hESCs, but was attenuated by the inhibition of A2bR. Such synthetic matrices that intrinsically support osteogenic commitment of hESCs are not only beneficial for bone tissue engineering but can also be used as a platform to study the effect of the physical and chemical cues to the extracellular milieu on stem cell commitment. Insights into the cell signaling during matrix-induced differentiation of stem cells will also help define the key processes and enable discovery of new targets that promote differentiation of pluripotent stem cells for bone tissue engineering. PMID:26618155

  7. Ceramic regenerator program

    NASA Technical Reports Server (NTRS)

    Franklin, Jerrold E.

    1991-01-01

    The feasibility of fabricating an Air Turbo Ramjet (ATR) regenerator containing intricate hydraulic passages from a ceramic material in order to allow operation with high temperature combustion gas and to reduce weight as compared with metallic materials was demonstrated. Platelet technology, ceramic tape casting, and multilayer ceramic packaging techniques were used in this fabrication of subscale silicon nitride components. Proof-of-concept demonstrations were performed to simulate a methane cooled regenerator for an ATR engine. The regenerator vane was designed to operate at realistic service conditions, i.e., 600 psi in a 3500 R (3040 F), 500 fps combustion gas environment. A total of six regenerators were fabricated and tested. The regenerators were shown to be able to withstand internal pressurization to 1575 psi. They were subjected to testing in 500 fps, 3560 R (3100 F) air/propane combustion products and were operated satisfactorily for an excess of 100 hr and 40 thermal cycles which exceeded 2460 R (2000 F).

  8. Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation

    NASA Astrophysics Data System (ADS)

    Li, Fengfu; Carlsson, David; Lohmann, Chris; Suuronen, Erik; Vascotto, Sandy; Kobuch, Karin; Sheardown, Heather; Munger, Rejean; Nakamura, Masatsugu; Griffith, May

    2003-12-01

    Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required. regenerative medicine | tissue engineering | cornea | implantation | innervation

  9. Random antagonistic matrices

    NASA Astrophysics Data System (ADS)

    Cicuta, Giovanni M.; Molinari, Luca Guido

    2016-09-01

    The ensemble of antagonistic matrices is introduced and studied. In antagonistic matrices the entries {{ A }}i,j and {{ A }}j,i are real and have opposite signs, or are both zero, and the diagonal is zero. This generalization of antisymmetric matrices is suggested by the linearized dynamics of competitive species in ecology.

  10. Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries

    PubMed Central

    Chow, Woon N.; Simpson, David G.; Bigbee, John W.; Colello, Raymond J.

    2008-01-01

    One of the many obstacles to spinal cord repair following trauma is the formation of a cyst that impedes axonal regeneration. Accordingly, we examined the potential use of electrospinning to engineer an implantable polarized matrix for axonal guidance. Polydioxanone, a resorbable material, was electrospun to fabricate matrices possessing either aligned or randomly oriented fibers. To assess the extent to which fiber alignment influences directional neuritic outgrowth, rat dorsal root ganglia (DRGs) were cultured on these matrices for 10 days. Using confocal microscopy, neurites displayed a directional growth that mimicked the fiber alignment of the underlying matrix. Because these matrices are generated from a material that degrades with time, we next determined whether a glial substrate might provide a more stable interface between the resorbable matrix and the outgrowing axons. Astrocytes seeded onto either aligned or random matrices displayed a directional growth pattern similar to that of the underlying matrix. Moreover, these glia-seeded matrices, once co-cultured with DRGs, conferred the matrix alignment to and enhanced outgrowth exuberance of the extending neurites. These experiments demonstrate the potential for electrospinning to generate an aligned matrix that influences both the directionality and growth dynamics of DRG neurites. PMID:18458759

  11. Random bistochastic matrices

    NASA Astrophysics Data System (ADS)

    Cappellini, Valerio; Sommers, Hans-Jürgen; Bruzda, Wojciech; Życzkowski, Karol

    2009-09-01

    Ensembles of random stochastic and bistochastic matrices are investigated. While all columns of a random stochastic matrix can be chosen independently, the rows and columns of a bistochastic matrix have to be correlated. We evaluate the probability measure induced into the Birkhoff polytope of bistochastic matrices by applying the Sinkhorn algorithm to a given ensemble of random stochastic matrices. For matrices of order N = 2 we derive explicit formulae for the probability distributions induced by random stochastic matrices with columns distributed according to the Dirichlet distribution. For arbitrary N we construct an initial ensemble of stochastic matrices which allows one to generate random bistochastic matrices according to a distribution locally flat at the center of the Birkhoff polytope. The value of the probability density at this point enables us to obtain an estimation of the volume of the Birkhoff polytope, consistent with recent asymptotic results.

  12. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    PubMed

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

  13. Translational research for injectable tissue-engineered bone regeneration using mesenchymal stem cells and platelet-rich plasma: from basic research to clinical case study.

    PubMed

    Yamada, Yoichi; Ueda, Minoru; Hibi, Hideharu; Nagasaka, Tetsuro

    2004-01-01

    Translational research involves application of basic scientific discoveries into clinically germane findings and, simultaneously, the generation of scientific questions based on clinical observations. At first, as basic research we investigated tissue-engineered bone regeneration using mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in a dog mandible model. We also confirmed the correlation between osseointegration in dental implants and the injectable bone. Bone defects made with a trephine bar were implanted with graft materials as follows: PRP, dog MSCs (dMSCs) and PRP, autogenous particulate cancellous bone and marrow (PCBM), and control (defect only). Two months later, dental implants were installed. According to the histological and histomorphometric observations at 2 months after implants, the amount of bone-implant contact at the bone-implant interface was significantly different between the PRP, PCBM, dMSCs/ PRP, native bone, and control groups. Significant differences were also found between the dMSCs/PRP, native bone, and control groups in bone density. These findings indicate that the use of a mixture of dMSCs/ PRP will provide good results in implant treatment compared with that achieved by autogenous PCBM. We then applied this injectable tissue-engineered bone to onlay plasty in the posterior maxilla or mandible in three human patients. Injectable tissue-engineered bone was grafted and, simultaneously, 2-3 threaded titanium implants were inserted into the defect area. The results of this investigation indicated that injectable tissue-engineered bone used for the plasty area with simultaneous implant placement provided stable and predictable results in terms of implant success. We regenerated bone with minimal invasiveness and good plasticity, which could provide a clinical alternative to autogenous bone grafts. This might be a good case of translational research from basic research to clinical application. PMID:15468676

  14. Evaluation of advanced regenerator systems

    NASA Technical Reports Server (NTRS)

    Cook, J. A.; Fucinari, C. A.; Lingscheit, J. N.; Rahnke, C. J.

    1978-01-01

    The major considerations are discussed which will affect the selection of a ceramic regenerative heat exchanger for an improved 100 HP automotive gas turbine engine. The regenerator considered for this application is about 36cm in diameter. Regenerator comparisons are made on the basis of material, method of fabrication, cost, and performance. A regenerator inlet temperature of 1000 C is assumed for performance comparisons, and laboratory test results are discussed for material comparisons at 1100 and 1200 C. Engine test results using the Ford 707 industrial gas turbine engine are also discussed.

  15. Regeneration inducers in limb regeneration.

    PubMed

    Satoh, Akira; Mitogawa, Kazumasa; Makanae, Aki

    2015-08-01

    Limb regeneration ability, which can be observed in amphibians, has been investigated as a representative phenomenon of organ regeneration. Recently, an alternative experimental system called the accessory limb model was developed to investigate early regulation of amphibian limb regeneration. The accessory limb model contributed to identification of limb regeneration inducers in urodele amphibians. Furthermore, the accessory limb model may be applied to other species to explore universality of regeneration mechanisms. This review aims to connect the insights recently gained to emboss universality of regeneration mechanisms among species. The defined molecules (BMP7 (or2) + FGF2 + FGF8) can transform skin wound healing to organ (limb) regeneration responses. The same molecules can initiate regeneration responses in some species. PMID:26100345

  16. Nanomaterials and bone regeneration

    PubMed Central

    Gong, Tao; Xie, Jing; Liao, Jinfeng; Zhang, Tao; Lin, Shiyu; Lin, Yunfeng

    2015-01-01

    The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part. PMID:26558141

  17. Limb regeneration.

    PubMed

    Simon, András; Tanaka, Elly M

    2013-01-01

    Limb regeneration is observed in certain members of the animal phyla. Some animals keep this ability during their entire life while others lose it at some time during development. How do animals regenerate limbs? Is it possible to find unifying, conserved mechanisms of limb regeneration or have different species evolved distinct means of replacing a lost limb? How is limb regeneration similar or different to limb development? Studies on many organisms, including echinoderms, arthropods, and chordates have provided significant knowledge about limb regeneration. In this focus article, we concentrate on tetrapod limb regeneration as studied in three model amphibians: newts, axolotls, and frogs. We review recent progress on tissue interactions during limb regeneration, and place those findings into an evolutionary context. PMID:24009038

  18. Effects of continuously regenerating diesel particulate filters on regulated emissions and number-size distribution of particles emitted from a diesel engine.

    PubMed

    Liu, Zhihua; Shah, Asad Naeem; Ge, Yunshan; Ding, Yan; Tan, Jianwei; Jiang, Lei; Yu, Linxiao; Zhao, Wei; Wang, Chu; Zeng, Tao

    2011-01-01

    The effects of continuously regenerating diesel particulate filter (CRDPF) systems on regulated gaseous emissions, and number-size distribution and mass of particles emanated from a diesel engine have been investigated in this study. Two CRDPF units (CRDPF-1 and CRDPF-2) with different specifications were separately retrofitted to the engine running with European steady-state cycle (ESC). An electrical low pressure impactor (ELPI) was used for particle number-size distribution measurement and mass estimation. The conversion/reduction rate (R(CR)) of hydrocarbons (HC) and carbon monoxide (CO) across CRDPF-1 was 83% and 96.3%, respectively. Similarly, the R(CR) of HC and CO and across CRDPF-2 was 91.8% and 99.1%, respectively. The number concentration of particles and their concentration peaks; nuclei mode, accumulation mode and total particles; and particle mass were highly reduced with the CRDPF units. The nuclei mode particles at downstream of CRDPF-1 and CRDPF-2 decreased by 99.9% to 100% and 97.8% to 99.8% respectively; and the particle mass reduced by 73% to 92.2% and 35.3% to 72.4%, respectively, depending on the engine conditions. In addition, nuclei mode particles increased with the increasing of engine speed due to the heterogeneous nucleation initiated by the higher exhaust temperature, while accumulation mode particles were higher at higher loads due to the decrease in the air-to-fuel ratio (A/F) at higher loads.

  19. Ceramic regenerator systems development program

    NASA Technical Reports Server (NTRS)

    Cook, J. A.; Fucinari, C. A.; Lingscheit, J. N.; Rahnke, C. J.; Rao, V. D.

    1978-01-01

    Ceramic regenerator cores are considered that can be used in passenger car gas turbine engines, Stirling engines, and industrial/truck gas turbine engines. Improved materials and design concepts aimed at reducing or eliminating chemical attack were placed on durability tests/in industrial gas turbine engines. A regenerator core made from aluminum silicate shows minimal evidence of chemical attack damage after 7804 hours of engine test at 800 C and another showed little distress after 4983 hours at 982 C. The results obtained in ceramic material screening tests, aerothermodynamic performance tests, stress analysis, cost studies, and material specifications are also included.

  20. Synthetic Phage for Tissue Regeneration

    PubMed Central

    Merzlyak, Anna; Lee, Seung-Wuk

    2014-01-01

    Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy. PMID:24991085

  1. Engineered 3D bioimplants using elastomeric scaffold, self-assembling peptide hydrogel, and adipose tissue-derived progenitor cells for cardiac regeneration

    PubMed Central

    Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Vallés-Lluch, Ana; Castells-Sala, Cristina; Martínez-Ramos, Cristina; Fernández-Muiños, Teresa; Chachques, Juan Carlos; Pradas, Manuel Monleón; Semino, Carlos E; Bayes-Genis, Antoni

    2014-01-01

    Contractile restoration of myocardial scars remains a challenge with important clinical implications. Here, a combination of porous elastomeric membrane, peptide hydrogel, and subcutaneous adipose tissue-derived progenitor cells (subATDPCs) was designed and evaluated as a bioimplant for cardiac regeneration in a mouse model of myocardial infarction. SubATDPCs were doubly transduced with lentiviral vectors to express bioluminescent-fluorescent reporters driven by constitutively active, cardiac tissue-specific promoters. Cells were seeded into an engineered bioimplant consisting of a scaffold (polycaprolactone methacryloyloxyethyl ester) filled with a peptide hydrogel (PuraMatrix™), and transplanted to cover injured myocardium. Bioluminescence and fluorescence quantifications showed de novo and progressive increases in promoter expression in bioactive implant-treated animals. The bioactive implant was well adapted to the heart, and fully functional vessels traversed the myocardium-bioactive implant interface. Treatment translated into a detectable positive effect on cardiac function, as revealed by echocardiography. Thus, this novel implant is a promising construct for supporting myocardial regeneration. PMID:24936221

  2. Cofactor Specificity Engineering of Streptococcus mutans NADH Oxidase 2 for NAD(P)(+) Regeneration in Biocatalytic Oxidations.

    PubMed

    Petschacher, Barbara; Staunig, Nicole; Müller, Monika; Schürmann, Martin; Mink, Daniel; De Wildeman, Stefaan; Gruber, Karl; Glieder, Anton

    2014-01-01

    Soluble water-forming NAD(P)H oxidases constitute a promising NAD(P)(+) regeneration method as they only need oxygen as cosubstrate and produce water as sole byproduct. Moreover, the thermodynamic equilibrium of O2 reduction is a valuable driving force for mostly energetically unfavorable biocatalytic oxidations. Here, we present the generation of an NAD(P)H oxidase with high activity for both cofactors, NADH and NADPH. Starting from the strictly NADH specific water-forming Streptococcus mutans NADH oxidase 2 several rationally designed cofactor binding site mutants were created and kinetic values for NADH and NADPH conversion were determined. Double mutant 193R194H showed comparable high rates and low K m values for NADPH (k cat 20 s(-1), K m 6 µM) and NADH (k cat 25 s(-1), K m 9 µM) with retention of 70% of wild type activity towards NADH. Moreover, by screening of a SeSaM library S. mutans NADH oxidase 2 variants showing predominantly NADPH activity were found, giving further insight into cofactor binding site architecture. Applicability for cofactor regeneration is shown for coupling with alcohol dehydrogenase from Sphyngobium yanoikuyae for 2-heptanone production.

  3. Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract.

    PubMed

    Blackmore, Murray G; Wang, Zimei; Lerch, Jessica K; Motti, Dario; Zhang, Yi Ping; Shields, Christopher B; Lee, Jae K; Goldberg, Jeffrey L; Lemmon, Vance P; Bixby, John L

    2012-05-01

    Axon regeneration in the central nervous system normally fails, in part because of a developmental decline in the intrinsic ability of CNS projection neurons to extend axons. Members of the KLF family of transcription factors regulate regenerative potential in developing CNS neurons. Expression of one family member, KLF7, is down-regulated developmentally, and overexpression of KLF7 in cortical neurons in vitro promotes axonal growth. To circumvent difficulties in achieving high neuronal expression of exogenous KLF7, we created a chimera with the VP16 transactivation domain, which displayed enhanced neuronal expression compared with the native protein while maintaining transcriptional activation and growth promotion in vitro. Overexpression of VP16-KLF7 overcame the developmental loss of regenerative ability in cortical slice cultures. Adult corticospinal tract (CST) neurons failed to up-regulate KLF7 in response to axon injury, and overexpression of VP16-KLF7 in vivo promoted both sprouting and regenerative axon growth in the CST of adult mice. These findings identify a unique means of promoting CST axon regeneration in vivo by reengineering a developmentally down-regulated, growth-promoting transcription factor. PMID:22529377

  4. Engineering of a novel carbonyl reductase with coenzyme regeneration in E. coli for efficient biosynthesis of enantiopure chiral alcohols.

    PubMed

    Wei, Ping; Gao, Jia-Xin; Zheng, Gao-Wei; Wu, Hong; Zong, Min-Hua; Lou, Wen-Yong

    2016-07-20

    The novel anti-Prelog stereospecific carbonyl reductase from Acetobacter sp. CCTCC M209061 was successfully expressed in E. coli combined with glucose dehydrogenase (GDH) to construct an efficient whole-cell biocatalyst with coenzyme NADH regeneration. The enzymatic activity of GAcCR (AcCR with a GST tag) reached 304.9U/g-dcw, even 9 folds higher than that of wild strain, and the activity of GDH for NADH regeneration recorded 46.0U/mg-protein in the recombinant E. coli. As a whole-cell biocatalyst, the recombinant E. coli BL21(DE3)pLysS (pETDuet-gaccr-gdh) possessed a broad substrate spectrum for kinds of carbonyl compounds with encouraging yield and stereoselectivity. Besides, the asymmetric reduction of ethyl 4-chloroacetoacetate (COBE) to optically pure ethyl 4-chloro-3-hydroxybutyrate (CHBE) catalyzed by the whole-cell biocatalyst was systematically investigated. Under the optimal reaction conditions, the optical purity of CHBE was over 99% e.e. for (S)-enantiomer, and the initial rate and product yield reached 8.04μmol/min and 99.4%, respectively. Moreover, the space-time yield was almost 20 folds higher than that catalyzed by the wild strain. Therefore, a new, high efficiency biocatalyst for asymmetric reductions was constructed successfully, and the enantioselective reduction of prochiral compounds using the biocatalyst was a promising approach for obtaining enantiopure chiral alcohols. PMID:27211999

  5. Retention of phosphorous ions on natural and engineered waste pumice: Characterization, equilibrium, competing ions, regeneration, kinetic, equilibrium and thermodynamic study

    NASA Astrophysics Data System (ADS)

    Karimaian, Kamal Aldin; Amrane, Abdeltif; Kazemian, Hossein; Panahi, Reza; Zarrabi, Mansur

    2013-11-01

    Natural and Mg2+ modified pumice were used for the removal of phosphorous. The adsorbents were characterized using XRF, XRD, SEM and FTIR instrumental techniques. In the optimal conditions, namely at equilibrium time (30 min), for a phosphorus concentration of 15 mg/L and pH 6, 69 and 97% phosphorus removals were achieved using 10 g/L of natural and modified pumice adsorbents, respectively. Maximum adsorption capacities were 11.88 and 17.71 mg/g by natural and modified pumice, respectively. Pseudo-second order kinetic model was the most relevant to describe the kinetic of phosphorus adsorption. External mass transfer coefficient decreased for increasing phosphorous concentration and film diffusion was found to be the rate-controlling step. Only a very low dissolution of the adsorbent was observed, leading to a low increase in conductivity and turbidity. Removal efficiency decreased for increasing ionic strength. It also decreased in the presence of competing ions; however modified pumice remained effective, since 67% of phosphorus was removed, versus only 17% for the natural pumice. The efficiency of the modified pumice was confirmed during the regeneration tests, since 96% regeneration yield was obtained after 510 min experiment, while only 22% was observed for the raw pumice.

  6. Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

    PubMed

    Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali

    2016-10-01

    Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan-gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan-gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan-gelatin scaffolds. Implantation of both the gelatin and chitosan-gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin-chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects. PMID:27590825

  7. Efficient quantum circuits for Toeplitz and Hankel matrices

    NASA Astrophysics Data System (ADS)

    Mahasinghe, A.; Wang, J. B.

    2016-07-01

    Toeplitz and Hankel matrices have been a subject of intense interest in a wide range of science and engineering related applications. In this paper, we show that quantum circuits can efficiently implement sparse or Fourier-sparse Toeplitz and Hankel matrices. This provides an essential ingredient for solving many physical problems with Toeplitz or Hankel symmetry in the quantum setting with deterministic queries.

  8. Simultaneous implant placement and bone regeneration around dental implants using tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-rich plasma.

    PubMed

    Ito, Kenji; Yamada, Yoichi; Naiki, Takahito; Ueda, Minoru

    2006-10-01

    This study was undertaken to evaluate the use of tissue-engineered bone as grafting material for alveolar augmentation with simultaneous implant placement. Twelve adult hybrid dogs were used in this study. One month after the extraction of teeth in the mandible region, bone defects on both sides of the mandible were induced using a trephine bar with a diameter of 10 mm. Dog mesenchymal stem cells (dMSCs) were obtained via iliac bone biopsy and cultured for 4 weeks before implantation. After installing the dental implants, the defects were simultaneously implanted with the following graft materials: (i) fibrin, (ii) dMSCs and fibrin (dMSCs/fibrin), (iii) dMSCs, platelet-rich plasma (PRP) and fibrin (dMSCs/PRP/fibrin) and (iv) control (defect only). The implants were assessed by histological and histomorphometric analysis, 2, 4 and 8 weeks after implantation. The implants exhibited varying degrees of bone-implant contact (BIC). The BIC was 17%, 19% and 29% (control), 20%, 22% and 25% (fibrin), 22%, 32% and 42% (dMSCs/fibrin) and 25%, 49% and 53% (dMSCs/PRP/fibrin) after 2, 4 and 8 weeks, respectively. This study suggests that tissue-engineered bone may be of sufficient quality for predictable enhancement of bone regeneration around dental implants when used simultaneous by with implant placement.

  9. Impact of a NO₂-regenerated diesel particulate filter on PAH and NPAH emissions from an EURO IV heavy duty engine.

    PubMed

    Carrara, Matteo; Niessner, Reinhard

    2011-12-01

    In this study the emissions of polycyclic aromatic hydrocarbons (PAH) and their nitro-derivates (NPAH) from a modern heavy duty engine were analysed. Focus was on the effects of the aftertreatment system. It consisted of an oxidation catalyst coupled to a diesel particulate filter (DPF). In such systems the process of PAH and NPAH degradation may compete with the NPAH formation. Scope of the study was to explain to which extent modern DPF could support the formation of highly mutagenic NPAH by nitration of pre-existing PAH. It was found that the diesel trap reduced the total amount of PAH and NPAH emitted both at low load and high load. Nevertheless, at low load the lower temperatures and the higher NO(2) concentration furnished better conditions for PAH nitration while they were more adverse to NPAH degradation. These effects were NPAH-specific. For these reasons, some NPAH like 3-nitrophenanthrene were still efficiently degraded but others were newly formed. For instance emissions of the highly toxic 1-benzo(a)pyrene and 6-nitrobenzo(a)pyrene where increased by a factor 15 at low load and, even if in lower amount, were formed also at high load. The super-mutagen 1,6-dinitropyrene, which was not present in raw exhaust, could be found only after the DPF, indicating a new formation. In regard to emissions from the active regeneration mode, tremendous high emissions of 1-nitropyrene were reported. More accurate investigation of such a regeneration mode would be of great interest for the future.

  10. Cell-engineered human elastic chondrocytes regenerate natural scaffold in vitro and neocartilage with neoperichondrium in the human body post-transplantation.

    PubMed

    Yanaga, Hiroko; Imai, Keisuke; Koga, Mika; Yanaga, Katsu

    2012-10-01

    We have developed a unique method that allows us to culture large volumes of chondrocyte expansion from a small piece of human elastic cartilage. The characteristic features of our culturing method are that fibroblast growth factor-2 (FGF2), which promotes proliferation of elastic chondrocytes, is added to a culture medium, and that cell-engineering techniques are adopted in the multilayered culture system that we have developed. We have subsequently discovered that once multilayered chondrocytes are transplanted into a human body, differentiation induction that makes use of surrounding tissue occurs in situ, and a large cartilage block is obtained through cartinogenesis and matrix formation. We have named this method two-stage transplantation. We have clinically applied this transplantation method to the congenital ear defect, microtia, and reported successful ear reconstruction. In our present study, we demonstrated that when FGF2 was added to elastic chondrocytes, the cell count increased and the level of hyaluronic acid, which is a major extracellular matrix (ECM) component, increased. We also demonstrated that these biochemical changes are reflected in the morphology, with the elastic chondrocytes themselves producing a matrix and fibers in vitro to form a natural scaffold. We then demonstrated that inside the natural scaffold thus formed, the cells overlap, connect intercellularly to each other, and reconstruct a cartilage-like three-dimensional structure in vitro. We further demonstrated by immunohistochemical analysis and electron microscopic analysis that when the multilayered chondrocytes are subsequently transplanted into a living body (abdominal subcutaneous region) in the two-stage transplantation process, neocartilage and neoperichondrium of elastic cartilage origin are regenerated 6 months after transplantation. Further, evaluation by dynamic mechanical analysis showed the regenerated neocartilage to have the same viscoelasticity as normal auricular

  11. Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration.

    PubMed

    Mauck, Robert L; Baker, Brendon M; Nerurkar, Nandan L; Burdick, Jason A; Li, Wan-Ju; Tuan, Rocky S; Elliott, Dawn M

    2009-06-01

    Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation.

  12. Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

    PubMed Central

    Baker, Brendon M.; Nerurkar, Nandan L.; Burdick, Jason A.; Li, Wan-Ju; Tuan, Rocky S.; Elliott, Dawn M.

    2009-01-01

    Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation. PMID:19207040

  13. [The possibilities and perspectives of using scaffold technology for bone regeneration].

    PubMed

    Ivanov, A N; Norkin, I A; Puchin'ian, D M

    2014-01-01

    The article deals with the one of the topical problem of tissue engineering--the design and implementation of biomaterials that could replace and repair bone defects. This review presents the recent studies of the potential of scaffold technology in bone tissue regeneration. This article contains information about the basic parameters and properties of modern scaffold systems. The results of experimental in vitro and in vivo studies on the use of matrices made of various materials are shown. Advantages and disadvantages of various materials used for the production of scaffolds are discussed. Attention is paid to the advantages combinations of different materials to achieve the desired structural and functional properties. Particular attention is paid to technologies and systems of targeted delivery and controlled release of factors that stimulate bone tissue regeneration. Different strategies for modulating tissue reactions and immune responses that take place during scaffold implantation are presented.

  14. Protein-based biorefining: metabolic engineering for production of chemicals and fuel with regeneration of nitrogen fertilizers.

    PubMed

    Wernick, David G; Liao, James C

    2013-02-01

    Threats to stable oil supplies and concerns over environmental emissions have pushed for renewable biofuel developments to minimize dependence on fossil resources. Recent biofuel progress has moved towards fossil resource-independent carbon cycles, but environmental issues regarding use of nitrogen fertilizers have not been addressed on a global scale. The recently demonstrated conversion of waste protein biomass into advanced biofuels and renewable chemicals, while recycling nitrogen fertilizers, offers a glimpse of the efforts needed to balance the nitrogen cycle at scale. In general, the catabolism of protein into biofuels is challenging because of physiological regulation and thermodynamic limitations. This conversion became possible with metabolic engineering around ammonia assimilation, intracellular nitrogen flux, and quorum sensing. This review highlights the metabolic engineering solutions in transforming those cellular processes into driving forces for the high yield of chemical products from protein.

  15. Biomaterials in tooth tissue engineering: a review.

    PubMed

    Sharma, Sarang; Srivastava, Dhirendra; Grover, Shibani; Sharma, Vivek

    2014-01-01

    Biomaterials play a crucial role in the field of tissue engineering. They are utilized for fabricating frameworks known as scaffolds, matrices or constructs which are interconnected porous structures that establish a cellular microenvironment required for optimal tissue regeneration. Several natural and synthetic biomaterials have been utilized for fabrication of tissue engineering scaffolds. Amongst different biomaterials, polymers are the most extensively experimented and employed materials. They can be tailored to provide good interconnected porosity, large surface area, adequate mechanical strengths, varying surface characterization and different geometries required for tissue regeneration. A single type of material may however not meet all the requirements. Selection of two or more biomaterials, optimization of their physical, chemical and mechanical properties and advanced fabrication techniques are required to obtain scaffold designs intended for their final application. Current focus is aimed at designing biomaterials such that they will replicate the local extra cellular environment of the native organ and enable cell-cell and cell-scaffold interactions at micro level required for functional tissue regeneration. This article provides an insight into the different biomaterials available and the emerging use of nano engineering principles for the construction of bioactive scaffolds in tooth regeneration.

  16. Biomaterials in Tooth Tissue Engineering: A Review

    PubMed Central

    Sharma, Sarang; Srivastava, Dhirendra; Grover, Shibani; Sharma, Vivek

    2014-01-01

    Biomaterials play a crucial role in the field of tissue engineering. They are utilized for fabricating frameworks known as scaffolds, matrices or constructs which are interconnected porous structures that establish a cellular microenvironment required for optimal tissue regeneration. Several natural and synthetic biomaterials have been utilized for fabrication of tissue engineering scaffolds. Amongst different biomaterials, polymers are the most extensively experimented and employed materials. They can be tailored to provide good interconnected porosity, large surface area, adequate mechanical strengths, varying surface characterization and different geometries required for tissue regeneration. A single type of material may however not meet all the requirements. Selection of two or more biomaterials, optimization of their physical, chemical and mechanical properties and advanced fabrication techniques are required to obtain scaffold designs intended for their final application. Current focus is aimed at designing biomaterials such that they will replicate the local extra cellular environment of the native organ and enable cell-cell and cell-scaffold interactions at micro level required for functional tissue regeneration. This article provides an insight into the different biomaterials available and the emerging use of nano engineering principles for the construction of bioactive scaffolds in tooth regeneration. PMID:24596804

  17. A Microfabricated Segmented-Involute-Foil Regenerator for Enhancing Reliability and Performance of Stirling Engines. Phase III Final Report for the Radioisotope Power Conversion Technology NRA

    NASA Technical Reports Server (NTRS)

    Ibrahim, Mounir B.; Gedeon, David; Wood, Gary; McLean, Jeffrey

    2009-01-01

    Under Phase III of NASA Research Announcement contract NAS3-03124, a prototype nickel segmented-involute-foil regenerator was microfabricated and tested in a Sunpower Frequency-Test-Bed (FTB) Stirling convertor. The team for this effort consisted of Cleveland State University, Gedeon Associates, Sunpower Inc. and International Mezzo Technologies. Testing in the FTB convertor produced about the same efficiency as testing with the original random-fiber regenerator. But the high thermal conductivity of the prototype nickel regenerator was responsible for a significant performance degradation. An efficiency improvement (by a 1.04 factor, according to computer predictions) could have been achieved if the regenerator was made from a low-conductivity material. Also, the FTB convertor was not reoptimized to take full advantage of the microfabricated regenerator s low flow resistance; thus, the efficiency would likely have been even higher had the FTB been completely reoptimized. This report discusses the regenerator microfabrication process, testing of the regenerator in the Stirling FTB convertor, and the supporting analysis. Results of the pre-test computational fluid dynamics (CFD) modeling of the effects of the regenerator-test-configuration diffusers (located at each end of the regenerator) are included. The report also includes recommendations for further development of involute-foil regenerators from a higher-temperature material than nickel.

  18. Method And Apparatus For Regenerating Nox Adsorbers

    DOEpatents

    Driscoll, J. Joshua; Endicott, Dennis L.; Faulkner, Stephen A.; Verkiel, Maarten

    2006-03-28

    Methods and apparatuses for regenerating a NOx adsorber coupled with an exhaust of an engine. An actuator drives a throttle valve to a first position when regeneration of the NOx adsorber is desired. The first position is a position that causes the regeneration of the NOx adsorber. An actuator drives the throttle valve to a second position while regeneration of the NOx adsorber is still desired. The second position being a position that is more open than the first position and operable to regenerate a NOx adsorber.

  19. Random cyclic matrices.

    PubMed

    Jain, Sudhir R; Srivastava, Shashi C L

    2008-09-01

    We present a Gaussian ensemble of random cyclic matrices on the real field and study their spectral fluctuations. These cyclic matrices are shown to be pseudosymmetric with respect to generalized parity. We calculate the joint probability distribution function of eigenvalues and the spacing distributions analytically and numerically. For small spacings, the level spacing distribution exhibits either a Gaussian or a linear form. Furthermore, for the general case of two arbitrary complex eigenvalues, leaving out the spacings among real eigenvalues, and, among complex conjugate pairs, we find that the spacing distribution agrees completely with the Wigner distribution for a Poisson process on a plane. The cyclic matrices occur in a wide variety of physical situations, including disordered linear atomic chains and the Ising model in two dimensions. These exact results are also relevant to two-dimensional statistical mechanics and nu -parametrized quantum chromodynamics. PMID:18851127

  20. A three-dimensional multiporous fibrous scaffold fabricated with regenerated spider silk protein/poly(l-lactic acid) for tissue engineering.

    PubMed

    Yu, Qiaozhen; Sun, Chengjun

    2015-02-01

    An axially aligned three-dimensional (3-D) fibrous scaffold was fabricated with regenerated spider silk protein (RSSP)/poly (l-lactic acid) (PLLA) through electrospinning and post treatment. The morphology, mechanical and degradation properties of the scaffold were controlled through the weight ratio of RSSP to PLLA, the thickness of the scaffold and the treatment time. The scaffold with a weight ratio of 2:3 (RSSP:PLLA) had a nanoleaves-on-nanofibers hierarchical nanostructure; the length and thickness of the nanoleaves were about 400 and 30 nm, respectively. The holes of the scaffolds ranged from hundreds of nanometers to several microns. The scaffold showed an ideal mechanical property that it was stiff when dry, but became soft once hydrated in the culture medium. Its degradation rate was very slow in the first 2 months, and then accelerated in the following 2 months. The pH values of the degradation mediums of all the samples remained in the range of 7.40-7.12 during degradation for 6 months. It had good biocompatibility with PC 12 cells. The aligned hierarchical nanostructure could guide the directions of the axon extension. This scaffold has a potential application in Tissue Engineering and controlled release. This study provides a method to produce synthetic or natural biodegradable polymer scaffold with tailored morphology, mechanical, and degradation properties. PMID:24825592

  1. A three-dimensional multiporous fibrous scaffold fabricated with regenerated spider silk protein/poly(l-lactic acid) for tissue engineering.

    PubMed

    Yu, Qiaozhen; Sun, Chengjun

    2015-02-01

    An axially aligned three-dimensional (3-D) fibrous scaffold was fabricated with regenerated spider silk protein (RSSP)/poly (l-lactic acid) (PLLA) through electrospinning and post treatment. The morphology, mechanical and degradation properties of the scaffold were controlled through the weight ratio of RSSP to PLLA, the thickness of the scaffold and the treatment time. The scaffold with a weight ratio of 2:3 (RSSP:PLLA) had a nanoleaves-on-nanofibers hierarchical nanostructure; the length and thickness of the nanoleaves were about 400 and 30 nm, respectively. The holes of the scaffolds ranged from hundreds of nanometers to several microns. The scaffold showed an ideal mechanical property that it was stiff when dry, but became soft once hydrated in the culture medium. Its degradation rate was very slow in the first 2 months, and then accelerated in the following 2 months. The pH values of the degradation mediums of all the samples remained in the range of 7.40-7.12 during degradation for 6 months. It had good biocompatibility with PC 12 cells. The aligned hierarchical nanostructure could guide the directions of the axon extension. This scaffold has a potential application in Tissue Engineering and controlled release. This study provides a method to produce synthetic or natural biodegradable polymer scaffold with tailored morphology, mechanical, and degradation properties.

  2. Depolarizing differential Mueller matrices.

    PubMed

    Ortega-Quijano, Noé; Arce-Diego, José Luis

    2011-07-01

    The evolution of a polarized beam can be described by the differential formulation of Mueller calculus. The nondepolarizing differential Mueller matrices are well known. However, they only account for 7 out of the 16 independent parameters that are necessary to model a general anisotropic depolarizing medium. In this work we present the nine differential Mueller matrices for general depolarizing media, highlighting the physical implications of each of them. Group theory is applied to establish the relationship between the differential matrix and the set of transformation generators in the Minkowski space, of which Lorentz generators constitute a particular subgroup. PMID:21725434

  3. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering.

    PubMed

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration-culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch. PMID:26989897

  4. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering.

    PubMed

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration-culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch.

  5. Experiments and Analysis of DPF Loading and Regeneration

    SciTech Connect

    Balakrishnan, Krishnan

    2000-08-20

    Particulate filter system consists of a filter and a regeneration strategy Commercial filters are very effective at removing PM, but regeneration is a challenge. In addition to removal of PM if is important to reduce other pollutants including NO, from diesel engine exhaust Particulate filter regeneration strategy can include catalysts, fuel additives, engine control, and fuel injection Regeneration 5M?-500 C without catalyst Near 350 C with fuel additive or catalyst coated DPF

  6. Ceramic regenerator systems development program

    NASA Technical Reports Server (NTRS)

    Fucinari, C. A.; Rahnke, C. J.; Rao, V. D. N.; Vallance, J. K.

    1980-01-01

    The DOE/NASA Ceramic Regenerator Design and Reliability Program aims to develop ceramic regenerator cores that can be used in passenger car and industrial/truck gas turbine engines. The major cause of failure of early gas turbine regenerators was found to be chemical attack of the ceramic material. Improved materials and design concepts aimed at reducing or eliminating chemical attack were placed on durability test in Ford 707 industrial gas turbine engines late in 1974. Results of 53,065 hours of turbine engine durability testing are described. Two materials, aluminum silicate and magnesium aluminum silicate, show promise. Five aluminum silicate cores attained the durability objective of 10,000 hours at 800 C (1472 F). Another aluminum silicate core shows minimal evidence of chemical attack after 8071 hours at 982 C (1800 F). Results obtained in ceramic material screening tests, aerothermodynamic performance tests, stress analysis, cost studies, and material specifications are included.

  7. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  8. Woven silk fabric-reinforced silk nanofibrous scaffolds for regenerating load-bearing soft tissues.

    PubMed

    Han, F; Liu, S; Liu, X; Pei, Y; Bai, S; Zhao, H; Lu, Q; Ma, F; Kaplan, D L; Zhu, H

    2014-02-01

    Although three-dimensional (3-D) porous regenerated silk scaffolds with outstanding biocompatibility, biodegradability and low inflammatory reactions have promising application in different tissue regeneration, the mechanical properties of regenerated scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This study presents woven silk fabric-reinforced silk nanofibrous scaffolds aimed at dermal tissue engineering. To improve the mechanical properties, silk scaffolds prepared by lyophilization were reinforced with degummed woven silk fabrics. The ultimate tensile strength, elongation at break and suture retention strength of the scaffolds were significantly improved, providing suitable mechanical properties strong enough for clinical applications. The stiffness and degradation behaviors were then further regulated by different after-treatment processes, making the scaffolds more suitable for dermal tissue regeneration. The in vitro cell culture results indicated that these scaffolds maintained their excellent biocompatibility after being reinforced with woven silk fabrics. Without sacrifice of porous structure and biocompatibility, the fabric-reinforced scaffolds with better mechanical properties could facilitate future clinical applications of silk as matrices in skin repair. PMID:24090985

  9. Engineering a multi-biofunctional composite using poly(ethylenimine) decorated graphene oxide for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Kumar, Sachin; Raj, Shammy; Sarkar, Kishor; Chatterjee, Kaushik

    2016-03-01

    Toward preparing strong multi-biofunctional materials, poly(ethylenimine) (PEI) conjugated graphene oxide (GO_PEI) was synthesized using poly(acrylic acid) (PAA) as a spacer and incorporated in poly(ε-caprolactone) (PCL) at different fractions. GO_PEI significantly promoted the proliferation and formation of focal adhesions in human mesenchymal stem cells (hMSCs) on PCL. GO_PEI was highly potent in inducing stem cell osteogenesis leading to near doubling of alkaline phosphatase expression and mineralization over neat PCL with 5% filler content and was ~50% better than GO. Remarkably, 5% GO_PEI was as potent as soluble osteoinductive factors. Increased adsorption of osteogenic factors due to the amine and oxygen containing functional groups on GO_PEI augment stem cell differentiation. GO_PEI was also highly efficient in imparting bactericidal activity with 85% reduction in counts of E. coli colonies compared to neat PCL at 5% filler content and was more than twice as efficient as GO. This may be attributed to the synergistic effect of the sharp edges of the particles along with the presence of the different chemical moieties. Thus, GO_PEI based polymer composites can be utilized to prepare bioactive resorbable biomaterials as an alternative to using labile biomolecules for fabricating orthopedic devices for fracture fixation and tissue engineering.Toward preparing strong multi-biofunctional materials, poly(ethylenimine) (PEI) conjugated graphene oxide (GO_PEI) was synthesized using poly(acrylic acid) (PAA) as a spacer and incorporated in poly(ε-caprolactone) (PCL) at different fractions. GO_PEI significantly promoted the proliferation and formation of focal adhesions in human mesenchymal stem cells (hMSCs) on PCL. GO_PEI was highly potent in inducing stem cell osteogenesis leading to near doubling of alkaline phosphatase expression and mineralization over neat PCL with 5% filler content and was ~50% better than GO. Remarkably, 5% GO_PEI was as potent as soluble

  10. Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways.

    PubMed

    Lim, Hyun-Chang; Nam, Ok Hyung; Kim, Mi-Joo; El-Fiqi, Ahmed; Yun, Hyung-Mun; Lee, Yoo-Mi; Jin, Guang-Zhen; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2016-01-01

    Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and β3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering. PMID:27354790

  11. Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways.

    PubMed

    Lim, Hyun-Chang; Nam, Ok Hyung; Kim, Mi-Joo; El-Fiqi, Ahmed; Yun, Hyung-Mun; Lee, Yoo-Mi; Jin, Guang-Zhen; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2016-01-01

    Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and β3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering.

  12. Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways

    PubMed Central

    Lim, Hyun-Chang; Nam, Ok Hyung; Kim, Mi-joo; El-Fiqi, Ahmed; Yun, Hyung-Mun; Lee, Yoo-Mi; Jin, Guang-Zhen; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2016-01-01

    Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and β3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering. PMID:27354790

  13. A tissue engineering approach for periodontal regeneration based on a biodegradable double-layer scaffold and adipose-derived stem cells.

    PubMed

    Requicha, João F; Viegas, Carlos A; Muñoz, Fernando; Azevedo, Jorge M; Leonor, Isabel B; Reis, Rui L; Gomes, Manuela E

    2014-09-01

    Human and canine periodontium are often affected by an inflammatory pathology called periodontitis, which is associated with severe damages across tissues, namely, in the periodontal ligament, cementum, and alveolar bone. However, the therapies used in the routine dental practice, often consisting in a combination of different techniques, do not allow to fully restore the functionality of the periodontium. Tissue Engineering (TE) appears as a valuable alternative approach to regenerate periodontal defects, but for this purpose, it is essential to develop supportive biomaterial and stem cell sourcing/culturing methodologies that address the complexity of the various tissues affected by this condition. The main aim of this work was to study the in vitro functionality of a newly developed double-layer scaffold for periodontal TE. The scaffold design was based on a combination of a three-dimensional (3D) fiber mesh functionalized with silanol groups and a membrane, both made of a blend of starch and poly-ɛ-(caprolactone). Adipose-derived stem cells (canine adipose stem cells [cASCs]) were seeded and cultured onto such scaffolds, and the obtained constructs were evaluated in terms of cellular morphology, metabolic activity, and proliferation. The osteogenic potential of the fiber mesh layer functionalized with silanol groups was further assessed concerning the osteogenic differentiation of the seeded and cultured ASCs. The obtained results showed that the proposed double-layer scaffold supports the proliferation and selectively promotes the osteogenic differentiation of cASCs seeded onto the functionalized mesh. These findings suggest that the 3D structure and asymmetric composition of the scaffold in combination with stem cells may provide the basis for developing alternative therapies to treat periodontal defects more efficiently.

  14. Molecular engineering of simple phenothiazine-based dyes to modulate dye aggregation, charge recombination, and dye regeneration in highly efficient dye-sensitized solar cells.

    PubMed

    Hua, Yong; Chang, Shuai; He, Jian; Zhang, Caishun; Zhao, Jianzhang; Chen, Tao; Wong, Wai-Yeung; Wong, Wai-Kwok; Zhu, Xunjin

    2014-05-19

    A series of simple phenothiazine-based dyes, namely, TP, EP, TTP, ETP, and EEP have been developed, in which the thiophene (T), ethylenedioxythiophene (E), their dimers, and mixtures are present to modulate dye aggregation, charge recombination, and dye regeneration for highly efficient dye-sensitized solar cell (DSSC) applications. Devices sensitized by the dyes TP and TTP display high power conversion efficiencies (PCEs) of 8.07 (Jsc = 15.2 mA cm(-2), Voc =0.783 V, fill factor (FF) = 0.679) and 7.87 % (Jsc = 16.1 mA cm(-2), Voc = 0.717 V, FF = 0.681), respectively; these were measured under simulated AM 1.5 sunlight in conjunction with the I(-)/I3(-) redox couple. By replacing the T group with the E unit, EP-based DSSCs had a slightly lower PCE of 7.98 % with a higher short-circuit photocurrent (Jsc) of 16.7 mA cm(-2). The dye ETP, with a mixture of E and T, had an even lower PCE of 5.62 %. Specifically, the cell based on the dye EEP, with a dimer of E, had inferior Jsc and Voc values and corresponded to the lowest PCE of 2.24 %. The results indicate that the photovoltaic performance can be finely modulated through structural engineering of the dyes. The selection of T analogues as donors can not only modulate light absorption and energy levels, but also have an impact on dye aggregation and interfacial charge recombination of electrons at the interface of titania, electrolytes, and/or oxidized dye molecules; this was demonstrated through DFT calculations, electrochemical impedance analysis, and transient photovoltage studies.

  15. Complete pulpodentin complex regeneration by modulating the stiffness of biomimetic matrix.

    PubMed

    Qu, Tiejun; Jing, Junjun; Ren, Yinshi; Ma, Chi; Feng, Jian Q; Yu, Qing; Liu, Xiaohua

    2015-04-01

    Dental caries is one of the most prevalent chronic diseases in all populations. The regeneration of dentin-pulp tissues (pulpodentin) using a scaffold-based tissue engineering strategy is a promising approach to replacing damaged dental structures and restoring their biological functions. However, the current scaffolding design for pulpodentin regeneration does not take into account the distinct difference between pulp and dentin, therefore, is incapable of regenerating a complete tooth-like pulpodentin complex. In this study, we determined that scaffolding stiffness is a crucial biophysical cue to modulate dental pulp stem cell (DPSC) differentiation. The DPSCs on a high-stiffness three-dimensional (3D) nanofibrous gelatin (NF-gelatin) scaffold had more organized cytoskeletons and a larger spreading area than on a low-stiffness NF-gelatin scaffold. In the same differentiation medium, a high-stiffness NF-gelatin facilitated DPSC differentiation to form a mineralized tissue, while a low-stiffness NF-gelatin promoted a soft pulp-like tissue formation from the DPSCs. A facile method was then developed to integrate the low- and high-stiffness gelatin matrices into a single scaffold (S-scaffold) for pulpodentin complex regeneration. A 4-week in vitro experiment showed that biomineralization took place only in the high-stiffness peripheral area and formed a ring-like structure surrounding the non-mineralized central area of the DPSC/S-scaffold construct. A complete pulpodentin complex similar to natural pulpodentin was successfully regenerated after subcutaneous implantation of the DPSC/S-scaffold in nude mice for 4weeks. Histological staining showed a significant amount of extracellular matrix (ECM) formation in the newly formed pulpodentin complex, and a number of blood vessels were observed in the pulp tissue. Taken together, this work shows that modulating the stiffness of the NF-gelatin scaffold is a successful approach to regenerating a complete tooth

  16. Singular Mueller matrices.

    PubMed

    Gil, José J; Ossikovski, Razvigor; José, Ignacio San

    2016-04-01

    Singular Mueller matrices play an important role in polarization algebra and have peculiar properties that stem from the fact that either the medium exhibits maximum diattenuation and/or polarizance or because its associated canonical depolarizer has the property of fully randomizing the circular component (at least) of the states of polarization of light incident on it. The formal reasons for which the Mueller matrix M of a given medium is singular are systematically investigated, analyzed, and interpreted in the framework of the serial decompositions and the characteristic ellipsoids of M. The analysis allows for a general classification and geometric representation of singular Mueller matrices, which are of potential usefulness to experimentalists dealing with such media. PMID:27140769

  17. Singular Mueller matrices.

    PubMed

    Gil, José J; Ossikovski, Razvigor; José, Ignacio San

    2016-04-01

    Singular Mueller matrices play an important role in polarization algebra and have peculiar properties that stem from the fact that either the medium exhibits maximum diattenuation and/or polarizance or because its associated canonical depolarizer has the property of fully randomizing the circular component (at least) of the states of polarization of light incident on it. The formal reasons for which the Mueller matrix M of a given medium is singular are systematically investigated, analyzed, and interpreted in the framework of the serial decompositions and the characteristic ellipsoids of M. The analysis allows for a general classification and geometric representation of singular Mueller matrices, which are of potential usefulness to experimentalists dealing with such media.

  18. Stable lepton mass matrices

    NASA Astrophysics Data System (ADS)

    Domcke, Valerie; Romanino, Andrea

    2016-06-01

    We study natural lepton mass matrices, obtained assuming the stability of physical flavour observables with respect to the variations of individual matrix elements. We identify all four possible stable neutrino textures from algebraic conditions on their entries. Two of them turn out to be uniquely associated to specific neutrino mass patterns. We then concentrate on the semi-degenerate pattern, corresponding to an overall neutrino mass scale within the reach of future experiments. In this context we show that i) the neutrino and charged lepton mixings and mass matrices are largely constrained by the requirement of stability, ii) naturalness considerations give a mild preference for the Majorana phase most relevant for neutrinoless double- β decay, α ˜ π/2, and iii) SU(5) unification allows to extend the implications of stability to the down quark sector. The above considerations would benefit from an experimental determination of the PMNS ratio | U 32 /U 31|, i.e. of the Dirac phase δ.

  19. Expediting the transition from replacement medicine to tissue engineering.

    PubMed

    Coury, Arthur J

    2016-06-01

    In this article, an expansive interpretation of "Tissue Engineering" is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: "Exerting systematic control of the body's cells, matrices and fluids." As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body's responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of "replacement medicine" where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body's tissues and functions by exploiting our expanding knowledge of the body's biological processes to produce natural, healthy outcomes.

  20. Regenerator cross arm seal assembly

    DOEpatents

    Jackman, Anthony V.

    1988-01-01

    A seal assembly for disposition between a cross arm on a gas turbine engine block and a regenerator disc, the seal assembly including a platform coextensive with the cross arm, a seal and wear layer sealingly and slidingly engaging the regenerator disc, a porous and compliant support layer between the platform and the seal and wear layer porous enough to permit flow of cooling air therethrough and compliant to accommodate relative thermal growth and distortion, a dike between the seal and wear layer and the platform for preventing cross flow through the support layer between engine exhaust and pressurized air passages, and air diversion passages for directing unregenerated pressurized air through the support layer to cool the seal and wear layer and then back into the flow of regenerated pressurized air.

  1. Scaffolds in vascular regeneration: current status

    PubMed Central

    Thottappillil, Neelima; Nair, Prabha D

    2015-01-01

    An ideal vascular substitute, especially in <6 mm diameter applications, is a major clinical essentiality in blood vessel replacement surgery. Blood vessels are structurally complex and functionally dynamic tissue, with minimal regeneration potential. These have composite extracellular matrix (ECM) and arrangement. The interplay between ECM components and tissue specific cells gives blood vessels their specialized functional attributes. The core of vascular tissue engineering and regeneration relies on the challenges in creating vascular conduits that match native vessels and adequately regenerate in vivo. Out of numerous vascular regeneration concerns, the relevance of ECM emphasizes much attention toward appropriate choice of scaffold material and further scaffold development strategies. The review is intended to be focused on the various approaches of scaffold materials currently in use in vascular regeneration and current state of the art. Scaffold of choice in vascular tissue engineering ranges from natural to synthetic, decellularized, and even scaffold free approach. The applicability of tubular scaffold for in vivo vascular regeneration is under active investigation. A patent conduit with an ample endothelial luminal layer that can regenerate in vivo remains an unanswered query in the field of small diameter vascular tissue engineering. Besides, scaffolds developed for vascular regeneration, should aim at providing functional substitutes for use in a regenerative approach from the laboratory bench to patient bedside. PMID:25632236

  2. The Molecular and Cellular Choreography of Appendage Regeneration.

    PubMed

    Tanaka, Elly M

    2016-06-16

    Recent advances in limb regeneration are revealing the molecular events that integrate growth control, cell fate programming, and positional information to yield the exquisite replacement of the amputated limb. Parallel progress in several invertebrate and vertebrate models has provided a broader context for understanding the mechanisms and the evolution of regeneration. Together, these discoveries provide a foundation for describing the principles underlying regeneration of complex, multi-tissue structures. As such these findings should provide a wealth of ideas for engineers seeking to reconstitute regeneration from constituent parts or to elicit full regeneration from partial regeneration events. PMID:27315477

  3. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering

    PubMed Central

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration—culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch. PMID:26989897

  4. Cell Therapy for Cardiovascular Regeneration

    PubMed Central

    2013-01-01

    A great numbers of cardiovascular disease patients all over the world are suffering in the poor outcomes. Under this situation, cardiac regeneration therapy to reorganize the postnatal heart that is defined as a terminal differentiated-organ is a very important theme and mission for human beings. However, the temporary success of several clinical trials using usual cell types with uncertain cell numbers has provided the transient effect of cell therapy to these patients. We therefore should redevelop the evidence of cell-based cardiovascular regeneration therapy, focusing on targets (disease, patient’s status, cardiac function), materials (cells, cytokines, genes), and methodology (transplantation route, implantation technology, tissue engineering). Meanwhile, establishment of the induced pluripotent stem (iPS) cells is an extremely innovative technology which should be proposed as embryonic stem (ES) cellularization of post natal somatic cells, and this application have also showed the milestones of the direct conversion to reconstruct cardiomyocyte from the various somatic cells, which does not need the acquisition of the re-pluripotency. This review discusses the new advance in cardiovascular regeneration therapy from cardiac regeneration to cardiac re-organization, which is involved in recent progress of on-going clinical trials, basic research in cardiovascular regeneration, and the possibility of tissue engineering technology. PMID:23825492

  5. The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair.

    PubMed

    Yin, Zi; Chen, Xiao; Zhu, Ting; Hu, Jia-jie; Song, Hai-xin; Shen, Wei-liang; Jiang, Liu-yun; Heng, Boon Chin; Ji, Jun-feng; Ouyang, Hong-Wei

    2013-12-01

    It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m(-1) vs.13.2 ± 5.9 Nm m(-1)) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon

  6. Cementum and Periodontal Ligament Regeneration.

    PubMed

    Menicanin, Danijela; Hynes, K; Han, J; Gronthos, S; Bartold, P M

    2015-01-01

    The unique anatomy and composition of the periodontium make periodontal tissue healing and regeneration a complex process. Periodontal regeneration aims to recapitulate the crucial stages of wound healing associated with periodontal development in order to restore lost tissues to their original form and function and for regeneration to occur, healing events must progress in an ordered and programmed sequence both temporally and spatially, replicating key developmental events. A number of procedures have been employed to promote true and predictable regeneration of the periodontium. Principally, the approaches are based on the use of graft materials to compensate for the bone loss incurred as a result of periodontal disease, use of barrier membranes for guided tissue regeneration and use of bioactive molecules. More recently, the concept of tissue engineering has been integrated into research and applications of regenerative dentistry, including periodontics, to aim to manage damaged and lost oral tissues, through reconstruction and regeneration of the periodontium and alleviate the shortcomings of more conventional therapeutic options. The essential components for generating effective cellular based therapeutic strategies include a population of multi-potential progenitor cells, presence of signalling molecules/inductive morphogenic signals and a conductive extracellular matrix scaffold or appropriate delivery system. Mesenchymal stem cells are considered suitable candidates for cell-based tissue engineering strategies owing to their extensive expansion rate and potential to differentiate into cells of multiple organs and systems. Mesenchymal stem cells derived from multiple tissue sources have been investigated in pre-clinical animal studies and clinical settings for the treatment and regeneration of the periodontium.

  7. Method for modifying trigger level for adsorber regeneration

    DOEpatents

    Ruth, Michael J.; Cunningham, Michael J.

    2010-05-25

    A method for modifying a NO.sub.x adsorber regeneration triggering variable. Engine operating conditions are monitored until the regeneration triggering variable is met. The adsorber is regenerated and the adsorbtion efficiency of the adsorber is subsequently determined. The regeneration triggering variable is modified to correspond with the decline in adsorber efficiency. The adsorber efficiency may be determined using an empirically predetermined set of values or by using a pair of oxygen sensors to determine the oxygen response delay across the sensors.

  8. Biological apatite (BAp) crystallographic orientation and texture as a new index for assessing the microstructure and function of bone regenerated by tissue engineering.

    PubMed

    Nakano, Takayoshi; Kaibara, Kazuhiro; Ishimoto, Takuya; Tabata, Yasuhiko; Umakoshi, Yukichi

    2012-10-01

    Recently, there have been remarkable advances in medical techniques for regenerating bone defects. To determine the degree of bone regeneration, it is essential to develop a new method that can analyze microstructure and related mechanical function. Here, quantitative analysis of the orientation distribution of biological apatite (BAp) crystallites by a microbeam X-ray diffractometer system is proposed as a new index of bone quality for the evaluation of regenerated bone microstructure. Preferential alignment of the BAp c-axis in the rabbit ulna and skull bone, regenerated by controlled release of basic fibroblast growth factor (bFGF) was investigated. The BAp c-axis orientation was evaluated by the relative intensity between the (002) and (310) diffraction peaks, or the three-dimensional texture for the (002) peak. It was found that new bone in the defects was initially produced without preferential alignment of the BAp c-axis, and subsequently reproduced to recover towards the original alignment. In other words, the BAp density recovered prior to the BAp orientation. Perfect recovery of BAp alignment was not achieved in the ulna and skull defects after 4 weeks and 12 weeks, respectively. Apparent recovery of the macroscopic shape and bio-mineralization of BAp was almost complete in the ulna defect after 4 weeks. However, an additional 2 weeks was required for complete repair of BAp orientation. It is finally concluded that orientation distribution of BAp crystallites offers an effective means of evaluating the degree of microstructural regeneration, and also the related mechanical function, in regenerated hard tissues.

  9. Regenerator seal

    DOEpatents

    Davis, Leonard C.; Pacala, Theodore; Sippel, George R.

    1981-01-01

    A method for manufacturing a hot side regenerator cross arm seal assembly having a thermally stablilized wear coating with a substantially flat wear surface thereon to seal between low pressure and high pressure passages to and from the hot inboard side of a rotary regenerator matrix includes the steps of forming a flat cross arm substrate member of high nickel alloy steel; fixedly securing the side edges of the substrate member to a holding fixture with a concave surface thereacross to maintain the substrate member to a slightly bent configuration on the fixture surface between the opposite ends of the substrate member to produce prestress therein; applying coating layers on the substrate member including a wear coating of plasma sprayed nickel oxide/calcium flouride material to define a wear surface of slightly concave form across the restrained substrate member between the free ends thereon; and thereafter subjecting the substrate member and the coating thereon to a heat treatment of 1600.degree. F. for sixteen hours to produce heat stabilizing growth in the coating layers on the substrate member and to produce a thermally induced growth stress in the wear surface that substantially equalizes the prestress in the substrate whereby when the cross arm is removed from the fixture surface following the heat treatment step a wear face is formed on the cross arm assembly that will be substantially flat between the ends.

  10. Generating random density matrices

    NASA Astrophysics Data System (ADS)

    Życzkowski, Karol; Penson, Karol A.; Nechita, Ion; Collins, Benoît

    2011-06-01

    We study various methods to generate ensembles of random density matrices of a fixed size N, obtained by partial trace of pure states on composite systems. Structured ensembles of random pure states, invariant with respect to local unitary transformations are introduced. To analyze statistical properties of quantum entanglement in bi-partite systems we analyze the distribution of Schmidt coefficients of random pure states. Such a distribution is derived in the case of a superposition of k random maximally entangled states. For another ensemble, obtained by performing selective measurements in a maximally entangled basis on a multi-partite system, we show that this distribution is given by the Fuss-Catalan law and find the average entanglement entropy. A more general class of structured ensembles proposed, containing also the case of Bures, forms an extension of the standard ensemble of structureless random pure states, described asymptotically, as N → ∞, by the Marchenko-Pastur distribution.

  11. Heart regeneration.

    PubMed

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  12. Enhancing Understanding of Transformation Matrices

    ERIC Educational Resources Information Center

    Dick, Jonathan; Childrey, Maria

    2012-01-01

    With the Common Core State Standards' emphasis on transformations, teachers need a variety of approaches to increase student understanding. Teaching matrix transformations by focusing on row vectors gives students tools to create matrices to perform transformations. This empowerment opens many doors: Students are able to create the matrices for…

  13. On Some Properties of Gamma Matrices

    ERIC Educational Resources Information Center

    Dumais, Jean-Francois

    1977-01-01

    Discusses the problem of the order, reducibility, and equivalence of systems of Dirac gamma matrices. Gives a simple systematic method for finding the matrices connecting different systems of 4 x 4 gamma matrices. (MLH)

  14. Apatite-mineralized polycaprolactone nanofibrous web as a bone tissue regeneration substrate.

    PubMed

    Yu, Hye-Sun; Jang, Jun-Hyeog; Kim, Tae-Il; Lee, Hae-Hyoung; Kim, Hae-Won

    2009-03-01

    Degradable synthetic polymers with a nanofibrous structure have shown great promise in populating and recruiting cells for the reconstruction of damaged tissues. However, poor cell affinity and lack of bioactivity have limited their potential usefulness in bone regeneration. We produced polymeric nanofiber poly(epsilon-caprolactone) (PCL) with its surface mineralized with bone-like apatite for use as bone regenerative and tissue engineering matrices. PCL was first electrospun into a nanofibrous web, and the surface was further mineralized with apatite following a series of solution treatments. The surface of the mineralized PCL nanofiber was observed to be almost fully covered with nanocrystalline apatites. Through mineralization, the wettability of the nanofiber matrix was greatly improved. Moreover, the murine-derived osteoblastic cells were shown to attach and grow actively on the apatite-mineralized nanofibrous substrate. In particular, the mineralized PCL nanofibrous substrate significantly stimulated the expression of bone-associated genes, including Runx2, collagen type I, alkaline phosphatase, and osteocalcin, when compared with the pure PCL nanofiber substrate without mineralization. The currently developed polymer nanofibrous web with the bioactive mineralized surface is considered to be potentially useful as bone regenerative and tissue engineering matrices.

  15. Electrically heated particulate filter regeneration methods and systems for hybrid vehicles

    DOEpatents

    Gonze, Eugene V.; Paratore, Jr., Michael J.

    2010-10-12

    A control system for controlling regeneration of a particulate filter for a hybrid vehicle is provided. The system generally includes a regeneration module that controls current to the particulate filter to initiate regeneration. An engine control module controls operation of an engine of the hybrid vehicle based on the control of the current to the particulate filter.

  16. Estimating sparse precision matrices

    NASA Astrophysics Data System (ADS)

    Padmanabhan, Nikhil; White, Martin; Zhou, Harrison H.; O'Connell, Ross

    2016-08-01

    We apply a method recently introduced to the statistical literature to directly estimate the precision matrix from an ensemble of samples drawn from a corresponding Gaussian distribution. Motivated by the observation that cosmological precision matrices are often approximately sparse, the method allows one to exploit this sparsity of the precision matrix to more quickly converge to an asymptotic 1/sqrt{N_sim} rate while simultaneously providing an error model for all of the terms. Such an estimate can be used as the starting point for further regularization efforts which can improve upon the 1/sqrt{N_sim} limit above, and incorporating such additional steps is straightforward within this framework. We demonstrate the technique with toy models and with an example motivated by large-scale structure two-point analysis, showing significant improvements in the rate of convergence. For the large-scale structure example, we find errors on the precision matrix which are factors of 5 smaller than for the sample precision matrix for thousands of simulations or, alternatively, convergence to the same error level with more than an order of magnitude fewer simulations.

  17. Scaffolds and tissue regeneration: An overview of the functional properties of selected organic tissues.

    PubMed

    Rebelo, Márcia A; Alves, Thais F R; de Lima, Renata; Oliveira, José M; Vila, Marta M D C; Balcão, Victor M; Severino, Patrícia; Chaud, Marco V

    2016-10-01

    Tissue engineering plays a significant role both in the re-establishment of functions and regeneration of organic tissues. Success in manufacturing projects for biological scaffolds, for the purpose of tissue regeneration, is conditioned by the selection of parameters such as the biomaterial, the device architecture, and the specificities of the cells making up the organic tissue to create, in vivo, a microenvironment that preserves and further enhances the proliferation of a specific cell phenotype. To support this approach, we have screened scientific publications that show biomedical applications of scaffolds, biomechanical, morphological, biochemical, and hemodynamic characteristics of the target organic tissues, and the possible interactions between different cell matrices and biological scaffolds. This review article provides an overview on the biomedical application of scaffolds and on the characteristics of the (bio)materials commonly used for manufacturing these biological devices used in tissue engineering, taking into consideration the cellular specificity of the target tissue. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1483-1494, 2016.

  18. Equine model for soft-tissue regeneration.

    PubMed

    Bellas, Evangelia; Rollins, Amanda; Moreau, Jodie E; Lo, Tim; Quinn, Kyle P; Fourligas, Nicholas; Georgakoudi, Irene; Leisk, Gary G; Mazan, Melissa; Thane, Kristen E; Taeymans, Olivier; Hoffman, A M; Kaplan, D L; Kirker-Head, C A

    2015-08-01

    Soft-tissue regeneration methods currently yield suboptimal clinical outcomes due to loss of tissue volume and a lack of functional tissue regeneration. Grafted tissues and natural biomaterials often degrade or resorb too quickly, while most synthetic materials do not degrade. In previous research we demonstrated that soft-tissue regeneration can be supported using silk porous biomaterials for at least 18 months in vivo in a rodent model. In the present study, we scaled the system to a survival study using a large animal model and demonstrated the feasibility of these biomaterials for soft-tissue regeneration in adult horses. Both slow and rapidly degrading silk matrices were evaluated in subcutaneous pocket and intramuscular defect depots. We showed that we can effectively employ an equine model over 6 months to simultaneously evaluate many different implants, reducing the number of animals needed. Furthermore, we were able to tailor matrix degradation by varying the initial format of the implanted silk. Finally, we demonstrate ultrasound imaging of implants to be an effective means for tracking tissue regeneration and implant degradation.

  19. Equine Model for Soft Tissue Regeneration

    PubMed Central

    Moreau, J.E.; Lo, T.; Quinn, K.P.; Fourligas, N.; Georgakoudi, I.; Leisk, G.G.; Mazan, M.; Thane, K.E.; Taeymans, O.; Hoffman, A.M.; Kaplan, D. L.; Kirker-Head, C.A.

    2016-01-01

    Soft tissue regeneration methods currently yield suboptimal clinical outcomes due to loss of tissue volume and a lack of functional tissue regeneration. Grafted tissues and natural biomaterials often degrade or resorb too quickly, while most synthetic materials do not degrade. In previous research we demonstrated that soft tissue regeneration can be supported using silk porous biomaterials for at least 18 months in vivo in a rodent model. In the present study, we scaled the system to a survival study using a large animal model and demonstrated the feasibility of these biomaterials for soft tissue regeneration in adult horses. Both slow and rapidly degrading silk matrices were evaluated in subcutaneous pocket and intramuscular defect depots. We showed that we can effectively employ an equine model over six months to simultaneously evaluate many different implants, reducing the number of animals needed. Furthermore, we were able to tailor matrix degradation by varying the initial format of the implanted silk. Finally, we demonstrate ultrasound imaging of implants to be an effective means for tracking tissue regeneration and implant degradation. PMID:25350377

  20. Computer-Access-Code Matrices

    NASA Technical Reports Server (NTRS)

    Collins, Earl R., Jr.

    1990-01-01

    Authorized users respond to changing challenges with changing passwords. Scheme for controlling access to computers defeats eavesdroppers and "hackers". Based on password system of challenge and password or sign, challenge, and countersign correlated with random alphanumeric codes in matrices of two or more dimensions. Codes stored on floppy disk or plug-in card and changed frequently. For even higher security, matrices of four or more dimensions used, just as cubes compounded into hypercubes in concurrent processing.

  1. Tissue engineering with the aid of inkjet printers.

    PubMed

    Campbell, Phil G; Weiss, Lee E

    2007-08-01

    Tissue engineering holds the promise to create revolutionary new therapies for tissue and organ regeneration. This emerging field is extremely broad and eclectic in its various approaches. However, all strategies being developed are based on the therapeutic delivery of one or more of the following types of tissue building-blocks: cells; extracellular matrices or scaffolds; and hormones or other signaling molecules. So far, most work has used essentially homogenous combinations of these components, with subsequent self-organization to impart some level of tissue functionality occurring during in vitro culture or after transplantation. Emerging 'bioprinting' methodologies are being investigated to create tissue engineered constructs initially with more defined spatial organization, motivated by the hypothesis that biomimetic patterns can achieve improved therapeutic outcomes. Bioprinting based on inkjet and related printing technologies can be used to fabricate persistent biomimetic patterns that can be used both to study the underlying biology of tissue regeneration and potentially be translated into effective clinical therapies. However, recapitulating nature at even the most primitive levels such that printed cells, extracellular matrices and hormones become integrated into hierarchical, spatially organized three-dimensional tissue structures with appropriate functionality remains a significant challenge.

  2. Regenerator matrix physical property data

    NASA Technical Reports Server (NTRS)

    Fucinari, C. A.

    1980-01-01

    Among several cellular ceramic structures manufactured by various suppliers for regenerator application in a gas turbine engine, three have the best potential for achieving durability and performance objectives for use in gas turbines, Stirling engines, and waste heat recovery systems: (1) an aluminum-silicate sinusoidal flow passage made from a corrugated wate paper process; (2) an extruded isosceles triangle flow passage; and (3) a second generation matrix incorporating a square flow passage formed by an embossing process. Key physical and thermal property data for these configurations presented include: heat transfer and pressure drop characteristics, compressive strength, tensile strength and elasticity, thermal expansion characteristics, chanical attack, and thermal stability.

  3. Silk fibroin in tissue engineering.

    PubMed

    Kasoju, Naresh; Bora, Utpal

    2012-07-01

    Tissue engineering (TE) is a multidisciplinary field that aims at the in vitro engineering of tissues and organs by integrating science and technology of cells, materials and biochemical factors. Mimicking the natural extracellular matrix is one of the critical and challenging technological barriers, for which scaffold engineering has become a prime focus of research within the field of TE. Amongst the variety of materials tested, silk fibroin (SF) is increasingly being recognized as a promising material for scaffold fabrication. Ease of processing, excellent biocompatibility, remarkable mechanical properties and tailorable degradability of SF has been explored for fabrication of various articles such as films, porous matrices, hydrogels, nonwoven mats, etc., and has been investigated for use in various TE applications, including bone, tendon, ligament, cartilage, skin, liver, trachea, nerve, cornea, eardrum, dental, bladder, etc. The current review extensively covers the progress made in the SF-based in vitro engineering and regeneration of various human tissues and identifies opportunities for further development of this field.

  4. Efficient whole-cell biocatalyst for acetoin production with NAD+ regeneration system through homologous co-expression of 2,3-butanediol dehydrogenase and NADH oxidase in engineered Bacillus subtilis.

    PubMed

    Bao, Teng; Zhang, Xian; Rao, Zhiming; Zhao, Xiaojing; Zhang, Rongzhen; Yang, Taowei; Xu, Zhenghong; Yang, Shangtian

    2014-01-01

    Acetoin (3-hydroxy-2-butanone), an extensively-used food spice and bio-based platform chemical, is usually produced by chemical synthesis methods. With increasingly requirement of food security and environmental protection, bio-fermentation of acetoin by microorganisms has a great promising market. However, through metabolic engineering strategies, the mixed acid-butanediol fermentation metabolizes a certain portion of substrate to the by-products of organic acids such as lactic acid and acetic acid, which causes energy cost and increases the difficulty of product purification in downstream processes. In this work, due to the high efficiency of enzymatic reaction and excellent selectivity, a strategy for efficiently converting 2,3-butandiol to acetoin using whole-cell biocatalyst by engineered Bacillus subtilis is proposed. In this process, NAD+ plays a significant role on 2,3-butanediol and acetoin distribution, so the NADH oxidase and 2,3-butanediol dehydrogenase both from B. subtilis are co-expressed in B. subtilis 168 to construct an NAD+ regeneration system, which forces dramatic decrease of the intracellular NADH concentration (1.6 fold) and NADH/NAD+ ratio (2.2 fold). By optimization of the enzymatic reaction and applying repeated batch conversion, the whole-cell biocatalyst efficiently produced 91.8 g/L acetoin with a productivity of 2.30 g/(L·h), which was the highest record ever reported by biocatalysis. This work indicated that manipulation of the intracellular cofactor levels was more effective than the strategy of enhancing enzyme activity, and the bioprocess for NAD+ regeneration may also be a useful way for improving the productivity of NAD+-dependent chemistry-based products. PMID:25036158

  5. Efficient Whole-Cell Biocatalyst for Acetoin Production with NAD+ Regeneration System through Homologous Co-Expression of 2,3-Butanediol Dehydrogenase and NADH Oxidase in Engineered Bacillus subtilis

    PubMed Central

    Rao, Zhiming; Zhao, Xiaojing; Zhang, Rongzhen; Yang, Taowei; Xu, Zhenghong; Yang, Shangtian

    2014-01-01

    Acetoin (3-hydroxy-2-butanone), an extensively-used food spice and bio-based platform chemical, is usually produced by chemical synthesis methods. With increasingly requirement of food security and environmental protection, bio-fermentation of acetoin by microorganisms has a great promising market. However, through metabolic engineering strategies, the mixed acid-butanediol fermentation metabolizes a certain portion of substrate to the by-products of organic acids such as lactic acid and acetic acid, which causes energy cost and increases the difficulty of product purification in downstream processes. In this work, due to the high efficiency of enzymatic reaction and excellent selectivity, a strategy for efficiently converting 2,3-butandiol to acetoin using whole-cell biocatalyst by engineered Bacillus subtilis is proposed. In this process, NAD+ plays a significant role on 2,3-butanediol and acetoin distribution, so the NADH oxidase and 2,3-butanediol dehydrogenase both from B. subtilis are co-expressed in B. subtilis 168 to construct an NAD+ regeneration system, which forces dramatic decrease of the intracellular NADH concentration (1.6 fold) and NADH/NAD+ ratio (2.2 fold). By optimization of the enzymatic reaction and applying repeated batch conversion, the whole-cell biocatalyst efficiently produced 91.8 g/L acetoin with a productivity of 2.30 g/(L·h), which was the highest record ever reported by biocatalysis. This work indicated that manipulation of the intracellular cofactor levels was more effective than the strategy of enhancing enzyme activity, and the bioprocess for NAD+ regeneration may also be a useful way for improving the productivity of NAD+-dependent chemistry-based products. PMID:25036158

  6. Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.

    PubMed

    Berner, Arne; Henkel, Jan; Woodruff, Maria A; Steck, Roland; Nerlich, Michael; Schuetz, Michael A; Hutmacher, Dietmar W

    2015-05-01

    Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.

  7. Reduced shedding regenerator and method

    DOEpatents

    Qiu, Songgang; Augenblick, John E.; Erbeznik, Raymond M.

    2007-05-22

    A reduced shedding regenerator and method are disclosed with regenerator surfaces to minimize shedding of particles from the regenerator thereby alleviating a source of potential damage and malfunction of a thermal regenerative machine using the regenerator.

  8. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  9. Microwave-Regenerated Diesel Exhaust Particulate Filter

    SciTech Connect

    Nixdorf, Richard D.; Green, Johney Boyd; Story, John M.; Wagner, Robert M.

    2001-03-05

    Development of a microwave-regenerated particulate filter system has evolved from bench scale work to actual diesel engine experimentation. The filter system was initially evaluated on a stationary mounted 1.2-L diesel engine and was able to remove a significant amount of carbon particles from the exhaust. The ability of the microwave energy to regenerate or clean the filter was also demonstrated on this engine under idle conditions. Based on the 1.2-L experiments, improvements to the filter design and materials were implemented and the system was re-evaluated on a vehicle equipped with a 7.3-L diesel engine. The 7.3-L engine was selected to achieve heavy filter loading in a relatively short period of time. The purpose of these experiments was to evaluate filter-loading capacity, power requirements for regeneration, and filter regeneration efficiency. A more detailed evaluation of the filter was performed on a stationary mounted 1.9-L diesel engine. The effect of exhaust flow rate, loading, transients, and regeneration on filter efficiency was evaluated with this setup. In addition, gaseous exhaust emissions were investigated with and without an oxidation catalyst on the filter cartridge during loading and regeneration. (SAE Paper SAE-2001-01-0903 © 2001 SAE International. This paper is published on this website with permission from SAE International. As a user of this website, you are permitted to view this paper on-line, download this pdf file and print one copy of this paper at no cost for your use only. The downloaded pdf file and printout of this SAE paper may not be copied, distributed or forwarded to others or for the use of others.)

  10. Effects of regenerator geometry on pulse tube refrigerator performance.

    PubMed

    Lewis, M; Kuriyama, T; Xiao, J H; Radebaugh, R

    1998-01-01

    This paper gives results of the cooling performance of a double-inlet pulse tube refrigerator using various regenerators. The same pulse tube was used for all the experiments and measured 4.76 mm in diameter and 46.2 mm in length. A commercial linear compressor with a swept volume of 4 cm3 was used in these experiments. The operating conditions were held constant at a mean pressure of 2.0 MPa and a frequency of 54 Hz. Using finite difference software called REGEN3.1, developed at NIST, and recent experiment results, we optimized a series of regenerators based on dimensions, materials and screen packing. The values used for calculating the thermal conduction through stacked screens by REGEN3.1 were based on recent experimental results from NIST. The regenerator tubes were designed using 316 stainless steel and titanium materials. The regenerator matrices investigated were 400-mesh and 500-mesh stainless steel screen. The valve settings for both orifices were adjusted to minimize the no-load temperature for all regenerators. A cooling capacity curve from 0 to 3 W was also determined. The performance of the pulse tube refrigerator using the different regenerators is discussed. The experimental results from the various regenerators are evaluated and compared with their corresponding numerically calculated coefficient of performance (COP) and regenerator design as determined by REGEN3.1.

  11. Effects of regenerator geometry on pulse tube refrigerator performance

    NASA Technical Reports Server (NTRS)

    Lewis, M.; Kuriyama, T.; Xiao, J. H.; Radebaugh, R.

    1998-01-01

    This paper gives results of the cooling performance of a double-inlet pulse tube refrigerator using various regenerators. The same pulse tube was used for all the experiments and measured 4.76 mm in diameter and 46.2 mm in length. A commercial linear compressor with a swept volume of 4 cm3 was used in these experiments. The operating conditions were held constant at a mean pressure of 2.0 MPa and a frequency of 54 Hz. Using finite difference software called REGEN3.1, developed at NIST, and recent experiment results, we optimized a series of regenerators based on dimensions, materials and screen packing. The values used for calculating the thermal conduction through stacked screens by REGEN3.1 were based on recent experimental results from NIST. The regenerator tubes were designed using 316 stainless steel and titanium materials. The regenerator matrices investigated were 400-mesh and 500-mesh stainless steel screen. The valve settings for both orifices were adjusted to minimize the no-load temperature for all regenerators. A cooling capacity curve from 0 to 3 W was also determined. The performance of the pulse tube refrigerator using the different regenerators is discussed. The experimental results from the various regenerators are evaluated and compared with their corresponding numerically calculated coefficient of performance (COP) and regenerator design as determined by REGEN3.1.

  12. Modulation of tissue repair by regeneration enhancer elements.

    PubMed

    Kang, Junsu; Hu, Jianxin; Karra, Ravi; Dickson, Amy L; Tornini, Valerie A; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A; Black, Brian L; Poss, Kenneth D

    2016-04-14

    How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.

  13. Tissue engineering principles in orthopaedic surgery.

    PubMed

    Jackson, D W; Simon, T M

    1999-10-01

    Advances in the fields of biotechnology and biomaterials offer the orthopaedic surgeon the exciting possibility of repair or regeneration of tissue lost to injury, disease, or aging. The promising area of tissue engineering represents a multidisciplinary approach aimed at solving some of the most perplexing biologic problems, namely, the creation of new tissues and organs similar to the original tissues and organs. In addition, strategies using new synthetic polymer formulations can facilitate tissue replacement and represent alternatives to tissue regeneration in certain conditions. Although biotechnology has broad application over many medical specialties, orthopaedics is receiving a large focus of the research effort devoted to techniques for developing bone, articular cartilage, ligaments, and tendons. Because bioengineered tissue and/or techniques to stimulate tissue regeneration soon may be used clinically, orthopaedic surgeons should have a working knowledge of the basic concepts involved. Terms, such as biomaterial, biotechnology, matrices of synthetic or biologic polymers or both, adhesion, cohesion, porosity, induction, conduction, stem cell, progenitor cell, mesenchymal cell, tissue growth factor, bone morphogenetic protein, mitogenic and chemotactic factors, and numerous other terms will become part of the working language of clinicians of the twenty-first century.

  14. A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

    PubMed Central

    Green, David W.; Padula, Matthew P.; Santos, Jerran; Chou, Joshua; Milthorpe, Bruce; Ben-Nissan, Besim

    2013-01-01

    A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-β) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use. PMID:23574983

  15. Biomaterials for periodontal regeneration

    PubMed Central

    Shue, Li; Yufeng, Zhang; Mony, Ullas

    2012-01-01

    Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect. PMID:23507891

  16. Truncations of random orthogonal matrices.

    PubMed

    Khoruzhenko, Boris A; Sommers, Hans-Jürgen; Życzkowski, Karol

    2010-10-01

    Statistical properties of nonsymmetric real random matrices of size M, obtained as truncations of random orthogonal N×N matrices, are investigated. We derive an exact formula for the density of eigenvalues which consists of two components: finite fraction of eigenvalues are real, while the remaining part of the spectrum is located inside the unit disk symmetrically with respect to the real axis. In the case of strong nonorthogonality, M/N=const, the behavior typical to real Ginibre ensemble is found. In the case M=N-L with fixed L, a universal distribution of resonance widths is recovered.

  17. Truncations of random orthogonal matrices

    NASA Astrophysics Data System (ADS)

    Khoruzhenko, Boris A.; Sommers, Hans-Jürgen; Życzkowski, Karol

    2010-10-01

    Statistical properties of nonsymmetric real random matrices of size M , obtained as truncations of random orthogonal N×N matrices, are investigated. We derive an exact formula for the density of eigenvalues which consists of two components: finite fraction of eigenvalues are real, while the remaining part of the spectrum is located inside the unit disk symmetrically with respect to the real axis. In the case of strong nonorthogonality, M/N=const , the behavior typical to real Ginibre ensemble is found. In the case M=N-L with fixed L , a universal distribution of resonance widths is recovered.

  18. Iterative methods for Toeplitz-like matrices

    SciTech Connect

    Huckle, T.

    1994-12-31

    In this paper the author will give a survey on iterative methods for solving linear equations with Toeplitz matrices, Block Toeplitz matrices, Toeplitz plus Hankel matrices, and matrices with low displacement rank. He will treat the following subjects: (1) optimal (w)-circulant preconditioners is a generalization of circulant preconditioners; (2) Optimal implementation of circulant-like preconditioners in the complex and real case; (3) preconditioning of near-singular matrices; what kind of preconditioners can be used in this case; (4) circulant preconditioning for more general classes of Toeplitz matrices; what can be said about matrices with coefficients that are not l{sub 1}-sequences; (5) preconditioners for Toeplitz least squares problems, for block Toeplitz matrices, and for Toeplitz plus Hankel matrices.

  19. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  20. Dentin Matrix Proteins in Bone Tissue Engineering.

    PubMed

    Ravindran, Sriram; George, Anne

    2015-01-01

    Dentin and bone are mineralized tissue matrices comprised of collagen fibrils and reinforced with oriented crystalline hydroxyapatite. Although both tissues perform different functionalities, they are assembled and orchestrated by mesenchymal cells that synthesize both collagenous and noncollagenous proteins albeit in different proportions. The dentin matrix proteins (DMPs) have been studied in great detail in recent years due to its inherent calcium binding properties in the extracellular matrix resulting in tissue calcification. Recent studies have shown that these proteins can serve both as intracellular signaling proteins leading to induction of stem cell differentiation and also function as nucleating proteins in the extracellular matrix. These properties make the DMPs attractive candidates for bone and dentin tissue regeneration. This chapter will provide an overview of the DMPs, their functionality and their proven and possible applications with respect to bone tissue engineering.

  1. Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells.

    PubMed

    Ko, Eunkyung; Alberti, Kyle; Lee, Jong Seung; Yang, Kisuk; Jin, Yoonhee; Shin, Jisoo; Yang, Hee Seok; Xu, Qiaobing; Cho, Seung-Woo

    2016-09-01

    Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due to their biochemical, biophysical, and mechanical similarity to native tissues. In this study, we report a nanostructured decellularized tendon scaffold with aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving method, we prepared decellularized tendon scaffolds from tissue slices of bovine Achilles and neck tendons with or without fixation, and investigated the effects on physical and mechanical properties of decellularized tendon scaffolds, based on the types and concentrations of cross-linking agents. In general, we found that decellularized tendon scaffolds without fixative treatments were more effective in inducing osteogenic differentiation and mineralization of hADSCs in vitro. When non-cross-linked decellularized tendon scaffolds were applied together with hydroxyapatite for hADSC transplantation in critical-sized bone defects, they promoted bone-specific collagen deposition and mineralized bone formation 4 and 8 weeks after hADSC transplantation, compared to conventional collagen type I scaffolds. Interestingly, stacking of decellularized tendon scaffolds cultured with osteogenically committed hADSCs and those containing human cord blood-derived endothelial progenitor cells (hEPCs) induced vascularized bone regeneration in the defects 8 weeks after transplantation. Our study suggests that biomimetic nanostructured scaffolds made of decellularized tissue matrices can serve as functional tissue-engineering scaffolds for enhanced osteogenesis of stem cells.

  2. Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells.

    PubMed

    Ko, Eunkyung; Alberti, Kyle; Lee, Jong Seung; Yang, Kisuk; Jin, Yoonhee; Shin, Jisoo; Yang, Hee Seok; Xu, Qiaobing; Cho, Seung-Woo

    2016-09-01

    Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due to their biochemical, biophysical, and mechanical similarity to native tissues. In this study, we report a nanostructured decellularized tendon scaffold with aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving method, we prepared decellularized tendon scaffolds from tissue slices of bovine Achilles and neck tendons with or without fixation, and investigated the effects on physical and mechanical properties of decellularized tendon scaffolds, based on the types and concentrations of cross-linking agents. In general, we found that decellularized tendon scaffolds without fixative treatments were more effective in inducing osteogenic differentiation and mineralization of hADSCs in vitro. When non-cross-linked decellularized tendon scaffolds were applied together with hydroxyapatite for hADSC transplantation in critical-sized bone defects, they promoted bone-specific collagen deposition and mineralized bone formation 4 and 8 weeks after hADSC transplantation, compared to conventional collagen type I scaffolds. Interestingly, stacking of decellularized tendon scaffolds cultured with osteogenically committed hADSCs and those containing human cord blood-derived endothelial progenitor cells (hEPCs) induced vascularized bone regeneration in the defects 8 weeks after transplantation. Our study suggests that biomimetic nanostructured scaffolds made of decellularized tissue matrices can serve as functional tissue-engineering scaffolds for enhanced osteogenesis of stem cells. PMID:27502160

  3. Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration.

    PubMed

    Badieyan, Zohreh Sadat; Berezhanskyy, Taras; Utzinger, Maximilian; Aneja, Manish Kumar; Emrich, Daniela; Erben, Reinhold; Schüler, Christiane; Altpeter, Philipp; Ferizi, Mehrije; Hasenpusch, Günther; Rudolph, Carsten; Plank, Christian

    2016-10-10

    Transcript therapies using chemically modified messenger RNAs (cmRNAs) are emerging as safe and promising alternatives for gene and recombinant protein therapies. However, their applications have been limited due to transient translation and relatively low stability of cmRNAs compared to DNA. Here we show that vacuum-dried cmRNA-loaded collagen sponges, termed transcript activated matrices (TAMs), can serve as depots for sustained delivery of cmRNA. TAMs provide steady state protein production for up to six days, and substantial residual expression until 11days post transfection. Another advantage of this technology was nearly 100% transfection efficiency as well as low toxicity in vitro. TAMs were stable for at least 6months at room temperature. Human BMP-2-encoding TAMs induced osteogenic differentiation of MC3T3-E1 cells in vitro and bone regeneration in a non-critical rat femoral bone defect model in vivo. In summary, TAMs are a promising tool for bone regeneration and potentially also for other applications in regenerative medicine and tissue engineering. PMID:27586186

  4. Sericin-carboxymethyl cellulose porous matrices as cellular wound dressing material.

    PubMed

    Nayak, Sunita; Kundu, S C

    2014-06-01

    In this study, porous three-dimensional (3D) hydrogel matrices are fabricated composed of silk cocoon protein sericin of non-mulberry silkworm Antheraea mylitta and carboxymethyl cellulose. The matrices are prepared via freeze-drying technique followed by dual cross-linking with glutaraldehyde and aluminum chloride. The microstructure of the hydrogel matrices is assessed using scanning electron microscopy and biophysical characterization are carried out using Fourier transform infrared spectroscopy and X-ray diffraction. The transforming growth factor β1 release from the cross-linked matrices as a growth factor is evaluated by immunosorbent assay. Live dead assay and 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyl tetrazolium bromide assay show no cytotoxicity of blended matrices toward human keratinocytes. The matrices support the cell attachment and proliferation of human keratinocytes as observed through scanning electron microscope and confocal images. Gelatin zymography demonstrates the low levels of matrix metalloproteinase 2 (MMP-2) and insignificant amount of MMP-9 in the culture media of cell seeded matrices. Low inflammatory response of the matrices is indicated through tumor necrosis factor alpha release assay. The results indicate that the fabricated matrices constitute 3D cell-interactive environment for tissue engineering applications and its potential use as a future cellular biological wound dressing material.

  5. Sericin-carboxymethyl cellulose porous matrices as cellular wound dressing material.

    PubMed

    Nayak, Sunita; Kundu, S C

    2014-06-01

    In this study, porous three-dimensional (3D) hydrogel matrices are fabricated composed of silk cocoon protein sericin of non-mulberry silkworm Antheraea mylitta and carboxymethyl cellulose. The matrices are prepared via freeze-drying technique followed by dual cross-linking with glutaraldehyde and aluminum chloride. The microstructure of the hydrogel matrices is assessed using scanning electron microscopy and biophysical characterization are carried out using Fourier transform infrared spectroscopy and X-ray diffraction. The transforming growth factor β1 release from the cross-linked matrices as a growth factor is evaluated by immunosorbent assay. Live dead assay and 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyl tetrazolium bromide assay show no cytotoxicity of blended matrices toward human keratinocytes. The matrices support the cell attachment and proliferation of human keratinocytes as observed through scanning electron microscope and confocal images. Gelatin zymography demonstrates the low levels of matrix metalloproteinase 2 (MMP-2) and insignificant amount of MMP-9 in the culture media of cell seeded matrices. Low inflammatory response of the matrices is indicated through tumor necrosis factor alpha release assay. The results indicate that the fabricated matrices constitute 3D cell-interactive environment for tissue engineering applications and its potential use as a future cellular biological wound dressing material. PMID:23853114

  6. Making almost commuting matrices commute

    SciTech Connect

    Hastings, Matthew B

    2008-01-01

    Suppose two Hermitian matrices A, B almost commute ({parallel}[A,B]{parallel} {<=} {delta}). Are they close to a commuting pair of Hermitian matrices, A', B', with {parallel}A-A'{parallel},{parallel}B-B'{parallel} {<=} {epsilon}? A theorem of H. Lin shows that this is uniformly true, in that for every {epsilon} > 0 there exists a {delta} > 0, independent of the size N of the matrices, for which almost commuting implies being close to a commuting pair. However, this theorem does not specifiy how {delta} depends on {epsilon}. We give uniform bounds relating {delta} and {epsilon}. The proof is constructive, giving an explicit algorithm to construct A' and B'. We provide tighter bounds in the case of block tridiagonal and tridiagnonal matrices. Within the context of quantum measurement, this implies an algorithm to construct a basis in which we can make a projective measurement that approximately measures two approximately commuting operators simultaneously. Finally, we comment briefly on the case of approximately measuring three or more approximately commuting operators using POVMs (positive operator-valued measures) instead of projective measurements.

  7. Fibonacci Identities, Matrices, and Graphs

    ERIC Educational Resources Information Center

    Huang, Danrun

    2005-01-01

    General strategies used to help discover, prove, and generalize identities for Fibonacci numbers are described along with some properties about the determinants of square matrices. A matrix proof for identity (2) that has received immense attention from many branches of mathematics, like linear algebra, dynamical systems, graph theory and others…

  8. Impacts of continuously regenerating trap and particle oxidation catalyst on the NO2 and particulate matter emissions emitted from diesel engine.

    PubMed

    Liu, Zhihua; Ge, Yunshan; Tan, Jianwei; He, Chao; Shah, Asad Naeem; Ding, Yan; Yu, Linxiao; Zhao, Wei

    2012-01-01

    Two continuously regenerating diesel particulate filter (CRDPF) with different configurations and one particles oxidation catalyst (POC) were employed to perform experiments in a controlled laboratory setting to evaluate their effects on NO2, smoke and particle number emissions. The results showed that the application of the after-treatments increased the emission ratios of NO2/NOx significantly. The results of smoke emissions and particle number (PN) emissions indicated that both CRDPFs had sufficient capacity to remove more than 90% of total particulate matter (PM) and more than 97% of solid particles. However, the POC was able to remove the organic components of total PM, and only partially to remove the carbonaceous particles with size less than 30 nm. The negligible effects of POC on larger particles were observed due to its honeycomb structure leads to an inadequate residence time to oxidize the solid particles or trap them. The particles removal efficiencies of CRDPFs had high degree of correlations with the emission ratio of NO2/NOx. The PN emission results from two CRDPFs indicated that more NO2 generating in diesel oxidation catalyst section could obtain the higher removal efficiency of solid particles. However this also increased the risk of NO2 exposure in atmosphere.

  9. Impacts of continuously regenerating trap and particle oxidation catalyst on the NO2 and particulate matter emissions emitted from diesel engine.

    PubMed

    Liu, Zhihua; Ge, Yunshan; Tan, Jianwei; He, Chao; Shah, Asad Naeem; Ding, Yan; Yu, Linxiao; Zhao, Wei

    2012-01-01

    Two continuously regenerating diesel particulate filter (CRDPF) with different configurations and one particles oxidation catalyst (POC) were employed to perform experiments in a controlled laboratory setting to evaluate their effects on NO2, smoke and particle number emissions. The results showed that the application of the after-treatments increased the emission ratios of NO2/NOx significantly. The results of smoke emissions and particle number (PN) emissions indicated that both CRDPFs had sufficient capacity to remove more than 90% of total particulate matter (PM) and more than 97% of solid particles. However, the POC was able to remove the organic components of total PM, and only partially to remove the carbonaceous particles with size less than 30 nm. The negligible effects of POC on larger particles were observed due to its honeycomb structure leads to an inadequate residence time to oxidize the solid particles or trap them. The particles removal efficiencies of CRDPFs had high degree of correlations with the emission ratio of NO2/NOx. The PN emission results from two CRDPFs indicated that more NO2 generating in diesel oxidation catalyst section could obtain the higher removal efficiency of solid particles. However this also increased the risk of NO2 exposure in atmosphere. PMID:22894096

  10. Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

    NASA Astrophysics Data System (ADS)

    Lienemann, Philipp S.; Metzger, Stéphanie; Kiveliö, Anna-Sofia; Blanc, Alain; Papageorgiou, Panagiota; Astolfo, Alberto; Pinzer, Bernd R.; Cinelli, Paolo; Weber, Franz E.; Schibli, Roger; Béhé, Martin; Ehrbar, Martin

    2015-05-01

    Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

  11. Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

    PubMed Central

    Lienemann, Philipp S.; Metzger, Stéphanie; Kiveliö, Anna-Sofia; Blanc, Alain; Papageorgiou, Panagiota; Astolfo, Alberto; Pinzer, Bernd R.; Cinelli, Paolo; Weber, Franz E.; Schibli, Roger; Béhé, Martin; Ehrbar, Martin

    2015-01-01

    Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials. PMID:25989250

  12. Virial expansion for almost diagonal random matrices

    NASA Astrophysics Data System (ADS)

    Yevtushenko, Oleg; Kravtsov, Vladimir E.

    2003-08-01

    Energy level statistics of Hermitian random matrices hat H with Gaussian independent random entries Higeqj is studied for a generic ensemble of almost diagonal random matrices with langle|Hii|2rangle ~ 1 and langle|Hi\

  13. Method and apparatus for PM filter regeneration

    DOEpatents

    Opris, Cornelius N.; Verkiel, Maarten

    2006-01-03

    A method and apparatus for initiating regeneration of a particulate matter (PM) filter in an exhaust system in an internal combustion engine. The method and apparatus includes determining a change in pressure of exhaust gases passing through the PM filter, and responsively varying an opening of an intake valve in fluid communication with a combustion chamber.

  14. Efficient one-step production of (S)-1-phenyl-1,2-ethanediol from (R)-enantiomer plus NAD+–NADPH in-situ regeneration using engineered Escherichia coli

    PubMed Central

    2012-01-01

    Background Candida parapsilosis CCTCC M203011 catalyzes the stereoinversion of (R)-1-phenyl-1,2-ethanediol (PED) through oxidation and reduction. Its NAD+-linked (R)-carbonyl reductase (RCR) catalyzes the oxidization of (R)-PED to 2-hydroxyacetophenone (HAP), and its NADPH-dependent (S)-carbonyl reductase (SCR) catalyzes the reduction of HAP to (S)-PED. The reactions require NAD+ and NADPH as cofactors. However, even if NAD+ and NADPH are added, the biotransformation of (S)-PED from the (R)-enantiomer by an Escherichia coli strain co-expressing RCR and SCR is slow and gives low yields, probably as a result of insufficient or imbalanced redox cofactors. To prepare (S)-PED from the (R)-enantiomer in one-step efficiently, plus redox cofactor regeneration, we introduced pyridine nucleotide transhydrogenases (PNTs) from E. coli to the metabolic pathway of (S)-PED. Results The PNTs were successfully introduced into the E. coli strain RSAB. Most of the PNT activities occurred in the cell membrane of E. coli. The introduction of PNTs increased intracellular NAD+ and NADH concentrations and decreased the NADPH pool without affecting the total nucleotide concentration and cell growth properties. The presence of PNTs increased the NADH/NAD+ ratio slightly and reduced the NADPH/NADP+ ratio about two-fold; the ratio of NADPH/NADP+ to NADH/NAD+ was reduced from 36 to 17. So, the PNTs rebalanced the cofactor pathways: the rate of RCR was increased, while the rate of SCR was decreased. When the ratio of NAD+/NADPH was 3.0 or higher, the RSAB strain produced (S)-PED with the highest optical purity, 97.4%, and a yield of 95.2% at 6 h. The introduction of PNTs stimulated increases of 51.5% and 80.6%, respectively, in optical purity and yield, and simultaneously reduced the reaction time seven-fold. Conclusions In this work, PNTs were introduced into E. coli to rebalance the cofactor pools within the engineered (S)-PED pathways. The efficient one-step production of (S)-PED plus NAD

  15. Desulfurization sorbent regeneration

    DOEpatents

    Jalan, V.M.; Frost, D.G.

    1982-07-07

    A spent solid sorbent resulting from the removal of hydrogen sulfide from a fuel gas flow is regenerated with a steam-air mixture. The mixture of steam and air may also include additional nitrogen or carbon dioxide. The gas mixture contacts the spent sorbent containing metal sulfide at a temperature above 500/sup 0/C to regenerate the sulfide to metal oxide or carbonate. Various metal species including the period four transition metals and the lanthanides are suitable sorbents that may be regenerated by this method. In addition, the introduction of carbon dioxide gas permits carbonates such as those of strontium, barium and calcium to be regenerated. The steam permits regeneration of spent sorbent without formation of metal sulfate. Moreover, the regeneration will proceed with low oxygen concentrations and will occur without the increase in temperature to minimize the risk of sintering and densification of the sorbent. This method may be used for high-temperature fuel cells.

  16. Surface treatment of silicone rubber by carbon negative-ion implantation for nerve regeneration

    NASA Astrophysics Data System (ADS)

    Tsuji, Hiroshi; Izukawa, Masayoshi; Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Sato, Hiroko; Gotoh, Yasuhito; Ishikawa, Junzo

    2004-07-01

    Surface treatment of silicone rubber by carbon negative ion-implantation was investigated for nerve regeneration by "tubulation". Silicone rubber had its surface property altered to be more hydrophilic by carbon negative-ion implantation. The extracellular matrices of proteins in culture medium adsorbed on the implanted surface rather than unimplanted ones. These improvements in wettability and adsorption properties of proteins were respected to contribute to the regeneration of a nerve-lacking system. An in vivo regeneration test of rat sciatic nerves with silicone-rubber tubes was performed. Using a tube in which the inner surface was implanted with carbon negative ions, the sciatic nerve was regenerated through the inter-stump gap of 15 mm between the proximal and distal nerve stumps and electrical stimulation was transported through the regenerated nerve. Thus, the nerve system was recovered. However, with the unimplanted tube, the nerve was not regenerated at all.

  17. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  18. Higher order matrix differential equations with singular coefficient matrices

    SciTech Connect

    Fragkoulis, V. C.; Kougioumtzoglou, I. A.; Pantelous, A. A.; Pirrotta, A.

    2015-03-10

    In this article, the class of higher order linear matrix differential equations with constant coefficient matrices and stochastic process terms is studied. The coefficient of the highest order is considered to be singular; thus, rendering the response determination of such systems in a straightforward manner a difficult task. In this regard, the notion of the generalized inverse of a singular matrix is used for determining response statistics. Further, an application relevant to engineering dynamics problems is included.

  19. Regeneration Heat Exchange

    SciTech Connect

    J. Lin

    2003-07-30

    The original project goals were to establish the viability of the proposed gas turbine regenerator concept by performing the following tasks: (1) Perform detailed design of a working model of the regenerator concept. (2) Construct a ''bench-top'' model of the regenerator concept based upon the detail design. (3) Test the bench-top model and gather data to support the concept's viability. The project funding was used to acquire the tools and material to perform the aforementioned tasks.

  20. Cell-based strategies for vascular regeneration.

    PubMed

    Zou, Tongqiang; Fan, Jiabing; Fartash, Armita; Liu, Haifeng; Fan, Yubo

    2016-05-01

    Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ. PMID:26864677

  1. S-matrices and integrability

    NASA Astrophysics Data System (ADS)

    Bombardelli, Diego

    2016-08-01

    In these notes we review the S-matrix theory in (1+1)-dimensional integrable models, focusing mainly on the relativistic case. Once the main definitions and physical properties are introduced, we discuss the factorization of scattering processes due to integrability. We then focus on the analytic properties of the two-particle scattering amplitude and illustrate the derivation of the S-matrices for all the possible bound states using the so-called bootstrap principle. General algebraic structures underlying the S-matrix theory and its relation with the form factors axioms are briefly mentioned. Finally, we discuss the S-matrices of sine-Gordon and SU(2), SU(3) chiral Gross–Neveu models. In loving memory of Lilia Grandi.

  2. S-matrices and integrability

    NASA Astrophysics Data System (ADS)

    Bombardelli, Diego

    2016-08-01

    In these notes we review the S-matrix theory in (1+1)-dimensional integrable models, focusing mainly on the relativistic case. Once the main definitions and physical properties are introduced, we discuss the factorization of scattering processes due to integrability. We then focus on the analytic properties of the two-particle scattering amplitude and illustrate the derivation of the S-matrices for all the possible bound states using the so-called bootstrap principle. General algebraic structures underlying the S-matrix theory and its relation with the form factors axioms are briefly mentioned. Finally, we discuss the S-matrices of sine-Gordon and SU(2), SU(3) chiral Gross-Neveu models. In loving memory of Lilia Grandi.

  3. Threaded Operations on Sparse Matrices

    SciTech Connect

    Sneed, Brett

    2015-09-01

    We investigate the use of sparse matrices and OpenMP multi-threading on linear algebra operations involving them. Several sparse matrix data structures are presented. Implementation of the multi- threading primarily occurs in the level one and two BLAS functions used within the four algorithms investigated{the Power Method, Conjugate Gradient, Biconjugate Gradient, and Jacobi's Method. The bene ts of launching threads once per high level algorithm are explored.

  4. Stirling Engine With Radial Flow Heat Exchangers

    NASA Technical Reports Server (NTRS)

    Vitale, N.; Yarr, George

    1993-01-01

    Conflict between thermodynamical and structural requirements resolved. In Stirling engine of new cylindrical configuration, regenerator and acceptor and rejector heat exchangers channel flow of working gas in radial direction. Isotherms in regenerator ideally concentric cylinders, and gradient of temperature across regenerator radial rather than axial. Acceptor and rejector heat exchangers located radially inward and outward of regenerator, respectively. Enables substantial increase in power of engine without corresponding increase in diameter of pressure vessel.

  5. Rotationally invariant ensembles of integrable matrices

    NASA Astrophysics Data System (ADS)

    Yuzbashyan, Emil A.; Shastry, B. Sriram; Scaramazza, Jasen A.

    2016-05-01

    We construct ensembles of random integrable matrices with any prescribed number of nontrivial integrals and formulate integrable matrix theory (IMT)—a counterpart of random matrix theory (RMT) for quantum integrable models. A type-M family of integrable matrices consists of exactly N -M independent commuting N ×N matrices linear in a real parameter. We first develop a rotationally invariant parametrization of such matrices, previously only constructed in a preferred basis. For example, an arbitrary choice of a vector and two commuting Hermitian matrices defines a type-1 family and vice versa. Higher types similarly involve a random vector and two matrices. The basis-independent formulation allows us to derive the joint probability density for integrable matrices, similar to the construction of Gaussian ensembles in the RMT.

  6. Osteogenic signaling on silk-based matrices.

    PubMed

    Midha, Swati; Murab, Sumit; Ghosh, Sourabh

    2016-08-01

    Bone tissue engineering has mainly focused on generating 3D grafts to repair bone defects. However, the underlying signaling mechanisms responsible for development of such 3D bone equivalents have largely been ignored. Here we describe the crucial aspects of embryonic osteogenesis and bone development including cell sources and general signaling cascades that guide mesenchymal progenitors towards osteogenic lineage. Drawing from the knowledge of developmental biology, we then review how silk biomaterial can regulate osteogenic signaling by focusing on the expression of cell surface markers, functional genomic information (mRNA) of stem cells cultured on silk matrices. In an attempt to recapitulate exact in vivo microenvironment of osteogenesis, role of scaffold architecture and material chemistry in regulating cellular differentiation is elaborated. The generated knowledge will not only improve our understanding of cell-material interactions but reveal newer strategies beyond a conventional tissue engineering paradigm and open new prospects for developing silk-based therapies against clinically relevant bone disorders. PMID:27163625

  7. Membrane reactors for continuous coenzyme regeneration

    NASA Astrophysics Data System (ADS)

    Wandrey, C.; Wichmann, R.

    1982-12-01

    The importance of continuous coenzyme regeneration is discussed with respect to chemical reaction engineering. The benefit of coenzymes covalently bound to water soluble polymers is especially stressed. The performance of membrane reactors for coenzyme regeneration is discussed in comparison with other reactor concepts. The coenzyme dependent production of L-amino acids from the corresponding alpha-keto acids is used to illustrate how precise turnover numbers as a function of enzyme/coenzyme ratio, initial substrate concentration, and conversion are obtained. Thus, it becomes possible to develop a concept for optimal operating points with respect to enzyme, coenzyme, and substrate costs per unit weight of product.

  8. Novel Factor-loaded Polyphosphazene Matrices

    PubMed Central

    Oredein-McCoy, Olugbemisola; Krogman, Nicholas R.; Weikel, Arlin L.; Hindenlang, Mark D.; Allcock, Harry R.; Laurencin, Cato T.

    2009-01-01

    Currently employed bone tissue engineered scaffolds often lack the potential for vascularization, which may be enhanced through the incorporation of and regulated release of angiogenic factors. For this reason, our objective was to fabricate and characterize protein-loaded amino acid ester polyphosphazene (Pphos)-based scaffolds and evaluate the novel sintering method used for protein incorporation, a method which will ultimately allow for the incorporation of proangiogenic agents. To test the hypothesis, Pphos and their composite microspheres with nanocrystalline hydroxyapatite (Pphos-HAp) were fabricated via the emulsion solvent evaporation method. Next, bovine serum albumin (BSA)-containing microsphere matrices were created using a novel solvent-non solvent approach for protein loading. The resulting protein (BSA) loaded-circular porous microsphere based scaffolds were characterized for morphology, porosity, protein structure, protein distribution, and subsequent protein release pattern. Scanning electron microscopy revealed porous microsphere scaffolds with a smooth surface and sufficient level of sintering, illustrated by fusion of adjacent microspheres. The porosity measured for the PNPhGly and PNPhGly-HAp scaffolds were 23 +/- 0.11% and 18+/- 4.02%, respectively, and within the range of trabecular bone. Circular dichroism confirmed an intact secondary protein structure for BSA following the solvent sintering method used for loading, and confocal microscopy verified that FITC-BSA was successfully entrapped both between adjacent microspheres and within the surface of the microspheres while sintering. For both Pphos and their composite microsphere scaffolds, BSA was released at a steady rate over a 21day time period, following a zero order release profile. HAp particles in the composite scaffolds served to improve the release profile pattern, underscoring the potential of HAp for growth factor delivery. Moreover, the results of this work suggests that the

  9. Stirling cycle piston engine

    SciTech Connect

    Morgan, G. R.

    1985-02-12

    This device is an improvement over the conventional type of Stirling cycle engine where the expander piston is connected to a crankshaft and the displacer piston is connected to the same or another crankshaft for operation. The improvement is based on both the expansion and displacer pistons being an integral unit having regenerating means which eliminate the mechanisms that synchronize the regeneration mode.

  10. Tissue-engineered regeneration of completely transected spinal cord using induced neural stem cells and gelatin-electrospun poly (lactide-co-glycolide)/polyethylene glycol scaffolds.

    PubMed

    Liu, Chang; Huang, Yong; Pang, Mao; Yang, Yang; Li, Shangfu; Liu, Linshan; Shu, Tao; Zhou, Wei; Wang, Xuan; Rong, Limin; Liu, Bin

    2015-01-01

    Tissue engineering has brought new possibilities for the treatment of spinal cord injury. Two important components for tissue engineering of the spinal cord include a suitable cell source and scaffold. In our study, we investigated induced mouse embryonic fibroblasts (MEFs) directly reprogrammed into neural stem cells (iNSCs), as a cell source. Three-dimensional (3D) electrospun poly (lactide-co-glycolide)/polyethylene glycol (PLGA-PEG) nanofiber scaffolds were used for iNSCs adhesion and growth. Cell growth, survival and proliferation on the scaffolds were investigated. Scanning electron microscopy (SEM) and nuclei staining were used to assess cell growth on the scaffolds. Scaffolds with iNSCs were then transplanted into transected rat spinal cords. Two or 8 weeks following transplantation, immunofluorescence was performed to determine iNSC survival and differentiation within the scaffolds. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Scale. Results indicated that iNSCs showed similar morphological features with wild-type neural stem cells (wt-NSCs), and expressed a variety of neural stem cell marker genes. Furthermore, iNSCs were shown to survive, with the ability to self-renew and undergo neural differentiation into neurons and glial cells within the 3D scaffolds in vivo. The iNSC-seeded scaffolds restored the continuity of the spinal cord and reduced cavity formation. Additionally, iNSC-seeded scaffolds contributed to functional recovery of the spinal cord. Therefore, PLGA-PEG scaffolds seeded with iNSCs may serve as promising supporting transplants for repairing spinal cord injury (SCI). PMID:25803031

  11. Spinal Injury: Regeneration, Recovery, and a Possible New Approach

    SciTech Connect

    Cohen, Avis

    2009-02-04

    Spinal injury is most frequent in young healthy men, desperate to walk. Most treatments have focused on regeneration of the injured axons, but no one has as yet achieved success with this approach. However, in the lamprey, a primitive fish with a spinal cord having all the critical features of the human spinal cored, spinal injury is followed by complete regeneration of injured axons. Additionally, the animal recovers the ability to swim, and in many, the swimming is normal. Unfortunately, in most others, it is highly abnormal. This talk will review evidence from the abnormal regeneration, why it bespeaks difficulties heretofore not considered, and suggest an alternate approach for the near future. In so doing, the speaker will introduce the normal function of the spinal cord, what happens in normal and abnormal regeneration, and the new techniques that employ methods from neuromorphic engineering, a synthesis of neuroscience and engineering to engineer smart devices.

  12. Spinal Injury: Regeneration, Recovery, and a Possible New Approach

    ScienceCinema

    Cohen, Avis [University of Maryland, College Park, Maryland, United States

    2016-07-12

    Spinal injury is most frequent in young healthy men, desperate to walk. Most treatments have focused on regeneration of the injured axons, but no one has as yet achieved success with this approach. However, in the lamprey, a primitive fish with a spinal cord having all the critical features of the human spinal cored, spinal injury is followed by complete regeneration of injured axons. Additionally, the animal recovers the ability to swim, and in many, the swimming is normal. Unfortunately, in most others, it is highly abnormal. This talk will review evidence from the abnormal regeneration, why it bespeaks difficulties heretofore not considered, and suggest an alternate approach for the near future. In so doing, the speaker will introduce the normal function of the spinal cord, what happens in normal and abnormal regeneration, and the new techniques that employ methods from neuromorphic engineering, a synthesis of neuroscience and engineering to engineer smart devices.

  13. Specialized progenitors and regeneration

    PubMed Central

    Reddien, Peter W.

    2013-01-01

    Planarians are flatworms capable of regenerating all body parts. Planarian regeneration requires neoblasts, a population of dividing cells that has been studied for over a century. Neoblast progeny generate new cells of blastemas, which are the regenerative outgrowths at wounds. If the neoblasts comprise a uniform population of cells during regeneration (e.g. they are all uncommitted and pluripotent), then specialization of new cell types should occur in multipotent, non-dividing neoblast progeny cells. By contrast, recent data indicate that some neoblasts express lineage-specific transcription factors during regeneration and in uninjured animals. These observations raise the possibility that an important early step in planarian regeneration is the specialization of neoblasts to produce specified rather than naïve blastema cells. PMID:23404104

  14. Engine

    SciTech Connect

    Shin, H.B.

    1984-02-28

    An internal combustion engine has a piston rack depending from each piston. This rack is connected to a power output shaft through a mechanical rectifier so that the power output shaft rotates in only one direction. A connecting rod is pivotally connected at one end to the rack and at the other end to the crank of a reduced function crankshaft so that the crankshaft rotates at the same angular velocity as the power output shaft and at the same frequency as the pistons. The crankshaft has a size, weight and shape sufficient to return the pistons back into the cylinders in position for the next power stroke.

  15. Hear the beat: decellularized mouse heart regenerated with human induced pluripotent stem cells.

    PubMed

    Lin, Bo; Lu, Tung-Ying; Yang, Lei

    2014-02-01

    Heart tissue engineering holds a great potential for human heart disease therapy. Regeneration of whole biofunctional human heart is the ultimate goal of tissue engineering. Recent advances take the first step towards whole heart regeneration. However, a substantial amount of challenges have to be overcome.

  16. Measurement of the matric potential of soil water in the rhizosphere.

    PubMed

    Whalley, W R; Ober, E S; Jenkins, M

    2013-10-01

    The availability of soil water, and the ability of plants to extract it, are important variables in plant research. The matric potential has been a useful way to describe water status in a soil-plant system. In soil it is the potential that is derived from the surface tension of water menisci between soil particles. The magnitude of matric potential depends on the soil water content, the size of the soil pores, the surface properties of the soil particles, and the surface tension of the soil water. Of all the measures of soil water, matric potential is perhaps the most useful for plant scientists. In this review, the relationship between matric potential and soil water content is explored. It is shown that for any given soil type, this relationship is not unique and therefore both soil water content and matric potential need to be measured for the soil water status to be fully described. However, in comparison with water content, approaches for measuring matric potential have received less attention until recently. In this review, a critique of current methods to measure matric potential is presented, together with their limitations as well as underexploited opportunities. The relative merits of both direct and indirect methods to measure matric potential are discussed. The different approaches needed in wet and dry soil are outlined. In the final part of the paper, the emerging technologies are discussed in so far as our current imagination allows. The review draws upon current developments in the field of civil engineering where the measurement of matric potential is also important. The approaches made by civil engineers have been more imaginative than those of plant and soil scientists. PMID:23526772

  17. Three-Dimensional Supermacroporous Carrageenan-Gelatin Cryogel Matrix for Tissue Engineering Applications

    PubMed Central

    Sharma, Archana; Bhat, Sumrita; Vishnoi, Tanushree; Nayak, Vijayashree; Kumar, Ashok

    2013-01-01

    A tissue-engineered polymeric scaffold should provide suitable macroporous structure similar to that of extracellular matrix which can induce cellular activities and guide tissue regeneration. Cryogelation is a technique in which appropriate monomers or polymeric precursors frozen at sub-zero temperature leads to the formation of supermacroporous cryogel matrices. In this study carrageenan-gelatin (natural polymers) cryogels were synthesized by using glutaraldehyde and 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride and N-hydroxysuccinimide (EDC-NHS) as crosslinking agent at optimum concentrations. Matrices showed large and interconnected pores which were in the range of 60–100 μm diameter. Unconfined compression analysis showed elasticity and physical integrity of all cryogels, as these matrices regained their original length after 90% compressing from the original size. Moreover Young's modulus was found to be in the range of 4–11 kPa for the dry cryogel sections. These cryogels also exhibited good in vitro degradation capacity at 37 °C within 4 weeks of incubation. Supermacroporous carrageenan-gelatin cryogels showed efficient cell adherence and proliferation of Cos-7 cells which was examined by SEM. PI nuclear stain was used to observe cell-matrix interaction. Cytotoxicity of the scaffolds was checked by MTT assay which showed that cryogels are biocompatible and act as a potential material for tissue engineering and regenerative medicine. PMID:23936806

  18. Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration.

    PubMed

    Kim, Hae-Won; Lee, Hae-Hyoung; Knowles, J C

    2006-12-01

    Development of fibrous matrices of bioceramic-biopolymer nanocomposite offers great potential in the field of bone regeneration and tissue engineering. However, in order to produce electrospun fibers with homogeneous structure, it is essential for the ceramic powder to be fine and to remain stable in suspension. Herein, we developed a novel method whereby the bioceramic hydroxyapatite (HA) was kept in suspension in biopolymer poly(lactic acid) (PLA). The strategy was to introduce a surfactant hydroxysteric acid (HSA) between the hydrophilic HA powder and the hydrophobic chloroform-dissolved PLA. The HA nanopowder was dispersed effectively in HSA and mixed homogeneously with PLA. Continuous and uniform fibers were generated successfully with diameters of approximately 1-2 microm, and featured a well-developed nanocomposite structure of HA nanopowder-dispersed PLA. Initial cellular assays showed excellent cell attachment and proliferation and also enhanced expression of alkaline phosphatase at 7 days of culturing. The HA-PLA nanocomposite fibers may be potentially useful in tissue engineering applications, particularly as three-dimensional substrates for bone growth.

  19. New insights into vertebrate skin regeneration.

    PubMed

    Seifert, Ashley W; Maden, Malcolm

    2014-01-01

    Regeneration biology has experienced a renaissance as clinicians, scientists, and engineers have combined forces to drive the field of regenerative medicine. Studies investigating the mechanisms that regulate wound healing in adult mammals have led to a good understanding of the stereotypical processes that lead to scarring. Despite comparative studies of fetal wound healing in which no scar is produced, the fact remains that insights from this work have failed to produce therapies that can regenerate adult human skin. In this review, we analyze past and contemporary accounts of wound healing in a variety of vertebrates, namely, fish, amphibians, and mammals, in order to demonstrate how examples of skin regeneration in adult organisms can impact traditional wound-healing research. When considered together, these studies suggest that inflammation and reepithelialization are necessary events preceding both scarring and regeneration. However, the extent to which these processes may direct one outcome over another is likely weaker than currently accepted. In contrast, the extent to which newly deposited extracellular matrix in the wound bed can be remodeled into new skin, and the intrinsic ability of new epidermis to regenerate appendages, appears to underlie the divergence between scar-free healing and the persistence of a scar. We discuss several ideas that may offer areas of overlap between researchers using these different model organisms and which may be of benefit to the ultimate goal of scar-free human wound healing. PMID:24725426

  20. Local Eigenvalue Density for General MANOVA Matrices

    NASA Astrophysics Data System (ADS)

    Erdős, László; Farrell, Brendan

    2013-09-01

    We consider random n× n matrices of the form where X and Y have independent entries with zero mean and variance one. These matrices are the natural generalization of the Gaussian case, which are known as MANOVA matrices and which have joint eigenvalue density given by the third classical ensemble, the Jacobi ensemble. We show that, away from the spectral edge, the eigenvalue density converges to the limiting density of the Jacobi ensemble even on the shortest possible scales of order 1/ n (up to log n factors). This result is the analogue of the local Wigner semicircle law and the local Marchenko-Pastur law for general MANOVA matrices.

  1. Chemical genetics and regeneration.

    PubMed

    Sengupta, Sumitra; Zhang, Liyun; Mumm, Jeff S

    2015-01-01

    Regeneration involves interactions between multiple signaling pathways acting in a spatially and temporally complex manner. As signaling pathways are highly conserved, understanding how regeneration is controlled in animal models exhibiting robust regenerative capacities should aid efforts to stimulate repair in humans. One way to discover molecular regulators of regeneration is to alter gene/protein function and quantify effect(s) on the regenerative process: dedifferentiation/reprograming, stem/progenitor proliferation, migration/remodeling, progenitor cell differentiation and resolution. A powerful approach for applying this strategy to regenerative biology is chemical genetics, the use of small-molecule modulators of specific targets or signaling pathways. Here, we review advances that have been made using chemical genetics for hypothesis-focused and discovery-driven studies aimed at furthering understanding of how regeneration is controlled.

  2. Axonal regeneration in zebrafish.

    PubMed

    Becker, Thomas; Becker, Catherina G

    2014-08-01

    In contrast to mammals, fish and amphibia functionally regenerate axons in the central nervous system (CNS). The strengths of the zebrafish model, that is, transgenics and mutant availability, ease of gene expression analysis and manipulation and optical transparency of larvae lend themselves to the analysis of successful axonal regeneration. Analyses in larval and adult zebrafish suggest a high intrinsic capacity for axon regrowth, yet signaling pathways employed in axonal growth and pathfinding are similar to those in mammals. However, the lesioned CNS environment in zebrafish shows remarkably little scarring or expression of inhibitory molecules and regenerating axons use molecular cues in the environment to successfully navigate to their targets. Future zebrafish research, including screening techniques, will complete our picture of the mechanisms behind successful CNS axon regeneration in this vertebrate model organism.

  3. Magnesium-Containing Nanostructured Hybrid Scaffolds for Enhanced Dentin Regeneration

    PubMed Central

    Qu, Tiejun; Jing, Junjun; Jiang, Yong; Taylor, Robert J.; Feng, Jian Q.; Geiger, Benjamin

    2014-01-01

    Dental caries is one of the most prevalent chronic diseases in the United States, affecting 92% of adults aged 20–64 years. Scaffold-based tissue engineering represents a promising strategy to replace damaged dental structures and restore their biological functions. Current single-component scaffolding materials used for dental tissue regeneration, however, cannot provide the proper microenvironment for dental stem/progenitor cell adhesion, proliferation, and differentiation; new biomimetic hybrid scaffolds are needed to promote better dental tissue formation. In this work, we developed a biomimetic approach to prepare three-dimensional (3D) nanofibrous gelatin/magnesium phosphate (NF-gelatin/MgP) hybrid scaffolds. These scaffolds not only mimic the nanostructured architecture and the chemical composition of natural dentin matrices but also constantly present favorable chemical signals (Mg ions) to dental pulp stem cells (DPSCs), thus providing a desirable microenvironment to facilitate DPSC proliferation, differentiation, and biomineralization. Synthesized hybrid NF-gelatin/MgP possesses natural extracellular matrix (ECM)-like architecture, high porosity, high pore interconnectivity, well-defined pore size, and controlled Mg ion release from the scaffold. Adding MgP into NF-gelatin also increased the mechanical strength of the hybrid scaffold. The sustained release of Mg ions from the NF-gelatin/MgP (MgP=10% wt/wt) scaffold significantly enhanced the proliferation, differentiation, and biomineralization of human DPSCs in vitro. The alkaline phosphatase (ALP) activity and the gene expressions for odontogenic differentiation (collagen I [Col I], ALP, osteocalcin [OCN], dentin sialophosphoprotein [DSPP], and dentin matrix protein 1 [DMP1]) were all significantly higher (p<0.05) in the NF-gelatin/MgP group than in the NF-gelatin group. Those results were further confirmed by hematoxylin and eosin (H&E) and von Kossa staining, as shown by greater ECM secretion and

  4. Magnesium-containing nanostructured hybrid scaffolds for enhanced dentin regeneration.

    PubMed

    Qu, Tiejun; Jing, Junjun; Jiang, Yong; Taylor, Robert J; Feng, Jian Q; Geiger, Benjamin; Liu, Xiaohua

    2014-09-01

    Dental caries is one of the most prevalent chronic diseases in the United States, affecting 92% of adults aged 20-64 years. Scaffold-based tissue engineering represents a promising strategy to replace damaged dental structures and restore their biological functions. Current single-component scaffolding materials used for dental tissue regeneration, however, cannot provide the proper microenvironment for dental stem/progenitor cell adhesion, proliferation, and differentiation; new biomimetic hybrid scaffolds are needed to promote better dental tissue formation. In this work, we developed a biomimetic approach to prepare three-dimensional (3D) nanofibrous gelatin/magnesium phosphate (NF-gelatin/MgP) hybrid scaffolds. These scaffolds not only mimic the nanostructured architecture and the chemical composition of natural dentin matrices but also constantly present favorable chemical signals (Mg ions) to dental pulp stem cells (DPSCs), thus providing a desirable microenvironment to facilitate DPSC proliferation, differentiation, and biomineralization. Synthesized hybrid NF-gelatin/MgP possesses natural extracellular matrix (ECM)-like architecture, high porosity, high pore interconnectivity, well-defined pore size, and controlled Mg ion release from the scaffold. Adding MgP into NF-gelatin also increased the mechanical strength of the hybrid scaffold. The sustained release of Mg ions from the NF-gelatin/MgP (MgP=10% wt/wt) scaffold significantly enhanced the proliferation, differentiation, and biomineralization of human DPSCs in vitro. The alkaline phosphatase (ALP) activity and the gene expressions for odontogenic differentiation (collagen I [Col I], ALP, osteocalcin [OCN], dentin sialophosphoprotein [DSPP], and dentin matrix protein 1 [DMP1]) were all significantly higher (p<0.05) in the NF-gelatin/MgP group than in the NF-gelatin group. Those results were further confirmed by hematoxylin and eosin (H&E) and von Kossa staining, as shown by greater ECM secretion and

  5. The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.

    PubMed

    Cheng, Hai-Ling Margaret; Loai, Yasir; Beaumont, Marine; Farhat, Walid A

    2010-08-01

    Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM-based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue-engineering and regeneration. Measured MR relaxation times (T(1), T(2)) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T(2) components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid.

  6. Regenerating functional heart tissue for myocardial repair

    PubMed Central

    Alcon, Andre; Bozkulak, Esra Cagavi; Qyang, Yibing

    2012-01-01

    Heart disease is one of the leading causes of death worldwide and the number of patients with the disease is likely to grow with the continual decline in health for most of the developed world. Heart transplantation is one of the only treatment options for heart failure due to an acute myocardial infarction, but limited donor supply and organ rejection limit its widespread use. Cellular cardiomyoplasty, or cellular implantation, combined with various tissue-engineering methods aims to regenerate functional heart tissue. This review highlights the numerous cell sources that have been used to regenerate the heart as well as cover the wide range of tissue-engineering strategies that have been devised to optimize the delivery of these cells. It will probably be a long time before an effective regenerative therapy can make a serious impact at the bedside. PMID:22388688

  7. Regenerating a kidney in a lymph node.

    PubMed

    Francipane, Maria Giovanna; Lagasse, Eric

    2016-10-01

    The ultimate treatment for end-stage renal disease (ESRD) is orthotopic transplantation. However, the demand for kidney transplantation far exceeds the number of available donor organs. While more than 100,000 Americans need a kidney, only 17,000 people receive a kidney transplant each year (National Kidney Foundation's estimations). In recent years, several regenerative medicine/tissue engineering approaches have been exploited to alleviate the kidney shortage crisis. Although these approaches have yielded promising results in experimental animal models, the kidney is a complex organ and translation into the clinical realm has been challenging to date. In this review, we will discuss cell therapy-based approaches for kidney regeneration and whole-kidney tissue engineering strategies, including our innovative approach to regenerate a functional kidney using the lymph node as an in vivo bioreactor.

  8. Biocompatibility of Experimental Polymeric Tracheal Matrices.

    PubMed

    Kiselevskii, M V; Chikileva, I O; Vlasenko, R Ya; Sitdikova, S M; Tenchurin, T Kh; Mamagulashvili, V G; Shepelev, A D; Grigoriev, T A; Chvalun, S N

    2016-08-01

    Biocompatibility of a new tracheal matrix is studied. The new matrix is based on polymeric ultra-fiber material colonized by mesenchymal multipotent stromal cells. The experiments demonstrate cytoconductivity of the synthetic matrices and no signs of their degradation within 2 months after their implantation to recipient mice. These data suggest further studies of the synthetic tracheal matrices on large laboratory animals. PMID:27591876

  9. Proper Values of Matrices and Some Applications.

    ERIC Educational Resources Information Center

    Amir-Moez, Ali R.

    1992-01-01

    Presents a short study of proper values of two-by-two matrices with real entries. Gives examples of symmetric matrices and applications to systems of linear equations of perpendicular lines intersecting at the origin and central conics rotated about the origin to eliminate the xy term from its equation. (MDH)

  10. In vivo tissue engineering of heart valves: evolution of a novel concept.

    PubMed

    Schleicher, Martina; Wendel, Hans Peter; Fritze, Olaf; Stock, Ulrich A

    2009-07-01

    Current tissue-engineering principles of heart valves include tissue- or stem cell-derived cells with subsequent in vitro incubation on various scaffolds prior to implantation. Limitations of this approach include a long in vitro culture, an accompanied risk of infection and sophisticated, cost-intensive infrastructures. An 'off-the-shelf' heart valve with in vivo endothelialization and tissue-regeneration potential would overcome these limitations. Additionally, the development of a heart valve with growth potential would be a huge improvement for pediatric patients. This article discusses different starter matrices, homing and immobilization strategies of host cells and masking approaches of inflammatory structures for in vivo surface and tissue engineering of heart valves. Novel concepts will be presented based on highly specific DNA-aptamers immobilized on the heart valve surface as capture molecules for endothelial progenitor cells circulating in the bloodstream.

  11. Products of Independent Elliptic Random Matrices

    NASA Astrophysics Data System (ADS)

    O'Rourke, Sean; Renfrew, David; Soshnikov, Alexander; Vu, Van

    2015-07-01

    For fixed , we study the product of independent elliptic random matrices as tends to infinity. Our main result shows that the empirical spectral distribution of the product converges, with probability , to the -th power of the circular law, regardless of the joint distribution of the mirror entries in each matrix. This leads to a new kind of universality phenomenon: the limit law for the product of independent random matrices is independent of the limit laws for the individual matrices themselves. Our result also generalizes earlier results of Götze-Tikhomirov (On the asymptotic spectrum of products of independent random matrices, available at http://arxiv.org/abs/1012.2710) and O'Rourke-Soshnikov (J Probab 16(81):2219-2245, 2011) concerning the product of independent iid random matrices.

  12. Proresolving nanomedicines activate bone regeneration in periodontitis.

    PubMed

    Van Dyke, T E; Hasturk, H; Kantarci, A; Freire, M O; Nguyen, D; Dalli, J; Serhan, C N

    2015-01-01

    Therapies to reverse tissue damage from osteolytic inflammatory diseases are limited by the inability of current tissue-engineering procedures to restore lost hard and soft tissues. There is a critical need for new therapeutics in regeneration. In addition to scaffolds, cells, and soluble mediators necessary for tissue engineering, control of endogenous inflammation is an absolute requirement for success. Although significant progress has been made in understanding natural resolution of inflammation pathways to limit uncontrolled inflammation in disease, harnessing the biomimetic properties of proresolving lipid mediators has not been demonstrated. Here, we report the use of nano-proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin A4, bLXA4) to promote regeneration of hard and soft tissues irreversibly lost to periodontitis in the Hanford miniature pig. In this proof-of-principle experiment, NPRM-bLXA4 dramatically reduced inflammatory cell infiltrate into chronic periodontal disease sites treated surgically and dramatically increased new bone formation and regeneration of the periodontal organ. These findings indicate that NPRM-bLXA4 is a mimetic of endogenous resolving mechanisms with potent bioactions that offers a new therapeutic tissue-engineering approach for the treatment of chronic osteolytic inflammatory diseases.

  13. Proresolving nanomedicines activate bone regeneration in periodontitis.

    PubMed

    Van Dyke, T E; Hasturk, H; Kantarci, A; Freire, M O; Nguyen, D; Dalli, J; Serhan, C N

    2015-01-01

    Therapies to reverse tissue damage from osteolytic inflammatory diseases are limited by the inability of current tissue-engineering procedures to restore lost hard and soft tissues. There is a critical need for new therapeutics in regeneration. In addition to scaffolds, cells, and soluble mediators necessary for tissue engineering, control of endogenous inflammation is an absolute requirement for success. Although significant progress has been made in understanding natural resolution of inflammation pathways to limit uncontrolled inflammation in disease, harnessing the biomimetic properties of proresolving lipid mediators has not been demonstrated. Here, we report the use of nano-proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin A4, bLXA4) to promote regeneration of hard and soft tissues irreversibly lost to periodontitis in the Hanford miniature pig. In this proof-of-principle experiment, NPRM-bLXA4 dramatically reduced inflammatory cell infiltrate into chronic periodontal disease sites treated surgically and dramatically increased new bone formation and regeneration of the periodontal organ. These findings indicate that NPRM-bLXA4 is a mimetic of endogenous resolving mechanisms with potent bioactions that offers a new therapeutic tissue-engineering approach for the treatment of chronic osteolytic inflammatory diseases. PMID:25389003

  14. Aligned natural-synthetic polyblend nanofibers for peripheral nerve regeneration.

    PubMed

    Wang, Chun-Yang; Zhang, Kui-Hua; Fan, Cun-Yi; Mo, Xiu-Mei; Ruan, Hong-Jiang; Li, Feng-Feng

    2011-02-01

    Peripheral nerve regeneration remains a significant clinical challenge to researchers. Progress in the design of tissue engineering scaffolds provides an alternative approach for neural regeneration. In this study aligned silk fibroin (SF) blended poly(L-lactic acid-co-ε-caprolactone) (P(LLA-CL)) nanofibrous scaffolds were fabricated by electrospinning methods and then reeled into aligned nerve guidance conduits (NGC) to promote nerve regeneration. The aligned SF/P(LLA-CL) NGC was used as a bridge implanted across a 10mm defect in the sciatic nerve of rats and the outcome in terms of of regenerated nerve at 4 and 8 weeks was evaluated by a combination of electrophysiological assessment and histological and immunohistological analysis, as well as electron microscopy. The electrophysiological examination showed that functional recovery of the regenerated nerve in the SF/P(LLA-CL) NGC group was superior to that in the P(LLA-CL) NGC group. The morphological analysis also indicated that the regenerated nerve in the SF/P(LLA-CL) NGC was more mature. All the results demonstrated that the aligned SF/P(LLA-CL) NGC promoted peripheral nerve regeneration significantly better in comparison with the aligned P(LLA-CL) NGC, thus suggesting a potential application in nerve regeneration.

  15. Community Detection for Correlation Matrices

    NASA Astrophysics Data System (ADS)

    MacMahon, Mel; Garlaschelli, Diego

    2015-04-01

    A challenging problem in the study of complex systems is that of resolving, without prior information, the emergent, mesoscopic organization determined by groups of units whose dynamical activity is more strongly correlated internally than with the rest of the system. The existing techniques to filter correlations are not explicitly oriented towards identifying such modules and can suffer from an unavoidable information loss. A promising alternative is that of employing community detection techniques developed in network theory. Unfortunately, this approach has focused predominantly on replacing network data with correlation matrices, a procedure that we show to be intrinsically biased because of its inconsistency with the null hypotheses underlying the existing algorithms. Here, we introduce, via a consistent redefinition of null models based on random matrix theory, the appropriate correlation-based counterparts of the most popular community detection techniques. Our methods can filter out both unit-specific noise and system-wide dependencies, and the resulting communities are internally correlated and mutually anticorrelated. We also implement multiresolution and multifrequency approaches revealing hierarchically nested subcommunities with "hard" cores and "soft" peripheries. We apply our techniques to several financial time series and identify mesoscopic groups of stocks which are irreducible to a standard, sectorial taxonomy; detect "soft stocks" that alternate between communities; and discuss implications for portfolio optimization and risk management.

  16. Hot gas engine heater head

    DOEpatents

    Berntell, John O.

    1983-01-01

    A heater head for a multi-cylinder double acting hot gas engine in which each cylinder is surrounded by an annular regenerator unit, and in which the tops of each cylinder and its surrounding regenerator are interconnected by a multiplicity of heater tubes. A manifold for the heater tubes has a centrally disposed duct connected to the top of the cylinder and surrounded by a wider duct connecting the other ends of the heater tubes with the regenerator unit.

  17. Muscle regeneration after sepsis.

    PubMed

    Bouglé, Adrien; Rocheteau, Pierre; Sharshar, Tarek; Chrétien, Fabrice

    2016-01-01

    Severe critical illness is often complicated by intensive care unit-acquired weakness (ICU-AW), which is associated with increased ICU and post-ICU mortality, delayed weaning from mechanical ventilation and long-term functional disability. Several mechanisms have been implicated in the pathophysiology of ICU-AW, but muscle regeneration has not been investigated to any extent in this context, even though its involvement is suggested by the protracted functional consequences of ICU-AW. Recent data suggest that muscle regeneration could be impaired after sepsis, and that mesenchymal stem cell treatment could improve the post-injury muscle recovery. PMID:27193340

  18. Human stem cells and articular cartilage regeneration.

    PubMed

    Inui, Atsuyuki; Iwakura, Takashi; Reddi, A Hari

    2012-11-05

    The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES) cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS) cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  19. Anatomy, biogenesis and regeneration of salivary glands.

    PubMed

    Holmberg, Kyle V; Hoffman, Matthew P

    2014-01-01

    An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients each year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients' quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland, which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting that nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of 3 general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph. PMID:24862590

  20. Kerov's interlacing sequences and random matrices

    SciTech Connect

    Bufetov, Alexey

    2013-11-15

    To a N × N real symmetric matrix Kerov assigns a piecewise linear function whose local minima are the eigenvalues of this matrix and whose local maxima are the eigenvalues of its (N − 1) × (N − 1) submatrix. We study the scaling limit of Kerov's piecewise linear functions for Wigner and Wishart matrices. For Wigner matrices the scaling limit is given by the Verhik-Kerov-Logan-Shepp curve which is known from asymptotic representation theory. For Wishart matrices the scaling limit is also explicitly found, and we explain its relation to the Marchenko-Pastur limit spectral law.

  1. Electrochemically regenerable carbon dioxide absorber

    NASA Technical Reports Server (NTRS)

    Woods, R. R.; Marshall, R. D.; Schubert, F. H.; Heppner, D. B.

    1979-01-01

    Preliminary designs were generated for two electrochemically regenerable carbon dioxide absorber concepts. Initially, an electrochemically regenerable absorption bed concept was designed. This concept incorporated the required electrochemical regeneration components in the absorber design, permitting the absorbent to be regenerated within the absorption bed. This hardware was identified as the electrochemical absorber hardware. The second hardware concept separated the functional components of the regeneration and absorption process. This design approach minimized the extravehicular activity component volume by eliminating regeneration hardware components within the absorber. The electrochemical absorber hardware was extensively characterized for major operating parameters such as inlet carbon dioxide partial pressure, process air flow rate, operational pressure, inlet relative humidity, regeneration current density and absorption/regeneration cycle endurance testing.

  2. Supercritical fluid regeneration of adsorbents

    NASA Astrophysics Data System (ADS)

    Defilippi, R. P.; Robey, R. J.

    1983-05-01

    The results of a program to perform studies supercritical (fluid) carbon dioxide (SCF CO2) regeneration of adsorbents, using samples of industrial wastewaters from manufacturing pesticides and synthetic solution, and to estimate the economics of the specific wastewater treatment regenerations, based on test data are given. Processing costs for regenerating granular activated carbon GAC) for treating industrial wastewaters depend on stream properties and regeneration throughput.

  3. The cell biology of regeneration

    PubMed Central

    King, Ryan S.

    2012-01-01

    Regeneration of complex structures after injury requires dramatic changes in cellular behavior. Regenerating tissues initiate a program that includes diverse processes such as wound healing, cell death, dedifferentiation, and stem (or progenitor) cell proliferation; furthermore, newly regenerated tissues must integrate polarity and positional identity cues with preexisting body structures. Gene knockdown approaches and transgenesis-based lineage and functional analyses have been instrumental in deciphering various aspects of regenerative processes in diverse animal models for studying regeneration. PMID:22391035

  4. Maxillofacial-derived stem cells regenerate critical mandibular bone defect.

    PubMed

    Steinhardt, Yair; Aslan, Hadi; Regev, Eran; Zilberman, Yoram; Kallai, Ilan; Gazit, Dan; Gazit, Zulma

    2008-11-01

    Stem cell-based bone tissue regeneration in the maxillofacial complex is a clinical necessity. Genetic engineering of mesenchymal stem cells (MSCs) to follow specific differentiation pathways may enhance the ability of these cells to regenerate and increase their clinical relevance. MSCs isolated from maxillofacial bone marrow (BM) are good candidates for tissue regeneration at sites of damage to the maxillofacial complex. In this study, we hypothesized that MSCs isolated from the maxillofacial complex can be engineered to overexpress the bone morphogenetic protein-2 gene and induce bone tissue regeneration in vivo. To demonstrate that the cells isolated from the maxillofacial complex were indeed MSCs, we performed a flow cytometry analysis, which revealed a high expression of mesenchyme-related markers and an absence of non-mesenchyme-related markers. In vitro, the MSCs were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Gene delivery of the osteogenic gene BMP2 via an adenoviral vector revealed high expression levels of BMP2 protein that induced osteogenic differentiation of these cells in vitro and induced bone formation in an ectopic site in vivo. In addition, implantation of genetically engineered maxillofacial BM-derived MSCs into a mandibular defect led to regeneration of tissue at the site of the defect; this was confirmed by performing micro-computed tomography analysis. Histological analysis of the mandibles revealed osteogenic differentiation of implanted cells as well as bone tissue regeneration. We conclude that maxillofacial BM-derived MSCs can be genetically engineered to induce bone tissue regeneration in the maxillofacial complex and that this finding may be clinically relevant. PMID:18636943

  5. Regeneration: rewarding, but potentially risky.

    PubMed

    Egger, Bernhard

    2008-12-01

    Some bilaterally symmetric animals, such as flatworms, annelids, and nemerteans, are renowned for their outstanding regeneration capacity-even a fraction of the body can give rise to a complete new animal. However, not all species of these taxa can regenerate equally well-some cannot regenerate at all. If regeneration was purely beneficial, why cannot all of members of the flat, round, and ribbon worms regenerate? At that, why cannot all other bilaterians, including humans, regenerate as well? Regeneration capacity is an obvious advantage in accidental, predatory, and parasitic loss of body parts and is also closely intertwined with asexual reproduction strategies. Regeneration is suspected to play a role in life span extension or even rejuvenation. An answer for reduced or missing regeneration capacity in many species may be found in limitations of the body plan, high costs, and inherent dangers of regeneration. Defects in adults and juveniles are shown, and similarities between development and regeneration are pointed out. With a focus on some worms, but also highlighting comparisons with other animal taxa, putative reasons for a limited and an advanced regeneration capacity are discussed in this article. PMID:19067421

  6. Tissue engineering in urology.

    PubMed

    Gustafson, C J; Kratz, G

    2001-05-01

    Techniques that are aimed at regeneration of human tissues and organs (tissue engineering) have recently entered into clinical practice. Tissue engineering is currently among the fastest growing areas in medicine, and involves the application of the principles of biology and engineering to the development of functional substitutes for damaged tissues. One of the main limitations of reconstructive surgery in the genitourinary tract is the lack of autologous tissue. This could be changed by the ability to cultivate the patient's own tissues in vitro, or by stimulating the cells in vivo into regeneration of new tissues. The present review discusses how tissue engineering can be used to regenerate some of the tissues of the genitourinary tract. Even though these methods have only recently been introduced clinically into genitourinary medicine, numerous scientific studies have been reported that indicate that these techniques may be of great importance in the near future.

  7. Tibetan medicine and regeneration.

    PubMed

    Dhondup, Lobsang; Husted, Cynthia

    2009-08-01

    An overview of the concept of regeneration in Tibetan medicine is presented with descriptions of detoxification and tonification longevity protocols. The body must be fortified before receiving stronger treatments for regeneration. All disease is brought into balance with understanding of the interplay of the five elements, three humors, and their qualities and locations. The example of multiple sclerosis (MS) is given. The macroscopic three-humor interpretation of MS agrees with the microscopic three-humor description of demyelination, providing a new framework for the understanding and treatment of MS. Treatments for MS and other chronic conditions are based on age, season, time of day, and the individual's three-humor and hot (excess) and cold (deficiency) balance. Treatments to promote regeneration include nutrition, gentle exercise, herbal formulas, accessory therapies such as herbal baths and oils, and meditation. It is built into the theory of Tibetan medicine to have predictions about outcome and distinguish different disease patterns in patients with MS and other disorders. Taking into account daily and seasonal variations coupled with the changing nature of MS, it is critical to frequently evaluate people with MS and other chronic conditions for monitoring and adjustment of treatment for regeneration.

  8. Regenerator seal design

    DOEpatents

    Eckart, Francis H.

    1982-01-01

    A rotary regenerator disc matrix has a face seal with a cross arm and arcuate rim segments joined by prestress clamps to prestrain the arcuate rim seals so as to compensate seal rim twisting or coning and resultant disc face seal leakage as produced by operating thermal gradients across the seal.

  9. ESTIMATION OF FUNCTIONALS OF SPARSE COVARIANCE MATRICES

    PubMed Central

    Fan, Jianqing; Rigollet, Philippe; Wang, Weichen

    2016-01-01

    High-dimensional statistical tests often ignore correlations to gain simplicity and stability leading to null distributions that depend on functionals of correlation matrices such as their Frobenius norm and other ℓr norms. Motivated by the computation of critical values of such tests, we investigate the difficulty of estimation the functionals of sparse correlation matrices. Specifically, we show that simple plug-in procedures based on thresholded estimators of correlation matrices are sparsity-adaptive and minimax optimal over a large class of correlation matrices. Akin to previous results on functional estimation, the minimax rates exhibit an elbow phenomenon. Our results are further illustrated in simulated data as well as an empirical study of data arising in financial econometrics. PMID:26806986

  10. Synchronous correlation matrices and Connes' embedding conjecture

    NASA Astrophysics Data System (ADS)

    Dykema, Kenneth J.; Paulsen, Vern

    2016-01-01

    In the work of Paulsen et al. [J. Funct. Anal. (in press); preprint arXiv:1407.6918], the concept of synchronous quantum correlation matrices was introduced and these were shown to correspond to traces on certain C*-algebras. In particular, synchronous correlation matrices arose in their study of various versions of quantum chromatic numbers of graphs and other quantum versions of graph theoretic parameters. In this paper, we develop these ideas further, focusing on the relations between synchronous correlation matrices and microstates. We prove that Connes' embedding conjecture is equivalent to the equality of two families of synchronous quantum correlation matrices. We prove that if Connes' embedding conjecture has a positive answer, then the tracial rank and projective rank are equal for every graph. We then apply these results to more general non-local games.

  11. A Computer Program for Clustering Large Matrices

    ERIC Educational Resources Information Center

    Koch, Valerie L.

    1976-01-01

    A Fortran V program is described derived for the Univac 1100 Series Computer for clustering into hierarchical structures large matrices, up to 1000 x 1000 and larger, of interassociations between objects. (RC)

  12. Regenerated Fe is tasty!

    NASA Astrophysics Data System (ADS)

    Nuester, J.; Twining, B. S.

    2012-12-01

    Bioavailability of nutrients is an essential factor controlling primary productivity in the ocean. In addition to macronutrients such as nitrogen and phosphorous, availability of the trace element iron unequivocally affects growth rates and community structure of phytoplankton and thereby primary productivity in many ocean regions. External sources of iron such as Aeolian dust, upwelling of Fe-rich waters, and hydrothermal are reduced in high-nutrient low-chlorophyll regions, and most Fe used by phytoplankton has been regenerated by zooplankton. While zooplankton regeneration of Fe was first shown two decades ago, major factors controlling this process such as chemical composition of prey and grazer taxonomy are not well constrained. As pH varies significantly in digestive systems between protozoa and mesozooplankton, we hypothesize that the extent and the bioavailability of regenerated Fe is a function of the digestive physiology. Furthermore, major element components such as silica for diatoms and calcium carbonate for cocolithophores may be able to buffer the pH of digestive systems of different grazer taxa. Such effects may further influence the magnitude and bioavailability of regenerated Fe. In order to constrain the effect of grazer taxonomy and chemical composition of prey on Fe bioavailability, 55Fe-labeled phytoplankton were fed to different grazers and unlabeled phytoplankton were subsequently inoculated to the filtrate of the grazing experiment in the regrowth phase of the experiment, and the uptake of 55Fe into the phytoplankton biomass was monitored over time. A parallel uptake experiment using inorganic 55Fe was used to compare the bioavailability of regenerated and inorganic Fe to the same phytoplankton species. Furthermore, some samples of the inorganic and the regenerated uptake experiments were treated with an oxalate rinse to remove any adsorbed Fe. This allowed us to estimate the adsorption of 55Fe from either source to the cell walls of

  13. Improvement of PHBV Scaffolds with Bioglass for Cartilage Tissue Engineering

    PubMed Central

    Li, Haiyan; Sun, Junying; Liu, Kai

    2013-01-01

    Polymer scaffold systems consisting of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) have proven to be possible matrices for the three-dimensional growth of chondrocyte cultures. However, the engineered cartilage grown on these PHBV scaffolds is currently unsatisfactory for clinical applications due to PHBV’s poor hydrophilicity, resulting in inadequate thickness and poor biomechanical properties of the engineered cartilage. It has been reported that the incorporation of Bioglass (BG) into PHBV can improve the hydrophilicity of the composites. In this study, we compared the effects of PHBV scaffolds and PHBV/BG composite scaffolds on the properties of engineered cartilage in vivo. Rabbit articular chondrocytes were seeded into PHBV scaffolds and PHBV/BG scaffolds. Short-term in vitro culture followed by long-term in vivo transplantation was performed to evaluate the difference in cartilage regeneration between the cartilage layers grown on PHBV and PHBV/BG scaffolds. The results show that the incorporation of BG into PHBV efficiently improved both the hydrophilicity of the composites and the percentage of adhered cells and promoted cell migration into the inner part the constructs. With prolonged incubation time in vivo, the chondrocyte-scaffold constructs in the PHBV/BG group formed thicker cartilage-like tissue with better biomechanical properties and a higher cartilage matrix content than the constructs in the PHBV/BG group. These results indicate that PHBV/BG scaffolds can be used to prepare better engineered cartilage than pure PHBV. PMID:23951190

  14. Expediting the transition from replacement medicine to tissue engineering

    PubMed Central

    Coury, Arthur J.

    2016-01-01

    In this article, an expansive interpretation of “Tissue Engineering” is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: “Exerting systematic control of the body’s cells, matrices and fluids.” As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body’s responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of “replacement medicine” where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body’s tissues and functions by exploiting our expanding knowledge of the body’s biological processes to produce natural, healthy outcomes. PMID:27047677

  15. Electrical stimulation: a novel tool for tissue engineering.

    PubMed

    Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

    2013-02-01

    New advances in tissue engineering are being made through the application of different types of electrical stimuli to influence cell proliferation and differentiation. Developments made in the last decade have allowed us to improve the structure and functionality of tissue-engineered products through the use of growth factors, hormones, drugs, physical stimuli, bioreactor use, and two-dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices (with various material properties and topography). Another potential type of stimulus is electricity, which is important in the physiology and development of the majority of all human tissues. Despite its great potential, its role in tissue regeneration and its ability to influence cell migration, orientation, proliferation, and differentiation has rarely been considered in tissue engineering. This review highlights the importance of endogenous electrical stimulation, gathering the current knowledge on its natural occurrence and role in vivo, discussing the novel methods of delivering this stimulus and examining its cellular and tissue level effects, while evaluating how the technique could benefit the tissue engineering discipline in the future.

  16. Tales of regeneration in zebrafish.

    PubMed

    Poss, Kenneth D; Keating, Mark T; Nechiporuk, Alex

    2003-02-01

    Complex tissue regeneration involves exquisitely coordinated proliferation and patterning of adult cells after severe injury or amputation. Certain lower vertebrates such as urodele amphibians and teleost fish have a greater capacity for regeneration than mammals. However, little is known about molecular mechanisms of regeneration, and cellular mechanisms are incompletely defined. To address this deficiency, we and others have focused on the zebrafish model system. Several helpful tools and reagents are available for use with zebrafish, including the potential for genetic approaches to regeneration. Recent studies have shed light on the remarkable ability of zebrafish to regenerate fins. PMID:12557199

  17. Cell- and Gene- Based Therapeutics for Periodontal Regeneration.

    PubMed

    Abbayya, Keshava; Zope, Sameer Anil; Naduwinmani, Sanjay; Pisal, Apurva; Puthanakar, Nagraj

    2015-01-01

    Periodontitis is a disease of the periodontium, characterized by loss of connective tissue attachment and supporting the alveolar bone. Therefore, to regenerate these lost tissues of the periodontium researchers have included a variety of surgical procedures including grafting materials growth factors and the use of barrier membranes, ultimately resulting into regeneration that is biologically possible but clinically unpredictable. Recently a newer approach of delivering DNA plasmids as therapeutic agents is gaining special attention and is called gene delivery method. Gene therapy being considered a novel approach have a potential to channel their signals in a very systematic and controlled manner thereby providing encoded proteins at all stages of tissue regeneration. The aim of this review was to enlighten a view on the application involving gene delivery and tissue engineering in periodontal regeneration.

  18. Bioactive and Biodegradable Nanocomposites and Hybrid Biomaterials for Bone Regeneration

    PubMed Central

    Allo, Bedilu A.; Costa, Daniel O.; Dixon, S. Jeffrey; Mequanint, Kibret; Rizkalla, Amin S.

    2012-01-01

    Strategies for bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix and act as templates onto which cells attach, multiply, migrate and function. Of particular interest are nanocomposites and organic-inorganic (O/I) hybrid biomaterials based on selective combinations of biodegradable polymers and bioactive inorganic materials. In this paper, we review the current state of bioactive and biodegradable nanocomposite and O/I hybrid biomaterials and their applications in bone regeneration. We focus specifically on nanocomposites based on nano-sized hydroxyapatite (HA) and bioactive glass (BG) fillers in combination with biodegradable polyesters and their hybrid counterparts. Topics include 3D scaffold design, materials that are widely used in bone regeneration, and recent trends in next generation biomaterials. We conclude with a perspective on the future application of nanocomposites and O/I hybrid biomaterials for regeneration of bone. PMID:24955542

  19. Emerging enzymes for ATP regeneration in biocatalytic processes.

    PubMed

    Andexer, Jennifer N; Richter, Michael

    2015-02-01

    Adenosine-5'-triphosphate-dependent enzyme catalysed reactions are widespread in nature. Consequently, the enzymes involved have an intrinsic potential for use in syntheses of high value products. Although regeneration systems for ATP starting from adenosine-5'-diphosphate are available, certain limitations exist for both in vitro and in vivo applications requiring ATP regeneration from adenosine-5'-monophosphate, or adenosine. Following a short overview of the chemical and thermodynamic background, this Minireview focuses on emerging enzymes and methodologies for ATP regeneration. A large range of as yet unexploited reactions will be accessible with new, powerful, multistep ATP regeneration systems that use cheap phosphate donors and provide high longevity, compatibility, and robustness under process conditions. Their potential might go far beyond the direct use of ATP in enzymatic reactions; enzyme discovery, and engineering, as well as immobilisation strategies, will help to realise such systems.

  20. Regeneration of the vocal fold using autologous mesenchymal stem cells.

    PubMed

    Kanemaru, Shin-Ichi; Nakamura, Tatsuo; Omori, Koichi; Kojima, Hisayoshi; Magrufov, Akhmar; Hiratsuka, Yasuyuki; Hirano, Shigeru; Ito, Juichi; Shimizu, Yasuhiko

    2003-11-01

    The aim of this study was to regenerate the injured vocal fold by means of selective cultured autologous mesenchymal stem cells (MSCs). Eight adult beagle dogs were used for this experiment. Selective incubation of MSCs from bone marrow was done. These MSCs were submitted to 3-dimensional incubation in 1% hydrochloric acid atelocollagen. Three-dimensional incubated MSCs were injected into the left vocal fold, and atelocollagen only was injected into the right vocal fold of the same dog as a control. Four days after injection, the posterior parts of the vocal folds were incised. The regeneration of the vocal fold was estimated by morphological and histologic evaluations. Our results showed that 3-dimensional incubated MSCs were useful in the regeneration of the injured vocal fold. This study shows that damaged tissues such as an injured vocal fold would be able to be regenerated by tissue engineering. PMID:14653358

  1. Regenerative rotary displacer Stirling engine

    SciTech Connect

    Isshiki, Naotsugu; Watanabe, Hiroichi; Raggi, L.; Isshiki, Seita; Hirata, Koichi

    1996-12-31

    A few rotary displacer Stirling engines in which the displacer has one gas pocket space at one side and rotates in a main enclosed cylinder, which is heated from one side and cooled from opposite side without any regenerator, have been studied for some time by the authors. The authors tried to improve this engine by equipping it with a regenerator, because without a regenerator, pressure oscillation and efficiency are too small. Here, several types of regenerative rotary displacer piston Stirling engines are proposed. One is the contra-rotating tandem two disc type displacer engine using axial heat conduction through side walls or by heat pipes and another is a single disc type with circulating fluid regenerator or heat pipes. Stirling engines of this new rotary displacer type are thought to attain high speed. Here, experimental results of the original rotary displacer Stirling engine without a regenerator, and one contra-rotating tandem displacer engine with side wall regenerator by axial heat conduction are reported accompanied with a discussion of the results.

  2. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration

    PubMed Central

    Calve, Sarah; Simon, Hans-Georg

    2012-01-01

    During forelimb regeneration in the newt Notophthalmus viridescens, the dynamic expression of a transitional matrix rich in hyaluronic acid, tenascin-C, and fibronectin controls muscle cell behavior in vivo and in vitro. However, the influence of extracellular matrix (ECM) remodeling on tissue stiffness and the cellular response to mechanical variations during regeneration was unknown. By measuring the transverse stiffness of tissues in situ, we found undifferentiated regenerative blastemas were less stiff than differentiated stump muscle (13.3±1.6 vs. 16.6±1.2 kPa). To directly determine how ECM and stiffness combine to affect skeletal muscle fragmentation, migration, and fusion, we coated silicone-based substrates ranging from 2 to 100 kPa with matrices representative of transitional (tenascin-C and fibronectin) and differentiated environments (laminin and Matrigel). Using live-cell imaging, we found softer tenascin-C-coated substrates significantly enhanced migration and fragmentation of primary newt muscle cells. In contrast, stiffer substrates coated with laminin, Matrigel, or fibronectin increased differentiation while suppressing migration and fragmentation. These data support our in vivo observations that a transitional matrix of reduced stiffness regulates muscle plasticity and progenitor cell recruitment into the regenerative blastema. These new findings will enable the determination of how biochemical and mechanical cues from the ECM control genetic pathways that drive regeneration.—Calve, S., Simon, H.-G. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration. PMID:22415307

  3. Development of A Microwave Assisted Particulate Filter Regeneration System

    SciTech Connect

    Popuri, Sriram

    2001-08-05

    The need for active regeneration of diesel particulate filters and the advantages of microwave assisted regeneration are discussed. The current study has multiple objectives, which include developing a microwave assisted particulate filter regeneration system for future generation light-duty diesel applications, including PNGV type applications. A variable power 2.0 kW microwave system and a tuned waveguide were employed. Cavity geometry is being optimized with the aid of computational modeling and temperature measurements during microwave heating. A wall-flow ceramic-fiber filter with superior thermal shock resistance, high filtration efficiency, and high soot capacity was used. The microwave assisted particulate filter regeneration system has operated for more than 100 hours in an engine test-cell with a 5.9-liter diesel engine with automated split exhaust flow and by-pass flow capabilities. Filter regeneration was demonstrated using soot loads up to 10 g/liter and engine exhaust at idling flow rates as the oxygen source. A parametric study to determine the optimal combination of soot loading, oxidant flow rate, microwave power and heating time is underway. Preliminary experimental results are reported.

  4. A Brief Historical Introduction to Matrices and Their Applications

    ERIC Educational Resources Information Center

    Debnath, L.

    2014-01-01

    This paper deals with the ancient origin of matrices, and the system of linear equations. Included are algebraic properties of matrices, determinants, linear transformations, and Cramer's Rule for solving the system of algebraic equations. Special attention is given to some special matrices, including matrices in graph theory and electrical…

  5. The role of the surface on microglia function: implications for central nervous system tissue engineering

    PubMed Central

    Pires, Liliana R.; Rocha, Daniela N.; Ambrosio, Luigi; Pêgo, Ana Paula

    2015-01-01

    In tissue engineering, it is well accepted that a scaffold surface has a decisive impact on cell behaviour. Here we focused on microglia—the resident immune cells of the central nervous system (CNS)—and on their response to poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) fibrous and flat surfaces obtained by electrospinning and solvent cast, respectively. This study aims to provide cues for the design of instructive surfaces that can contribute to the challenging process of CNS regeneration. Cell morphology was evidently affected by the substrate, mirroring the surface main features. Cells cultured on flat substrates presented a round shape, while cells with elongated processes were observed on the electrospun fibres. A higher concentration of the pro-inflammatory cytokine tumour necrosis factor-α was detected in culture media from microglia on fibres. Still, astrogliosis is not exacerbated when astrocytes are cultured in the presence of microglia-conditioned media obtained from cultures in contact with either substrate. Furthermore, a significant percentage of microglia was found to participate in the process of myelin phagocytosis, with the formation of multinucleated giant cells being observed only on films. Altogether, the results presented suggest that microglia in contact with the tested substrates may contribute to the regeneration process, putting forward P(TMC-CL) substrates as supporting matrices for nerve regeneration. PMID:25540243

  6. Response of human macrophages to wound matrices in vitro.

    PubMed

    Witherel, Claire E; Graney, Pamela L; Freytes, Donald O; Weingarten, Michael S; Spiller, Kara L

    2016-05-01

    Chronic wounds remain a major burden to the global healthcare system. Myriad wound matrices are commercially available but their mechanisms of action are poorly understood. Recent studies have shown that macrophages are highly influenced by their microenvironment, but it is not known how different biomaterials affect this interaction. Here, it was hypothesized that human macrophages respond differently to changes in biomaterial properties in vitro with respect to phenotype, including pro-inflammatory M1, anti-inflammatory M2a, known for facilitating extracellular matrix deposition and proliferation, and M2c, which has recently been associated with tissue remodeling. Using multiple donors, it was found that collagen scaffolds cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) promoted the least inflammatory phenotype in primary human macrophages compared with scaffolds cross-linked with formaldehyde or glutaraldehyde. Importantly, gene expression analysis trends were largely conserved between donors, especially TNFa (M1), CCL22 (M2a), and MRC1 (M2a). Then the response of primary and THP1 monocyte-derived macrophages to four commercially available wound matrices were compared-Integra Dermal Regeneration Template (Integra), PriMatrix Dermal Repair Scaffold (PriMatrix), AlloMend Acellular Dermal Matrix (AlloMend), and Oasis Wound Matrix (Oasis). Gene expression trends were different between primary and THP1 monocyte-derived macrophages for all six genes analyzed in this study. Finally, the behavior of primary macrophages cultured onto the wound matrices over time was analyzed. Integra and Oasis caused down-regulation of M2a markers CCL22 and TIMP3. PriMatrix caused up-regulation of TNFa (M1) and CD163 (M2c) and down-regulation of CCL22 and TIMP3 (both M2a). AlloMend caused up-regulation in CD163 (M2c). Lastly, Oasis promoted the largest increase in the combinatorial M1/M2 score, defined as the sum of M1 genes divided by

  7. Condition number estimation of preconditioned matrices.

    PubMed

    Kushida, Noriyuki

    2015-01-01

    The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hager's method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Pei's matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Pei's matrix, and matrices generated with the finite element method.

  8. Tissue regeneration with photobiomodulation

    NASA Astrophysics Data System (ADS)

    Tang, Elieza G.; Arany, Praveen R.

    2013-03-01

    Low level light therapy (LLLT) has been widely reported to reduce pain and inflammation and enhance wound healing and tissue regeneration in various settings. LLLT has been noted to have both stimulatory and inhibitory biological effects and these effects have been termed Photobiomodulation (PBM). Several elegant studies have shown the key role of Cytochrome C oxidase and ROS in initiating this process. The downstream biological responses remain to be clearly elucidated. Our work has demonstrated activation of an endogenous latent growth factor complex, TGF-β1, as one of the major biological events in PBM. TGF-β1 has critical roles in various biological processes especially in inflammation, immune responses, wound healing and stem cell biology. This paper overviews some of the studies demonstrating the efficacy of PBM in promoting tissue regeneration.

  9. Regenerable adsorption system

    NASA Technical Reports Server (NTRS)

    Roychoudhury, Subir (Inventor); Perry, Jay (Inventor); Walsh, Dennis (Inventor)

    2006-01-01

    A method for regenerable adsorption includes providing a substrate that defines at least one layer of ultra short channel length mesh capable of conducting an electrical current therethrough, coating at least a portion of the substrate with a desired sorbent for trace contaminant control or CO.sub.2 sorption, resistively heating the substrate, and passing a flowstream through the substrate and in contact with the sorbent.

  10. In situ tissue regeneration through host stem cell recruitment

    PubMed Central

    Ko, In Kap; Lee, Sang Jin; Atala, Anthony; Yoo, James J

    2013-01-01

    The field of tissue engineering has made steady progress in translating various tissue applications. Although the classical tissue engineering strategy, which involves the use of culture-expanded cells and scaffolds to produce a tissue construct for implantation, has been validated, this approach involves extensive cell expansion steps, requiring a lot of time and laborious effort before implantation. To bypass this ex vivo process, a new approach has been introduced. In situ tissue regeneration utilizes the body's own regenerating capacity by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the site of injury. This approach relies on development of a target-specific biomaterial scaffolding system that can effectively control the host microenvironment and mobilize host stem/progenitor cells to target tissues. An appropriate microenvironment provided by implanted scaffolds would facilitate recruitment of host cells that can be guided to regenerating structural and functional tissues. PMID:24232256

  11. Bayesian Nonparametric Clustering for Positive Definite Matrices.

    PubMed

    Cherian, Anoop; Morellas, Vassilios; Papanikolopoulos, Nikolaos

    2016-05-01

    Symmetric Positive Definite (SPD) matrices emerge as data descriptors in several applications of computer vision such as object tracking, texture recognition, and diffusion tensor imaging. Clustering these data matrices forms an integral part of these applications, for which soft-clustering algorithms (K-Means, expectation maximization, etc.) are generally used. As is well-known, these algorithms need the number of clusters to be specified, which is difficult when the dataset scales. To address this issue, we resort to the classical nonparametric Bayesian framework by modeling the data as a mixture model using the Dirichlet process (DP) prior. Since these matrices do not conform to the Euclidean geometry, rather belongs to a curved Riemannian manifold,existing DP models cannot be directly applied. Thus, in this paper, we propose a novel DP mixture model framework for SPD matrices. Using the log-determinant divergence as the underlying dissimilarity measure to compare these matrices, and further using the connection between this measure and the Wishart distribution, we derive a novel DPM model based on the Wishart-Inverse-Wishart conjugate pair. We apply this model to several applications in computer vision. Our experiments demonstrate that our model is scalable to the dataset size and at the same time achieves superior accuracy compared to several state-of-the-art parametric and nonparametric clustering algorithms. PMID:27046838

  12. Laminin Functionalized Biomimetic Nanofibers For Nerve Tissue Engineering

    PubMed Central

    Junka, Radoslaw; Valmikinathan, Chandra M; Kalyon, Dilhan M; Yu, Xiaojun

    2013-01-01

    Large-gap peripheral nerve injuries present a significant challenge for nerve regeneration due to lack of suitable grafts, insufficient cell penetration, and repair. Biomimetic nanofibrous scaffolds, functionalized on the surface with extracellular matrix proteins, can lead to novel therapies for repair and regeneration of damaged peripheral nerves. Here, nanofibrous scaffolds electrospun from blends of poly(caprolactone) (PCL) and chitosan were fabricated. Taking advantage of the amine groups on the chitosan, the surface of the scaffolds were functionalized with laminin by carbodiimide based crosslinking. Crosslinking allowed laminin to be attached to the surfaces of the PCL-chitosan nanofibers at relatively high concentrations that were not possible using conventional adsorption methods. The nanofibrous meshes were tested for wettability, mechanical properties and cell attachment and proliferation. Blending of chitosan with PCL provided more favorable surfaces for attachment of Schwann cells due to the reduction of the contact angle in comparison to neat PCL. Proliferation rates of Schwann cells grown on PCL-chitosan scaffolds with crosslinked laminin were significantly higher than the rates for PCL-chitosan nanofibrous matrices with adsorbed laminin. PCL-chitosan scaffolds with modified surfaces via crosslinking of laminin could potentially serves as versatile substrates with excellent mechanical and surface properties for in vivo cell delivery for nerve tissue engineering applications. PMID:24083073

  13. Biomimetic materials design for cardiac tissue regeneration.

    PubMed

    Dunn, David A; Hodge, Alexander J; Lipke, Elizabeth A

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. In the absence of sufficient numbers of organs for heart transplant, alternate approaches for healing or replacing diseased heart tissue are under investigation. Designing biomimetic materials to support these approaches will be essential to their overall success. Strategies for cardiac tissue engineering include injection of cells, implantation of three-dimensional tissue constructs or patches, injection of acellular materials, and replacement of valves. To replicate physiological function and facilitate engraftment into native tissue, materials used in these approaches should have properties that mimic those of the natural cardiac environment. Multiple aspects of the cardiac microenvironment have been emulated using biomimetic materials including delivery of bioactive factors, presentation of cell-specific adhesion sites, design of surface topography to guide tissue alignment and dictate cell shape, modulation of mechanical stiffness and electrical conductivity, and fabrication of three-dimensional structures to guide tissue formation and function. Biomaterials can be engineered to assist in stem cell expansion and differentiation, to protect cells during injection and facilitate their retention and survival in vivo, and to provide mechanical support and guidance for engineered tissue formation. Numerous studies have investigated the use of biomimetic materials for cardiac regeneration. Biomimetic material design will continue to exploit advances in nanotechnology to better recreate the cellular environment and advance cardiac regeneration. Overall, biomimetic materials are moving the field of cardiac regenerative medicine forward and promise to deliver new therapies in combating heart disease.

  14. Transplantation of rat hepatic stem-like (HSL) cells with collagen matrices.

    PubMed

    Ueno, Yasuharu; Nagai, Hirokazu; Watanabe, Go; Ishikawa, Kiyoshi; Yoshikawa, Kiwamu; Koizumi, Yukio; Kameda, Takashi; Sugiyama, Toshihiro

    2005-12-01

    Organ restitution using somatic stem cells is of great clinical interest. Recent advances in the field of tissue engineering have demonstrated that the use of collagen matrices as scaffolds facilitates tissue reconstruction. Here, we examine the efficacy of transplantation of HSL cells, a previously established liver epithelial cell line with a potential for differentiation, using collagen scaffolds. To this end, HSL cells were transplanted into Nagase's analbuminemic rat with spongy or gelatinous type I collagen matrices. Consequently, immunohistochemical analyses and genomic PCR experiments revealed engraftment of the transplanted cells. Furthermore, the levels of serum albumin in recipient rats were found to increase up to 2.5-fold relative to controls after transplantation. These findings suggest that HSL cells are able to differentiate into functional hepatocytes in vivo, and that biodegradable collagen matrices enhance this phenomenon by providing an appropriate microenvironment for hepatocytic repopulation.

  15. Rapid Self-Integrating, Injectable Hydrogel for Tissue Complex Regeneration.

    PubMed

    Hou, Sen; Wang, Xuefei; Park, Sean; Jin, Xiaobing; Ma, Peter X

    2015-07-15

    A novel rapid self-integrating, injectable, and bioerodible hydrogel is developed for bone-cartilage tissue complex regeneration. The hydrogels are able to self-integrate to form various structures, as can be seen after dying some hydrogel disks pink with rodamine. This hydrogel is demonstrated to engineer cartilage-bone complex.

  16. Regenerated cellulose fiber and film immobilized with lysozyme

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present work reports an initial engineering approach for fabricating lysozyme-bound regenerated cellulose fiber and film. Glycine-esterified cotton was dissolved in an ionic liquid solvent 1–Butyl–3–methylimidazolium Chloride (BMIMCl) in which lysozyme was activated and covalently attached to c...

  17. Tissue engineering a small diameter vessel substitute: engineering constructs with select biomaterials and cells.

    PubMed

    McBane, Joanne E; Sharifpoor, Soroor; Labow, Rosalind S; Ruel, Marc; Suuronen, Erik J; Santerre, J Paul

    2012-05-01

    Cardiovascular disease (CVD) is a leading cause of death and hospitalization worldwide. The need for small caliber vessels ( < 6mm) to treat CVD patients has grown; however the availability of autologous vessels in cardiac and peripheral bypass candidates is limited. The search for an alternative vessel source is widespread with both natural and synthetic tissue engineered materials being investigated as scaffolds. Despite decades of exhaustive studies with decellularized extracellular matrices (ECM) and synthetic graft materials, the field remains in search of a commercially viable biomaterial construct substitute. While the previous materials have been assessed by evaluating their compatibility with fibroblasts, smooth muscle cells and endothelial cells, current materials are being conceived based on their interactions with stem cells, progenitor cells and monocytes, as the latter may hold the key to repair and regeneration. The graft's ability to recruit and maintain these cells has become a major research focus. The successful tissue engineering of a small caliber vessel graft requires the use of optimal material chemistry and biological function to promote cell recruitment into the graft while maintaining each functional phenotype during vessel tissue maturation. The discussion of these significant research challenges constitutes the focus of this review.

  18. Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

    PubMed

    Hasan, Anwarul; Waters, Renae; Roula, Boustany; Dana, Rahbani; Yara, Seif; Alexandre, Toubia; Paul, Arghya

    2016-07-01

    Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. PMID:26953627

  19. Advanced incomplete factorization algorithms for Stiltijes matrices

    SciTech Connect

    Il`in, V.P.

    1996-12-31

    The modern numerical methods for solving the linear algebraic systems Au = f with high order sparse matrices A, which arise in grid approximations of multidimensional boundary value problems, are based mainly on accelerated iterative processes with easily invertible preconditioning matrices presented in the form of approximate (incomplete) factorization of the original matrix A. We consider some recent algorithmic approaches, theoretical foundations, experimental data and open questions for incomplete factorization of Stiltijes matrices which are {open_quotes}the best{close_quotes} ones in the sense that they have the most advanced results. Special attention is given to solving the elliptic differential equations with strongly variable coefficients, singular perturbated diffusion-convection and parabolic equations.

  20. Origin of symmetric PMNS and CKM matrices

    NASA Astrophysics Data System (ADS)

    Rodejohann, Werner; Xu, Xun-Jie

    2015-03-01

    The Pontecorvo-Maki-Nakagawa-Sakata and Cabibbo-Kobayashi-Maskawa matrices are phenomenologically close to symmetric, and a symmetric form could be used as zeroth-order approximation for both matrices. We study the possible theoretical origin of this feature in flavor symmetry models. We identify necessary geometric properties of discrete flavor symmetry groups that can lead to symmetric mixing matrices. Those properties are actually very common in discrete groups such as A4 , S4 , or Δ (96 ) . As an application of our theorem, we generate a symmetric lepton mixing scheme with θ12=θ23=36.21 ° ; θ13=12.20 ° , and δ =0 , realized with the group Δ (96 ) .

  1. The asymptotic spectra of banded Toeplitz and quasi-Toeplitz matrices

    NASA Technical Reports Server (NTRS)

    Beam, Richard M.; Warming, Robert F.

    1991-01-01

    Toeplitz matrices occur in many mathematical, as well as, scientific and engineering investigations. This paper considers the spectra of banded Toeplitz and quasi-Toeplitz matrices with emphasis on non-normal matrices of arbitrarily large order and relatively small bandwidth. These are the type of matrices that appear in the investigation of stability and convergence of difference approximations to partial differential equations. Quasi-Toeplitz matrices are the result of non-Dirichlet boundary conditions for the difference approximations. The eigenvalue problem for a banded Toeplitz or quasi-Toeplitz matrix of large order is, in general, analytically intractable and (for non-normal matrices) numerically unreliable. An asymptotic (matrix order approaches infinity) approach partitions the eigenvalue analysis of a quasi-Toeplitz matrix into two parts, namely the analysis for the boundary condition independent spectrum and the analysis for the boundary condition dependent spectrum. The boundary condition independent spectrum is the same as the pure Toeplitz matrix spectrum. Algorithms for computing both parts of the spectrum are presented. Examples are used to demonstrate the utility of the algorithms, to present some interesting spectra, and to point out some of the numerical difficulties encountered when conventional matrix eigenvalue routines are employed for non-normal matrices of large order. The analysis for the Toeplitz spectrum also leads to a diagonal similarity transformation that improves conventional numerical eigenvalue computations. Finally, the algorithm for the asymptotic spectrum is extended to the Toeplitz generalized eigenvalue problem which occurs, for example, in the stability of Pade type difference approximations to differential equations.

  2. Effect of carbohydrates attached to polystyrene on hepatocyte morphology on sugar-derivatized polystyrene matrices.

    PubMed

    Kim, Sang-Heon; Hoshiba, Takashi; Akaike, Toshihiro

    2003-12-15

    Sugar-carrying polymers have been utilized as artificial matrices for cell adhesion in tissue engineering. We have developed sugar-derivatized polystyrenes (PV-sugars) as artificial matrices, which control hepatocyte adhesion and hepatic function. Hepatocytes adhere to PV-sugar matrices in a receptor-mediated manner. In this study, we designed a new galactose-derivatized PV-sugar, poly-(6-O-p-vinylbenzyl-alpha-D-galactose) (PV6Gal) and evaluated the role of carbohydrate attached to polystyrene (PS) backbone in the morphological difference of hepatocyte cultured on PV-sugar matrices. Hepatocytes spread on monosaccharide-derivatized PV-sugars but not on disaccharide-derivatized PV-sugars. The actin filament remained aggregated in the central area of the cell body on disaccharide-derivatized PV-sugars. Hepatocyte cell bodies fully were spread on collagen, and the actin filament was almost completely reorganized. Hepatocyte spreading on monosaccharide-derivatized PV-sugars, however, was caused by protrusive cell-matrix contact like lamellipodia and the actin filament was not completely reorganized. This indicated that hepatocyte spreading on PV-sugar matrices was restricted compared with ECM-mediated cell spreading. In addition, typical spheroid formation of hepatocytes was promoted on disaccharide-derivatized PV-sugars compared with monosaccharide-derivatized PV-sugars. Although hepatocytes adhered with different affinities to PV-sugar matrices, hepatocyte morphology was not affected by the adhesion affinity. We suggest that the type of carbohydrate attached to the PS backbone governs the morphology of hepatocyte cultured on PV-sugar matrices.

  3. Regenerating Water-Sterilizing Resins

    NASA Technical Reports Server (NTRS)

    Colombo, G. V.; Putnam, D. F.

    1982-01-01

    Iodine-dispensing resin can be regenerated after iodine content has been depleted, without being removed from water system. Resin is used to make water potable by killing bacteria, fungi, and viruses. Regeneration technique may be come basis of water purifier for very long space missions. Enough crystalline iodine for multiple regenerations during mission can be stored in one small cartridge. Cartridge could be inserted in waterline as necessary on signal from iodine monitor or timer.

  4. Endothelial progenitor cells from peripheral blood support bone regeneration by provoking an angiogenic response.

    PubMed

    Goerke, Sebastian M; Obermeyer, Julia; Plaha, Julia; Stark, G Björn; Finkenzeller, Günter

    2015-03-01

    Neovascularization is crucial for fracture healing and plays an important role in long-time graft survival in tissue engineering applications. Endothelial progenitor cells (EPCs) can be isolated from peripheral blood avoiding donor site morbidity, which makes them attractive for autologous cell-based engineering of neovessels. However, contradictory results are published concerning the vasculogenic potential of this cell type. We could previously show that implanted human endothelial vein cells (HUVECs) gave rise to the formation of a complex functional human neovasculature in a heterotopic (subcutaneous) as well as in an orthotopic (calvarial defect) model of severe combined immunodeficiency (SCID) mice, where vessel formation could even be increased by coimplanting mesenchymal stem cells (MSCs) functioning as perivascular cells. In this study, we investigated whether coimplantation of MSCs which have been predifferentiated in vitro into SMCs (SMC-MSCs) may enable pbEPCs to form blood vessels upon implantation and, if this would be the case, whether the resulting enhanced vascularization may support bone regeneration. For this purpose, pbEPCs and SMC-MSCs were mono- or cocultured in collagen matrices and seeded into scaffolds consisting of decalcified processed bovine cancellous bone (PBCB, Tutobone). Neovascularization and osteogenesis were evaluated using a calvarial bone defect-model in SCID mice. Our experiments could show that the missing vasculogenic potential of pbEPCs is not rescued by coimplantation of SMCs derived from MSCs predifferentiated along the vascular smooth muscle lineage. However, implantation of both cell types alone, or in combination induced an angiogenic response, which correlated in a positive manner with bone formation within the implants.

  5. Sparse Matrices in MATLAB: Design and Implementation

    NASA Technical Reports Server (NTRS)

    Gilbert, John R.; Moler, Cleve; Schreiber, Robert

    1992-01-01

    The matrix computation language and environment MATLAB is extended to include sparse matrix storage and operations. The only change to the outward appearance of the MATLAB language is a pair of commands to create full or sparse matrices. Nearly all the operations of MATLAB now apply equally to full or sparse matrices, without any explicit action by the user. The sparse data structure represents a matrix in space proportional to the number of nonzero entries, and most of the operations compute sparse results in time proportional to the number of arithmetic operations on nonzeros.

  6. Spectral properties of ghost Neumann matrices

    SciTech Connect

    Bonora, L.; Santos, R. J. Scherer; Tolla, D. D.

    2008-05-15

    We continue the analysis of the ghost wedge states in the oscillator formalism by studying the spectral properties of the ghost matrices of Neumann coefficients. We show that the traditional spectral representation is not valid for these matrices and propose a new heuristic formula that allows one to reconstruct them from the knowledge of their eigenvalues and eigenvectors. It turns out that additional data, which we call boundary data, are needed in order to actually implement the reconstruction. In particular our result lends support to the conjecture that there exists a ghost three strings vertex with properties parallel to those of the matter three strings vertex.

  7. Factorization Of Positive Definite, Banded Hermitian Matrices

    NASA Technical Reports Server (NTRS)

    Salama, Moktar A.; Utku, Senol; Melosh, Robert

    1989-01-01

    Report discusses application of Cholesky factorization algorithm to positive definite, banded Hermitian matrices. Begins by extending Cholesky factorization algorithm to cover uniformly-partitioned, banded, positive definite matrices of rank n that is real symmetric or Hermitian. Then two stratagems given for use of algorithm in concurrent-processing system in which N less than it has to be to enable factorization of matrix in as few serial steps as possible and where uniformly high efficiency expected from all processing elements. One of major purposes of this and related studies to maximize speedup and efficiency in system of concurrent-data-processing elements.

  8. Enamel Regeneration in Making a Bioengineered Tooth.

    PubMed

    Xu, Ruoshi; Zhou, Yachuan; Zhang, Binpeng; Shen, Jiefei; Gao, Bo; Xu, Xin; Ye, Ling; Zheng, Liwei; Zhou, Xuedong

    2015-01-01

    Overall enamel is the hard tissue overlying teeth that is vulnerable to caries, congenital defects, and damage due to trauma. Not only is enamel incapable of self-repair in most species, but it is also subject to attrition. Besides the use of artificial materials to restore enamel, enamel regeneration is a promising approach to repair enamel damage. In order to comprehend the progression and challenges in tissue-engineered enamel, this article elaborates alternative stem cells potential for enamel secretion and expounds fined strategies for enamel regeneration in bioengineered teeth. Consequently, more and more cell types have been induced to differentiate into ameloblasts and to secrete enamel, and an increasing number of reports have emerged to provide various potential approaches to induce cells to secrete enamel based on recombination experiments, artificial bioactive nano-materials, or gene manipulation. Accordingly, it is expected to further project more optimal conditions for enamel formation in bioengineering based on a more thorough knowledge of reciprocal epithelial-mesenchymal interactions, by which the procedures of enamel regeneration are able to be practically recapitulated and widely spread for the potential clinical value of enamel repair.

  9. Stem cells sources for intervertebral disc regeneration.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

  10. Novel applications of statins for bone regeneration

    PubMed Central

    Shah, Sarita R.; Werlang, Caroline A.; Kasper, F. Kurtis; Mikos, Antonios G.

    2015-01-01

    The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID:26543666

  11. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  12. Stem cells sources for intervertebral disc regeneration.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  13. Solid electrolyte oxygen regeneration system

    NASA Technical Reports Server (NTRS)

    Shumar, J. W.; See, G. G.; Schubert, F. H.; Powell, J. D.

    1976-01-01

    A program to design, develop, fabricate and assemble a one-man, self-contained, solid electrolyte oxygen regeneration system (SX-1) incorporating solid electrolyte electrolyzer drums was completed. The SX-1 is a preprototype engineering model designed to produce 0.952 kg (2.1 lb)/day of breathable oxygen (O2) from the electrolysis of metabolic carbon dioxide (CO2) and water vapor. The CO2 supply rate was established based on the metabolic CO2 generation rate for one man of 0.998 kg (2.2 lb)/day. The water supply rate (0.254 kg (0.56 lb)/day) was designed to be sufficient to make up the difference between the 0.952 kg (2.1 lb)/day O2 generation specification and the O2 available through CO2 electrolysis, 0.726 kg (1.6 lb)/day. The SX-1 was successfully designed, fabricated and assembled. Design verification tests (DVT) or the CO Disproportionators, H2 separators, control instrumentation, monitor instrumentation, water feed mechanism were successfully completed. The erratic occurrence of electrolyzer drum leakage prevented the completion of the CO2 electrolyzer module and water electrolyzer module DVT's and also prevented the performance of SX-1 integrated testing. Further development work is required to improve the solid electrolyte cell high temperature seals.

  14. Oligomers Modulate Interfibril Branching and Mass Transport Properties of Collagen Matrices

    PubMed Central

    Whittington, Catherine F.; Brandner, Eric; Teo, Ka Yaw; Han, Bumsoo; Nauman, Eric; Voytik-Harbin, Sherry L.

    2013-01-01

    Mass transport within collagen-based matrices is critical to tissue development, repair, and pathogenesis as well as the design of next generation tissue engineering strategies. This work shows how collagen precursors, specified by intermolecular cross-link composition, provide independent control of collagen matrix mechanical and transport properties. Collagen matrices were prepared from tissue-extracted monomers or oligomers. Viscoelastic behavior was measured in oscillatory shear and unconfined compression. Matrix permeability and diffusivity were measured using gravity-driven permeametry and integrated optical imaging, respectively. Both collagen types showed an increase in stiffness and permeability hindrance with increasing collagen concentration (fibril density); however, different physical property-concentration relationships were noted. Diffusivity wasn’t affected by concentration for either collagen type over the range tested. In general, oligomer matrices exhibited a substantial increase in stiffness and only a modest decrease in transport properties when compared to monomer matrices prepared at the same concentration. The observed differences in viscoelastic and transport properties were largely attributed to increased levels of interfibril branching within oligomer matrices. The ability to relate physical properties to relevant microstructure parameters, including fibril density and interfibril branching, is expected to advance the understanding of cell-matrix signaling as well as facilitate model-based prediction and design of matrix-based therapeutic strategies. PMID:23842082

  15. Understanding Urban Regeneration in Turkey

    NASA Astrophysics Data System (ADS)

    Candas, E.; Flacke, J.; Yomralioglu, T.

    2016-06-01

    In Turkey, rapid population growth, informal settlements, and buildings and infrastructures vulnerable to natural hazards are seen as the most important problems of cities. Particularly disaster risk cannot be disregarded, as large parts of various cities are facing risks from earthquakes, floods and landslides and have experienced loss of lives in the recent past. Urban regeneration is an important planning tool implemented by local and central governments in order to reduce to disaster risk and to design livable environments for the citizens. The Law on the Regeneration of Areas under Disaster Risk, commonly known as the Urban Regeneration Law, was enacted in 2012 (Law No.6306, May 2012). The regulation on Implementation of Law No. 6306 explains the fundamental steps of the urban regeneration process. The relevant institutions furnished with various authorities such as expropriation, confiscation and changing the type and place of your property which makes urban regeneration projects very important in terms of property rights. Therefore, urban regeneration projects have to be transparent, comprehensible and acceptable for all actors in the projects. In order to understand the urban regeneration process, the legislation and projects of different municipalities in Istanbul have been analyzed. While some steps of it are spatial data demanding, others relate to land values. In this paper an overview of the urban regeneration history and activities in Turkey is given. Fundamental steps of the urban regeneration process are defined, and particularly spatial-data demanding steps are identified.

  16. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications

    PubMed Central

    Fortunato, Tiago M.; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A.; Pula, Giordano

    2016-01-01

    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs. PMID:27141997

  17. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.

    PubMed

    Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano

    2016-01-01

    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs. PMID:27141997

  18. Engineering complex tissues.

    PubMed

    Atala, Anthony; Kasper, F Kurtis; Mikos, Antonios G

    2012-11-14

    Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of functional living tissues and organs. The complexity of many tissues and organs, coupled with confounding factors that may be associated with the injury or disease underlying the need for repair, is a challenge to traditional engineering approaches. Biomaterials, cells, and other factors are needed to design these constructs, but not all tissues are created equal. Flat tissues (skin); tubular structures (urethra); hollow, nontubular, viscus organs (vagina); and complex solid organs (liver) all present unique challenges in tissue engineering. This review highlights advances in tissue engineering technologies to enable regeneration of complex tissues and organs and to discuss how such innovative, engineered tissues can affect the clinic.

  19. Closed end regeneration method

    DOEpatents

    Yang, Arthur Jing-Min; Zhang, Yuehua

    2006-06-27

    A nanoporous reactive adsorbent incorporates a relatively small number of relatively larger reactant, e.g. metal, enzyme, etc. particles (10) forming a discontinuous or continuous phase interspersed among and surrounded by a continuous phase of smaller adsorbent particles (12) and connected interstitial pores (14) therebetween. The reactive adsorbent can effectively remove inorganic or organic impurities in a liquid by causing the liquid to flow through the adsorbent. For example, silver ions may be adsorbed by the adsorbent particles (12) and reduced to metallic silver by reducing metal, such as irons, as the reactant particles (10). The column can be regenerated by backwashing with the liquid effluent containing, for example, acetic acid.

  20. Regenerable solid imine sorbents

    DOEpatents

    Gray, McMahan; Champagne, Kenneth J.; Fauth, Daniel; Beckman, Eric

    2013-09-10

    Two new classes of amine-based sorbents are disclosed. The first class comprises new polymer-immobilized tertiary amine sorbents; the second class new polymer-bound amine sorbents. Both classes are tailored to facilitate removal of acid anhydrides, especially carbon dioxide (CO.sub.2), from effluent gases. The amines adsorb acid anhydrides in a 1:1 molar ratio. Both classes of amine sorbents adsorb in the temperature range from about 20.degree. C. upwards to 90.degree. C. and can be regenerated by heating upwards to 100.degree. C.

  1. Bioengineering strategies for regeneration of craniofacial bone: a review of emerging technologies.

    PubMed

    Ward, B B; Brown, S E; Krebsbach, P H

    2010-11-01

    Although advances in surgical techniques and bone grafting have significantly improved the functional and cosmetic restoration of craniofacial structures lost because of trauma or disease, there are still significant limitations in our ability to regenerate these tissues. The regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science, and engineering technology. Tissue engineering is an interdisciplinary field of study that addresses this challenge by applying the principles of engineering to biology and medicine toward the development of biological substitutes that restore, maintain, and improve normal function. This review will explore the impact of biomaterials design, stem cell biology and gene therapy on craniofacial tissue engineering.

  2. Malware analysis using visualized image matrices.

    PubMed

    Han, KyoungSoo; Kang, BooJoong; Im, Eul Gyu

    2014-01-01

    This paper proposes a novel malware visual analysis method that contains not only a visualization method to convert binary files into images, but also a similarity calculation method between these images. The proposed method generates RGB-colored pixels on image matrices using the opcode sequences extracted from malware samples and calculates the similarities for the image matrices. Particularly, our proposed methods are available for packed malware samples by applying them to the execution traces extracted through dynamic analysis. When the images are generated, we can reduce the overheads by extracting the opcode sequences only from the blocks that include the instructions related to staple behaviors such as functions and application programming interface (API) calls. In addition, we propose a technique that generates a representative image for each malware family in order to reduce the number of comparisons for the classification of unknown samples and the colored pixel information in the image matrices is used to calculate the similarities between the images. Our experimental results show that the image matrices of malware can effectively be used to classify malware families both statically and dynamically with accuracy of 0.9896 and 0.9732, respectively. PMID:25133202

  3. Tsirelson's problem and asymptotically commuting unitary matrices

    SciTech Connect

    Ozawa, Narutaka

    2013-03-15

    In this paper, we consider quantum correlations of bipartite systems having a slight interaction, and reinterpret Tsirelson's problem (and hence Kirchberg's and Connes's conjectures) in terms of finite-dimensional asymptotically commuting positive operator valued measures. We also consider the systems of asymptotically commuting unitary matrices and formulate the Stronger Kirchberg Conjecture.

  4. SPECIATION OF ARSENIC IN EXPOSURE ASSESSMENT MATRICES

    EPA Science Inventory

    The speciaton of arsenic in water, food and urine are analytical capabilities which are an essential part in arsenic risk assessment. The cancer risk associated with arsenic has been the driving force in generating the analytical research in each of these matrices. This presentat...

  5. Noisy covariance matrices and portfolio optimization

    NASA Astrophysics Data System (ADS)

    Pafka, S.; Kondor, I.

    2002-05-01

    According to recent findings [#!bouchaud!#,#!stanley!#], empirical covariance matrices deduced from financial return series contain such a high amount of noise that, apart from a few large eigenvalues and the corresponding eigenvectors, their structure can essentially be regarded as random. In [#!bouchaud!#], e.g., it is reported that about 94% of the spectrum of these matrices can be fitted by that of a random matrix drawn from an appropriately chosen ensemble. In view of the fundamental role of covariance matrices in the theory of portfolio optimization as well as in industry-wide risk management practices, we analyze the possible implications of this effect. Simulation experiments with matrices having a structure such as described in [#!bouchaud!#,#!stanley!#] lead us to the conclusion that in the context of the classical portfolio problem (minimizing the portfolio variance under linear constraints) noise has relatively little effect. To leading order the solutions are determined by the stable, large eigenvalues, and the displacement of the solution (measured in variance) due to noise is rather small: depending on the size of the portfolio and on the length of the time series, it is of the order of 5 to 15%. The picture is completely different, however, if we attempt to minimize the variance under non-linear constraints, like those that arise e.g. in the problem of margin accounts or in international capital adequacy regulation. In these problems the presence of noise leads to a serious instability and a high degree of degeneracy of the solutions.

  6. Spectral averaging techniques for Jacobi matrices

    SciTech Connect

    Rio, Rafael del; Martinez, Carmen; Schulz-Baldes, Hermann

    2008-02-15

    Spectral averaging techniques for one-dimensional discrete Schroedinger operators are revisited and extended. In particular, simultaneous averaging over several parameters is discussed. Special focus is put on proving lower bounds on the density of the averaged spectral measures. These Wegner-type estimates are used to analyze stability properties for the spectral types of Jacobi matrices under local perturbations.

  7. Malware Analysis Using Visualized Image Matrices

    PubMed Central

    Im, Eul Gyu

    2014-01-01

    This paper proposes a novel malware visual analysis method that contains not only a visualization method to convert binary files into images, but also a similarity calculation method between these images. The proposed method generates RGB-colored pixels on image matrices using the opcode sequences extracted from malware samples and calculates the similarities for the image matrices. Particularly, our proposed methods are available for packed malware samples by applying them to the execution traces extracted through dynamic analysis. When the images are generated, we can reduce the overheads by extracting the opcode sequences only from the blocks that include the instructions related to staple behaviors such as functions and application programming interface (API) calls. In addition, we propose a technique that generates a representative image for each malware family in order to reduce the number of comparisons for the classification of unknown samples and the colored pixel information in the image matrices is used to calculate the similarities between the images. Our experimental results show that the image matrices of malware can effectively be used to classify malware families both statically and dynamically with accuracy of 0.9896 and 0.9732, respectively. PMID:25133202

  8. Malware analysis using visualized image matrices.

    PubMed

    Han, KyoungSoo; Kang, BooJoong; Im, Eul Gyu

    2014-01-01

    This paper proposes a novel malware visual analysis method that contains not only a visualization method to convert binary files into images, but also a similarity calculation method between these images. The proposed method generates RGB-colored pixels on image matrices using the opcode sequences extracted from malware samples and calculates the similarities for the image matrices. Particularly, our proposed methods are available for packed malware samples by applying them to the execution traces extracted through dynamic analysis. When the images are generated, we can reduce the overheads by extracting the opcode sequences only from the blocks that include the instructions related to staple behaviors such as functions and application programming interface (API) calls. In addition, we propose a technique that generates a representative image for each malware family in order to reduce the number of comparisons for the classification of unknown samples and the colored pixel information in the image matrices is used to calculate the similarities between the images. Our experimental results show that the image matrices of malware can effectively be used to classify malware families both statically and dynamically with accuracy of 0.9896 and 0.9732, respectively.

  9. The Rank of Reduced Dispersion Matrices.

    ERIC Educational Resources Information Center

    Bekker, Paul A.; de Leeuw, Jan

    1987-01-01

    Psychometricians working in factor analysis and econometricians working in regression with measurement error in all variables are both interested in the rank of dispersion matrices under variation of diagonal elements. This paper reviews both fields; points out various small errors; and presents a methodological comparision of factor analysis and…

  10. Regeneration in insects.

    PubMed

    Marsh, J L; Theisen, H

    1999-08-01

    @9cIntroduction@21T issues exhibit an impressive ability to respond to a myriad of insults by repairing and regenerating complex structures. The elegant and orderly process of regeneration provides clues to the mechanisms of pattern formation but also offers the hope that the process might one day be manipulated to replace damaged body parts. To manipulate the process, it will be necessary to understand the genetic basis of the process. In the case of the insect leg, we are coming close to such a level of understanding and many of the lessons learned are relevant to vertebrate systems. A dynamic web of gene regulatory networks appears to create a robust self-organizing system that is at once extremely intricate but also perhaps simple in its reliance on a few key signaling pathways and a few simple processes, e.g. autoactivation and lateral inhibition. Here we will summarize what has been learned about the networks of gene regulation present in the Drosophila leg discs and then we will explore how the regenerative responses to different insults can be understood as predictable responses to these networks. Each of the regulatory networks could themselves serve as the subject of a detailed review and that is beyond the scope of this discussion. Here we will focus on the interplay between the regulatory networks in patterning the tissue.

  11. Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 1: Regeneration of Lacrimal Gland Tissue: Can We Stimulate Lacrimal Gland Renewal In Vivo?

    PubMed

    Dietrich, Jana; Massie, Isobel; Roth, Mathias; Geerling, Gerd; Mertsch, Sonja; Schrader, Stefan

    2016-09-01

    Severe dry eye syndrome (DES) is a complex disease that is commonly caused by inflammatory and degenerative changes in the lacrimal gland, and can result in severe pain and disruption to visual acuity. In healthy subjects, the ocular surface is continually lubricated by the tear film that ensures that the ocular surface remains moist and free of debris, enabling normal vision. The lacrimal fluid, mid-layer of the tear film, is mainly produced by the lacrimal gland and if this is dysfunctional for any reason, severe DES can develop. Currently, only palliative treatments for DES exist that aim to either replace or retain tears and/or minimize inflammation. A curative approach that aims to trigger the regeneration of existing lacrimal gland tissue in situ may, therefore, be very beneficial to DES patients. This article reviews the different approaches that have been explored toward lacrimal gland regeneration. Progress to date in vitro, in vivo, and in man is described with a focus on clinical feasibility and efficacy. Promising candidates for drug-dependent treatment of DES are growth factors and cytokines, such as hepatocyte growth factor (HGF) and tumor necrosis factor α-stimulated gene 6 protein (TSG-6). Only a few studies have evaluated gene therapy for lacrimal gland deficiencies, but with promising results. However gene therapy carries a variety of risks regarding carcinogenesis and therefore a treatment in the near future using this approach seems to be unlikely. Cell therapies utilizing mesenchymal stem cells (MSCs) seem to be more applicable than those using human amniotic membrane (hAM) epithelial cells or induced pluripotent stem (iPS) cells, since MSCs combine the favorable traits of both (multipotency, capability to stimulate regeneration immunomodulatory and non-immunogenic properties).

  12. [Histological aspects of posttraumatic regeneration].

    PubMed

    Truupyl'd Aiu

    1976-02-01

    A number of histological aspects (regeneration capacity, origins of regeneration, means of reparation) are discussed on the example of the reparative regeneration of the adrenal cortex. The adrenal cortex is found to possess high regeneration capacity after a traumatic injury of the organ. Realization of this capacity is dependent on general and local conditions, the character and the volume of the injury and the degree of involvment of cambial zones being of substantial significance. Among these zones are the glomerular zone and the external part of the bundle zone, whose proliferating cells are the source of the reparative regeneration of the cortical substance. The reparation of the functioning mass of the adrenal cortex is performed by the type of regenerative hypertrophy or the reparative regeneration depending on the character of the trauma. After the first type, the division of cells and their differentiation occur within the limits of the available structural elements, after the second type- of the newly formed ones. Both types are evolutionally conditioned and are definitely similar eather to postnatal growth and physiological regeneration (regenerative hypertrophy), or to the embryonic histogenesis of the definitive adrenal cortex (reparative regeneration).

  13. Regenerable Iodine Water-Disinfection System

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Colombo, Gerald V.; Jolly, Clifford D.

    1994-01-01

    Iodinated resin bed for disinfecting water regenerated to extend useful life. Water flows through regeneration bed of crystalline iodine during regeneration. At other times, flow diverted around regeneration bed. Although regeneration cycle manually controlled readily automated to start and stop according to signals from concentration sensors. Further benefit of regeneration is bed provides highly concentrated biocide source when needed. Concentrated biocide used to superiodinate system after contamination from routine maintenance or unexpected introduction of large concentration of microbes.

  14. Insights to regenerate materials: learning from nature

    NASA Astrophysics Data System (ADS)

    García-Aznar, J. M.; Valero, C.; Gómez-Benito, M. J.; Javierre, E.

    2016-08-01

    Self-healing materials, both biological and engineered, integrate the ability to repair themselves and recover their functionality using the resources inherently available to them. Although significant advances have been made, in recent years, for the design of different concepts of self-healing materials, this work aims to provide some insights into how living materials are able to regenerate or heal when a fracture or injury occurs. The main sensors that regulate this adaptive and regenerative behavior are the cells. These are able to sense the mechanical alterations in their surroundings and regulate their activity in order to remove dead tissue and/or create new tissue. Therefore, understanding how cells are able to regenerate tissues under complex and multiphysics conditions can define the biomimetics guidelines to heal through inert or traditional engineering materials. In this work, we present a combination of experiments and different kinds of multiscale and multiphysics models in order to understand how mechanics regulate some mechanisms at cell and tissue level. This combination of results aims to gain insight into the development of novel strategies for self-healing materials, mimicking the behavior induced by cells and biological tissues.

  15. Efficient 9α-hydroxy-4-androstene-3,17-dione production by engineered Bacillus subtilis co-expressing Mycobacterium neoaurum 3-ketosteroid 9α-hydroxylase and B. subtilis glucose 1-dehydrogenase with NADH regeneration.

    PubMed

    Zhang, Xian; Rao, Zhiming; Zhang, Lele; Xu, Meijuan; Yang, Taowei

    2016-01-01

    3-Ketosteroid 9α-hydroxylase (KSH, consisting of KshA and KshB), a key enzyme in steroid metabolism, can catalyze the transformation of 4-androstene-3,17-dione (AD) to 9α-hydroxy-4-androstene-3,17-dione (9OHAD) with NADH as coenzyme. In this work, KSH from Mycobacterium neoaurum JC-12 was successfully cloned and overexpressed in Bacillus subtilis 168. The expression and purification of KSH was analyzed by SDS-PAGE and KSH activity assay. Preliminary characterization of KSH was performed using purified KshA and KshB. The results showed that KSH was very unstable, and its activity was inhibited by most metal ions, especially Zn(2+). The whole-cells of recombinant B. subtilis, co-expression of KSH and glucose 1-dehydrogenase (GDH), were used as biocatalyst to convert AD to 9OHAD. The biocatalyst, in which the intracellular NADH was regenerated, efficiently catalyzed the bioconversion of AD to 9OHAD with a conversion rate of 90.4 % and productivity of 0.45 g (L h)(-1), respectively. This work proposed a strategy for efficiently producing 9OHAD by using B. subtilis as a promising whole-cell biocatalyst host and co-expressing KSH and GDH to construct a NADH regeneration system. PMID:27516945

  16. Implication of two different regeneration systems in limb regeneration

    PubMed Central

    Makanae, Aki; Mitogawa, Kazumasa

    2014-01-01

    Abstract Limb regeneration is a representative phenomenon of organ regeneration in urodele amphibians, such as an axolotl. An amputated limb starts regenerating from a remaining stump (proximal) to lost finger tips (distal). In the present case, proximal−distal (PD) reorganization takes place in a regenerating tissue, called a blastema. It has been a mystery how an induced blastema recognizes its position and restores an exact replica of missing parts. Recently, a new experimental system called the accessory limb model (ALM) has been established. The gained ALM phenotypes are demanding to reconsider the reorganization PD positional values. Based on the ALM phenotype, it is reasonable to hypothesize that reorganization of positional values has a certain discontinuity and that two different regeneration systems cooperatively reorganize the PD axis to restore an original structure. In this review, PD axis reestablishments are focused on limb regeneration. Knowledge from ALM studies in axolotls and Xenopus is providing a novel concept of PD axis reorganization in limb regeneration. PMID:27499860

  17. A brief historical introduction to matrices and their applications

    NASA Astrophysics Data System (ADS)

    Debnath, L.

    2014-04-01

    This paper deals with the ancient origin of matrices, and the system of linear equations. Included are algebraic properties of matrices, determinants, linear transformations, and Cramer's Rule for solving the system of algebraic equations. Special attention is given to some special matrices, including matrices in graph theory and electrical networks. It contains a wide variety of important materials accessible to college and even high school students and teachers at all levels.

  18. Regenerable biocide delivery unit

    NASA Technical Reports Server (NTRS)

    Colombo, Gerald V.; Jolly, Clifford D.; Sauer, Richard L.

    1991-01-01

    The Microbial Check Valve (MCV) is used on the Space Shuttle to impart an iodine residual to the drinking water to maintain microbial control. Approximately twenty MCV locations have been identified in the Space Station Freedom design, each with a 90-day life. This translates to 2400 replacement units in 30 years of operation. An in situ regeneration concept has been demonstrated that will reduce this replacement requirement to less than 300 units based on data to date. A totally automated system will result in significant savings in crew time, resupply requirements, and replacement costs. An additional feature of the device is the ability to provide a concentrated biocide source (200 mg/liter of I2) that can be used to superiodinate systems routinely or after a microbial upset.

  19. Bone regeneration in dentistry

    PubMed Central

    Tonelli, Paolo; Duvina, Marco; Barbato, Luigi; Biondi, Eleonora; Nuti, Niccolò; Brancato, Leila; Rose, Giovanna Delle

    2011-01-01

    Summary The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological principles of osteogenesis, osteoinduction and osteoconduction. Several techniques combine these principles with different results, due to the condition of the bone base on which we operate changes, the surgical technique that we use, and finally for the bone metabolic conditions of the patient who can be in a state of systemic osteopenia or osteoporosis; these can also affect the result of jaw bone reconstruction. PMID:22461825

  20. Stiffness and mass matrices for shells of revolution (SAMMSOR II)

    NASA Technical Reports Server (NTRS)

    Tillerson, J. R.; Haisler, W. E.

    1974-01-01

    Utilizing element properties, structural stiffness and mass matrices are generated for as many as twenty harmonics and stored on magnetic tape. Matrices generated constitute input data to be used by other stiffness of revolution programs. Variety of boundary and loading conditions can be employed without having to create new mass and stiffness matrices for each case.

  1. 19 CFR 10.90 - Master records and metal matrices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301,...

  2. 19 CFR 10.90 - Master records and metal matrices.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301,...

  3. 19 CFR 10.90 - Master records and metal matrices.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301,...

  4. 19 CFR 10.90 - Master records and metal matrices.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301,...

  5. 19 CFR 10.90 - Master records and metal matrices.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Master records and metal matrices. 10.90 Section... Master Records, and Metal Matrices § 10.90 Master records and metal matrices. (a) Consumption entries... made, of each master record or metal matrix covered thereby. (c) A bond on Customs Form 301,...

  6. Improved Separability Criteria Based on Bloch Representation of Density Matrices

    PubMed Central

    Shen, Shu-Qian; Yu, Juan; Li, Ming; Fei, Shao-Ming

    2016-01-01

    The correlation matrices or tensors in the Bloch representation of density matrices are encoded with entanglement properties. In this paper, based on the Bloch representation of density matrices, we give some new separability criteria for bipartite and multipartite quantum states. Theoretical analysis and some examples show that the proposed criteria can be more efficient than the previous related criteria. PMID:27350031

  7. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy.

    PubMed

    Pessina, Patrizia; Kharraz, Yacine; Jardí, Mercè; Fukada, So-ichiro; Serrano, Antonio L; Perdiguero, Eusebio; Muñoz-Cánoves, Pura

    2015-06-01

    Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component. PMID:25981413

  8. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy.

    PubMed

    Pessina, Patrizia; Kharraz, Yacine; Jardí, Mercè; Fukada, So-ichiro; Serrano, Antonio L; Perdiguero, Eusebio; Muñoz-Cánoves, Pura

    2015-06-01

    Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

  9. Skeletal tissue regeneration: where can hydrogels play a role?

    PubMed

    Moreira Teixeira, Liliana S; Patterson, Jennifer; Luyten, Frank P

    2014-09-01

    The emerging field of tissue engineering reveals promising approaches for the repair and regeneration of skeletal tissues including the articular cartilage, bone, and the entire joint. Amongst the myriad of biomaterials available to support this strategy, hydrogels are highly tissue mimicking substitutes and thus of great potential for the regeneration of functional tissues. This review comprises an overview of the novel and most promising hydrogels for articular cartilage, osteochondral and bone defect repair. Chondro- and osteo-conductive and -instructive hydrogels are presented, highlighting successful combinations with inductive signals and cell sources. Moreover, advantages, drawbacks, and future perspectives of the role of hydrogels in skeletal regeneration are addressed, pointing out the current state of this rising approach. PMID:24968789

  10. Cardiac Regeneration and Stem Cells.

    PubMed

    Zhang, Yiqiang; Mignone, John; MacLellan, W Robb

    2015-10-01

    After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.

  11. FLAGELLAR REGENERATION IN PROTOZOAN FLAGELLATES

    PubMed Central

    Rosenbaum, Joel L.; Child, F. M.

    1967-01-01

    The flagella of populations of three protozoan species (Ochromonas, Euglena, and Astasia) were amputated and allowed to regenerate. The kinetics of regeneration in all species were characterized by a lag phase during which there was no apparent flagellar elongation; this phase was followed by elongation at a rate which constantly decelerated as the original length was regained. Inhibition by cycloheximide applied at the time of flagellar amputation showed that flagellar regeneration was dependent upon de novo protein synthesis. This was supported by evidence showing that a greater amount of leucine was incorporated into the proteins of regenerating than nonregenerating flagella. The degree of inhibition of flagellar elongation observed with cycloheximide depended on how soon after flagellar amputation it was applied: when applied to cells immediately following amputation, elongation was almost completely inhibited, but its application at various times thereafter permitted considerable elongation to occur prior to complete inhibition of flagellar elongation. Hence, a sufficient number of precursors were synthesized and accumulated prior to addition of cycloheximide so that their assembly (elongation) could occur for a time under conditions in which protein synthesis had been inhibited. Evidence that the site of this assembly may be at the tip of the elongating flagellum was obtained from radioautographic studies in which the flagella of Ochromonas were permitted to regenerate part way in the absence of labeled leucine and to complete their regeneration in the presence of the isotope. Possible mechanisms which may be operating to control flagellar regeneration are discussed in light of these and other observations. PMID:6033540

  12. Biomaterial selection for tooth regeneration.

    PubMed

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y; Zhou, Hong; Chen, Lili; Mao, Jeremy J

    2011-10-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth.

  13. Cardiac Regeneration and Stem Cells

    PubMed Central

    Zhang, Yiqiang; Mignone, John; MacLellan, W. Robb

    2015-01-01

    After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world. PMID:26269526

  14. Proximodistal patterning during limb regeneration.

    PubMed

    Echeverri, Karen; Tanaka, Elly M

    2005-03-15

    Regeneration is an ability that has been observed extensively throughout metazoan phylogeny. Amongst vertebrates, the urodele amphibians stand out for their exceptional capacity to regenerate body parts such as the limb. During this process, only the missing portion of the limb is precisely replaced--amputation in the upper arm results in regeneration of the entire limb, while amputation at the wrist produces a hand. Limb regeneration occurs through the formation of a local proliferative zone called the blastema. Here, we examine how proximodistal identity is established in the blastema. Using cell marking and transplantation experiments, we show that distal identities have already been established in the earliest stages of blastemas examined. Transplantation of cells into new environments is not sufficient to respecify cell identity. However, overexpression of the CD59, a cell surface molecule previously implicated in proximodistal identity during limb regeneration, causes distal blastema cells to translocate to a more proximal location and causes defects in the patterning of the distal elements of the regenerate. We suggest a model for the limb regeneration blastema where by 4 days post-amputation the blastema is already divided into distinct growth zones; the cells of each zone are already specified to give rise to upper arm, lower arm, and hand. PMID:15733667

  15. Biomaterial Selection for Tooth Regeneration

    PubMed Central

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y.; Zhou, Hong

    2011-01-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth. PMID:21699433

  16. Biomaterials for Bone Regenerative Engineering.

    PubMed

    Yu, Xiaohua; Tang, Xiaoyan; Gohil, Shalini V; Laurencin, Cato T

    2015-06-24

    Strategies for bone tissue regeneration have been continuously evolving for the last 25 years since the introduction of the "tissue engineering" concept. The convergence of the life, physical, and engineering sciences has brought in several advanced technologies available to tissue engineers and scientists. This resulted in the creation of a new multidisciplinary field termed as "regenerative engineering". In this article, the role of biomaterials in bone regenerative engineering is systematically reviewed to elucidate the new design criteria for the next generation of biomaterials for bone regenerative engineering. The exemplary design of biomaterials harnessing various materials characteristics towards successful bone defect repair and regeneration is highlighted. Particular attention is given to the attempts of incorporating advanced materials science, stem cell technologies, and developmental biology into biomaterials design to engineer and develop the next generation bone grafts.

  17. Approximate inverse preconditioners for general sparse matrices

    SciTech Connect

    Chow, E.; Saad, Y.

    1994-12-31

    Preconditioned Krylov subspace methods are often very efficient in solving sparse linear matrices that arise from the discretization of elliptic partial differential equations. However, for general sparse indifinite matrices, the usual ILU preconditioners fail, often because of the fact that the resulting factors L and U give rise to unstable forward and backward sweeps. In such cases, alternative preconditioners based on approximate inverses may be attractive. We are currently developing a number of such preconditioners based on iterating on each column to get the approximate inverse. For this approach to be efficient, the iteration must be done in sparse mode, i.e., we must use sparse-matrix by sparse-vector type operatoins. We will discuss a few options and compare their performance on standard problems from the Harwell-Boeing collection.

  18. Characteristic Matrices for Spherical Shell Photonic Systems

    NASA Technical Reports Server (NTRS)

    Fuller, Kirk A.; Smith, David D.

    2004-01-01

    We establish a parallel between the transfer matrix used in the study of plane-parallel photonic structures and the matrix characterizing transfer of partial waves in concentric spheres. We derive explicit expressions for the elements of the transfer matrix for concentric spherical layers, and from those expressions derive the scattering coefficients of a multilayered sphere. The transfer matrices are 4x4 block diagonal with only four independent elements. Matrix elements for the case of TM waves are related to those for the case of TE waves through simple interchange and multiplicative constants. In analogy with plane parallel layers, the transfer matrix for concentric multilayers is simply the product of the transfer matrices of the individual layers.

  19. Evolutionary Games with Randomly Changing Payoff Matrices

    NASA Astrophysics Data System (ADS)

    Yakushkina, Tatiana; Saakian, David B.; Bratus, Alexander; Hu, Chin-Kun

    2015-06-01

    Evolutionary games are used in various fields stretching from economics to biology. In most of these games a constant payoff matrix is assumed, although some works also consider dynamic payoff matrices. In this article we assume a possibility of switching the system between two regimes with different sets of payoff matrices. Potentially such a model can qualitatively describe the development of bacterial or cancer cells with a mutator gene present. A finite population evolutionary game is studied. The model describes the simplest version of annealed disorder in the payoff matrix and is exactly solvable at the large population limit. We analyze the dynamics of the model, and derive the equations for both the maximum and the variance of the distribution using the Hamilton-Jacobi equation formalism.

  20. Stirling engine power control

    DOEpatents

    Fraser, James P.

    1983-01-01

    A power control method and apparatus for a Stirling engine including a valved duct connected to the junction of the regenerator and the cooler and running to a bypass chamber connected between the heater and the cylinder. An oscillating zone of demarcation between the hot and cold portions of the working gas is established in the bypass chamber, and the engine pistons and cylinders can run cold.

  1. Some physical applications of random hierarchical matrices

    SciTech Connect

    Avetisov, V. A.; Bikulov, A. Kh.; Vasilyev, O. A.; Nechaev, S. K.; Chertovich, A. V.

    2009-09-15

    The investigation of spectral properties of random block-hierarchical matrices as applied to dynamic and structural characteristics of complex hierarchical systems with disorder is proposed for the first time. Peculiarities of dynamics on random ultrametric energy landscapes are discussed and the statistical properties of scale-free and polyscale (depending on the topological characteristics under investigation) random hierarchical networks (graphs) obtained by multiple mapping are considered.

  2. Analysis of thematic map classification error matrices.

    USGS Publications Warehouse

    Rosenfield, G.H.

    1986-01-01

    The classification error matrix expresses the counts of agreement and disagreement between the classified categories and their verification. Thematic mapping experiments compare variables such as multiple photointerpretation or scales of mapping, and produce one or more classification error matrices. This paper presents a tutorial to implement a typical problem of a remotely sensed data experiment for solution by the linear model method.-from Author

  3. Parameterization of a Conventional and Regenerated UHB Turbofan

    NASA Astrophysics Data System (ADS)

    Oliveira, Fábio; Brójo, Francisco

    2015-09-01

    The attempt to improve aircraft engines efficiency resulted in the evolution from turbojets to the first generation low bypass ratio turbofans. Today, high bypass ratio turbofans are the most traditional type of engine in commercial aviation. Following many years of technological developments and improvements, this type of engine has proved to be the most reliable facing the commercial aviation requirements. In search of more efficiency, the engine manufacturers tend to increase the bypass ratio leading to ultra-high bypass ratio (UHB) engines. Increased bypass ratio has clear benefits in terms of propulsion system like reducing the specific fuel consumption. This study is aimed at a parametric analysis of a UHB turbofan engine focused on short haul flights. Two cycle configurations (conventional and regenerated) were studied, and estimated values of their specific fuel consumption (TSFC) and specific thrust (Fs) were determined. Results demonstrate that the regenerated cycle may contribute towards a more economic and friendly aero engines in a higher range of bypass ratio.

  4. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-19

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

  5. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  6. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

    PubMed Central

    Akram, Khondoker M.; Patel, Neil; Spiteri, Monica A.; Forsyth, Nicholas R.

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  7. Calcium phosphate-alginate microspheres as enzyme delivery matrices.

    PubMed

    Ribeiro, C C; Barrias, C C; Barbosa, M A

    2004-08-01

    The present study concerns the preparation and initial characterisation of novel calcium titanium phosphate-alginate (CTP-alginate) and hydroxyapatite-alginate (HAp-alginate) microspheres, which are intended to be used as enzyme delivery matrices and bone regeneration templates. Microspheres were prepared using different concentrations of polymer solution (1% and 3% w/v) and different ceramic-to-polymer solution ratios (0.1, 0.2 and 0.4 w/w). Ceramic powders were characterised using X-ray diffraction, laser granulometry, Brunauer, Emmel and Teller (BET) method for the determination of surface area, zeta potential and Fourier transform infrared spectroscopy (FT-IR). Alginate was characterised using high performance size exclusion chromatography. The methodology followed in this investigation enabled the preparation of homogeneous microspheres with a uniform size. Studies on the immobilisation and release of the therapeutic enzyme glucocerebrosidase, employed in the treatment of Gaucher disease, were also performed. The enzyme was incorporated into the ceramic-alginate matrix before gel formation in two different ways: pre-adsorbed onto the ceramic particles or dispersed in the polymeric matrix. The two strategies resulted in distinct release profiles. Slow release was obtained after adsorption of the enzyme to the ceramic powders, prior to preparation of the microspheres. An initial fast release was achieved when the enzyme and the ceramic particles were dispersed in the alginate solution before producing the microspheres. The latter profile is very similar to that of alginate microspheres. The different patterns of enzyme release increase the range of possible applications of the system investigated in this work.

  8. Microwave regenerated particulate trap

    SciTech Connect

    McDonald, A.C. Jr.; Yonushonis, T.M.; Haberkamp, W.C.; Mako, F.; Len, L.K,; Silberglitt, R.; Ahmed, I.

    1997-12-31

    It has been demonstrated that a fibrous particulate filter can extract particulate matter from the diesel exhaust. However, additional engineering efforts remains to achieve the design target of 90%. It has also be shown that with minor modifications magnetrons produced for home ovens can endure a simulated diesel operating environment. Much work remains to develop a robust product ready to complete extensive engine testing and evaluation. These efforts include: (1) additional environmental testing of magnetrons; (2) vibration testing of the filter in the housing; (3) evaluating alternative methods/designs to seal the center bore; and (4) determining the optimum coating thickness that provides sufficient structural integrity while maintaining rapid heating rates.

  9. Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices

    PubMed Central

    Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen

    2013-01-01

    In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588

  10. Deterministic sensing matrices in compressive sensing: a survey.

    PubMed

    Nguyen, Thu L N; Shin, Yoan

    2013-01-01

    Compressive sensing is a sampling method which provides a new approach to efficient signal compression and recovery by exploiting the fact that a sparse signal can be suitably reconstructed from very few measurements. One of the most concerns in compressive sensing is the construction of the sensing matrices. While random sensing matrices have been widely studied, only a few deterministic sensing matrices have been considered. These matrices are highly desirable on structure which allows fast implementation with reduced storage requirements. In this paper, a survey of deterministic sensing matrices for compressive sensing is presented. We introduce a basic problem in compressive sensing and some disadvantage of the random sensing matrices. Some recent results on construction of the deterministic sensing matrices are discussed.

  11. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    NASA Astrophysics Data System (ADS)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang-Seok; Hong, Suck Won; Han, Dong-Wook; Kim, Chuntae; Oh, Jin-Woo

    2015-01-01

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic- co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  12. Regenerable Iodine Water-Disinfection System

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Colombo, Gerald V.; Jolly, Clifford D.

    1994-01-01

    Iodinated resin bed for disinfecting water regenerated to extend its useful life. Water flows through regeneration bed of crystalline iodine during regeneration. At other times, flow diverted around regeneration bed. Although regeneration cycle was manually controlled in demonstration, readily automated to start and stop according to signals and stop according to signals from concentration sensors. Further benefit of regeneration is that regeneration bed provides highly concentrated biocide source (200 mg/L) when needed. Concentrated biocide used to superiodinate system after contamination from routine maintenance or unexpected introduction of large concentration of microbes.

  13. Effect of Polycaprolactone Scaffold Permeability on Bone Regeneration In Vivo

    PubMed Central

    Mitsak, Anna G.; Kemppainen, Jessica M.; Harris, Matthew T.

    2011-01-01

    Successful bone tissue engineering depends on the scaffold's ability to allow nutrient diffusion to and waste removal from the regeneration site, as well as provide an appropriate mechanical environment. Since bone is highly vascularized, scaffolds that provide greater mass transport may support increased bone regeneration. Permeability encompasses the salient features of three-dimensional porous scaffold architecture effects on scaffold mass transport. We hypothesized that higher permeability scaffolds will enhance bone regeneration for a given cell seeding density. We manufactured poly-ɛ-caprolactone scaffolds, designed to have the same internal pore design and either a low permeability (0.688×10−7m4/N-s) or a high permeability (3.991×10−7m4/N-s), respectively. Scaffolds were seeded with bone morphogenic protein-7-transduced human gingival fibroblasts and implanted subcutaneously in immune-compromised mice for 4 and 8 weeks. Micro-CT evaluation showed better bone penetration into high permeability scaffolds, with blood vessel infiltration visible at 4 weeks. Compression testing showed that scaffold design had more influence on elastic modulus than time point did and that bone tissue infiltration increased the mechanical properties of the high permeability scaffolds at 8 weeks. These results suggest that for polycaprolactone, a more permeable scaffold with regular architecture is best for in vivo bone regeneration. This finding is an important step toward the end goal of optimizing a scaffold for bone tissue engineering. PMID:21395465

  14. Regeneration in Alfalfa Tissue Culture

    PubMed Central

    Skokut, Thomas A.; Manchester, Jill; Schaefer, Jacob

    1985-01-01

    The production of somatic embryos in alfalfa (Medicago sativa L., cv Regen S) is increased 5- to 10-fold by alanine and proline. However, utilization of nitrogen for synthesis of protein from alanine, proline, glutamate, and glycine is not qualitatively different, even though the latter two amino acids do not increase somatic embryo formation. These determinations were made by 15N labeling with detection by nuclear magnetic resonance. Overall metabolism of the nitrogen of proline, alanine, glutamate, and glycine is also similar in two regenerating and nonregenerating genotypes with similar germplasm, except that the levels of free amino acids are consistently higher in the nonregenerating line. In addition, when regeneration is suppressed in either of the two regenerating lines, the level of intracellular free amino acids increases. This increased level of metabolites is the only direct evidence provided by analysis of nitrogen metabolism of differences between the regenerating and nonregenerating states in alfalfa. PMID:16664455

  15. Control of growth during regeneration.

    PubMed

    Sun, Gongping; Irvine, Kenneth D

    2014-01-01

    Regeneration is a process by which organisms replace damaged or amputated organs to restore normal body parts. Regeneration of many tissues or organs requires proliferation of stem cells or stem cell-like blastema cells. This regenerative growth is often initiated by cell death pathways induced by damage. The executors of regenerative growth are a group of growth-promoting signaling pathways, including JAK/STAT, EGFR, Hippo/YAP, and Wnt/β-catenin. These pathways are also essential to developmental growth, but in regeneration, they are activated in distinct ways and often at higher strengths, under the regulation by certain stress-responsive signaling pathways, including JNK signaling. Growth suppressors are important in termination of regeneration to prevent unlimited growth and also contribute to the loss of regenerative capacity in nonregenerative organs. Here, we review cellular and molecular growth regulation mechanisms induced by organ damage in several models with different regenerative capacities. PMID:24512707

  16. Reinforcement of cement-based matrices with graphite nanomaterials

    NASA Astrophysics Data System (ADS)

    Sadiq, Muhammad Maqbool

    Cement-based materials offer a desirable balance of compressive strength, moisture resistance, durability, economy and energy-efficiency; their tensile strength, fracture energy and durability in aggressive environments, however, could benefit from further improvements. An option for realizing some of these improvements involves introduction of discrete fibers into concrete. When compared with today's micro-scale (steel, polypropylene, glass, etc.) fibers, graphite nanomaterials (carbon nanotube, nanofiber and graphite nanoplatelet) offer superior geometric, mechanical and physical characteristics. Graphite nanomaterials would realize their reinforcement potential as far as they are thoroughly dispersed within cement-based matrices, and effectively bond to cement hydrates. The research reported herein developed non-covalent and covalent surface modification techniques to improve the dispersion and interfacial interactions of graphite nanomaterials in cement-based matrices with a dense and well graded micro-structure. The most successful approach involved polymer wrapping of nanomaterials for increasing the density of hydrophilic groups on the nanomaterial surface without causing any damage to the their structure. The nanomaterials were characterized using various spectrometry techniques, and SEM (Scanning Electron Microscopy). The graphite nanomaterials were dispersed via selected sonication procedures in the mixing water of the cement-based matrix; conventional mixing and sample preparation techniques were then employed to prepare the cement-based nanocomposite samples, which were subjected to steam curing. Comprehensive engineering and durability characteristics of cement-based nanocomposites were determined and their chemical composition, microstructure and failure mechanisms were also assessed through various spectrometry, thermogravimetry, electron microscopy and elemental analyses. Both functionalized and non-functionalized nanomaterials as well as different

  17. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

    PubMed Central

    Daly, W.; Yao, L.; Zeugolis, D.; Windebank, A.; Pandit, A.

    2012-01-01

    Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative—hollow nerve guidance conduits (NGCs)—have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell–material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic. PMID:22090283

  18. Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

    PubMed Central

    Xu, Hui; Sandor, Maryellen; Lombardi, Jared

    2013-01-01

    Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of

  19. Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

    PubMed

    Alberti, C

    2016-01-01

    To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

  20. Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

    PubMed Central

    ALBERTI, C.

    2016-01-01

    To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering. Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either “unseeded” (cell free) or autologous “cell seeded” tissue engineering scaffolds. Different categories of cell sources – from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells – have been taken into consideration to reach the construction of suitable “cell seeded” templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications. PMID:27142819

  1. The surface molecular functionality of decellularized extracellular matrices

    PubMed Central

    Barnes, Christopher A.; Brison, Jeremy; Michel, Roger; Brown, Bryan N.; Castner, David G.; Badylak, Stephen F.

    2010-01-01

    Decellularization of tissues and organs is a successful platform technology for creating scaffolding materials for tissue engineering and regenerative medicine. It has been suggested that the success of these materials upon implantation is due to the molecular signals provided by the remaining scaffold extracellular matrix (ECM) components presented to probing cells in vivo as they repopulate the surface. For this study, decellularized matrices were created from esophagus, bladder, and small intestine harvested from adult male Fischer 344 rats. The three decellularized matrices (each originating from source tissues which included an epithelial lining on their luminal surfaces) were immunostained for collagen IV and laminin to determine basement membrane retention. Scanning electron micrographs of the surfaces were used to provide insight into the surface topography of each of the decellularized tissues. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to generate high-resolution mass spectra for the surfaces of each scaffold. This surface sensitive technique allows for detailed molecular analysis of the outermost 1–2 nm of a material and has been applied previously to thin protein films and secreted ECM proteins on poly(N-isopropyl acrylamide) (polyNIPAAM) surfaces. To extract trends from within the complex ToF-SIMS dataset, a multivariate analysis technique, principal component analysis (PCA), was employed. Using this method, a molecular fingerprint of each surface was created and separation was seen in the PCA scores between the decellularized esophagus and the decellularized small intestine samples. The PCA scores for the decellularized bladder sample fell between the previous two decellularized samples. Protein films of common extracellular matrix constituents (collagen IV, collagen I, laminin, and Matrigel ) were also investigated. The PCA results from these protein films were used to develop qualitative hypotheses for the relationship of

  2. A leaf-based regeneration and transformation system for maize (Zea mays L.).

    PubMed

    Ahmadabadi, Mohammad; Ruf, Stephanie; Bock, Ralph

    2007-08-01

    Efficient methods for in vitro propagation, regeneration, and transformation of plants are of pivotal importance to both basic and applied research. While being the world's major food crops, cereals are among the most difficult-to-handle plants in tissue culture which severely limits genetic engineering approaches. In maize, immature zygotic embryos provide the predominantly used material for establishing regeneration-competent cell or callus cultures for genetic transformation experiments. The procedures involved are demanding, laborious and time consuming and depend on greenhouse facilities. We have developed a novel tissue culture and plant regeneration system that uses maize leaf tissue and thus is independent of zygotic embryos and greenhouse facilities. We report here: (i) a protocol for the efficient induction of regeneration-competent callus from maize leaves in the dark, (ii) a protocol for inducing highly regenerable callus in the light, and (iii) the use of leaf-derived callus for the generation of stably transformed maize plants.

  3. New Model and Measurement Principle of Flowing and Heat Transfer Characteristics of Regenerator

    NASA Astrophysics Data System (ADS)

    Chen, Y. Y.; Luo, E. C.; Dai, W.

    2008-03-01

    Regenerators play key role in oscillating-flow cryocoolers or thermoacoustic heat engine systems. However, their flowing and heat transfer mechanism is still not well understood. The complexities of the oscillating flow regenerator make traditional method of heat transfer research become difficult or helpless. In this paper, a model for porous media regenerator was given based on the linear thermoacoustic theory. Then the correlations for characteristic parameters were obtained by deducing universal expressions for thermoacoustic viscous function Fv and thermal function FT. A simple acoustical method and experimental system to get Fv and FT via measurements of isothermal regenerators were presented. Some measurements of packed stainless screen regenerators were performed, and preliminary experimental results for flow and convective coefficients were derived, which showing flowing friction factor is approximately within 132/Re to 173/Re.

  4. Thymic generation and regeneration.

    PubMed

    Gill, Jason; Malin, Mark; Sutherland, Jayne; Gray, Daniel; Hollander, George; Boyd, Richard

    2003-10-01

    The thymus is a complex epithelial organ in which thymocyte development is dependent upon the sequential contribution of morphologically and phenotypically distinct stromal cell compartments. It is these microenvironments that provide the unique combination of cellular interactions, cytokines, and chemokines to induce thymocyte precursors to undergo a differentiation program that leads to the generation of functional T cells. Despite the indispensable role of thymic epithelium in the generation of T cells, the mediators of this process and the differentiation pathway undertaken by the primordial thymic epithelial cells are not well defined. There is a lack of lineage-specific cell-surface-associated markers, which are needed to characterize putative thymic epithelial stem cell populations. This review explores the role of thymic stromal cells in T-cell development and thymic organogenesis, as well as the molecular signals that contribute to the growth and expansion of primordial thymic epithelial cells. It highlights recent advances in these areas, which have allowed for a lineage relationship amongst thymic epithelial cell subsets to be proposed. While many fundamental questions remain to be addressed, collectively these works have broadened our understanding of how the thymic epithelium becomes specialized in the ability to support thymocyte differentiation. They should also facilitate the development of novel, rationally based therapeutic strategies for the regeneration and manipulation of thymic function in the treatment of many clinical conditions in which defective T cells have an important etiological role.

  5. Regenerable biocide delivery unit

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L. (Inventor); Colombo, Gerald V. (Inventor); Jolly, Clifford D. (Inventor)

    1993-01-01

    A method and apparatus are disclosed for maintaining continuous, long-term microbial control in the water supply for potable, hygiene, and experimental water for space activities, as well as treatment of water supplies on Earth. The water purification is accomplished by introduction of molecular iodine into the water supply to impart a desired iodine residual. The water is passed through an iodinated anion exchange resin bed. The iodine is bound as I-(sub n) at the anion exchange sites and releases I(sub 2) into the water stream flowing through the bed. The concentration of I(sub 2) in the flowing water gradually decreases and, in the prior art, the ion-exchange bed has had to be replaced. In a preferred embodiment, a bed of iodine crystals is provided with connections for flowing water therethrough to produce a concentrated (substantially saturated) aqueous iodine solution which is passed through the iodinated resin bed to recharge the bed with bound iodine. The bed of iodine crystals is connected in parallel with the iodinated resin bed and is activated periodically (e.g., by timer, by measured flow of water, or by iodine residual level) to recharge the bed. Novelty resides in the capability of inexpensively and repeatedly regenerating the ion-exchange bed in situ.

  6. Fast Whole-Engine Stirling Analysis

    NASA Technical Reports Server (NTRS)

    Dyson, Rodger W.; Wilson, Scott D.; Tew, Roy C.; Demko, Rikako

    2006-01-01

    This presentation discusses the simulation approach to whole-engine for physical consistency, REV regenerator modeling, grid layering for smoothness, and quality, conjugate heat transfer method adjustment, high-speed low cost parallel cluster, and debugging.

  7. Futuristic concepts in engines and components

    SciTech Connect

    1995-12-31

    This publication includes papers on two-stroke engines and components, Brayton Stirling and Otto Cycles, alternative cycles, advanced combustion, and other related topics. Contents include: Paving the way to controlled combustion engines (CCE); A new class of stratified-charge internal combustion engine; Internal combustion (IC) engine with minimum number of moving parts; New type of heat engine -- externally heated air engine; A porous media burner for reforming methanol for fuel cell powered electric vehicles; Using a Stirling engine simulation program as a regenerator design aid; In-cylinder regenerated engines; High speed electronic fuel injection for direct injected rotary engine; and The characteristics of fuel consumption and exhaust emissions of the side exhaust port rotary engine.

  8. Physicochemical properties of 3D collagen-CS scaffolds for potential use in neural tissue engineering.

    PubMed

    Pietrucha, Krystyna

    2015-09-01

    Collagen-based composite scaffolds have considerable potential due to their well-known ability to regenerate skin, bone and cartilage. However, the precise composition and structure of scaffolds that optimize their interaction with neural cells remains incompletely understood and yet to be explored. In the present study, a new family of bi-component 3D scaffolds consisting of collagen (Col) and chondroitin sulphate (CS) were synthesized using a two-stage process: multiple freeze-drying followed by carbodiimide modification. Col-CS matrices had an average pore diameter of 31 μm and a relatively high surface area to pore volume ratio. Importantly, the FTIR data indicated that the ratio between the intensity of amide III and 1452 cm(-1) for Col-CS scaffold was 0.87, which indicates that the Col triple helix was preserved during the formation of the bond between Col and CS. All experiments also clearly showed that the Col-CS matrices have a lower enzyme sensitivity and higher thermal resistance than Col alone. These differences are likely due to the relatively large amount of CS in the collagen sponges, which hinders access for attack at specific active sites of the Col triple helix. Improved binary composite scaffolds were designed for neural tissue engineering applications.

  9. Recent advances in cell sheet technology for periodontal regeneration.

    PubMed

    Wang, Jing; Zhang, Rui; Shen, Yun; Xu, Chenyuan; Qi, Shengcai; Lu, Liyan; Wang, Raorao; Xu, Yuanzhi

    2014-05-01

    Tissue engineering has yielded several successes in early clinical trials of regenerative medicine with grafting therapeutic cells seeded into biodegradable scaffolds. However this conventional cell delivery method has limited the field's progress. In recent decades, we have developed a novel cell transferring method, cell sheet technology that allows for controlled attachment and detachment of cells via simple temperature variations of a surface-intelligent temperatureresponsive polymer:poly (N-isopropylacrylamide). It has been widely applied to create functional tissue sheets with cells derived from various tissues to treat a wide range of diseases. Periodontal cell sheets non-invasively harvested from temperature- responsive culture surfaces have been successfully manufactured, resulting in communicative multilayered constructs. Transplantation of cell sheets onto periodontal defects has improved bone and tissue regeneration in animal models and humans and shows low immunogenicity. In this review, we summarize the recent advances of techniques in cell sheet engineering and its application for periodontal regeneration.

  10. Design Strategies of Biodegradable Scaffolds for Tissue Regeneration

    PubMed Central

    Bitar, Khalil N; Zakhem, Elie

    2014-01-01

    There are numerous available biodegradable materials that can be used as scaffolds in regenerative medicine. Currently, there is a huge emphasis on the designing phase of the scaffolds. Materials can be designed to have different properties in order to match the specific application. Modifying scaffolds enhances their bioactivity and improves the regeneration capacity. Modifications of the scaffolds can be later characterized using several tissue engineering tools. In addition to the material, cell source is an important component of the regeneration process. Modified materials must be able to support survival and growth of different cell types. Together, cells and modified biomaterials contribute to the remodeling of the engineered tissue, which affects its performance. This review focuses on the recent advancements in the designs of the scaffolds including the physical and chemical modifications. The last part of this review also discusses designing processes that involve viability of cells. PMID:25288907

  11. Heat exchanger module for stirling engines

    SciTech Connect

    Darche, M. J. P.; Carlquist, S.

    1985-02-12

    The invention relates to Stirling engines and provides a modular assembly composed of a cylinder head, a heater, a regenerator, a cooler and a cold duct, and making it possible by mounting a plurality of identical modules on an engine assembly to construct a multi-cylinder double acting Stirling engine of the indirect heating type.

  12. Elemental sulfur from regenerable FGD processes

    SciTech Connect

    Little, R.C.; Nelson, S.G.

    1995-12-31

    Sorbent Technologies Corporation (Sorbtech) engineers recently discovered a new catalyst that effectively reduces sulfur dioxide (SO{sub 2}) in concentrated SO{sub 2} streams directly to elemental sulfur as a one-step process. The discovery was made during Sorbtech`s development work with the Magsorbent Process, a new regenerable Flue Gas Desulfurization (FGD) process. In laboratory studies, the catalyst demonstrated good SO{sub 2}-to-elemental sulfur yields. Yields of 95% or more were observed. The process, which is carried out at atmospheric pressure, employs reformed methane and the catalyst, which is heated, to reduce SO{sub 2} to elemental sulfur. The new catalyst process should be of interest to anyone who currently has an SO{sub 2} stream containing high concentrations of SO{sub 2}, and wishes to convert it into a useful product. The process is expected to be a low-cost alternative to a modified Claus plant. This paper describes laboratory tests that were conducted to examine the effects of gas composition, sulfur dioxide concentration, and long-term use on the performance of the catalyst. It also describes the scale up of the new technology to a size suitable for treating the total SO{sub 2}-rich regenerator off-gas stream at DOE`s new Copper Oxide Process flue-gas desulfurization pilot facility, located at the Pittsburgh Energy Technology Center.

  13. Tooth development: 2. Regenerating teeth in the laboratory.

    PubMed

    Onyekwelu, Obinna; Seppala, Maisa; Zoupa, Maria; Cobourne, Martyn T

    2007-01-01

    Tooth loss can occur for a number of reasons and a variety of prosthetic tooth replacement solutions are available to the dental practitioner. This article discusses current approaches in the use of tissue engineering to replace teeth or repair dental tissues. These strategies will depend upon the manipulation of stem cells in the laboratory and, whilst much progress has recently been made, it is likely that successful human tooth regeneration is still some years ahead.

  14. Rapid self-integrating, injectable hydrogel for tissue complex regeneration

    PubMed Central

    Hou, Sen; Wang, Xuefei; Park, Sean; Jin, Xiaobing

    2015-01-01

    A novel rapid self-integrating, injectable, and bio-erodible hydrogel is developed for tissue complex regeneration. The figure shows the self-integration of the hydrogel pieces to form various structures. In the figure, some hydrogel disks were dyed pink with rodamine and the others were left with the original light yellow color to visualize the interfaces (scale bar=5mm). This hydrogel is demonstrated to engineer cartilage-bone complex. PMID:25946414

  15. Self-assembling peptide nanofiber hydrogels for central nervous system regeneration

    NASA Astrophysics Data System (ADS)

    Liu, Xi; Pi, Bin; Wang, Hui; Wang, Xiu-Mei

    2015-03-01

    Central nervous system (CNS) presents a complex regeneration problem due to the inability of central neurons to regenerate correct axonal and dendritic connections. However, recent advances in developmental neurobiology, cell signaling, cell-matrix interaction, and biomaterials technologies have forced a reconsideration of CNS regeneration potentials from the viewpoint of tissue engineering and regenerative medicine. The applications of a novel tissue regeneration-inducing biomaterial and stem cells are thought to be critical for the mission. The use of peptide nanofiber hydrogels in cell therapy and tissue engineering offers promising perspectives for CNS regeneration. Self-assembling peptide undergo a rapid transformation from liquid to gel upon addition of counterions or pH adjustment, directly integrating with the host tissue. The peptide nanofiber hydrogels have mechanical properties that closely match the native central nervous extracellular matrix, which could enhance axonal growth. Such materials can provide an optimal three dimensional microenvironment for encapsulated cells. These materials can also be tailored with bioactive motifs to modulate the wound environment and enhance regeneration. This review intends to detail the recent status of self-assembling peptide nanofiber hydrogels for CNS regeneration.

  16. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    SciTech Connect

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  17. Decontamination of matrices containing actinide oxides

    SciTech Connect

    Villarreal, Robert

    1997-12-01

    There is provided a method for removing actinides and actinide oxides, particularly fired actinides, from soil and other contaminated matrices, comprising: (a) contacting a contaminated material with a solution of at least one inhibited fluoride and an acid to form a mixture; (b) heating the mixture of contaminated material and solution to a temperature in the range from about 30 C to about 90 C while stirring; (c) separating the solution from any undissolved matrix material in the mixture; (d) washing the undissolved matrix material to remove any residual materials; and (e) drying and returning the treated matrix material to the environment.

  18. Generalized Jones matrices for anisotropic media.

    PubMed

    Ortega-Quijano, Noé; Arce-Diego, José Luis

    2013-03-25

    The interaction of arbitrary three-dimensional light beams with optical elements is described by the generalized Jones calculus, which has been formally proposed recently [Azzam, J. Opt. Soc. Am. A 28, 2279 (2011)]. In this work we obtain the parametric expression of the 3×3 differential generalized Jones matrix (dGJM) for arbitrary optical media assuming transverse light waves. The dGJM is intimately connected to the Gell-Mann matrices, and we show that it provides a versatile method for obtaining the macroscopic GJM of media with either sequential or simultaneous anisotropic effects. Explicit parametric expressions of the GJM for some relevant optical elements are provided.

  19. Parallel mergs sort using comparison matrices. I

    SciTech Connect

    Romm, Y.E.

    1995-05-01

    The topics discussed in this paper are connected with internal merge sorting by a key (in short, M-sorting or M-sort). Originally developed by von Neumann, this is one of the first sorting methods. It still remains one of the fastest, involving Nlog{sub 2}N comparisons. The purpose of our article is to demonstrate the use of comparison matrices (CMs) for merging in M-sort. While preserving the known advantages of the sequential implementation of M-sort. CMs ensure more efficient use of main memory (one of the known weaknesses of M-sort is its large memory requirements) and effective parallelizability.

  20. Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds.

    PubMed

    Sakata, Ryosuke; Iwakura, Takashi; Reddi, A Hari

    2015-10-01

    that support further advances in tissue engineering for the optimal articular cartilage surface regeneration. PMID:25951707

  1. Photocrosslinkable and elastomeric hydrogels for bone regeneration.

    PubMed

    Thakur, Teena; Xavier, Janet R; Cross, Lauren; Jaiswal, Manish K; Mondragon, Eli; Kaunas, Roland; Gaharwar, Akhilesh K

    2016-04-01

    Nanocomposite biomaterials are extensively investigated for cell and tissue engineering applications due their unique physical, chemical and biological characteristics. Here, we investigated the mechanical, rheological, and degradation properties of photocrosslinkable and elastomeric nanocomposite hydrogels from nanohydroxyapatite (nHAp) and gelatin methacryloyl (GelMA). The addition of nHAp resulted in a significant increase in mechanical stiffness and physiological stability. Cells readily adhere and proliferate on the nanocomposite surfaces. Cyclic stretching of cells on the elastomeric nanocomposites revealed that nHAp elicited a stronger alignment response in the direction of strain. In vitro studies highlight enhanced bioactivity of nanocomposites as determined by alkaline phosphate (ALP) activity. Overall, the elastomeric and photocrosslinkable nanocomposite hydrogels can be used for minimally invasive therapy for bone regeneration.

  2. Guiding tissue regeneration with ultrasound in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Dalecki, Diane; Comeau, Eric S.; Raeman, Carol H.; Child, Sally Z.; Hobbs, Laura; Hocking, Denise C.

    2015-05-01

    Developing new technologies that enable the repair or replacement of injured or diseased tissues is a major focus of regenerative medicine. This paper will discuss three ultrasound technologies under development in our laboratories to guide tissue regeneration both in vitro and in vivo. A critical obstacle in tissue engineering is the need for rapid and effective tissue vascularization strategies. To address this challenge, we are developing acoustic patterning techniques for microvascular tissue engineering. Acoustic radiation forces associated with ultrasound standing wave fields provide a rapid, non-invasive approach to spatially pattern cells in three dimensions without affecting cell viability. Acoustic patterning of endothelial cells leads to the rapid formation of microvascular networks throughout the volumes of three-dimensional hydrogels, and the morphology of the resultant microvessel networks can be controlled by design of the ultrasound field. A second technology under development uses ultrasound to noninvasively control the microstructure of collagen fibers within engineered tissues. The microstructure of extracellular matrix proteins provides signals that direct cell functions critical to tissue regeneration. Thus, controlling collagen microfiber structure with ultrasound provides a noninvasive approach to regulate the mechanical properties of biomaterials and control cellular responses. The third technology employs therapeutic ultrasound to enhance the healing of chronic wounds. Recent studies demonstrate increased granulation tissue thickness and collagen deposition in murine dermal wounds exposed to pulsed ultrasound. In summary, ultrasound technologies offer noninvasive approaches to control cell behaviors and extracellular matrix organization and thus hold great promise to advance tissue regeneration in vitro and in vivo.

  3. Nanofibrous structured biomimetic strategies for skin tissue regeneration.

    PubMed

    Jayarama Reddy, Venugopal; Radhakrishnan, Sridhar; Ravichandran, Rajeswari; Mukherjee, Shayanti; Balamurugan, Ramalingam; Sundarrajan, Subramanian; Ramakrishna, Seeram

    2013-01-01

    Mimicking porous topography of natural extracellular matrix is advantageous for successful regeneration of damaged tissues or organs. Nanotechnology being one of the most promising and growing technology today shows an extremely huge potential in the field of tissue engineering. Nanofibrous structures that mimic the native extracellular matrix and promote the adhesion of various cells are being developed as tissue-engineered scaffolds for skin, bone, vasculature, heart, cornea, nervous system, and other tissues. A range of novel biocomposite materials has been developed to enhance the bioactive or therapeutic properties of these nanofibrous scaffolds via surface modifications, including the immobilization of functional cell-adhesive ligands and bioactive molecules such as drugs, enzymes, and cytokines. In skin tissue engineering, usage of allogeneic skin is avoided to reestablish physiological continuity and also to address the challenge of curing acute and chronic wounds, which remains as the area of exploration with various biomimetic approaches. Two-dimensional, three-dimensional scaffolds and stem cells are presently used as dermal regeneration templates for the treatment of full-thickness skin defects resulting from injuries and severe burns. The present review elaborates specifically on the fabrication of nanofibrous structured strategies for wound dressings, wound healing, and controlled release of growth factors for skin tissue regeneration.

  4. Realization of the cooperation between traveling wave component and standing wave component in thermoacoustic regenerator

    NASA Astrophysics Data System (ADS)

    Gang, Zhou; Qing, Li

    2014-01-01

    The regenerator is the core of a thermoacoustic engine or refrigerator, which consists of smooth or tortuous porous media, such as parallel plates or stainless stacked-screen. Due to regenerator presence, the real acoustic field is neither a pure standing wave nor a pure travelling wave and the thermoacoustic effect is the hybrid effect of the traveling wave component (TWC) and the standing wave component (SWC). To achieve both high efficiency and gain for a given temperature ratio, one has to choose an optimum phase lead Φm of the oscillating pressure relative to velocity in the middle of the regenerator to give the best combination of TWC and SWC. In this paper, based on linear thermoacoustic theory, the phase lead Φm which can make both the traveling wave and the standing wave contribute to the thermoacoustic conversions, are analyzed and optimized. To realize cooperation between TWC and SWC in thermoacoustic regenerator, a mathematical model of a 1/2 wavelength duct with a regenerator driven by double speakers was built, which can provide an appropriate traveling-wave field in the regenerator by changing the driving conditions including amplitude and the phase difference of the driving voltages. According to this, the influence of the acoustic field and the regenerator's structure on the thermoacoustic conversion is analyzed, and the optimum condition for the thermoacoustic conversion is discussed. This work is significant to understand thermoacoustic conversion mechanisms of regenerators in the real acoustic field.

  5. Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum).

    PubMed

    Satoh, Akira; Cummings, Gillian M C; Bryant, Susan V; Gardiner, David M

    2010-01-15

    The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a "critical-size defect" (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment. PMID:19944088

  6. Injectable Biomaterials for Regenerating Complex Craniofacial Tissues**

    PubMed Central

    Kretlow, James D.; Young, Simon; Klouda, Leda; Wong, Mark; Mikos, Antonios G.

    2009-01-01

    Engineering complex tissues requires a precisely formulated combination of cells, spatiotemporally released bioactive factors, and a specialized scaffold support system. Injectable materials, particularly those delivered in aqueous solution, are considered ideal delivery vehicles for cells and bioactive factors and can also be delivered through minimally invasive methods and fill complex 3D shapes. In this review, we examine injectable materials that form scaffolds or networks capable of both replacing tissue function early after delivery and supporting tissue regeneration over a time period of weeks to months. The use of these materials for tissue engineering within the craniofacial complex is challenging but ideal as many highly specialized and functional tissues reside within a small volume in the craniofacial structures and the need for minimally invasive interventions is desirable due to aesthetic considerations. Current biomaterials and strategies used to treat craniofacial defects are examined, followed by a review of craniofacial tissue engineering, and finally an examination of current technologies used for injectable scaffold development and drug and cell delivery using these materials. PMID:19750143

  7. Human umbilical cord mesenchymal stromal cells in a sandwich approach for osteochondral tissue engineering

    PubMed Central

    Wang, Limin; Zhao, Liang; Detamore, Michael S.

    2013-01-01

    Cell sources and tissue integration between cartilage and bone regions are critical to successful osteochondral regeneration. In this study, human umbilical cord mesenchymal stromal cells (hUCMSCs), derived from Wharton’s jelly, were introduced to the field of osteochondral tissue engineering and a new strategy for osteochondral integration was developed by sandwiching a layer of cells between chondrogenic and osteogenic constructs before suturing them together. Specifically, hUCMSCs were cultured in biodegradable poly-l-lactic acid scaffolds for 3 weeks in either chondrogenic or osteogenic medium to differentiate cells toward cartilage or bone lineages, respectively. A highly concentrated cell solution containing undifferentiated hUCMSCs was pasted onto the surface of the bone layer at week 3 and the two layers were then sutured together to form an osteochondral composite for another 3 week culture period. Chondrogenic and osteogenic differentiation was initiated during the first 3 weeks, as evidenced by the expression of type II collagen and runt-related transcription factor 2 genes, respectively, and continued with the increase of extracellular matrix during the last 3 weeks. Histological and immunohistochemical staining, such as for glycosaminoglycans, type I collagen and calcium, revealed better integration and transition of these matrices between two layers in the composite group containing sandwiched cells compared to other control composites. These results suggest that hUCMSCs may be a suitable cell source for osteochondral regeneration, and the strategy of sandwiching cells between two layers may facilitate scaffold and tissue integration. PMID:21953869

  8. Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering.

    PubMed

    Won, Jong-Eun; Yun, Ye-Rang; Jang, Jun-Hyeog; Yang, Sung-Hee; Kim, Joong-Hyun; Chrzanowski, Wojciech; Wall, Ivan B; Knowles, Jonathan C; Kim, Hae-Won

    2015-07-01

    Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

  9. The Approximation of Two-Mode Proximity Matrices by Sums of Order-Constrained Matrices.

    ERIC Educational Resources Information Center

    Hubert, Lawrence; Arabie, Phipps

    1995-01-01

    A least-squares strategy is proposed for representing a two-mode proximity matrix as an approximate sum of a small number of matrices that satisfy certain simple order constraints on their entries. The primary class of constraints considered defines Q-forms for particular conditions in a two-mode matrix. (SLD)

  10. Frequency filtering decompositions for unsymmetric matrices and matrices with strongly varying coefficients

    SciTech Connect

    Wagner, C.

    1996-12-31

    In 1992, Wittum introduced the frequency filtering decompositions (FFD), which yield a fast method for the iterative solution of large systems of linear equations. Based on this method, the tangential frequency filtering decompositions (TFFD) have been developed. The TFFD allow the robust and efficient treatment of matrices with strongly varying coefficients. The existence and the convergence of the TFFD can be shown for symmetric and positive definite matrices. For a large class of matrices, it is possible to prove that the convergence rate of the TFFD and of the FFD is independent of the number of unknowns. For both methods, schemes for the construction of frequency filtering decompositions for unsymmetric matrices have been developed. Since, in contrast to Wittums`s FFD, the TFFD needs only one test vector, an adaptive test vector can be used. The TFFD with respect to the adaptive test vector can be combined with other iterative methods, e.g. multi-grid methods, in order to improve the robustness of these methods. The frequency filtering decompositions have been successfully applied to the problem of the decontamination of a heterogeneous porous medium by flushing.

  11. Human pluripotent stem cell-derived limbal epithelial stem cells on bioengineered matrices for corneal reconstruction.

    PubMed

    Mikhailova, Alexandra; Ilmarinen, Tanja; Ratnayake, Anjula; Petrovski, Goran; Uusitalo, Hannu; Skottman, Heli; Rafat, Mehrdad

    2016-05-01

    Corneal epithelium is renewed by limbal epithelial stem cells (LESCs), a type of tissue-specific stem cells located in the limbal palisades of Vogt at the corneo-scleral junction. Acute trauma or inflammatory disorders of the ocular surface can destroy these stem cells, leading to limbal stem cell deficiency (LSCD) - a painful and vision-threatening condition. Treating these disorders is often challenging and complex, especially in bilateral cases with extensive damage. Human pluripotent stem cells (hPSCs) provide new opportunities for corneal reconstruction using cell-based therapy. Here, we investigated the use of hPSC-derived LESC-like cells on bioengineered collagen matrices in serum-free conditions, aiming for clinical applications to reconstruct the corneal epithelium and partially replace the damaged stroma. Differentiation of hPSCs towards LESC-like cells was directed using small-molecule induction followed by maturation in corneal epithelium culture medium. After four to five weeks of culture, differentiated cells were seeded onto bioengineered matrices fabricated as transparent membranes of uniform thickness, using medical-grade porcine collagen type I and a hybrid cross-linking technology. The bioengineered matrices were fully transparent, with high water content and swelling capacity, and parallel lamellar microstructure. Cell proliferation of hPSC-LESCs was significantly higher on bioengineered matrices than on collagen-coated control wells after two weeks of culture, and LESC markers p63 and cytokeratin 15, along with proliferation marker Ki67 were expressed even after 30 days in culture. Overall, hPSC-LESCs retained their capacity to self-renew and proliferate, but were also able to terminally differentiate upon stimulation, as suggested by protein expression of cytokeratins 3 and 12. We propose the use of bioengineered collagen matrices as carriers for the clinically-relevant hPSC-derived LESC-like cells, as a novel tissue engineering approach for

  12. The stress relaxation characteristics of composite matrices etched to produce nanoscale surface features.

    PubMed

    Mirani, Rahul D; Pratt, Jonathan; Iyer, Pooja; Madihally, Sundararajan V

    2009-02-01

    Many synthetic and xenogenic natural matrices have been explored in tissue regeneration, however, they lack either mechanical strength or cell colonization characteristics found in natural tissue. Moreover natural matrices such as small intestinal submucosa (SIS) lack sample to sample homogeneity, leading to unpredictable clinical outcomes. This work explored a novel fabrication technique by blending together the useful characteristics of synthetic and natural polymers to form a composite structure by using a NaOH etching process that produces nanoscale surface features. The composite scaffold was formed by sandwiching a thin layer of PLGA between porous layers of gelatin-chitosan. The etching process increased the surface roughness of PLGA membrane, allowing easy spreading of the hydrophilic gelatin-chitosan solution on its hydrophobic surface and reducing the scaffold thickness by nearly 50% than otherwise. The viscoelastic properties of the scaffold, an area of mechanical analysis which remains largely unexplored in tissue regeneration was assessed. Stress relaxation experiments of the "ramp and hold" type performed at variable ranges of temperature (25 degrees C and 37 degrees C), loading rates (3.125% s(-1) and 12.5% s(-1)) and relaxation times (60 s, 100 s and 200 s) found stress relaxation to be sensitive to temperature and the loading rate but less dependent on the relaxation time. Stress relaxation behavior of the composite matrix was compared with SIS structures at 25 degrees C (hydrated), 3.125% s(-1) loading rate and 100 s relaxation time which showed that the synthetic matrix was found to be strain softening as compared to the strain hardening behavior exhibited by SIS. Popularly used quasi-linear viscoelastic (QLV) model to describe biomechanics of soft tissues was utilized. The QLV model predicted the loading behavior with an average error of 3%. The parameters of the QLV model predicted using nonlinear regression analysis appear to be in concurrence

  13. Hindlimb suspension reduces muscle regeneration

    NASA Technical Reports Server (NTRS)

    Mozdziak, P. E.; Truong, Q.; Macius, A.; Schultz, E.

    1998-01-01

    Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

  14. Median Approximations for Genomes Modeled as Matrices.

    PubMed

    Zanetti, Joao Paulo Pereira; Biller, Priscila; Meidanis, Joao

    2016-04-01

    The genome median problem is an important problem in phylogenetic reconstruction under rearrangement models. It can be stated as follows: Given three genomes, find a fourth that minimizes the sum of the pairwise rearrangement distances between it and the three input genomes. In this paper, we model genomes as matrices and study the matrix median problem using the rank distance. It is known that, for any metric distance, at least one of the corners is a [Formula: see text]-approximation of the median. Our results allow us to compute up to three additional matrix median candidates, all of them with approximation ratios at least as good as the best corner, when the input matrices come from genomes. We also show a class of instances where our candidates are optimal. From the application point of view, it is usually more interesting to locate medians farther from the corners, and therefore, these new candidates are potentially more useful. In addition to the approximation algorithm, we suggest a heuristic to get a genome from an arbitrary square matrix. This is useful to translate the results of our median approximation algorithm back to genomes, and it has good results in our tests. To assess the relevance of our approach in the biological context, we ran simulated evolution tests and compared our solutions to those of an exact DCJ median solver. The results show that our method is capable of producing very good candidates. PMID:27072561

  15. Hydrodynamical spectral evolution for random matrices

    NASA Astrophysics Data System (ADS)

    Forrester, Peter J.; Grela, Jacek

    2016-02-01

    The eigenvalues of the matrix structure X+{X}(0), where X is a random Gaussian Hermitian matrix and {X}(0) is non-random or random independent of X, are closely related to Dyson Brownian motion. Previous works have shown how an infinite hierarchy of equations satisfied by the dynamical correlations become triangular in the infinite density limit, and give rise to the complex Burgers equation for the Green’s function of the corresponding one-point density function. We show how this and analogous partial differential equations, for chiral, circular and Jacobi versions of Dyson Brownian motion follow from a macroscopic hydrodynamical description involving the current density and continuity equation. The method of characteristics gives a systematic approach to solving the PDEs, and in the chiral case we show how this efficiently reclaims the characterization of the global eigenvalue density for non-central Wishart matrices due to Dozier and Silverstein. Collective variables provide another approach to deriving the complex Burgers equation in the Gaussian case, and we show that this approach applies equally as well to chiral matrices. We relate both the Gaussian and chiral cases to the asymptotics of matrix integrals.

  16. Generalized Eigenvalues for pairs on heritian matrices

    NASA Technical Reports Server (NTRS)

    Rublein, George

    1988-01-01

    A study was made of certain special cases of a generalized eigenvalue problem. Let A and B be nxn matrics. One may construct a certain polynomial, P(A,B, lambda) which specializes to the characteristic polynomial of B when A equals I. In particular, when B is hermitian, that characteristic polynomial, P(I,B, lambda) has real roots, and one can ask: are the roots of P(A,B, lambda) real when B is hermitian. We consider the case where A is positive definite and show that when N equals 3, the roots are indeed real. The basic tools needed in the proof are Shur's theorem on majorization for eigenvalues of hermitian matrices and the interlacing theorem for the eigenvalues of a positive definite hermitian matrix and one of its principal (n-1)x(n-1) minors. The method of proof first reduces the general problem to one where the diagonal of B has a certain structure: either diag (B) = diag (1,1,1) or diag (1,1,-1), or else the 2 x 2 principal minors of B are all 1. According as B has one of these three structures, we use an appropriate method to replace A by a positive diagonal matrix. Since it can be easily verified that P(D,B, lambda) has real roots, the result follows. For other configurations of B, a scaling and a continuity argument are used to prove the result in general.

  17. Fabrication of reconfigurable protein matrices by cracking

    NASA Astrophysics Data System (ADS)

    Zhu, Xiaoyue; Mills, Kristen L.; Peters, Portia R.; Bahng, Joong Hwan; Liu, Elizabeth Ho; Shim, Jeongsup; Naruse, Keiji; Csete, Marie E.; Thouless, M. D.; Takayama, Shuichi

    2005-05-01

    The interface between extracellular matrices and cells is a dynamic environment that is crucial for regulating important cellular processes such as signal transduction, growth, differentiation, motility and apoptosis. In vitro cellular studies and the development of new biomaterials would benefit from matrices that allow reversible modulation of the cell adhesive signals at a scale that is commensurate with individual adhesion complexes. Here, we describe the fabrication of substrates containing arrays of cracks in which cell-adhesive proteins are selectively adsorbed. The widths of the cracks (120-3,200 nm) are similar in size to individual adhesion complexes (typically 500-3,000 nm) and can be modulated by adjusting the mechanical strain applied to the substrate. Morphology of cells can be reversibly manipulated multiple times through in situ adjustment of crack widths and hence the amount of the cell-adhesive proteins accessible to the cell. These substrates provide a new tool for assessing cellular responses associated with exposure to matrix proteins.

  18. Bromination of selected pharmaceuticals in water matrices.

    PubMed

    Benitez, F Javier; Acero, Juan L; Real, Francisco J; Roldan, Gloria; Casas, Francisco

    2011-11-01

    The bromination of five selected pharmaceuticals (metoprolol, naproxen, amoxicillin, phenacetin, and hydrochlorothiazide) was studied with these compounds individually dissolved in ultra-pure water. The apparent rate constants for the bromination reaction were determined as a function of the pH, obtaining the sequence amoxicillin>naproxen>hydrochlorothiazide≈phenacetin≈metoprolol. A kinetic mechanism specifying the dissociation reactions and the species formed for each compound according to its pK(a) value and the pH allowed the intrinsic rate constants to be determined for each elementary reaction. There was fairly good agreement between the experimental and calculated values of the apparent rate constants, confirming the goodness of the proposed reaction mechanism. In a second stage, the bromination of the selected pharmaceuticals simultaneously dissolved in three water matrices (a groundwater, a surface water from a public reservoir, and a secondary effluent from a WWTP) was investigated. The pharmaceutical elimination trend agreed with the previously determined rate constants. The influence of the main operating conditions (pH, initial bromine dose, and characteristics of the water matrix) on the degradation of the pharmaceuticals was established. An elimination concentration profile for each pharmaceutical in the water matrices was proposed based on the use of the previously evaluated apparent rate constants, and the theoretical results agreed satisfactorily with experiment. Finally, chlorination experiments performed in the presence of bromide showed that low bromide concentrations slightly accelerate the oxidation of the selected pharmaceuticals during chlorine disinfection.

  19. Median Approximations for Genomes Modeled as Matrices.

    PubMed

    Zanetti, Joao Paulo Pereira; Biller, Priscila; Meidanis, Joao

    2016-04-01

    The genome median problem is an important problem in phylogenetic reconstruction under rearrangement models. It can be stated as follows: Given three genomes, find a fourth that minimizes the sum of the pairwise rearrangement distances between it and the three input genomes. In this paper, we model genomes as matrices and study the matrix median problem using the rank distance. It is known that, for any metric distance, at least one of the corners is a [Formula: see text]-approximation of the median. Our results allow us to compute up to three additional matrix median candidates, all of them with approximation ratios at least as good as the best corner, when the input matrices come from genomes. We also show a class of instances where our candidates are optimal. From the application point of view, it is usually more interesting to locate medians farther from the corners, and therefore, these new candidates are potentially more useful. In addition to the approximation algorithm, we suggest a heuristic to get a genome from an arbitrary square matrix. This is useful to translate the results of our median approximation algorithm back to genomes, and it has good results in our tests. To assess the relevance of our approach in the biological context, we ran simulated evolution tests and compared our solutions to those of an exact DCJ median solver. The results show that our method is capable of producing very good candidates.

  20. Tensor Dictionary Learning for Positive Definite Matrices.

    PubMed

    Sivalingam, Ravishankar; Boley, Daniel; Morellas, Vassilios; Papanikolopoulos, Nikolaos

    2015-11-01

    Sparse models have proven to be extremely successful in image processing and computer vision. However, a majority of the effort has been focused on sparse representation of vectors and low-rank models for general matrices. The success of sparse modeling, along with popularity of region covariances, has inspired the development of sparse coding approaches for these positive definite descriptors. While in earlier work, the dictionary was formed from all, or a random subset of, the training signals, it is clearly advantageous to learn a concise dictionary from the entire training set. In this paper, we propose a novel approach for dictionary learning over positive definite matrices. The dictionary is learned by alternating minimization between sparse coding and dictionary update stages, and different atom update methods are described. A discriminative version of the dictionary learning approach is also proposed, which simultaneously learns dictionaries for different classes in classification or clustering. Experimental results demonstrate the advantage of learning dictionaries from data both from reconstruction and classification viewpoints. Finally, a software library is presented comprising C++ binaries for all the positive definite sparse coding and dictionary learning approaches presented here.