Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C.

PubMed

Koppes, Abigail N; Kamath, Megha; Pfluger, Courtney A; Burkey, Daniel D; Dokmeci, Mehmet; Wang, Lin; Carrier, Rebecca L

2016-08-22

Native small intestine possesses distinct multi-scale structures (e.g., crypts, villi) not included in traditional 2D intestinal culture models for drug delivery and regenerative medicine. The known impact of structure on cell function motivates exploration of the influence of intestinal topography on the phenotype of cultured epithelial cells, but the irregular, macro- to submicron-scale features of native intestine are challenging to precisely replicate in cellular growth substrates. Herein, we utilized chemical vapor deposition of Parylene C on decellularized porcine small intestine to create polymeric intestinal replicas containing biomimetic irregular, multi-scale structures. These replicas were used as molds for polydimethylsiloxane (PDMS) growth substrates with macro to submicron intestinal topographical features. Resultant PDMS replicas exhibit multiscale resolution including macro- to micro-scale folds, crypt and villus structures, and submicron-scale features of the underlying basement membrane. After 10 d of human epithelial colorectal cell culture on PDMS substrates, the inclusion of biomimetic topographical features enhanced alkaline phosphatase expression 2.3-fold compared to flat controls, suggesting biomimetic topography is important in induced epithelial differentiation. This work presents a facile, inexpensive method for precisely replicating complex hierarchal features of native tissue, towards a new model for regenerative medicine and drug delivery for intestinal disorders and diseases.

Biofabrication strategies for 3D in vitro models and regenerative medicine

NASA Astrophysics Data System (ADS)

Moroni, Lorenzo; Burdick, Jason A.; Highley, Christopher; Lee, Sang Jin; Morimoto, Yuya; Takeuchi, Shoji; Yoo, James J.

2018-05-01

Organs are complex systems composed of different cells, proteins and signalling molecules that are arranged in a highly ordered structure to orchestrate a myriad of functions in our body. Biofabrication strategies can be applied to engineer 3D tissue models in vitro by mimicking the structure and function of native tissue through the precise deposition and assembly of materials and cells. This approach allows the spatiotemporal control over cell-cell and cell-extracellular matrix communication and thus the recreation of tissue-like structures. In this Review, we examine biofabrication strategies for the construction of functional tissue replacements and organ models, focusing on the development of biomaterials, such as supramolecular and photosensitive materials, that can be processed using biofabrication techniques. We highlight bioprinted and bioassembled tissue models and survey biofabrication techniques for their potential to recreate complex tissue properties, such as shape, vasculature and specific functionalities. Finally, we discuss challenges, such as scalability and the foreign body response, and opportunities in the field and provide an outlook to the future of biofabrication in regenerative medicine.

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering.

PubMed

Jessop, Zita M; Javed, Muhammad; Otto, Iris A; Combellack, Emman J; Morgan, Siân; Breugem, Corstiaan C; Archer, Charles W; Khan, Ilyas M; Lineaweaver, William C; Kon, Moshe; Malda, Jos; Whitaker, Iain S

2016-01-28

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites.

Development of hydrogels for regenerative engineering.

PubMed

Guan, Xiaofei; Avci-Adali, Meltem; Alarçin, Emine; Cheng, Hao; Kashaf, Sara Saheb; Li, Yuxiao; Chawla, Aditya; Jang, Hae Lin; Khademhosseini, Ali

2017-05-01

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano- and micro-technologies. In addition, current hydrogel-based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ECM-Based Materials in Cardiovascular Applications: Inherent Healing Potential and Augmentation of Native Regenerative Processes

PubMed Central

Piterina, Anna V.; Cloonan, Aidan J.; Meaney, Claire L.; Davis, Laura M.; Callanan, Anthony; Walsh, Michael T.; McGloughlin, Tim M.

2009-01-01

The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the progress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment. PMID:20057951

Dynamically Tunable Cell Culture Platforms for Tissue Engineering and Mechanobiology

PubMed Central

Uto, Koichiro; Tsui, Jonathan H.; DeForest, Cole A.; Kim, Deok-Ho

2016-01-01

Human tissues are sophisticated ensembles of many distinct cell types embedded in the complex, but well-defined, structures of the extracellular matrix (ECM). Dynamic biochemical, physicochemical, and mechano-structural changes in the ECM define and regulate tissue-specific cell behaviors. To recapitulate this complex environment in vitro, dynamic polymer-based biomaterials have emerged as powerful tools to probe and direct active changes in cell function. The rapid evolution of polymerization chemistries, structural modulation, and processing technologies, as well as the incorporation of stimuli-responsiveness, now permit synthetic microenvironments to capture much of the dynamic complexity of native tissue. These platforms are comprised not only of natural polymers chemically and molecularly similar to ECM, but those fully synthetic in origin. Here, we review recent in vitro efforts to mimic the dynamic microenvironment comprising native tissue ECM from the viewpoint of material design. We also discuss how these dynamic polymer-based biomaterials are being used in fundamental cell mechanobiology studies, as well as towards efforts in tissue engineering and regenerative medicine. PMID:28522885

Seed production and dispersal of sulfur cinquefoil in northeast Oregon

Treesearch

Kathleen A. Dwire; Catherine G. Parks; Michael L. McInnis; Bridgett J. Naylor

2006-01-01

Sulfur cinquefoil (family Rosaceae) is an invasive, herbaceous perennial, native to Eurasia. It has wide ecological amplitude and has become established throughout North America in numerous habitat types. Sulfur cinquefoil reproduces only by seed (achenes); however, little is known about its regenerative strategy or reproductive biology. To improve understanding of the...

Ex vivo regenerative effects of a spring water.

PubMed

Nicoletti, Giovanni; Saler, Marco; Pellegatta, Tommaso; Tresoldi, Marco Mario; Bonfanti, Viola; Malovini, Alberto; Faga, Angela; Riva, Federica

2017-12-01

Previous experiments by our group have indicated the regenerative effects of a spring water (Comano), which was possibly associated with the native non-pathogenic bacterial flora. The present study aimed to confirm these regenerative properties in a human ex vivo experimental model in the context of physiological wound healing. Human 6-mm punch skin biopsies harvested during plastic surgery sessions were injured in their central portion to induce skin loss and were cultured in either conventional medium (controls) or medium powder reconstituted with filtered Comano spring water (treated samples). At 24, 48 and 72 h the specimens were observed following staining with hematoxylin and eosin, Picrosirius Red, orcein and anti-proliferating cell nuclear antigen. Compared with the controls, the treated samples exhibited reduced overall cell infiltration, evidence of fibroblasts, stimulation of cell proliferation and collagen and elastic fiber regeneration. In the spring water, in addition to 12 resident non-pathogenic bacterial strains exhibiting favorable metabolic activities, more unknown non-pathogenic species are being identified by genomic analysis. In the present study, the efficacy of this 'germ-free', filtered spring water in wound regeneration was indicated. Thus, the Comano spring water microbiota should be acknowledged for its regenerative properties.

Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

PubMed Central

Makris, Eleftherios A.; Responte, Donald J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2014-01-01

The inability to recapitulate native tissue biomechanics, especially tensile properties, hinders progress in regenerative medicine. To address this problem, strategies have focused on enhancing collagen production. However, manipulating collagen cross-links, ubiquitous throughout all tissues and conferring mechanical integrity, has been underinvestigated. A series of studies examined the effects of lysyl oxidase (LOX), the enzyme responsible for the formation of collagen cross-links. Hypoxia-induced endogenous LOX was applied in multiple musculoskeletal tissues (i.e., cartilage, meniscus, tendons, ligaments). Results of these studies showed that both native and engineered tissues are enhanced by invoking a mechanism of hypoxia-induced pyridinoline (PYR) cross-links via intermediaries like LOX. Hypoxia was shown to enhance PYR cross-linking 1.4- to 6.4-fold and, concomitantly, to increase the tensile properties of collagen-rich tissues 1.3- to 2.2-fold. Direct administration of exogenous LOX was applied in native cartilage and neocartilage generated using a scaffold-free, self-assembling process of primary chondrocytes. Exogenous LOX was found to enhance native tissue tensile properties 1.9-fold. LOX concentration- and time-dependent increases in PYR content (∼16-fold compared with controls) and tensile properties (approximately fivefold compared with controls) of neocartilage were also detected, resulting in properties on par with native tissue. Finally, in vivo subcutaneous implantation of LOX-treated neocartilage in nude mice promoted further maturation of the neotissue, enhancing tensile and PYR content approximately threefold and 14-fold, respectively, compared with in vitro controls. Collectively, these results provide the first report, to our knowledge, of endogenous (hypoxia-induced) and exogenous LOX applications for promoting collagen cross-linking and improving the tensile properties of a spectrum of native and engineered tissues both in vitro and in vivo. PMID:25349395

In vivo xenogeneic scaffold fate is determined by residual antigenicity and extracellular matrix preservation.

PubMed

Wong, Maelene L; Wong, Janelle L; Vapniarsky, Natalia; Griffiths, Leigh G

2016-06-01

The immunological potential of animal-derived tissues and organs is the critical hurdle to increasing their clinical implementation. Glutaraldehyde-fixation cross-links proteins in xenogeneic tissues (e.g., bovine pericardium) to delay immune rejection, but also compromises the regenerative potential of the resultant biomaterial. Unfixed xenogeneic biomaterials in which xenoantigenicity has been ameliorated and native extracellular matrix (ECM) architecture has been maintained have the potential to overcome limitations of current clinically utilized glutaraldehyde-fixed biomaterials. The objective of this work was to determine how residual antigenicity and ECM architecture preservation modulate recipient immune and regenerative responses towards unfixed bovine pericardium (BP) ECM scaffolds. Disruption of ECM architecture during scaffold generation, with either SDS-decellularization or glutaraldehyde-fixation, stimulated recipient foreign body response and resultant fibrotic encapsulation following leporine subpannicular implantation. Conversely, BP scaffolds subjected to stepwise removal of hydrophilic and lipophilic antigens using amidosulfobetaine-14 (ASB-14) maintained native ECM architecture and thereby avoided fibrotic encapsulation. Removal of hydrophilic and lipophilic antigens significantly decreased local and systemic graft-specific, adaptive immune responses and subsequent calcification of BP scaffolds compared to scaffolds undergoing hydrophile removal only. Critically, removal of antigenic components and preservation of ECM architecture with ASB-14 promoted full-thickness recipient non-immune cellular repopulation of the BP scaffold. Further, unlike clinically utilized fixed BP, ASB-14-treated scaffolds fostered rapid intimal and medial vessel wall regeneration in a porcine carotid patch angioplasty model. This work highlights the importance of residual antigenicity and ECM architecture preservation in modulating recipient immune and regenerative responses towards xenogeneic biomaterial generation. Copyright © 2016. Published by Elsevier Ltd.

Bioactive nanofibers enable the identification of thrombospondin 2 as a key player in enamel regeneration.

PubMed

Huang, Zhan; Newcomb, Christina J; Lei, Yaping; Zhou, Yan; Bornstein, Paul; Amendt, Brad A; Stupp, Samuel I; Snead, Malcolm L

2015-08-01

Tissue regeneration and development involves highly synchronized signals both between cells and with the extracellular environment. Biomaterials can be tuned to mimic specific biological signals and control cell response(s). As a result, these materials can be used as tools to elucidate cell signaling pathways and candidate molecules involved with cellular processes. In this work, we explore enamel-forming cells, ameloblasts, which have a limited regenerative capacity. By exposing undifferentiated cells to a self-assembling matrix bearing RGDS epitopes, we elicited a regenerative signal at will that subsequently led to the identification of thrombospondin 2 (TSP2), an extracellular matrix protein that has not been previously recognized as a key player in enamel development and regeneration. Targeted disruption of the thrombospondin 2 gene (Thbs2) resulted in enamel formation with a disordered architecture that was highly susceptible to wear compared to their wild-type counterparts. To test the regenerative capacity, we injected the bioactive matrix into the enamel organ and discovered that the enamel organic epithelial cells in TSP-null mice failed to polarize on the surface of the artificial matrix, greatly reducing integrin β1 and Notch1 expression levels, which represent signaling pathways known to be associated with TSP2. These results suggest TSP2 plays an important role in regulating cell-matrix interactions during enamel formation. Exploiting the signaling pathways activated by biomaterials can provide insight into native signaling mechanisms crucial for tooth development and cell-based strategies for enamel regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

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 and ECM-based designs that provide necessary osteo- and chondro-conductive and inductive features for enhancing EC ossification. In addition, critical perspectives on existing stem cell-based therapeutic strategies will be discussed with a focus on their use as an extension of the acellular ECM-based designs for specific clinical indications. Within this framework, a novel realm of unexplored design strategies for bone tissue engineering will be introduced into the collective consciousness of the regenerative medicine field. PMID:25336144

Capturing extracellular matrix properties in vitro: Microengineering materials to decipher cell and tissue level processes.

PubMed

Abdeen, Amr A; Lee, Junmin; Kilian, Kristopher A

2016-05-01

Rapid advances in biology have led to the establishment of new fields with tremendous translational potential including regenerative medicine and immunoengineering. One commonality to these fields is the need to extract cells for manipulation in vitro; however, results obtained in laboratory cell culture will often differ widely from observations made in vivo. To more closely emulate native cell biology in the laboratory, designer engineered environments have proved a successful methodology to decipher the properties of the extracellular matrix that govern cellular decision making. Here, we present an overview of matrix properties that affect cell behavior, strategies for recapitulating important parameters in vitro, and examples of how these properties can affect cell and tissue level processes, with emphasis on leveraging these tools for immunoengineering. © 2016 by the Society for Experimental Biology and Medicine.

Histone-Targeted Nucleic Acid Delivery for Tissue Regenerative Applications

NASA Astrophysics Data System (ADS)

Munsell, Erik V.

Nucleic acid delivery has garnered significant attention as an innovative therapeutic approach for treating a wide variety of diseases. However, the design of non-viral delivery systems that negotiate efficient intracellular trafficking and nuclear entry represents a significant challenge. Overcoming these hurdles requires a combination of well-controlled materials approaches with techniques to understand and direct cellular delivery. Recent investigations have highlighted the roles histone tail sequences play in directing nuclear delivery and retention, as well as activating DNA transcription. We established the ability to recapitulate these natural histone tail activities within non-viral gene nanocarriers, driving gene transfer/expression by enabling effective navigation to the nucleus via retrograde vesicular trafficking. A unique finding of this histone-targeted approach was that nanocarriers gained enhanced access to the nucleus during mitosis. The work described in this dissertation builds off of these fundamental insights to facilitate the translation of this histone-targeted delivery approach toward regenerative medicine applications. During native tissue repair, actively proliferating mesenchymal stem cells (MSCs) respond to a complex series of growth factor signals that direct their differentiation. Accordingly, the investigations in this work focused on utilizing the histone-targeted nanocarriers to enhance osteogenic growth factor gene transfer in dividing MSCs leading to augmented MSC chondrogenic differentiation, an essential first step in skeletal tissue repair. Concurrently, additional studies focused on optimizing the histone-targeted nanocarrier design strategy to enable improved plasmid DNA (pDNA) binding stability and tunable harnessing of native cellular processing pathways for enhanced gene transfer. Overall, the work presented herein demonstrated substantial increases in growth factor expression following histone-targeted gene transfer. This enhanced expression enabled more robust levels of chondrogenesis in MSCs than treatments with equivalent amounts of recombinant growth factor protein. Additionally, nanocarrier design optimization provided effective pDNA condensation and controllable interactions with native histone effectors. Importantly, these optimized nanocarriers conferred stable nanoplex formation and maintained transfection efficiency under physiologically relevant conditions. Taken together, these advances may help drive the clinical translation of histone-targeted nucleic acid delivery strategies for the regeneration of damaged tissue following traumatic injury.

Fabrication of Extracellular Matrix-derived Foams and Microcarriers as Tissue-specific Cell Culture and Delivery Platforms.

PubMed

Kornmuller, Anna; Brown, Cody F C; Yu, Claire; Flynn, Lauren E

2017-04-11

Cell function is mediated by interactions with the extracellular matrix (ECM), which has complex tissue-specific composition and architecture. The focus of this article is on the methods for fabricating ECM-derived porous foams and microcarriers for use as biologically-relevant substrates in advanced 3D in vitro cell culture models or as pro-regenerative scaffolds and cell delivery systems for tissue engineering and regenerative medicine. Using decellularized tissues or purified insoluble collagen as a starting material, the techniques can be applied to synthesize a broad array of tissue-specific bioscaffolds with customizable geometries. The approach involves mechanical processing and mild enzymatic digestion to yield an ECM suspension that is used to fabricate the three-dimensional foams or microcarriers through controlled freezing and lyophilization procedures. These pure ECM-derived scaffolds are highly porous, yet stable without the need for chemical crosslinking agents or other additives that may negatively impact cell function. The scaffold properties can be tuned to some extent by varying factors such as the ECM suspension concentration, mechanical processing methods, or synthesis conditions. In general, the scaffolds are robust and easy to handle, and can be processed as tissues for most standard biological assays, providing a versatile and user-friendly 3D cell culture platform that mimics the native ECM composition. Overall, these straightforward methods for fabricating customized ECM-derived foams and microcarriers may be of interest to both biologists and biomedical engineers as tissue-specific cell-instructive platforms for in vitro and in vivo applications.

Experimental and Computational Investigation of Viscoelasticity of Native and Engineered Ligament and Tendon

NASA Astrophysics Data System (ADS)

Ma, J.; Narayanan, H.; Garikipati, K.; Grosh, K.; Arruda, E. M.

The important mechanisms by which soft collagenous tissues such as ligament and tendon respond to mechanical deformation include non-linear elasticity, viscoelasticity and poroelasticity. These contributions to the mechanical response are modulated by the content and morphology of structural proteins such as type I collagen and elastin, other molecules such as glycosaminoglycans, and fluid. Our ligament and tendon constructs, engineered from either primary cells or bone marrow stromal cells and their autogenous matricies, exhibit histological and mechanical characteristics of native tissues of different levels of maturity. In order to establish whether the constructs have optimal mechanical function for implantation and utility for regenerative medicine, constitutive relationships for the constructs and native tissues at different developmental levels must be established. A micromechanical model incorporating viscoelastic collagen and non-linear elastic elastin is used to describe the non-linear viscoelastic response of our homogeneous engineered constructs in vitro. This model is incorporated within a finite element framework to examine the heterogeneity of the mechanical responses of native ligament and tendon.

Microvalve-based bioprinting - process, bio-inks and applications.

PubMed

Ng, Wei Long; Lee, Jia Min; Yeong, Wai Yee; Win Naing, May

2017-03-28

Bioprinting is an emerging research field that has attracted tremendous attention for various applications; it offers a highly automated, advanced manufacturing platform for the fabrication of complex bioengineered constructs. Different bio-inks comprising multiple types of printable biomaterials and cells are utilized during the bioprinting process to improve the homology to native tissues and/or organs in a highly reproducible manner. This paper, presenting a first-time comprehensive yet succinct review of microvalve-based bioprinting, provides an in-depth analysis and comparison of different drop-on-demand bioprinting systems and highlights the important considerations for microvalve-based bioprinting systems. This review paper reports a detailed analysis of its printing process, bio-ink properties and cellular components on the printing outcomes. Lastly, this review highlights the significance of drop-on-demand bioprinting for various applications such as high-throughput screening, fundamental cell biology research, in situ bioprinting and fabrication of in vitro tissue constructs and also presents future directions to transform the microvalve-based bioprinting technology into imperative tools for tissue engineering and regenerative medicine.

Stem cell responses to plasma surface modified electrospun polyurethane scaffolds.

PubMed

Zandén, Carl; Hellström Erkenstam, Nina; Padel, Thomas; Wittgenstein, Julia; Liu, Johan; Kuhn, H Georg

2014-07-01

The topographical effects from functional materials on stem cell behavior are currently of interest in tissue engineering and regenerative medicine. Here we investigate the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell (hESC) and rat postnatal neural stem cell (NSC) responses. The plasma gases were found to induce three combinations of fiber surface functionalities and roughness textures. On randomly oriented fibers, plasma treatments lead to substantially increased hESC attachment and proliferation as compared to native fibers. Argon plasma was found to induce the most optimal combination of surface functionality and roughness for cell expansion. Contact guided migration of cells and alignment of cell processes were observed on aligned fibers. Neuronal differentiation around 5% was found for all samples and was not significantly affected by the induced variations of surface functional group distribution or individual fiber topography. In this study the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell and rat postnatal neural stem cell (NSC) responses is studied with the goal of clarifying the potential effects of functional materials on stem cell behavior, a topic of substantial interest in tissue engineering and regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Space Station Freedom ECLSS: A step toward autonomous regenerative life support systems

NASA Technical Reports Server (NTRS)

Dewberry, Brandon S.

1990-01-01

The Environmental Control and Life Support System (ECLSS) is a Freedom Station distributed system with inherent applicability to extensive automation primarily due to its comparatively long control system latencies. These allow longer contemplation times in which to form a more intelligent control strategy and to prevent and diagnose faults. The regenerative nature of the Space Station Freedom ECLSS will contribute closed loop complexities never before encountered in life support systems. A study to determine ECLSS automation approaches has been completed. The ECLSS baseline software and system processes could be augmented with more advanced fault management and regenerative control systems for a more autonomous evolutionary system, as well as serving as a firm foundation for future regenerative life support systems. Emerging advanced software technology and tools can be successfully applied to fault management, but a fully automated life support system will require research and development of regenerative control systems and models. The baseline Environmental Control and Life Support System utilizes ground tests in development of batch chemical and microbial control processes. Long duration regenerative life support systems will require more active chemical and microbial feedback control systems which, in turn, will require advancements in regenerative life support models and tools. These models can be verified using ground and on orbit life support test and operational data, and used in the engineering analysis of proposed intelligent instrumentation feedback and flexible process control technologies for future autonomous regenerative life support systems, including the evolutionary Space Station Freedom ECLSS.

Is nanotechnology the key to unravel and engineer biological processes?

PubMed

Navarro, Melba; Planell, Josep A

2012-01-01

Regenerative medicine is an emerging field aiming to the development of new reparative strategies to treat degenerative diseases, injury, and trauma through developmental pathways in order to rebuild the architecture of the original injured organ and take over its functionality. Most of the processes and interactions involved in the regenerative process take place at subcellular scale. Nanotechnology provides the tools and technology not only to detect, to measure, or to image the interactions between the different biomolecules and biological entities, but also to control and guide the regenerative process. The relevance of nanotechnology for the development of regenerative medicine as well as an overview of the different tools that contribute to unravel and engineer biological systems are presented in this chapter. In addition, general data about the social impact and global investment in nanotechnology are provided.

Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury.

PubMed

Jones, Iwan; Novikova, Liudmila N; Novikov, Lev N; Renardy, Monika; Ullrich, Andreas; Wiberg, Mikael; Carlsson, Leif; Kingham, Paul J

2018-04-01

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair. © 2018 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Tissue-engineering-based Strategies for Regenerative Endodontics

PubMed Central

Albuquerque, M.T.P.; Valera, M.C.; Nakashima, M.; Nör, J.E.; Bottino, M.C.

2014-01-01

Stemming from in vitro and in vivo pre-clinical and human models, tissue-engineering-based strategies continue to demonstrate great potential for the regeneration of the pulp-dentin complex, particularly in necrotic, immature permanent teeth. Nanofibrous scaffolds, which closely resemble the native extracellular matrix, have been successfully synthesized by various techniques, including but not limited to electrospinning. A common goal in scaffold synthesis has been the notion of promoting cell guidance through the careful design and use of a collection of biochemical and physical cues capable of governing and stimulating specific events at the cellular and tissue levels. The latest advances in processing technologies allow for the fabrication of scaffolds where selected bioactive molecules can be delivered locally, thus increasing the possibilities for clinical success. Though electrospun scaffolds have not yet been tested in vivo in either human or animal pulpless models in immature permanent teeth, recent studies have highlighted their regenerative potential both from an in vitro and in vivo (i.e., subcutaneous model) standpoint. Possible applications for these bioactive scaffolds continue to evolve, with significant prospects related to the regeneration of both dentin and pulp tissue and, more recently, to root canal disinfection. Nonetheless, no single implantable scaffold can consistently guide the coordinated growth and development of the multiple tissue types involved in the functional regeneration of the pulp-dentin complex. The purpose of this review is to provide a comprehensive perspective on the latest discoveries related to the use of scaffolds and/or stem cells in regenerative endodontics. The authors focused this review on bioactive nanofibrous scaffolds, injectable scaffolds and stem cells, and pre-clinical findings using stem-cell-based strategies. These topics are discussed in detail in an attempt to provide future direction and to shed light on their potential translation to clinical settings. PMID:25201917

Hierarchical Design of Tissue Regenerative Constructs.

PubMed

Rose, Jonas C; De Laporte, Laura

2018-03-01

The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell-induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer-scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native-like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM.

PubMed

Liu, Y; Cecílio, N T; Carvalho, F C; Roque-Barreira, M C; Feizi, T

2015-12-01

This article contains data related to the researc.h article entitled "Yeast-derived ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM" by Cecílio et al. (2015) [1]. ArtinM, a D-mannose-binding lectin isolated from the seeds of Artocarpus heterophyllus, exerts immunomodulatory and regenerative activities through its Carbohydrate Recognition Domain (CRD) (Souza et al., 2013; Mariano et al., 2014 [2], [3]). The limited availability of the native lectin (n-ArtinM) led us to characterize a recombinant form of the protein, obtained by expression in Saccharomyces cerevisiae (y-ArtinM). We compared the carbohydrate-binding specificities of y-ArtinM and n-ArtinM by analyzing the binding of biotinylated preparations of the two lectin forms using a neoglycolipid (NGL)-based glycan microarray. Data showed that y-ArtinM mirrored the specificity exhibited by n-ArtinM.

FDA and NIST collaboration on standards development activities supporting innovation and translation of regenerative medicine products.

PubMed

Arcidiacono, Judith A; Bauer, Steven R; Kaplan, David S; Allocca, Clare M; Sarkar, Sumona; Lin-Gibson, Sheng

2018-06-01

The development of standards for the field of regenerative medicine has been noted as a high priority by several road-mapping activities. Additionally, the U.S. Congress recognizes the importance of standards in the 21st Century Cure Act. Standards will help to accelerate and streamline cell and gene therapy product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Although there is general agreement for the need of additional standards for regenerative medicine products, a shared understanding of standards is required for real progress toward the development of standards to advance regenerative medicine. Here, we describe the roles of standards in regenerative medicine as well as the process for standards development and the interactions of different entities in the standards development process. Highlighted are recent coordinated efforts between the U.S. Food and Drug Administration and the National Institute of Standards and Technology to facilitate standards development and foster science that underpins standards development. Published by Elsevier Inc.

Evaluation strategy of regenerative braking energy for supercapacitor vehicle.

PubMed

Zou, Zhongyue; Cao, Junyi; Cao, Binggang; Chen, Wen

2015-03-01

In order to improve the efficiency of energy conversion and increase the driving range of electric vehicles, the regenerative energy captured during braking process is stored in the energy storage devices and then will be re-used. Due to the high power density of supercapacitors, they are employed to withstand high current in the short time and essentially capture more regenerative energy. The measuring methods for regenerative energy should be investigated to estimate the energy conversion efficiency and performance of electric vehicles. Based on the analysis of the regenerative braking energy system of a supercapacitor vehicle, an evaluation system for energy recovery in the braking process is established using USB portable data-acquisition devices. Experiments under various braking conditions are carried out. The results verify the higher efficiency of energy regeneration system using supercapacitors and the effectiveness of the proposed measurement method. It is also demonstrated that the maximum regenerative energy conversion efficiency can reach to 88%. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Long-term culture of bovine nucleus pulposus explants in a native environment.

PubMed

van Dijk, Bart G M; Potier, Esther; Ito, Keita

2013-04-01

Chronic low back pain is a disease with tremendous financial and social implications, and it is often caused by intervertebral disc degeneration. Regenerative therapies for disc repair are promising treatments, but they need to be tested in physiological models. To develop a physiological in vitro explant model that incorporates the native environment of the intervertebral disc, for example, hypoxia, low glucose, and high tissue osmolarity. Bovine nucleus pulposus (NP) explants were cultured for 42 days in conditions mimicking the native physiological environment. Two different approaches were used to balance the swelling pressure of the NP: raised medium osmolarity or an artificial annulus. Bovine NP explants were either cultured in media with osmolarity balanced at isotonic and hypertonic levels compared with the native tissue or cultured inside a fiber jacket used as an artificial annulus. Oxygen and glucose levels were set at either standard (21% O2 and 4.5 g/L glucose) or physiological (5% O2 and 1 g/L glucose) levels. Samples were analyzed at Day 0, 3, and 42 for tissue composition (water, sulfated glycosaminoglycans, DNA, and hydroxyproline contents and fixed charge density), tissue histology, cell viability, and cellular behavior with messenger RNA (mRNA) expression. Both the hypertonic culture and the artificial annulus approach maintained the tissue matrix composition for 42 days. At Day 3, mRNA expressions of aggrecan, collagen Type I, and collagen Type II in both hypertonic and artificial annulus cultures were not different from Day 0; however, at Day 42, the artificial annulus preserved the mRNA expression closer to Day 0. Gene expressions of matrix metalloprotease 13, tissue inhibitor of matrix metalloprotease 1, and tissue inhibitor of matrix metalloprotease 2 were downregulated under physiological O2 and glucose levels, whereas the other parameters analyzed were not affected. Although the hypertonic culture and the artificial annulus approach are both promising models to test regenerative therapies, the artificial annulus was better able to maintain a cellular behavior closer to the native tissue in longer term cultures. Copyright © 2013 Elsevier Inc. All rights reserved.

Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

PubMed

Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

2017-06-01

In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

Whole-organ re-engineering: a regenerative medicine approach to digestive organ replacement.

PubMed

Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Kitagawa, Yuko

2013-06-01

Recovery from end-stage organ failure presents a challenge for the medical community, considering the limitations of extracorporeal assist devices and the shortage of donors when organ replacement is needed. There is a need for new methods to promote recovery from organ failure and regenerative medicine is an option that should be considered. Recent progress in the field of tissue engineering has opened avenues for potential clinical applications, including the use of microfluidic devices for diagnostic purposes, and bioreactors or cell/tissue-based therapies for transplantation. Early attempts to engineer tissues produced thin, planar constructs; however, recent approaches using synthetic scaffolds and decellularized tissue have achieved a more complex level of tissue organization in organs such as the urinary bladder and trachea, with some success in clinical trials. In this context, the concept of decellularization technology has been applied to produce whole organ-derived scaffolds by removing cellular content while retaining all the necessary vascular and structural cues of the native organ. In this review, we focus on organ decellularization as a new regenerative medicine approach for whole organs, which may be applied in the field of digestive surgery.

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

PubMed

Lu, Kai; Gordon, Richard; Cao, Tong

2015-03-01

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

Construction and histological analysis of a 3D human arterial wall model containing vasa vasorum using a layer-by-layer technique.

PubMed

Shima, Fumiaki; Narita, Hirokazu; Hiura, Ayami; Shimoda, Hiroshi; Akashi, Mitsuru

2017-03-01

There is considerable global demand for three-dimensional (3D) functional tissues which mimic our native organs and tissues for use as in vitro drug screening systems and in regenerative medicine. In particular, there has been an increasing number of patients who suffer from arterial diseases such as arteriosclerosis. As such, in vitro 3D arterial wall models that can evaluate the effects of novel medicines and a novel artificial graft for the treatment are required. In our previous study, we reported the rapid construction of 3D tissues by employing a layer-by-layer (LbL) technique and revealed their potential applications in the pharmaceutical fields and tissue engineering. In this study, we successfully constructed a 3D arterial wall model containing vasa vasorum by employing a LbL technique for the first time. The cells were coated with extracellular matrix nanofilms and seeded into a culture insert using a cell accumulation method. This model had a three-layered hierarchical structure: a fibroblast layer, a smooth muscle layer, and an endothelial layer, which resembled the native arterial wall. Our method could introduce vasa vasorum into a fibroblast layer in vitro and the 3D arterial wall model showed barrier function which was evaluated by immunostaining and transendothelial electrical resistance measurement. Furthermore, electron microscopy observations revealed that the vasa vasorum was composed of single-layered endothelial cells, and the endothelial tubes were surrounded by the basal lamina, which are known to promote maturation and stabilization in native blood capillaries. These models should be useful for tissue engineering, regenerative medicine, and pharmaceutical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 814-823, 2017. © 2016 Wiley Periodicals, Inc.

Intrinsic regenerative potential of murine cochlear supporting cells.

PubMed

Sinkkonen, Saku T; Chai, Renjie; Jan, Taha A; Hartman, Byron H; Laske, Roman D; Gahlen, Felix; Sinkkonen, Wera; Cheng, Alan G; Oshima, Kazuo; Heller, Stefan

2011-01-01

The lack of cochlear regenerative potential is the main cause for the permanence of hearing loss. Albeit quiescent in vivo, dissociated non-sensory cells from the neonatal cochlea proliferate and show ability to generate hair cell-like cells in vitro. Only a few non-sensory cell-derived colonies, however, give rise to hair cell-like cells, suggesting that sensory progenitor cells are a subpopulation of proliferating non-sensory cells. Here we purify from the neonatal mouse cochlea four different non-sensory cell populations by fluorescence-activated cell sorting (FACS). All four populations displayed proliferative potential, but only lesser epithelial ridge and supporting cells robustly gave rise to hair cell marker-positive cells. These results suggest that cochlear supporting cells and cells of the lesser epithelial ridge show robust potential to de-differentiate into prosensory cells that proliferate and undergo differentiation in similar fashion to native prosensory cells of the developing inner ear.

Research on motor rotational speed measurement in regenerative braking system of electric vehicle

NASA Astrophysics Data System (ADS)

Pan, Chaofeng; Chen, Liao; Chen, Long; Jiang, Haobin; Li, Zhongxing; Wang, Shaohua

2016-01-01

Rotational speed signals acquisition and processing techniques are widely used in rotational machinery. In order to realized precise and real-time control of motor drive and regenerative braking process, rotational speed measurement techniques are needed in electric vehicles. Obtaining accurate motor rotational speed signal will contribute to the regenerative braking force control steadily and realized higher energy recovery rate. This paper aims to develop a method that provides instantaneous speed information in the form of motor rotation. It addresses principles of motor rotational speed measurement in the regenerative braking systems of electric vehicle firstly. The paper then presents ideal and actual Hall position sensor signals characteristics, the relation between the motor rotational speed and the Hall position sensor signals is revealed. Finally, Hall position sensor signals conditioning and processing circuit and program for motor rotational speed measurement have been carried out based on measurement error analysis.

Synthetic Light-Curable Polymeric Materials Provide a Supportive Niche for Dental Pulp Stem Cells.

PubMed

Vining, Kyle H; Scherba, Jacob C; Bever, Alaina M; Alexander, Morgan R; Celiz, Adam D; Mooney, David J

2018-01-01

Dental disease annually affects billions of patients, and while regenerative dentistry aims to heal dental tissue after injury, existing polymeric restorative materials, or fillings, do not directly participate in the healing process in a bioinstructive manner. There is a need for restorative materials that can support native functions of dental pulp stem cells (DPSCs), which are capable of regenerating dentin. A polymer microarray formed from commercially available monomers to rapidly identify materials that support DPSC adhesion is used. Based on these findings, thiol-ene chemistry is employed to achieve rapid light-curing and minimize residual monomer of the lead materials. Several triacrylate bulk polymers support DPSC adhesion, proliferation, and differentiation in vitro, and exhibit stiffness and tensile strength similar to existing dental materials. Conversely, materials composed of a trimethacrylate monomer or bisphenol A glycidyl methacrylate, which is a monomer standard in dental materials, do not support stem cell adhesion and negatively impact matrix and signaling pathways. Furthermore, thiol-ene polymerized triacrylates are used as permanent filling materials at the dentin-pulp interface in direct contact with irreversibly injured pulp tissue. These novel triacrylate-based biomaterials have potential to enable novel regenerative dental therapies in the clinic by both restoring teeth and providing a supportive niche for DPSCs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials.

PubMed

Modulevsky, Daniel J; Cuerrier, Charles M; Pelling, Andrew E

2016-01-01

There is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6-9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson's Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial.

Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials

PubMed Central

Pelling, Andrew E.

2016-01-01

There is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6–9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson’s Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial. PMID:27328066

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI.

PubMed

Liu, Li; Tseng, Lanya; Ye, Qing; Wu, Yijen L; Bain, Daniel J; Ho, Chien

2016-05-18

Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new "bio-mimicry" method by making use of the "in-vivo environment" of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 ± 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin-protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 ± 7.2 μm to 19.5 ± 5.2 μm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies.

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI

PubMed Central

Liu, Li; Tseng, Lanya; Ye, Qing; Wu, Yijen L.; Bain, Daniel J.; Ho, Chien

2016-01-01

Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new “bio-mimicry” method by making use of the “in-vivo environment” of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 ± 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin-protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 ± 7.2 μm to 19.5 ± 5.2 μm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies. PMID:27188664

Evaluation of Polycaprolactone Scaffold with Basic Fibroblast Growth Factor and Fibroblasts in an Athymic Rat Model for Anterior Cruciate Ligament Reconstruction

PubMed Central

Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A.; McAllister, David R.

2015-01-01

Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft. PMID:25744933

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Advancing biomaterials of human origin for tissue engineering

PubMed Central

Chen, Fa-Ming; Liu, Xiaohua

2015-01-01

Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for restoration. In particular, there is increasing interest in separating ECMs into simplified functional domains and/or biopolymeric assemblies so that these components/constituents can be discretely exploited and manipulated for the production of bioscaffolds and new biomimetic biomaterials. Here, following an overview of tissue auto-/allo-transplantation, we discuss the recent trends and advances as well as the challenges and future directions in the evolution and application of human-derived biomaterials for reconstructive surgery and tissue engineering. In particular, we focus on an exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications and to provide inspiration for the design of future biomaterials. PMID:27022202

Engineering hydrogels as extracellular matrix mimics

PubMed Central

Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun

2010-01-01

Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. PMID:20394538

Changes in Regenerative Capacity through Lifespan

PubMed Central

Yun, Maximina H.

2015-01-01

Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging. PMID:26512653

Surface functionalization of nanobiomaterials for application in stem cell culture, tissue engineering, and regenerative medicine.

PubMed

Rana, Deepti; Ramasamy, Keerthana; Leena, Maria; Jiménez, Constanza; Campos, Javier; Ibarra, Paula; Haidar, Ziyad S; Ramalingam, Murugan

2016-05-01

Stem cell-based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial-based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell-based tissue engineering and regenerative medicine. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554-567, 2016. © 2016 American Institute of Chemical Engineers.

An Intrinsic MicroRNA Timer Regulates Progressive Decline in Shoot Regenerative Capacity in Plants

PubMed Central

Zhang, Tian-Qi; Lian, Heng; Tang, Hongbo; Dolezal, Karel; Zhou, Chuan-Miao; Yu, Sha; Chen, Juan-Hua; Chen, Qi; Liu, Hongtao; Ljung, Karin

2015-01-01

Plant cells are totipotent and competent to regenerate from differentiated organs. It has been shown that two phytohormones, auxin and cytokinin, play critical roles within this process. As in animals, the regenerative capacity declines with age in plants, but the molecular basis for this phenomenon remains elusive. Here, we demonstrate that an age-regulated microRNA, miR156, regulates shoot regenerative capacity. As a plant ages, the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors leads to the progressive decline in shoot regenerative capacity. In old plants, SPL reduces shoot regenerative capacity by attenuating the cytokinin response through binding with the B-type ARABIDOPSIS RESPONSE REGULATORs, which encode the transcriptional activators in the cytokinin signaling pathway. Consistently, the increased amount of exogenous cytokinin complements the reduced shoot regenerative capacity in old plants. Therefore, the recruitment of age cues in response to cytokinin contributes to shoot regenerative competence. PMID:25649435

Physiological regeneration of skin appendages and implications for regenerative medicine

PubMed Central

Chuong, Cheng-Ming; Randall, Valerie A; Widelitz, Randall B.; Wu, Ping; Jiang, Ting-Xin

2013-01-01

The concept of regenerative medicine is relatively new, but animals are well known to remake their hair and feathers regularly by normal regenerative physiological processes. Here we focus on 1) how extra-follicular environments can regulate hair and feather stem cell activities and 2) how different configurations of stem cells can shape organ forms in different body regions to fulfil changing physiological needs. PMID:22505663

25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

PubMed Central

Annabi, Nasim; Tamayol, Ali; Uquillas, Jorge Alfredo; Akbari, Mohsen; Bertassoni, Luiz E.; Cha, Chaenyung; Camci-Unal, Gulden; Dokmeci, Mehmet R.

2014-01-01

Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life. PMID:24741694

Elucidating Multiscale Periosteal Mechanobiology: A Key to Unlocking the Smart Properties and Regenerative Capacity of the Periosteum?

PubMed Central

Evans, Sarah F.; Chang, Hana

2013-01-01

The periosteum, a thin, fibrous tissue layer covering most bones, resides in a dynamic, mechanically loaded environment. The periosteum also provides a niche for mesenchymal stem cells. The mechanics of periosteum vary greatly between species and anatomical locations, indicating the specialized role of periosteum as bone's bounding membrane. Furthermore, periosteum exhibits stress-state-dependent mechanical and material properties, hallmarks of a smart material. This review discusses what is known about the multiscale mechanical and material properties of the periosteum as well as their potential effect on the mechanosensitive progenitor cells within the tissue. Furthermore, this review addresses open questions and barriers to understanding periosteum's multiscale structure–function relationships. Knowledge of the smart material properties of the periosteum will maximize the translation of periosteum and substitute periosteum to regenerative medicine, facilitate the development of biomimetic tissue-engineered periosteum for use in instances where the native periosteum is lacking or damaged, and provide inspiration for a new class of smart, advanced materials. PMID:23189933

Regenerative Medicine Build-Out.

PubMed

Terzic, Andre; Pfenning, Michael A; Gores, Gregory J; Harper, C Michel

2015-12-01

Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Regenerative medicine is at the vanguard of health care poised to offer solutions for many of today's incurable diseases. Accordingly, there is a pressing need to develop, deploy, and demonstrate a viable framework for rollout of a regenerative medicine model of care. Translation of regenerative medicine principles into practice is feasible, yet clinical validity and utility must be established to ensure approval and adoption. Standardized and scaled-up regenerative products and services across medical and surgical specialties must in turn achieve a value-added proposition, advancing intended outcome beyond current management strategies. ©AlphaMed Press.

Regenerative Medicine Build-Out

PubMed Central

Pfenning, Michael A.; Gores, Gregory J.; Harper, C. Michel

2015-01-01

Summary Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Significance Regenerative medicine is at the vanguard of health care poised to offer solutions for many of today’s incurable diseases. Accordingly, there is a pressing need to develop, deploy, and demonstrate a viable framework for rollout of a regenerative medicine model of care. Translation of regenerative medicine principles into practice is feasible, yet clinical validity and utility must be established to ensure approval and adoption. Standardized and scaled-up regenerative products and services across medical and surgical specialties must in turn achieve a value-added proposition, advancing intended outcome beyond current management strategies. PMID:26537392

Tumor suppressors: enhancers or suppressors of regeneration?

PubMed Central

Pomerantz, Jason H.; Blau, Helen M.

2013-01-01

Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine. PMID:23715544

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering.

PubMed

Narayanan, Ganesh; Vernekar, Varadraj N; Kuyinu, Emmanuel L; Laurencin, Cato T

2016-12-15

Regenerative engineering converges tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate complex tissues such as whole limbs. Regenerative engineering scaffolds provide mechanical support and nanoscale control over architecture, topography, and biochemical cues to influence cellular outcome. In this regard, poly (lactic acid) (PLA)-based biomaterials may be considered as a gold standard for many orthopaedic regenerative engineering applications because of their versatility in fabrication, biodegradability, and compatibility with biomolecules and cells. Here we discuss recent developments in PLA-based biomaterials with respect to processability and current applications in the clinical and research settings for bone, ligament, meniscus, and cartilage regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Sidestream Darkfield Microscopy for Real-Time Imaging Acellular Dermal Matrix Revascularization.

PubMed

DeGeorge, Brent R; Olenczak, J Bryce; Cottler, Patrick S; Drake, David B; Lin, Kant Y; Morgan, Raymond F; Campbell, Christopher A

2016-06-01

Acellular dermal matrices (ADMs) serve as a regenerative framework for host cell integration and collagen deposition to augment the soft tissue envelope in ADM-assisted breast reconstruction-a process dependent on vascular ingrowth. To date noninvasive intra-operative imaging techniques have been inadequate to evaluate the revascularization of ADM. We investigated the safety, feasibility, and efficacy of sidestream darkfield (SDF) microscopy to assess the status of ADM microvascular architecture in 8 patients at the time of tissue expander to permanent implant exchange during 2-stage ADM-assisted breast reconstruction. The SDF microscopy is a handheld device, which can be used intraoperatively for the real-time assessment of ADM blood flow, vessel density, vessel size, and branching pattern. The SDF microscopy was used to assess the microvascular architecture in the center and border zone of the ADM and to compare the native, non-ADM-associated capsule in each patient as a within-subject control. No incidences of periprosthetic infection, explantation, or adverse events were reported after SDF image acquisition. Native capsules demonstrate a complex, layered architecture with an average vessel area density of 14.9 mm/mm and total vessel length density of 12.3 mm/mm. In contrast to native periprosthetic capsules, ADM-associated capsules are not uniformly vascularized structures and demonstrate 2 zones of microvascular architecture. The ADM and native capsule border zone demonstrates palisading peripheral vascular arcades with continuous antegrade flow. The central zone of the ADM demonstrates punctate perforating vascular plexi with intermittent, sluggish flow, and intervening 2- to 3-cm watershed zones. Sidestream darkfield microscopy allows for real-time intraoperative assessment of ADM revascularization and serves as a potential methodology to compare revascularization parameters among commercially available ADMs. Thr SDF microscopy demonstrates that the periprosthetic capsule in ADM-assisted implant-based breast reconstruction is not a uniformly vascularized structure.

Translating Periosteum's Regenerative Power: Insights From Quantitative Analysis of Tissue Genesis With a Periosteum Substitute Implant

PubMed Central

Moore, Shannon R.; Heu, Céline; Yu, Nicole Y.C.; Whan, Renee M.; Knothe, Ulf R.; Milz, Stefan

2016-01-01

An abundance of surgical studies during the past 2 centuries provide empirical evidence of periosteum's regenerative power for reconstructing tissues as diverse as trachea and bone. This study aimed to develop quantitative, efficacy-based measures, thereby providing translational guidelines for the use of periosteum to harness the body's own healing potential and generate target tissues. The current study quantitatively and qualitatively demonstrated tissue generation modulated by a periosteum substitute membrane that replicates the structural constituents of native periosteum (elastin, collagen, progenitor cells) and its barrier, extracellular, and cellular properties. It shows the potentiation of the periosteum's regenerative capacity through the progenitor cells that inhabit the tissue, biological factors intrinsic to the extracellular matrix of periosteum, and mechanobiological factors related to implant design and implementation. In contrast to the direct intramembranous bone generated in defects surrounded by patent periosteum in situ, tissue generation in bone defects bounded by the periosteum substitute implant occurred primarily via endochondral mechanisms whereby cartilage was first generated and then converted to bone. In addition, in defects treated with the periosteum substitute, tissue generation was highest along the major centroidal axis, which is most resistant to prevailing bending loads. Taken together, these data indicate the possibility of designing modular periosteum substitute implants that can be tuned for vectorial and spatiotemporal delivery of biological agents and facilitation of target tissue genesis for diverse surgical scenarios and regenerative medicine approaches. It also underscores the potential to develop physical therapy protocols to maximize tissue genesis via the implant's mechanoactive properties. Significance In the past 2 centuries, the periosteum, a niche for stem cells and super-smart biological material, has been used empirically in surgery to repair tissues as diverse as trachea and bone. In the past 25 years, the number of articles indexed in PubMed for the keywords “periosteum and tissue engineering” and “periosteum and regenerative medicine” has burgeoned. Yet the biggest limitation to the prescriptive use of periosteum is lack of easy access, giving impetus to the development of periosteum substitutes. Recent studies have opened up the possibility to bank periosteal tissues (e.g., from the femoral neck during routine resection for implantation of hip replacements). This study used an interdisciplinary, quantitative approach to assess tissue genesis in modular periosteum substitute implants, with the aim to provide translational strategies for regenerative medicine and tissue engineering. PMID:27465072

Translating Periosteum's Regenerative Power: Insights From Quantitative Analysis of Tissue Genesis With a Periosteum Substitute Implant.

PubMed

Moore, Shannon R; Heu, Céline; Yu, Nicole Y C; Whan, Renee M; Knothe, Ulf R; Milz, Stefan; Knothe Tate, Melissa L

2016-12-01

: An abundance of surgical studies during the past 2 centuries provide empirical evidence of periosteum's regenerative power for reconstructing tissues as diverse as trachea and bone. This study aimed to develop quantitative, efficacy-based measures, thereby providing translational guidelines for the use of periosteum to harness the body's own healing potential and generate target tissues. The current study quantitatively and qualitatively demonstrated tissue generation modulated by a periosteum substitute membrane that replicates the structural constituents of native periosteum (elastin, collagen, progenitor cells) and its barrier, extracellular, and cellular properties. It shows the potentiation of the periosteum's regenerative capacity through the progenitor cells that inhabit the tissue, biological factors intrinsic to the extracellular matrix of periosteum, and mechanobiological factors related to implant design and implementation. In contrast to the direct intramembranous bone generated in defects surrounded by patent periosteum in situ, tissue generation in bone defects bounded by the periosteum substitute implant occurred primarily via endochondral mechanisms whereby cartilage was first generated and then converted to bone. In addition, in defects treated with the periosteum substitute, tissue generation was highest along the major centroidal axis, which is most resistant to prevailing bending loads. Taken together, these data indicate the possibility of designing modular periosteum substitute implants that can be tuned for vectorial and spatiotemporal delivery of biological agents and facilitation of target tissue genesis for diverse surgical scenarios and regenerative medicine approaches. It also underscores the potential to develop physical therapy protocols to maximize tissue genesis via the implant's mechanoactive properties. In the past 2 centuries, the periosteum, a niche for stem cells and super-smart biological material, has been used empirically in surgery to repair tissues as diverse as trachea and bone. In the past 25 years, the number of articles indexed in PubMed for the keywords "periosteum and tissue engineering" and "periosteum and regenerative medicine" has burgeoned. Yet the biggest limitation to the prescriptive use of periosteum is lack of easy access, giving impetus to the development of periosteum substitutes. Recent studies have opened up the possibility to bank periosteal tissues (e.g., from the femoral neck during routine resection for implantation of hip replacements). This study used an interdisciplinary, quantitative approach to assess tissue genesis in modular periosteum substitute implants, with the aim to provide translational strategies for regenerative medicine and tissue engineering. ©AlphaMed Press.

The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

PubMed

Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

2015-11-01

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

PubMed

Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

2017-05-01

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Biodegradable composite scaffolds: a strategy to modulate stem cell behaviour.

PubMed

Armentano, Ilaria; Fortunati, Elena; Mattioli, Samantha; Rescignano, Nicolatta; Kenny, José M

2013-04-01

The application of new biomaterial technologies offers the potential to direct the stem cell fate, targeting the delivery of cells and reducing immune rejection, thereby supporting the development of regenerative medicine. Cells respond to their surrounding structure and with nanostructures exhibit unique proliferative and differentiation properties. This review presents the relevance, the promising perspectives and challenges of current biodegradable composite scaffolds in terms of material properties, processing technology and surface modification, focusing on significant recent patents in these fields. It has been reported how biodegradable porous composite scaffolds can be engineered with initial properties that reproduce the anisotropy, viscoelasticity, tension-compression non-linearity of different tissues by introducing specific nanostructures. Moreover the modulation of electrical, morphological, surface and topographic scaffold properties enables specific stem cell response. Recent advances in nanotechnology have allowed to engineer novel biomaterials with these complexity levels. Understanding the specific biological response triggered by various aspects of the fibrous environment is important in guiding the design and engineering of novel substrates that mimic the native cell matrix interactions in vivo.

3D Bioprinting for Tissue and Organ Fabrication

PubMed Central

Zhang, Yu Shrike; Yang, Jingzhou; Jia, Weitao; Dell’Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

2016-01-01

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development. PMID:27126775

3D Bioprinting for Tissue and Organ Fabrication.

PubMed

Zhang, Yu Shrike; Yue, Kan; Aleman, Julio; Moghaddam, Kamyar Mollazadeh; Bakht, Syeda Mahwish; Yang, Jingzhou; Jia, Weitao; Dell'Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

2017-01-01

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.

Investigation of electroforming techniques. [fabrication of regeneratively cooled thrust chambers

NASA Technical Reports Server (NTRS)

Malone, G. A.

1975-01-01

Copper and nickel electroforming was examined for the purpose of establishing the necessary processes and procedures for repeatable, successful fabrication of the outer structures of regeneratively cooled thrust chambers. The selection of electrolytes for copper and nickel deposition is described. The development studies performed to refine and complete the processes necessary for successful chamber shell fabrication and the testing employed to verify the applicability of the processes and procedures to small scale hardware are described. Specifications were developed to afford a guideline for the electroforming of high quality outer shells on regeneratively cooled thrust chamber liners. Test results indicated repeatable mechanical properties could be produced in copper deposits from the copper sulfate electrolyte with periodic current reversal and in nickel deposits from the sulfamate solution. Use of inert, removable channel fillers and the conductivizing of such is described. Techniques (verified by test) which produce high integrity bonds to copper and copper alloy liners are discussed.

Printing of Three-Dimensional Tissue Analogs for Regenerative Medicine

PubMed Central

Lee, Vivian K.; Dai, Guohao

2016-01-01

3-D cell printing, which can accurately deposit cells, biomaterial scaffolds and growth factors in precisely defined spatial patterns to form biomimetic tissue structures, has emerged as a powerful enabling technology to create live tissue and organ structures for drug discovery and tissue engineering applications. Unlike traditional 3-D printing that uses metals, plastics and polymers as the printing materials, cell printing has to be compatible with living cells and biological matrix. It is also required that the printing process preserves the biological functions of the cells and extracellular matrix, and to mimic the cell-matrix architectures and mechanical properties of the native tissues. Therefore, there are significant challenges in order to translate the technologies of traditional 3-D printing to cell printing, and ultimately achieve functional outcomes in the printed tissues. So it is essential to develop new technologies specially designed for cell printing and in-depth basic research in the bioprinted tissues, such as developing novel biomaterials specifically for cell printing applications, understanding the complex cell-matrix remodeling for the desired mechanical properties and functional outcomes, establishing proper vascular perfusion in bioprinted tissues, etc. In recent years, many exciting research progresses have been made in the 3-D cell printing technology and its application in engineering live tissue constructs. This review paper summarized the current development in 3-D cell printing technologies; focus on the outcomes of the live printed tissues and their potential applications in drug discovery and regenerative medicine. Current challenges and limitations are highlighted, and future directions of 3-D cell printing technology are also discussed. PMID:27066784

Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies

PubMed Central

Hunsberger, Joshua; Harrysson, Ola; Shirwaiker, Rohan; Starly, Binil; Wysk, Richard; Cohen, Paul; Allickson, Julie; Yoo, James

2015-01-01

Summary The Regenerative Medicine Foundation Annual Conference held on May 6 and 7, 2014, had a vision of assisting with translating tissue engineering and regenerative medicine (TERM)-based technologies closer to the clinic. This vision was achieved by assembling leaders in the field to cover critical areas. Some of these critical areas included regulatory pathways for regenerative medicine therapies, strategic partnerships, coordination of resources, developing standards for the field, government support, priorities for industry, biobanking, and new technologies. The final day of this conference featured focused sessions on manufacturing, during which expert speakers were invited from industry, government, and academia. The speakers identified and accessed roadblocks plaguing the field where improvements in advanced manufacturing offered many solutions. The manufacturing sessions included (a) product development toward commercialization in regenerative medicine, (b) process challenges to scale up manufacturing in regenerative medicine, and (c) infrastructure needs for manufacturing in regenerative medicine. Subsequent to this, industry was invited to participate in a survey to further elucidate the challenges to translation and scale-up. This perspective article will cover the lessons learned from these manufacturing sessions and early results from the survey. We also outline a road map for developing the manufacturing infrastructure, resources, standards, capabilities, education, training, and workforce development to realize the promise of TERM. PMID:25575525

Bio-inspired design of a magnetically active trilayered scaffold for cartilage tissue engineering.

PubMed

Brady, Mariea A; Talvard, Lucien; Vella, Alain; Ethier, C Ross

2017-04-01

An important topic in cartilage tissue engineering is the development of biomimetic scaffolds which mimic the depth-dependent material properties of the native tissue. We describe an advanced trilayered nanocomposite hydrogel (ferrogel) with a gradient in compressive modulus from the top to the bottom layers (p < 0.05) of the construct. Further, the scaffold was able to respond to remote external stimulation, exhibiting an elastic, depth-dependent strain gradient. When bovine chondrocytes were seeded into the ferrogels and cultured for up to 14 days, there was good cell viability and a biochemical gradient was measured with sulphated glycosaminoglycan increasing with depth from the surface. This novel construct provides tremendous scope for tailoring location-specific cartilage replacement tissue; by varying the density of magnetic nanoparticles, concentration of base hydrogel and number of cells, physiologically relevant depth-dependent gradients may be attained. © 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. © 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Regenerative fuel cell study

NASA Technical Reports Server (NTRS)

Wynveen, R. A.; Schubert, F. H.

1972-01-01

The completion of the study is reported for the regenerative fuel cell subsystem (RFCS) as an energy storage process for use aboard the space shuttle launched modular space station (MSS). The MSS mission requirements, and RFCS are discussed, and a comparison between RFCS and a nickel cadmium battery subsystem is presented. Development costs are also discussed.

Regenerative endodontics.

PubMed

Simon, S; Smith, A J

2014-03-01

Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

PubMed

Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

2018-02-27

Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates.

PubMed

Lee-Liu, Dasfne; Edwards-Faret, Gabriela; Tapia, Víctor S; Larraín, Juan

2013-08-01

Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative-permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. Copyright © 2013 Wiley Periodicals, Inc.

Tissue Regeneration and Biomineralization in Sea Urchins: Role of Notch Signaling and Presence of Stem Cell Markers

PubMed Central

Reinardy, Helena C.; Emerson, Chloe E.; Manley, Jason M.; Bodnar, Andrea G.

2015-01-01

Echinoderms represent a phylum with exceptional regenerative capabilities that can reconstruct both external appendages and internal organs. Mechanistic understanding of the cellular pathways involved in regeneration in these animals has been hampered by the limited genomic tools and limited ability to manipulate regenerative processes. We present a functional assay to investigate mechanisms of tissue regeneration and biomineralization by measuring the regrowth of amputated tube feet (sensory and motor appendages) and spines in the sea urchin, Lytechinus variegatus. The ability to manipulate regeneration was demonstrated by concentration-dependent inhibition of regrowth of spines and tube feet by treatment with the mitotic inhibitor, vincristine. Treatment with the gamma-secretase inhibitor DAPT resulted in a concentration-dependent inhibition of regrowth, indicating that both tube feet and spine regeneration require functional Notch signaling. Stem cell markers (Piwi and Vasa) were expressed in tube feet and spine tissue, and Vasa-positive cells were localized throughout the epidermis of tube feet by immunohistochemistry, suggesting the existence of multipotent progenitor cells in these highly regenerative appendages. The presence of Vasa protein in other somatic tissues (e.g. esophagus, radial nerve, and a sub-population of coelomocytes) suggests that multipotent cells are present throughout adult sea urchins and may contribute to normal homeostasis in addition to regeneration. Mechanistic insight into the cellular pathways governing the tremendous regenerative capacity of echinoderms may reveal processes that can be modulated for regenerative therapies, shed light on the evolution of regeneration, and enable the ability to predict how these processes will respond to changing environmental conditions. PMID:26267358

Strong-Field Emission From High Aspect Ratio Si Emitter Arrays

NASA Astrophysics Data System (ADS)

Keathley, Phillip; Swanwick, Michael; Sell, Alexander; Putnam, William; Guerrera, Stephen; Velásquez-García, Luis; Kärtner, Franz

2013-03-01

We discuss photoelectron emission from an arrays of high aspect ratio, sharp Si emitters both experimentally and theoretically. The structures are prepared from highly doped single-crystal silicon having a pencil-like shape with end radii of curvature of around 10 nm. The tips were illuminated at a grazing incidence of roughly 84deg.with a laser pulse having a center wavelength of 800 nm, and a pulse duration of 35 fs from a regenerative amplifier system. Native oxide coated Si tips were characterized using a time of flight (TOF) electron energy spectrometer. An annealing process was observed, resulting in a red shift of the energy spectra along with an increased electron yield. Total current yield from samples having the oxide stripped were also studied. Apeak total emission of 0.68 pC/bunch, corresponding to around 1.5x103 electrons/tip/pulse was observed at a DC bias of 70 V. Both spectral and current characterization results are consistent with a stong-field photoemission process at the surface of the tip apex. This work was funded by Defense Advanced Research Projects Agency (DARPA)/Microsystems Technology Office and the Space and Naval Warfare Systems Center (SPAWAR) under contract N66001-11-1-4192.

First pulse effect self-suppression picosecond regenerative amplifier (Conference Presentation)

NASA Astrophysics Data System (ADS)

Fan, Haitao; Chang, Liang; Zhang, Yi; Yao, Siyi; Lu, Wei; Yang, Xiaohong

2017-03-01

First pulse effect, commonly seen in nanosecond cavity-dumped lasers and picosecond regenerative amplifiers, not only leads to degradation of processing quality, but also acts as potential threat to optical switching elements. Several methods have been developed to suppress that effect, including electronic controls, polarization controls, and diffraction controls. We present a new way for first pulse self-suppression without any additional components. By carefully arranging the cavity mirror of a regenerative amplifier, we realized `parasitic lasing like' radiation. When the regenerative amplifier works in `operation ready' status, the parasitic lasing occurs and prevents the gain crystal from saturation. When the regenerative amplifier starts working and amplifying pulses, the first pulse in a pulse train will not get much more gain and energy than pulses following it. As parasitic lasing disappears at the same time, the average output power of the amplifier does not significantly reduce. This cost effective method does not require any additional component. In addition, as it is not polarization dependent, this method is widely suitable for different kinds of regenerative amplifiers. It's the easiest and cheapest way to suppress first pulse effect, to the best of our knowledge.

Lizard tail regeneration as an instructive model of enhanced healing capabilities in an adult amniote.

PubMed

Lozito, Thomas P; Tuan, Rocky S

2017-03-01

The ability to regenerate damaged or lost tissues has remained the lofty goal of regenerative medicine. Unfortunately, humans, like most mammals, suffer from very minimal natural regenerative capabilities. Certain non-mammalian animal species, however, are not so limited in their healing capabilities, and several have attracted the attention of researchers hoping to recreate enhanced healing responses in humans. This review focuses on one such animal group with remarkable regenerative abilities, the lizards. As the closest relatives of mammals that exhibit enhanced regenerative abilities as adults, lizards potentially represent the most relevant model for direct comparison and subsequent improvement of mammalian healing. Lizards are able to regenerate amputated tails and exhibit adaptations that both limit tissue damage in response to injury and initiate coordinated regenerative responses. This review summarizes the salient aspects of lizard tail regeneration as they relate to the overall regenerative process and also presents the relevant information pertaining to regrowth of specific tissues, including skeletal, muscular, nervous, and vascular tissues. The goal of this review is to introduce the topic of lizard tail regeneration to new audiences with the hope of expanding the knowledge base of this underutilized but potentially powerful model organism.

Biological computational approaches: new hopes to improve (re)programming robustness, regenerative medicine and cancer therapeutics.

PubMed

Ebrahimi, Behnam

2016-01-01

Hundreds of transcription factors (TFs) are expressed and work in each cell type, but the identity of the cells is defined and maintained through the activity of a small number of core TFs. Existing reprogramming strategies predominantly focus on the ectopic expression of core TFs of an intended fate in a given cell type regardless of the state of native/somatic gene regulatory networks (GRNs) of the starting cells. Interestingly, an important point is that how much products of the reprogramming, transdifferentiation and differentiation (programming) are identical to their in vivo counterparts. There is evidence that shows that direct fate conversions of somatic cells are not complete, with target cell identity not fully achieved. Manipulation of core TFs provides a powerful tool for engineering cell fate in terms of extinguishment of native GRNs, the establishment of a new GRN, and preventing installation of aberrant GRNs. Conventionally, core TFs are selected to convert one cell type into another mostly based on literature and the experimental identification of genes that are differentially expressed in one cell type compared to the specific cell types. Currently, there is not a universal standard strategy for identifying candidate core TFs. Remarkably, several biological computational platforms are developed, which are capable of evaluating the fidelity of reprogramming methods and refining existing protocols. The current review discusses some deficiencies of reprogramming technologies in the production of a pure population of authentic target cells. Furthermore, it reviews the role of computational approaches (e.g. CellNet, KeyGenes, Mogrify, etc.) in improving (re)programming methods and consequently in regenerative medicine and cancer therapeutics. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Caenorhabditis elegans in regenerative medicine: a simple model for a complex discipline.

PubMed

Aitlhadj, Layla; Stürzenbaum, Stephen R

2014-06-01

Stem cell research is a major focus of regenerative medicine, which amalgamates diverse disciplines ranging from developmental cell biology to chemical and genetic therapy. Although embryonic stem cells have provided the foundation of stem cell therapy, they offer an in vitro study system that might not provide the best insight into mechanisms and behaviour of cells within living organisms. Caenorhabditis elegans is a well defined model organism with highly conserved cell development and signalling processes that specify cell fate. Its genetic amenability coupled with its chemical screening applicability make the nematode well suited as an in vivo system in which regenerative therapy and stem cell processes can be explored. Here, we describe some of the major advances in stem cell research from the worm's perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Summary of: Regenerative endodontics.

PubMed

Clark, Stephen J

2014-03-01

Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

Tissue engineering therapies for the vocal fold lamina propria.

PubMed

Kutty, Jaishankar K; Webb, Ken

2009-09-01

The vocal folds are laryngeal connective tissues with complex matrix composition/organization that provide the viscoelastic mechanical properties required for voice production. Vocal fold injury results in alterations in tissue structure and corresponding changes in tissue biomechanics that reduce vocal quality. Recent work has begun to elucidate the biochemical changes underlying injury-induced pathology and to apply tissue engineering principles to the prevention and reversal of vocal fold scarring. Based on the extensive history of injectable biomaterials in laryngeal surgery, a major focus of regenerative therapies has been the development of novel scaffolds with controlled in vivo residence time and viscoelastic properties approximating the native tissue. Additional strategies have included cell transplantation and delivery of the antifibrotic cytokine hepatocyte growth factor, as well as investigation of the effects of the unique vocal fold vibratory microenvironment using in vitro dynamic culture systems. Recent achievements of significant reductions in fibrosis and improved recovery of native tissue viscoelasticity and vibratory/functional performance in animal models are rapidly moving vocal fold tissue engineering toward clinical application.

Molecular assessment of collagen denaturation in decellularized tissues using a collagen hybridizing peptide.

PubMed

Hwang, Jeongmin; San, Boi Hoa; Turner, Neill J; White, Lisa J; Faulk, Denver M; Badylak, Stephen F; Li, Yang; Yu, S Michael

2017-04-15

Decellularized extracellular matrix (ECM) derived from tissues and organs are emerging as important scaffold materials for regenerative medicine. Many believe that preservation of the native ECM structure during decellularization is highly desirable. However, because effective techniques to assess the structural damage in ECM are lacking, the disruptive effects of a decellularization method and the impact of the associated structural damage upon the scaffold's regenerative capacity are often debated. Using a novel collagen hybridizing peptide (CHP) that specifically binds to unfolded collagen chains, we investigated the molecular denaturation of collagen in the ECM decellularized by four commonly used cell-removing detergents: sodium dodecyl sulfate (SDS), 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), sodium deoxycholate (SD), and Triton X-100. Staining of the detergent-treated porcine ligament and urinary bladder matrix with carboxyfluorescein-labeled CHP demonstrated that SDS and Triton X-100 denature the triple helical collagen molecule while CHAPS and SD do not, although second harmonic generation imaging and transmission electron microscopy (TEM) revealed that all four detergents disrupt collagen fibrils. Our findings from the CHP staining were further confirmed by the circular dichroism spectra of intact triple helical collagen molecules in CHAPS and SD solutions, and the TEM images of CHP-conjugated gold nanoparticles binding only to the SDS and Triton X-100 treated collagen fibrils. CHP is a powerful new tool for direct and reliable measurement of denatured collagen molecules in decellularized tissues. It is expected to have wide applications in the development and standardization of the tissue/organ decellularization technology. Preservation of the native ECM structure in decellularized tissues is highly desirable, since denaturation of ECM molecules (e.g., collagen) during decellularization can strongly influence the cellular response. Unfortunately, conventional techniques (SEM, SHG) are not conducive to identifying denatured collagen molecules in tissues. We demonstrate the first investigation into the molecular denaturation of collagen in decellularized ECM enabled by a novel Collagen Hybridizing Peptide (CHP) that specifically binds to unfolded collagen chains. We show that SDS and Triton X-100 denature collagen molecules while CHAPS and SD cannot. Such detection has been nearly impossible with other existing techniques. The CHP technique will advance our understanding about the effect of the cell-removing process on ECM, and lead to development of the decellularization technology. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Molecular assessment of collagen denaturation in decellularized tissues using a collagen hybridizing peptide

PubMed Central

Hwang, Jeongmin; San, Boi Hoa; Turner, Neill J.; White, Lisa J.; Faulk, Denver M.; Badylak, Stephen F.; Li, Yang; Yu, S. Michael

2017-01-01

Decellularized extracellular matrix (ECM) derived from tissues and organs are emerging as important scaffold materials for regenerative medicine. Many believe that preservation of the native ECM structure during decellularization is highly desirable. However, because effective techniques to assess the structural damage in ECM are lacking, the disruptive effects of a decellularization method and the impact of the associated structural damage upon the scaffold’s regenerative capacity are often debated. Using a novel collagen hybridizing peptide (CHP) that specifically binds to unfolded collagen chains, we investigated the molecular denaturation of collagen in the ECM decellularized by four commonly used cellremoving detergents: sodium dodecyl sulfate (SDS), 3-[(3-cholamidopropyl)dimethylammonio]-1-propa nesulfonate (CHAPS), sodium deoxycholate (SD), and Triton X-100. Staining of the detergent-treated porcine ligament and urinary bladder matrix with carboxyfluorescein-labeled CHP demonstrated that SDS and Triton X-100 denature the triple helical collagen molecule while CHAPS and SD do not, although second harmonic generation imaging and transmission electron microscopy (TEM) revealed that all four detergents disrupt collagen fibrils. Our findings from the CHP staining were further confirmed by the circular dichroism spectra of intact triple helical collagen molecules in CHAPS and SD solutions, and the TEM images of CHP-conjugated gold nanoparticles binding only to the SDS and Triton X-100 treated collagen fibrils. CHP is a powerful new tool for direct and reliable measurement of denatured collagen molecules in decellularized tissues. It is expected to have wide applications in the development and standardization of the tissue/organ decellularization technology. Statement of Significance Preservation of the native ECM structure in decellularized tissues is highly desirable, since denaturation of ECM molecules (e.g., collagen) during decellularization can strongly influence the cellular response. Unfortunately, conventional techniques (SEM, SHG) are not conducive to identifying denatured collagen molecules in tissues. We demonstrate the first investigation into the molecular denaturation of collagen in decellularized ECM enabled by a novel Collagen Hybridizing Peptide (CHP) that specifically binds to unfolded collagen chains. We show that SDS and Triton X-100 denature collagen molecules while CHAPS and SD cannot. Such detection has been nearly impossible with other existing techniques. The CHP technique will advance our understanding about the effect of the cell-removing process on ECM, and lead to development of the decellularization technology. PMID:28161576

A Regeneratively Cooled Thrust Chamber For The Fastrac Engine

NASA Technical Reports Server (NTRS)

Brown, Kendall K.; Sparks, Dave; Woodcock, Gordon

2000-01-01

Abstract This paper presents the development of a low-cost, regeneratively-cooled thrust chamber for the Fastrac engine. The chamber was fabricated using hydraformed copper tubing to form the coolant jacket and wrapped with a fiber reinforced polymer composite Material to form a structural jacket. The thrust chamber design and fabrication approach was based upon Space America. Inc.'s 12,000 lb regeneratively-cooled LOX/kerosene rocket engine. Fabrication of regeneratively cooled thrust chambers by tubewall construction dates back to the early US ballistic missile programs. The most significant innovations in this design was the development of a low-cost process for fabrication from copper tubing (nickel alloy was the usual practice) and use of graphite composite overwrap as the pressure containment, which yields an easily fabricated, lightweight pressure jacket around the copper tubes A regeneratively-cooled reusable thrust chamber can benefit the Fastrac engine program by allowing more efficient (cost and scheduler testing). A proof-of-concept test article has been fabricated and will he tested at Marshall Space Flight Center in the late Summer or Fall of 2000.

Current Therapeutic Strategies for Stem Cell-Based Cartilage Regeneration

PubMed Central

Nam, Yoojun; Lee, Jennifer

2018-01-01

The process of cartilage destruction in the diarthrodial joint is progressive and irreversible. This destruction is extremely difficult to manage and frustrates researchers, clinicians, and patients. Patients often take medication to control their pain. Surgery is usually performed when pain becomes uncontrollable or joint function completely fails. There is an unmet clinical need for a regenerative strategy to treat cartilage defect without surgery due to the lack of a suitable regenerative strategy. Clinicians and scientists have tried to address this using stem cells, which have a regenerative potential in various tissues. Cartilage may be an ideal target for stem cell treatment because it has a notoriously poor regenerative potential. In this review, we describe past, present, and future strategies to regenerate cartilage in patients. Specifically, this review compares a surgical regenerative technique (microfracture) and cell therapy, cell therapy with and without a scaffold, and therapy with nonaggregated and aggregated cells. We also review the chondrogenic potential of cells according to their origin, including autologous chondrocytes, mesenchymal stem cells, and induced pluripotent stem cells. PMID:29765426

[The specific features of the development of metabolic and regenerative processes under the action of low-intensity electromagnetic radiation in radiation exposure conditions (an experimental study)].

PubMed

Korolev, Yu N; Mihajlik, L V; Nikulina, L A; Geniatulina, M S

The experiments on male white rats with the use of biochemical, photo-optical, and electron-microscopic techniques have demonstrated that the use of low-intensity electromagnetic radiation of ultrahigh frequency (EMR UHF) and low-intensity low-frequency magnetic field (MF) during the post-irradiation period (within 21 days after exposure to radiation) enhanced the metabolic and regenerative processes in the testes and liver. It was shown that the application of MF largely intensified the antioxidant activity whereas EMR UHF preferentially stimulated the biosynthetic processes as well as the processes of cellular and intracellular regeneration.

Multiscale assembly for tissue engineering and regenerative medicine

PubMed Central

Inci, Fatih; Tasoglu, Savas; Erkmen, Burcu; Demirci, Utkan

2015-01-01

Our understanding of cell biology and its integration with materials science has led to technological innovations in the bioengineering of tissue-mimicking grafts that can be utilized in clinical and pharmaceutical applications. Bio-engineering of native-like multiscale building blocks provides refined control over the cellular microenvironment, thus enabling functional tissues. In this review, we focus on assembling building blocks from the biomolecular level to the millimeter scale. We also provide an overview of techniques for assembling molecules, cells, spheroids, and microgels and achieving bottom-up tissue engineering. Additionally, we discuss driving mechanisms for self- and guided assembly to create micro-to-macro scale tissue structures. PMID:25796488

Regenerative adsorbent heat pump

NASA Technical Reports Server (NTRS)

Jones, Jack A. (Inventor)

1991-01-01

A regenerative adsorbent heat pump process and system is provided which can regenerate a high percentage of the sensible heat of the system and at least a portion of the heat of adsorption. A series of at least four compressors containing an adsorbent is provided. A large amount of heat is transferred from compressor to compressor so that heat is regenerated. The process and system are useful for air conditioning rooms, providing room heat in the winter or for hot water heating throughout the year, and, in general, for pumping heat from a lower temperature to a higher temperature.

Hypoxia-based strategies for regenerative dentistry-Views from the different dental fields.

PubMed

Müller, Anna Sonja; Janjić, Klara; Lilaj, Bledar; Edelmayer, Michael; Agis, Hermann

2017-09-01

The understanding of the cell biological processes underlying development and regeneration of oral tissues leads to novel regenerative approaches. Over the past years, knowledge on key roles of the hypoxia-based response has become more profound. Based on these findings, novel regenerative approaches for dentistry are emerging, which target cellular oxygen sensors. These approaches include hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in studies on hypoxia and hypoxia-based strategies in regenerative dentistry highlights the growing attention to hypoxia's role in regeneration and its underlying biology, as well as its application in a therapeutic setting. In this narrative review, we present the current knowledge on the role of hypoxia in oral tissues and review the proposed hypoxia-based approaches in different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accelerating regenerative medicine: the Japanese experiment in ethics and regulation.

PubMed

Lysaght, Tamra

2017-09-01

In 2014, the Japanese National Diet introduced new laws aimed at promoting the clinical translation of stem cells and regenerative medicine. The basic action of these laws is to allow the early introduction of regenerative medicine products into the Japanese market through an accelerated approval process, while providing patients with access to certain types of stem cell and cell-based therapies in the context of private clinical practice. While this framework appears to offer enormous opportunities for the translation of stem cell science, it raises ethical challenges that have not yet been fully explored. This paper critically analyzes this framework with respect to the prioritization of safety over clinical benefit, distributive justice and public trust in science and medicine. It is argued that the framework unfairly burdens patients and strained healthcare systems without any clear benefits, and may undermine the credibility of the regenerative medicine field as it emerges.

[Translational/regulatory science researches of NIHS for regenerative medicine and cellular therapy products].

PubMed

Sato, Yoji

2014-01-01

In 2013, the Japanese Diet passed the Regenerative Medicine Promotion Act and the revisions to the Pharmaceutical Affairs Act, which was also renamed as the Therapeutic Products Act (TPA). One of the aims of the new/revised Acts is to promote the development and translation of and access to regenerative/cellular therapies. In the TPA, a product derived from processing cells is categorized as a subgroup of "regenerative medicine, cellular therapy and gene therapy products" (RCGPs), products distinct from pharmaceuticals and medical devices, allowing RCGPs to obtain a conditional and time- limited marketing authorization much earlier than that under the conventional system. To foster not only RCGPs, but also innovative pharmaceuticals and medical devices, the Ministry of Health, Labour and Welfare recently launched Translational Research Program for Innovative Pharmaceuticals, Medical Devices and RCGPs. This mini-review introduces contributions of the National Institute of Health Sciences (NIHS) to research projects on RCGPs in the Program.

Regenerative (Regen) ECLSS Operations Water Balance

NASA Technical Reports Server (NTRS)

Tobias, Barry

2010-01-01

In November 2008, the Water Regenerative System racks were launched aboard Space Shuttle flight, STS-126 (ULF2) and installed and activated on the International Space Station (ISS). These racks, consisting of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA), completed the installation of the Regenerative (Regen) ECLSS systems which includes the Oxygen Generator Assembly (OGA) that was launched 2 years prior. With the onset of active water management on the US segment of the ISS, a new operational concept was required, that of "water balance." Even more recently, in 2010 the Sabatier system came online which converts H2 and CO2 into water and methane. The Regen ECLSS systems accept condensation from the atmosphere, urine from crew, and processes that fluid via various means into potable water which is used for crew drinking, building up skip-cycle water inventory, and water for electrolysis to produce oxygen. Specification rates of crew urine output, condensate output, O2 requirements, toilet flush water and drinking needs are well documented and used as a general plan when Regen ECLSS came online. Spec rates are useful in long term planning, however, daily or weekly rates are dependent on a number of variables. The constantly changing rates created a new challenge for the ECLSS flight controllers, who are responsible for operating the ECLSS systems onboard ISS. This paper will review the various inputs to rate changes and inputs to planning events, including but not limited to; crew personnel makeup, Regen ECLSS system operability, vehicle traffic, water containment availability, and Carbon Dioxide Removal Assembly (CDRA) capability. Along with the inputs that change the various rates, the paper will review the different systems, their constraints and finally the operational means by which flight controllers manage this new challenge of "water balance."

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

3D Cell Printed Tissue Analogues: A New Platform for Theranostics

PubMed Central

Choi, Yeong-Jin; Yi, Hee-Gyeong; Kim, Seok-Won; Cho, Dong-Woo

2017-01-01

Stem cell theranostics has received much attention for noninvasively monitoring and tracing transplanted therapeutic stem cells through imaging agents and imaging modalities. Despite the excellent regenerative capability of stem cells, their efficacy has been limited due to low cellular retention, low survival rate, and low engraftment after implantation. Three-dimensional (3D) cell printing provides stem cells with the similar architecture and microenvironment of the native tissue and facilitates the generation of a 3D tissue-like construct that exhibits remarkable regenerative capacity and functionality as well as enhanced cell viability. Thus, 3D cell printing can overcome the current concerns of stem cell therapy by delivering the 3D construct to the damaged site. Despite the advantages of 3D cell printing, the in vivo and in vitro tracking and monitoring of the performance of 3D cell printed tissue in a noninvasive and real-time manner have not been thoroughly studied. In this review, we explore the recent progress in 3D cell technology and its applications. Finally, we investigate their potential limitations and suggest future perspectives on 3D cell printing and stem cell theranostics. PMID:28839468

Bioelectric modulation of macrophage polarization

NASA Astrophysics Data System (ADS)

Li, Chunmei; Levin, Michael; Kaplan, David L.

2016-02-01

Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells’ resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine.

Biological and MRI characterization of biomimetic ECM scaffolds for cartilage tissue regeneration.

PubMed

Ravindran, Sriram; Kotecha, Mrignayani; Huang, Chun-Chieh; Ye, Allen; Pothirajan, Padmabharathi; Yin, Ziying; Magin, Richard; George, Anne

2015-12-01

Osteoarthritis is the most common joint disorder affecting millions of people. Most scaffolds developed for cartilage regeneration fail due to vascularization and matrix mineralization. In this study we present a chondrogenic extracellular matrix (ECM) incorporated collagen/chitosan scaffold (chondrogenic ECM scaffold) for potential use in cartilage regenerative therapy. Biochemical characterization showed that these scaffolds possess key pro-chondrogenic ECM components and growth factors. MRI characterization showed that the scaffolds possess mechanical properties and diffusion characteristics important for cartilage tissue regeneration. In vivo implantation of the chondrogenic ECM scaffolds with bone marrow derived mesenchymal stem cells (MSCs) triggered chondrogenic differentiation of the MSCs without the need for external stimulus. Finally, results from in vivo MRI experiments indicate that the chondrogenic ECM scaffolds are stable and possess MR properties on par with native cartilage. Based on our results, we envision that such ECM incorporated scaffolds have great potential in cartilage regenerative therapy. Additionally, our validation of MR parameters with histology and biochemical analysis indicates the ability of MRI techniques to track the progress of our ECM scaffolds non-invasively in vivo; highlighting the translatory potential of this technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

PubMed Central

Qian, Li; Huang, Yu; Spencer, C. Ian; Foley, Amy; Vedantham, Vasanth; Liu, Lei; Conway, Simon J.; Fu, Ji-dong; Srivastava, Deepak

2012-01-01

SUMMARY The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here, we use genetic lineage-tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became bi-nucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast activating peptide, Thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes. PMID:22522929

The Application of Microwave Incineration to Regenerative Life Support

NASA Technical Reports Server (NTRS)

Sun, Sidney C.; Srinivasan, Venkatesh; Covington, Al (Technical Monitor)

1995-01-01

Future human exploration missions will require life support systems that are highly regenerative, requiring minimum resupply, enabling the crews to be largely self-sufficient. Solid wastes generated in space will be processed to recover usable material. Researchers at NASA Ames Research Center are studying a commercially-produced microwave incinerator as a solid waste processor. This paper will describe the results of testing to-date.

Cell-laden composite suture threads for repairing damaged tendons.

PubMed

Costa-Almeida, Raquel; Domingues, Rui M A; Fallahi, Afsoon; Avci, Huseyin; Yazdi, Iman K; Akbari, Mohsen; Reis, Rui L; Tamayol, Ali; Gomes, Manuela E; Khademhosseini, Ali

2018-04-01

Tendons have limited regenerative capacity due to their low cellularity and hypovascular nature, which results in poor clinical outcomes of presently used therapies. As tendon injuries are often observed in active adults, it poses an increasing socio-economic burden on healthcare systems. Currently, suture threads are used during surgical repair to anchor the tissue graft or to connect injured ends. Here, we created composite suture threads coated with a layer of cell-laden hydrogel that can be used for bridging the injured tissue aiming at tendon regeneration. In addition, the fibres can be used to engineer 3-dimensional constructs through textile processes mimicking the architecture and mechanical properties of soft tissues, including tendons and ligaments. Encapsulated human tendon-derived cells migrated within the hydrogel and aligned at the surface of the core thread. An up-regulation of tendon-related genes (scleraxis and tenascin C) and genes involved in matrix remodelling (matrix metalloproteinases 1, matrix metalloproteinases 2) was observed. Cells were able to produce a collagen-rich matrix, remodelling their micro-environment, which is structurally comparable to native tendon tissue. Copyright © 2017 John Wiley & Sons, Ltd.

Citrate chemistry and biology for biomaterials design.

PubMed

Ma, Chuying; Gerhard, Ethan; Lu, Di; Yang, Jian

2018-05-04

Leveraging the multifunctional nature of citrate in chemistry and inspired by its important role in biological tissues, a class of highly versatile and functional citrate-based materials (CBBs) has been developed via facile and cost-effective polycondensation. CBBs exhibiting tunable mechanical properties and degradation rates, together with excellent biocompatibility and processability, have been successfully applied in vitro and in vivo for applications ranging from soft to hard tissue regeneration, as well as for nanomedicine designs. We summarize in the review, chemistry considerations for CBBs design to tune polymer properties and to introduce functionality with a focus on the most recent advances, biological functions of citrate in native tissues with the new notion of degradation products as cell modulator highlighted, and the applications of CBBs in wound healing, nanomedicine, orthopedic, cardiovascular, nerve and bladder tissue engineering. Given the expansive evidence for citrate's potential in biology and biomaterial science outlined in this review, it is expected that citrate based materials will continue to play an important role in regenerative engineering. Copyright © 2018 Elsevier Ltd. All rights reserved.

Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation.

PubMed

Wei, Jiao; Herrler, Tanja; Han, Dong; Liu, Kai; Huang, Rulin; Guba, Markus; Dai, Chuanchang; Li, Qingfeng

2016-11-28

Joint defects are complex and difficult to reconstruct. By exploiting the body's own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach.

Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation

PubMed Central

Wei, Jiao; Herrler, Tanja; Han, Dong; Liu, Kai; Huang, Rulin; Guba, Markus; Dai, Chuanchang; Li, Qingfeng

2016-01-01

Joint defects are complex and difficult to reconstruct. By exploiting the body’s own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach. PMID:27892493

Hyaluronan Benzyl Ester as a Scaffold for Tissue Engineering

PubMed Central

Vindigni, Vincenzo; Cortivo, Roberta; Iacobellis, Laura; Abatangelo, Giovanni; Zavan, Barbara

2009-01-01

Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on “smart scaffolds” for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF®). HYAFF® can be processed to obtain several types of devices such as tubes, membranes, non-woven fabrics, gauzes, and sponges. All these scaffolds are highly biocompatible. In the human body they do not elicit any adverse reactions and are resorbed by the host tissues. Human hepatocytes, dermal fibroblasts and keratinocytes, chondrocytes, Schwann cells, bone marrow derived mesenchymal stem cells and adipose tissue derived mesenchymal stem cells have been successfully cultured in these meshes. The same scaffolds, in tube meshes, has been applied for vascular tissue engineering that has emerged as a promising technology for the design of an ideal, responsive, living conduit with properties similar to that of native tissue. PMID:19742179

Human cartilage tissue fabrication using three-dimensional inkjet printing technology.

PubMed

Cui, Xiaofeng; Gao, Guifang; Yonezawa, Tomo; Dai, Guohao

2014-06-10

Bioprinting, which is based on thermal inkjet printing, is one of the most attractive enabling technologies in the field of tissue engineering and regenerative medicine. With digital control cells, scaffolds, and growth factors can be precisely deposited to the desired two-dimensional (2D) and three-dimensional (3D) locations rapidly. Therefore, this technology is an ideal approach to fabricate tissues mimicking their native anatomic structures. In order to engineer cartilage with native zonal organization, extracellular matrix composition (ECM), and mechanical properties, we developed a bioprinting platform using a commercial inkjet printer with simultaneous photopolymerization capable for 3D cartilage tissue engineering. Human chondrocytes suspended in poly(ethylene glycol) diacrylate (PEGDA) were printed for 3D neocartilage construction via layer-by-layer assembly. The printed cells were fixed at their original deposited positions, supported by the surrounding scaffold in simultaneous photopolymerization. The mechanical properties of the printed tissue were similar to the native cartilage. Compared to conventional tissue fabrication, which requires longer UV exposure, the viability of the printed cells with simultaneous photopolymerization was significantly higher. Printed neocartilage demonstrated excellent glycosaminoglycan (GAG) and collagen type II production, which was consistent with gene expression. Therefore, this platform is ideal for accurate cell distribution and arrangement for anatomic tissue engineering.

Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guarino, Vincenzo, E-mail: vguarino@unina.it; Altobelli, Rosaria; Cirillo, Valentina

A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow tomore » produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.« less

Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

NASA Astrophysics Data System (ADS)

Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

2015-12-01

A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial's manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell-biomaterial and cell- cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

Teleost fish as a model system to study successful regeneration of the central nervous system.

PubMed

Zupanc, Günther K H; Sîrbulescu, Ruxandra F

2013-01-01

Traumatic brain injury and spinal cord injury are devastating conditions that may result in death or long-term disability. A promising strategy for the development of effective cell replacement therapies involves the study of regeneration-competent organisms. Among this group, teleost fish are distinguished by their excellent potential to regenerate nervous tissue and to regain function after injury to the central nervous system. In this chapter, we summarize our current understanding of the cellular processes that mediate this regenerative potential, and we show that several of these processes are shared with the normal development of the intact central nervous system; we describe how the spontaneous self-repair of the teleostean central nervous system leads to functional recovery, at physiological and behavioral levels; we discuss the possible function of molecular factors associated with the degenerative and regenerative processes after injury; and, finally, we speculate on evolutionary aspects of adult neurogenesis and neuronal regeneration, and on how a better understanding of these aspects could catalyze the development of therapeutic strategies to overcome the regenerative limits of the mammalian CNS.

Microfabricated Modular Scale-Down Device for Regenerative Medicine Process Development

PubMed Central

Reichen, Marcel; Macown, Rhys J.; Jaccard, Nicolas; Super, Alexandre; Ruban, Ludmila; Griffin, Lewis D.; Veraitch, Farlan S.; Szita, Nicolas

2012-01-01

The capacity of milli and micro litre bioreactors to accelerate process development has been successfully demonstrated in traditional biotechnology. However, for regenerative medicine present smaller scale culture methods cannot cope with the wide range of processing variables that need to be evaluated. Existing microfabricated culture devices, which could test different culture variables with a minimum amount of resources (e.g. expensive culture medium), are typically not designed with process development in mind. We present a novel, autoclavable, and microfabricated scale-down device designed for regenerative medicine process development. The microfabricated device contains a re-sealable culture chamber that facilitates use of standard culture protocols, creating a link with traditional small-scale culture devices for validation and scale-up studies. Further, the modular design can easily accommodate investigation of different culture substrate/extra-cellular matrix combinations. Inactivated mouse embryonic fibroblasts (iMEF) and human embryonic stem cell (hESC) colonies were successfully seeded on gelatine-coated tissue culture polystyrene (TC-PS) using standard static seeding protocols. The microfluidic chip included in the device offers precise and accurate control over the culture medium flow rate and resulting shear stresses in the device. Cells were cultured for two days with media perfused at 300 µl.h−1 resulting in a modelled shear stress of 1.1×10−4 Pa. Following perfusion, hESC colonies stained positively for different pluripotency markers and retained an undifferentiated morphology. An image processing algorithm was developed which permits quantification of co-cultured colony-forming cells from phase contrast microscope images. hESC colony sizes were quantified against the background of the feeder cells (iMEF) in less than 45 seconds for high-resolution images, which will permit real-time monitoring of culture progress in future experiments. The presented device is a first step to harness the advantages of microfluidics for regenerative medicine process development. PMID:23284952

Transient switching control strategy from regenerative braking to anti-lock braking with a semi-brake-by-wire system

NASA Astrophysics Data System (ADS)

Li, Liang; Li, Xujian; Wang, Xiangyu; Liu, Yahui; Song, Jian; Ran, Xu

2016-02-01

Regenerative braking is an important technology in improving fuel economy of an electric vehicle (EV). However, additional motor braking will change the dynamic characteristics of the vehicle, leading to braking instability, especially when the anti-lock braking system (ABS) is triggered. In this paper, a novel semi-brake-by-wire system, without the use of a pedal simulator and fail-safe device, is proposed. In order to compensate for the hysteretic characteristics of the designed brake system while ensure braking reliability and fuel economy when the ABS is triggered, a novel switching compensation control strategy using sliding mode control is brought forward. The proposed strategy converts the complex coupling braking process into independent control of hydraulic braking and regenerative braking, through which a balance between braking performance, braking reliability, braking safety and fuel economy is achieved. Simulation results show that the proposed strategy is effective and adaptable in different road conditions while the large wheel slip rate is triggered during a regenerative braking course. The research provides a new possibility of low-cost equipment and better control performance for the regenerative braking in the EV and the hybrid EV.

Translating cell-based regenerative medicines from research to successful products: challenges and solutions.

PubMed

Bayon, Yves; Vertès, Alain A; Ronfard, Vincent; Egloff, Matthieu; Snykers, Sarah; Salinas, Gabriella Franco; Thomas, Robert; Girling, Alan; Lilford, Richard; Clermont, Gaelle; Kemp, Paul

2014-08-01

The Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart intend to address the specific challenges and needs facing the industry in translating academic research into commercial products. Over the last 3 years, the TERMIS-EU Industry Committee has worked with commercial bodies to deliver programs that encourage academics to liaise with industry in proactive collaborations. The TERMIS-EU 2013 Industry Symposium aimed to build on this commercial agenda by focusing on two topics: Operations Management (How to move a process into the good manufacturing practice [GMP] environment) and Clinical Translation (Moving a GMP process into robust trials). These topics were introduced by providing the synergistic business perspective of partnering between the multiple regenerative medicine stakeholders, throughout the life cycle of product development. Seven industry leaders were invited to share their experience, expertise, and strategies. Due to the complex nature of regenerative medicine products, partnering for their successful commercial development seems inevitable to overcome all obstacles by sharing experiences and expertise of all stakeholders. When ideally implemented, the "innovation quotient" of a virtual team resulting from the combination of internal and external project teams can be maximized through maximizing the three main dimensions: core competences, technology portfolio, and alliance management.

Precision manufacturing for clinical-quality regenerative medicines.

PubMed

Williams, David J; Thomas, Robert J; Hourd, Paul C; Chandra, Amit; Ratcliffe, Elizabeth; Liu, Yang; Rayment, Erin A; Archer, J Richard

2012-08-28

Innovations in engineering applied to healthcare make a significant difference to people's lives. Market growth is guaranteed by demographics. Regulation and requirements for good manufacturing practice-extreme levels of repeatability and reliability-demand high-precision process and measurement solutions. Emerging technologies using living biological materials add complexity. This paper presents some results of work demonstrating the precision automated manufacture of living materials, particularly the expansion of populations of human stem cells for therapeutic use as regenerative medicines. The paper also describes quality engineering techniques for precision process design and improvement, and identifies the requirements for manufacturing technology and measurement systems evolution for such therapies.

Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management

PubMed Central

Chicharro-Alcántara, Deborah; Damiá-Giménez, Elena; Carrillo-Poveda, José M.; Peláez-Gorrea, Pau

2018-01-01

The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process. PMID:29346333

Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians.

PubMed

Newmark, Phillip A; Reddien, Peter W; Cebrià, Francesc; Sánchez Alvarado, Alejandro

2003-09-30

Freshwater planarian flatworms are capable of regenerating complete organisms from tiny fragments of their bodies; the basis for this regenerative prowess is an experimentally accessible stem cell population that is present in the adult planarian. The study of these organisms, classic experimental models for investigating metazoan regeneration, has been revitalized by the application of modern molecular biological approaches. The identification of thousands of unique planarian ESTs, coupled with large-scale whole-mount in situ hybridization screens, and the ability to inhibit planarian gene expression through double-stranded RNA-mediated genetic interference, provide a wealth of tools for studying the molecular mechanisms that regulate tissue regeneration and stem cell biology in these organisms. Here we show that, as in Caenorhabditis elegans, ingestion of bacterially expressed double-stranded RNA can inhibit gene expression in planarians. This inhibition persists throughout the process of regeneration, allowing phenotypes with disrupted regenerative patterning to be identified. These results pave the way for large-scale screens for genes involved in regenerative processes.

Evolving the use of peptides as biomaterials components

PubMed Central

Collier, Joel H.; Segura, Tatiana

2012-01-01

This manuscript is part of a debate on the statement that “the use of short synthetic adhesion peptides, like RGD, is the best approach in the design of biomaterials that guide cell behavior for regenerative medicine and tissue engineering”. We take the position that although there are some acknowledged disadvantages of using short peptide ligands within biomaterials, it is not necessary to discard the notion of using peptides within biomaterials entirely, but rather to reinvent and evolve their use. Peptides possess advantageous chemical definition, access to non-native chemistries, amenability to de novo design, and applicability within parallel approaches. Biomaterials development programs that require such aspects may benefit from a peptide-based strategy. PMID:21515167

Advances in hydrogel delivery systems for tissue regeneration.

PubMed

Toh, Wei Seong; Loh, Xian Jun

2014-12-01

Hydrogels are natural or synthetic polymer networks that have high water-absorbing capacity and closely mimic native extracellular matrices. As hydrogel-based cell delivery systems are being increasingly employed in regenerative medicine, several advances have been made in the hydrogel chemistry and modification for enhanced control of cell fate and functions, and modulation of cell and tissue responses against oxidative stress and inflammation in the tissue environment. This review aims to provide the state-of-the-art overview of the recent advances in field, discusses new perspectives and challenges in the regeneration of specific tissues, and highlights some of the limitations of current systems for possible future advancements. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Sox2+ progenitors in sharks link taste development with the evolution of regenerative teeth from denticles

PubMed Central

Martin, Kyle J.; Rasch, Liam J.; Cooper, Rory L.; Johanson, Zerina; Fraser, Gareth J.

2016-01-01

Teeth and denticles belong to a specialized class of mineralizing epithelial appendages called odontodes. Although homology of oral teeth in jawed vertebrates is well supported, the evolutionary origin of teeth and their relationship with other odontode types is less clear. We compared the cellular and molecular mechanisms directing development of teeth and skin denticles in sharks, where both odontode types are retained. We show that teeth and denticles are deeply homologous developmental modules with equivalent underlying odontode gene regulatory networks (GRNs). Notably, the expression of the epithelial progenitor and stem cell marker sex-determining region Y-related box 2 (sox2) was tooth-specific and this correlates with notable differences in odontode regenerative ability. Whereas shark teeth retain the ancestral gnathostome character of continuous successional regeneration, new denticles arise only asynchronously with growth or after wounding. Sox2+ putative stem cells associated with the shark dental lamina (DL) emerge from a field of epithelial progenitors shared with anteriormost taste buds, before establishing within slow-cycling cell niches at the (i) superficial taste/tooth junction (T/TJ), and (ii) deep successional lamina (SL) where tooth regeneration initiates. Furthermore, during regeneration, cells from the superficial T/TJ migrate into the SL and contribute to new teeth, demonstrating persistent contribution of taste-associated progenitors to tooth regeneration in vivo. This data suggests a trajectory for tooth evolution involving cooption of the odontode GRN from nonregenerating denticles by sox2+ progenitors native to the oral taste epithelium, facilitating the evolution of a novel regenerative module of odontodes in the mouth of early jawed vertebrates: the teeth. PMID:27930309

Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine

PubMed Central

Renth, Amanda N.

2012-01-01

Components found within the extracellular matrix (ECM) have emerged as an essential subset of biomaterials for tissue engineering scaffolds. Collagen, glycosaminoglycans, bioceramics, and ECM-based matrices are the main categories of “raw materials” used in a wide variety of tissue engineering strategies. The advantages of raw materials include their inherent ability to create a microenvironment that contains physical, chemical, and mechanical cues similar to native tissue, which prove unmatched by synthetic biomaterials alone. Moreover, these raw materials provide a head start in the regeneration of tissues by providing building blocks to be bioresorbed and incorporated into the tissue as opposed to being biodegraded into waste products and removed. This article reviews the strategies and applications of employing raw materials as components of tissue engineering constructs. Utilizing raw materials holds the potential to provide both a scaffold and a signal, perhaps even without the addition of exogenous growth factors or cytokines. Raw materials contain endogenous proteins that may also help to improve the translational success of tissue engineering solutions to progress from laboratory bench to clinical therapies. Traditionally, the tissue engineering triad has included cells, signals, and materials. Whether raw materials represent their own new paradigm or are categorized as a bridge between signals and materials, it is clear that they have emerged as a leading strategy in regenerative medicine. The common use of raw materials in commercial products as well as their growing presence in the research community speak to their potential. However, there has heretofore not been a coordinated or organized effort to classify these approaches, and as such we recommend that the use of raw materials be introduced into the collective consciousness of our field as a recognized classification of regenerative medicine strategies. PMID:22462759

A graphite-lined regeneratively cooled thrust chamber

NASA Technical Reports Server (NTRS)

Stubbs, V. R.

1972-01-01

Design concepts, based on use of graphite as a thermal barrier for regeneratively cooled FLOX-methane thrust chambers, have been screened and concepts selected for detailed thermodynamic, stress, and fabrication analyses. A single design employing AGCarb-101, a fibrous graphite composite material, for a thermal barrier liner and an electroformed nickel structure with integral coolant passages was selected for fabrication and testing. The fabrication processes and the test results are described and illustrated.

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.

Regenerative Endodontic Treatment of an Immature Necrotic Molar with Arrested Root Development by Using Recombinant Human Platelet-derived Growth Factor: A Case Report.

PubMed

Zhujiang, Annie; Kim, Sahng G

2016-01-01

Regenerative endodontic treatment has provided a treatment option that aims to allow root maturation. The present report describes the regenerative endodontic treatment of a necrotic, immature molar by using recombinant human platelet-derived growth factor (rhPDGF-BB) and shows the continued root maturation in the tooth with arrested root development. A regenerative endodontic procedure that used a growth factor was performed for a necrotic molar with arrested root formation in a 20-year-old patient. Thorough disinfection by using mechanical instrumentation and copious irrigation of antimicrobial agents as well as intracanal medication with calcium hydroxide was performed throughout the first 2 appointments. At the third appointment, the root canals were irrigated with an antimicrobial solution and 17% EDTA, and bleeding was evoked by passing sterile paper points beyond the apex in each canal. Small pieces of a collagen membrane saturated with rhPDGF-BB solution from GEM 21S were packed into each canal. Mineral trioxide aggregate was placed, and Cavit and composite resin were used to restore the tooth. Complete root maturation and resolution of a periapical radiolucency were observed at the 15-month follow-up. The present report presents a regenerative endodontic procedure that uses rhPDGF-BB for a necrotic molar with arrested root development. The finding of continued root development in the present case suggests that regenerative endodontic treatment may be able to resume the root maturation process in teeth with arrested root formation. Further clinical studies are required to investigate the efficacy of rhPDGF-BB in regenerative endodontic treatment. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Mechanomimetic hydrogels for vocal fold lamina propria regeneration.

PubMed

Kutty, Jaishankar K; Webb, Ken

2009-01-01

Vocal fold injury commonly leads to reduced vocal quality due to scarring-induced alterations in matrix composition and tissue biomechanics. The long-term hypothesis motivating our work is that rapid restoration of phonation and the associated dynamic mechanical environment will reduce scarring and promote regenerative healing. Toward this end, the objective of this study was to develop mechanomimetic, degradable hydrogels approximating the viscoelastic properties of the vocal ligament and mucosa that may be photopolymerized in situ to restore structural integrity to vocal fold tissues. The tensile and rheological properties of hydrogels (targeting the vocal ligament and mucosa, respectively) were varied as a function of macromer concentration. PEG diacrylate-based hydrogels exhibited linear stress-strain response and elastic modulus consistent with the properties of the vocal ligament at low strains (0-15%), but did not replicate the non-linear behavior observed in native tissue at higher strains. Methacrylated hyaluronic acid hydrogels displayed dynamic viscosity consistent with native vocal mucosa, while elastic shear moduli values were several-fold higher. Cell culture studies indicated that both hydrogels supported spreading, proliferation and collagen/proteoglycan matrix deposition by encapsulated fibroblasts throughout the 3D network.

Stem cells have the potential to rejuvenate regenerative medicine research.

PubMed

Eve, David J; Fillmore, Randolph; Borlongan, Cesar V; Sanberg, Paul R

2010-10-01

The increasing number of publications featuring the use of stem cells in regenerative processes supports the idea that they are revolutionizing regenerative medicine research. In an analysis of the articles published in the journal Cell Transplantation - The Regenerative Medicine Journal between 2008 and 2009, which reveals the topics and categories that are on the cutting edge of regenerative medicine research, stem cells are becoming increasingly relevant as the "runner-up" category to "neuroscience" related articles. The high volume of stem cell research casts a bright light on the hope for stem cells and their role in regenerative medicine as a number of reports deal with research using stem cells entering, or seeking approval for, clinical trials. The "methods and new technologies" and "tissue engineering" sections were almost equally as popular, and in part, reflect attempts to maximize the potential of stem cells and other treatments for the repair of damaged tissue. Transplantation studies were again more popular than non-transplantation, and the contribution of stem cell-related transplants was greater than other types of transplants. The non-transplantation articles were predominantly related to new methods for the preparation, isolation and manipulation of materials for transplant by specific culture media, gene therapy, medicines, dietary supplements, and co-culturing with other cells and further elucidation of disease mechanisms. A sizeable proportion of the transplantation articles reported on how previously new methods may have aided the ability of the cells or tissue to exert beneficial effects following transplantation.

Leaf and shoot water content and leaf dry matter content of Mediterranean woody species with different post-fire regenerative strategies.

PubMed

Saura-Mas, S; Lloret, F

2007-03-01

Post-fire regeneration is a key process in Mediterranean shrubland dynamics, strongly determining the functional properties of the community. In this study, a test is carried out to determine whether there is co-variation between species regenerative types and functional attributes related to water use. An analysis was made of the seasonal variations in leaf relative water content (RWC), leaf dry matter content (LDMC), leaf moisture (LM) and live fine fuel moisture (LFFM) in 30 woody species of a coastal shrubland, with different post-fire regenerative strategies (seeding, resprouting or both). RWC results suggest that the studied resprouters have more efficient mechanisms to reduce water losses and maintain water supply between seasons. In contrast, seeders are more drought tolerant. LDMC is higher in resprouters over the course of the year, suggesting a more efficient conservation of nutrients. The weight of the phylogenetic constraint to understand differences between regenerative strategies tends to be important for LDMC, while it is not the case for variables such as RWC. Groups of species with different post-fire regenerative strategies (seeders and resprouters) have different functional traits related to water use. In addition to the role of phylogenetical constraints, these differences are also likely to be related to the respective life history characteristics. Therefore, the presence and abundance of species with different post-fire regenerative responses influence the functional properties of the communities.

Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration

PubMed Central

Walters, Brad; Zuo, Jian

2012-01-01

The organ of Corti in the mammalian inner ear is comprised of mechanosensory hair cells (HCs) and nonsensory supporting cells (SCs), both of which are believed to be terminally postmitotic beyond late embryonic ages. Consequently, regeneration of HCs and SCs does not occur naturally in the adult mammalian cochlea, though recent evidence suggests that these cells may not be completely or irreversibly quiescent in at earlier postnatal ages. Furthermore, regenerative processes can be induced by genetic and pharmacological manipulations, but, more and more reports suggest that regenerative potential declines as the organ of Corti continues to age. In numerous mammalian systems, such effects of aging on regenerative potential are well established. However, in the cochlea, the problem of regeneration has not been traditionally viewed as one of aging. This is an important consideration as current models are unable to elicit widespread regeneration or full recovery of function at adult ages yet regenerative therapies will need to be developed specifically for adult populations. Still, the advent of gene targeting and other genetic manipulations has established mice as critically important models for the study of cochlear development and HC regeneration and suggests that auditory HC regeneration in adult mammals may indeed be possible. Thus, this review will focus on the pursuit of regeneration in the postnatal and adult mouse cochlea and highlight processes that occur during postnatal development, maturation, and aging that could contribute to an age-related decline in regenerative potential. Second, we will draw upon the wealth of knowledge pertaining to age related senescence in tissues outside of the ear to synthesize new insights and potentially guide future research aimed at promoting HC regeneration in the adult cochlea. PMID:23164734

Regenerative medicine in kidney disease: where we stand and where to go.

PubMed

Borges, Fernanda T; Schor, Nestor

2017-07-22

The kidney is a complex organ with more than 20 types of specialized cells that play an important role in maintaining the body's homeostasis. The epithelial tubular cell is formed during embryonic development and has little proliferative capacity under physiological conditions, but after acute injury the kidney does have regenerative capacity. However, after repetitive or severe lesions, it may undergo a maladaptation process that predisposes it to chronic kidney injury. Regenerative medicine includes various repair and regeneration techniques, and these have gained increasing attention in the scientific literature. In the future, not only will these techniques contribute to the repair and regeneration of the human kidney, but probably also to the construction of an entire organ. New mechanisms studied for kidney regeneration and repair include circulating stem cells as mesenchymal stromal/stem cells and their paracrine mechanisms of action; renal progenitor stem cells; the leading role of tubular epithelial cells in the tubular repair process; the study of zebrafish larvae to understand the process of nephron development, kidney scaffold and its repopulation; and, finally, the development of organoids. This review elucidates where we are in terms of current scientific knowledge regarding these mechanisms and the promises of future scientific perspectives.

Cell/tissue processing information system for regenerative medicine.

PubMed

Iwayama, Daisuke; Yamato, Masayuki; Tsubokura, Tetsuya; Takahashi, Minoru; Okano, Teruo

2016-11-01

When conducting clinical studies of regenerative medicine, compliance to good manufacturing practice (GMP) is mandatory, and thus much time is needed for manufacturing and quality management. It is therefore desired to introduce the manufacturing execution system (MES), which is being adopted by factories manufacturing pharmaceutical products. Meanwhile, in manufacturing human cell/tissue processing autologous products, it is necessary to protect patients' personal information, prevent patients from being identified and obtain information for cell/tissue identification. We therefore considered it difficult to adopt conventional MES to regenerative medicine-related clinical trials, and so developed novel software for production/quality management to be used in cell-processing centres (CPCs), conforming to GMP. Since this system satisfies the requirements of regulations in Japan and the USA for electronic records and electronic signatures (ER/ES), the use of ER/ES has been allowed, and the risk of contamination resulting from the use of recording paper has been eliminated, thanks to paperless operations within the CPC. Moreover, to reduce the risk of mix-up and cross-contamination due to contact during production, we developed a touchless input device with built-in radio frequency identification (RFID) reader-writer devices and optical sensors. The use of this system reduced the time to prepare and issue manufacturing instructions by 50% or more, compared to the conventional handwritten system. The system contributes to producing more large-scale production and to reducing production costs for cell and tissue products in regenerative medicine. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.

PubMed

Fraser, John K; Hicok, Kevin C; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution ® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

Regenerative braking strategies, vehicle safety and stability control systems: critical use-case proposals

NASA Astrophysics Data System (ADS)

Oleksowicz, Selim A.; Burnham, Keith J.; Southgate, Adam; McCoy, Chris; Waite, Gary; Hardwick, Graham; Harrington, Cian; McMurran, Ross

2013-05-01

The sustainable development of vehicle propulsion systems that have mainly focused on reduction of fuel consumption (i.e. CO2 emission) has led, not only to the development of systems connected with combustion processes but also to legislation and testing procedures. In recent years, the low carbon policy has made hybrid vehicles and fully electric vehicles (H/EVs) popular. The main virtue of these propulsion systems is their ability to restore some of the expended energy from kinetic movement, e.g. the braking process. Consequently new research and testing methods for H/EVs are currently being developed. This especially concerns the critical 'use-cases' for functionality tests within dynamic events for both virtual simulations, as well as real-time road tests. The use-case for conventional vehicles for numerical simulations and road tests are well established. However, the wide variety of tests and their great number (close to a thousand) creates a need for selection, in the first place, and the creation of critical use-cases suitable for testing H/EVs in both virtual and real-world environments. It is known that a marginal improvement in the regenerative braking ratio can significantly improve the vehicle range and, therefore, the economic cost of its operation. In modern vehicles, vehicle dynamics control systems play the principal role in safety, comfort and economic operation. Unfortunately, however, the existing standard road test scenarios are insufficient for H/EVs. Sector knowledge suggests that there are currently no agreed tests scenarios to fully investigate the effects of brake blending between conventional and regenerative braking as well as the regenerative braking interaction with active driving safety systems (ADSS). The paper presents seven manoeuvres, which are considered to be suitable and highly informative for the development and examination of H/EVs with regenerative braking capability. The critical manoeuvres presented are considered to be appropriate for examination of the regenerative braking mode according to ADSS. The manoeuvres are also important for investigation of regenerative braking system properties/functionalities that are specified by the legal requirements concerning H/EVs braking systems. The last part of this paper shows simulation results for one of the proposed manoeuvres that explicitly shows the usefulness of the manoeuvre.

The effects of platelet lysate patches on the activity of tendon-derived cells.

PubMed

Costa-Almeida, Raquel; Franco, Albina R; Pesqueira, Tamagno; Oliveira, Mariana B; Babo, Pedro S; Leonor, Isabel B; Mano, João F; Reis, Rui L; Gomes, Manuela E

2018-03-01

Platelet-derived biomaterials are widely explored as cost-effective sources of therapeutic factors, holding a strong potential for endogenous regenerative medicine. Particularly for tendon repair, treatment approaches that shift the injury environment are explored to accelerate tendon regeneration. Herein, genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of human-derived therapeutic factors in patch augmentation strategies aiming at tendon repair. Developed PL patches exhibited a controlled release profile of PL proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an antibacterial effect by preventing the adhesion, proliferation and biofilm formation by S. aureus, a common pathogen in orthopaedic surgical site infections. Furthermore, these patches supported the activity of human tendon-derived cells (hTDCs). Cells were able to proliferate over time and an up-regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon-related extracellular matrix proteins, namely collagen type I and tenascin C. In summary, PL patches can act as a reservoir of biomolecules derived from PL and support the activity of native tendon cells, being proposed as bioinstructive patches for tendon regeneration. Platelet-derived biomaterials hold great interest for the delivery of therapeutic factors for applications in endogenous regenerative medicine. In the particular case of tendon repair, patch augmentation strategies aiming at shifting the injury environment are explored to improve tendon regeneration. In this study, PL patches were developed with remarkable features, including the controlled release of growth factors and antibacterial efficacy. Remarkably, PL patches supported the activity of native tendon cells by up-regulating tenogenic genes and enabling the deposition of ECM proteins. This patch holds great potential towards simultaneously reducing post-implantation surgical site infections and promoting tendon regeneration for prospective in vivo applications. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Creation of a Bioengineered Skin Flap Scaffold with a Perfusable Vascular Pedicle.

PubMed

Jank, Bernhard J; Goverman, Jeremy; Guyette, Jacques P; Charest, Jon M; Randolph, Mark; Gaudette, Glenn R; Gershlak, Joshua R; Purschke, Martin; Javorsky, Emilia; Nazarian, Rosalynn M; Leonard, David A; Cetrulo, Curtis L; Austen, William G; Ott, Harald C

2017-07-01

Full-thickness skin loss is a challenging problem due to limited reconstructive options, demanding 75 million surgical procedures annually in the United States. Autologous skin grafting is the gold standard treatment, but results in donor-site morbidity and poor aesthetics. Numerous skin substitutes are available on the market to date, however, none truly functions as full-thickness skin due to lack of a vascular network. The creation of an autologous full-thickness skin analogue with a vascular pedicle would result in a paradigm shift in the management of wounds and in reconstruction of full-thickness skin defects. To create a clinically relevant foundation, we generated an acellular skin flap scaffold (SFS) with a perfusable vascular pedicle of clinically relevant size by perfusion decellularization of porcine fasciocutaneous flaps. We then analyzed the yielded SFS for mechanical properties, biocompatibility, and regenerative potential in vitro and in vivo. Furthermore, we assessed the immunological response using an in vivo model. Finally, we recellularized the vascular compartment of an SFS and reconnected it to a recipient's blood supply to test for perfusability. Perfusion decellularization removed all cellular components with preservation of native extracellular matrix composition and architecture. Biaxial testing revealed preserved mechanical properties. Immunologic response and biocompatibility assessed via implantation and compared with native xenogenic skin and commercially available dermal substitutes revealed rapid neovascularization and complete tissue integration. Composition of infiltrating immune cells showed no evidence of allorejection and resembled the inflammatory phase of wound healing. Implantation into full-thickness skin defects demonstrated good tissue integration and skin regeneration without cicatrization. We have developed a protocol for the generation of an SFS of clinically relevant size, containing a vascular pedicle, which can be utilized for perfusion decellularization and, ultimately, anastomosis to the recipient vascular system after precellularization. The observed favorable immunological response and good tissue integration indicate the substantial regenerative potential of this platform.

Fabrication and Evaluation of Electrospun, 3D-Bioplotted, and Combination of Electrospun/3D-Bioplotted Scaffolds for Tissue Engineering Applications

PubMed Central

Mellor, Liliana F.; Huebner, Pedro; Cai, Shaobo; Taylor, Michael A.; Spang, Jeffrey

2017-01-01

Electrospun scaffolds provide a dense framework of nanofibers with pore sizes and fiber diameters that closely resemble the architecture of native extracellular matrix. However, it generates limited three-dimensional structures of relevant physiological thicknesses. 3D printing allows digitally controlled fabrication of three-dimensional single/multimaterial constructs with precisely ordered fiber and pore architecture in a single build. However, this approach generally lacks the ability to achieve submicron resolution features to mimic native tissue. The goal of this study was to fabricate and evaluate 3D printed, electrospun, and combination of 3D printed/electrospun scaffolds to mimic the native architecture of heterogeneous tissue. We assessed their ability to support viability and proliferation of human adipose derived stem cells (hASC). Cells had increased proliferation and high viability over 21 days on all scaffolds. We further tested implantation of stacked-electrospun scaffold versus combined electrospun/3D scaffold on a cadaveric pig knee model and found that stacked-electrospun scaffold easily delaminated during implantation while the combined scaffold was easier to implant. Our approach combining these two commonly used scaffold fabrication technologies allows for the creation of a scaffold with more close resemblance to heterogeneous tissue architecture, holding great potential for tissue engineering and regenerative medicine applications of osteochondral tissue and other heterogeneous tissues. PMID:28536700

Construction of a human corneal stromal equivalent with non-transfected human corneal stromal cells and acellular porcine corneal stromata.

PubMed

Diao, Jin-Mei; Pang, Xin; Qiu, Yue; Miao, Ying; Yu, Miao-Miao; Fan, Ting-Jun

2015-03-01

A tissue-engineered human corneal stroma (TE-HCS) has been developed as a promising equivalent to the native corneal stroma for replacement therapy. However, there is still a crucial need to improve the current approaches to render the TE-HCS equivalent more favorable for clinical applications. At the present study, we constructed a TE-HCS by incubating non-transfected human corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS) scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 °C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS had a suitable tensile strength for transplantation, and a transparency that is comparable to native cornea. The TE-HCS had a normal histological structure which contained regularly aligned collagen fibers and differentiated HCS cells with positive expression of marker and functional proteins, mimicking a native HCS. After transplantation into rabbit models, the TE-HCS reconstructed normal corneal stroma in vivo and function well in maintaining corneal clarity and thickness, indicating that the completely biological TE-HCS could be used as a HCS equivalent. The constructed TE-HCS has promising potentials in regenerative medicine and treatment of diseases caused by corneal stromal disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

PubMed Central

Goh, Saik-Kia; Bertera, Suzanne; Olsen, Phillip; Candiello, Joe; Halfter, Willi; Uechi, Guy; Balasubramani, Manimalha; Johnson, Scott; Sicari, Brian; Kollar, Elizabeth; Badylak, Stephen F.; Banerjee, Ipsita

2013-01-01

Approximately 285 million people worldwide suffer from diabetes, with insulin supplementation as the most common treatment measure. Regenerative medicine approaches such as a bioengineered pancreas has been proposed as potential therapeutic alternatives. A bioengineered pancreas will benefit from the development of a bioscaffold that supports and enhances cellular function and tissue development. Perfusion-decellularized organs are a likely candidate for use in such scaffolds since they mimic compositional, architectural and biomechanical nature of a native organ. In this study, we investigate perfusion-decellularization of whole pancreas and the feasibility to recellularize the whole pancreas scaffold with pancreatic cell types. Our result demonstrates that perfusion-decellularization of whole pancreas effectively removes cellular and nuclear material while retaining intricate three-dimensional microarchitecture with perfusable vasculature and ductal network and crucial extracellular matrix (ECM) components. To mimic pancreatic cell composition, we recellularized the whole pancreas scaffold with acinar and beta cell lines and cultured up to 5 days. Our result shows successful cellular engraftment within the decellularized pancreas, and the resulting graft gave rise to strong up-regulation of insulin gene expression. These findings support biological utility of whole pancreas ECM as a biomaterials scaffold for supporting and enhancing pancreatic cell functionality and represent a step toward bioengineered pancreas using regenerative medicine approaches. PMID:23787110

Putting out the fire: what terminates calcium-induced calcium release in cardiac muscle?

PubMed

Stern, Michael D; Cheng, Heping

2004-06-01

The majority of contractile calcium in cardiac muscle is released from stores in the sarcoplasmic reticulum (SR), by a process of calcium-induced calcium release (CICR) through ryanodine receptors. Because CICR is intrinsically self-reinforcing, the stability of and graded regulation of cardiac EC coupling appear paradoxical. It is now well established that this gradation results from the stochastic recruitment of varying numbers of elementary local release events, which may themselves be regenerative, and which can be directly observed as calcium sparks. Ryanodine receptors (RyRs) are clustered in dense lattices, and most calcium sparks are now believed to involve activation of multiple RyRs. This implies that local CICR is regenerative, requiring a mechanism to terminate it. It was initially assumed that this mechanism was inactivation of the RyR, but during the decade since the discovery of sparks, no sufficiently strong inactivation mechanism has been demonstrated in vitro and all empirically determined gating schemes for the RyR give unstable EC coupling in Monte Carlo simulations. We consider here possible release termination mechanisms. Stochastic attrition is the spontaneous decay of active clusters due to random channel closure; calculations show that it is much too slow unless assisted by another process. Calcium-dependent RyR inactivation involving third-party proteins remains a viable but speculative mechanism; current candidates include calmodulin and sorcin. Local depletion of SR release terminal calcium could terminate release, however calculations and measurements leave it uncertain whether a sufficient diffusion resistance exists within the SR to sustain such depletion. Depletion could be assisted by dependence of RyR activity on SR lumenal [Ca(2+)]. There is substantial evidence for such lumenal activation, but it is not clear if it is a strong enough effect to account for the robust termination of sparks. The existence of direct interactions among clustered RyRs might account for the discrepancy between the inactivation properties of isolated RyRs and intact clusters. Such coupled gating remains controversial. Determining the mechanism of release termination is the outstanding unsolved problem of cardiac EC coupling, and will probably require extensive genetic manipulation of the EC coupling apparatus in its native environment to unravel the solution.

Destructive and regenerative changes in the albino rat kidney during mercuric chloride necrotizing nephrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreev, V.P.

1985-08-01

This paper describes the results of a morphological analysis of destructive and regenerative changes observed during a study of serial semithin sections of the kidneys of albino rats with mercuric chloride necrotizing nephrosis. The results of this investigation indicate that injury to the epithelium of the urinary tubules by mercuric chloride is heterogenous in depth, and this has a substantial influence on the viability of the animals and on the subsequent process of repair of the damage.

Optical fiber sensors for life support applications

NASA Technical Reports Server (NTRS)

Lieberman, R. A.; Schmidlin, E. M.; Ferrell, D. J.; Syracuse, S. J.

1992-01-01

Preliminary experimental results on systems designed to demonstrate sensor operation in regenerative food production and crew air supply applications are presented. The systems use conventional fibers and sources in conjunction with custom wavelength division multiplexers in their optical signal processing sections and nonstandard porous optical fibers in the optical sensing elements. It is considered to be possible to create practical sensors for life-support system applications, and particularly, in regenerative food production environments, based on based on reversible sensors for oxygen, carbon monoxide, and humidity.

Inhibition of the Activin Receptor Type-2B Pathway Restores Regenerative Capacity in Satellite Cell-Depleted Skeletal Muscle.

PubMed

Formicola, Luigi; Pannérec, Alice; Correra, Rosa Maria; Gayraud-Morel, Barbara; Ollitrault, David; Besson, Vanessa; Tajbakhsh, Shahragim; Lachey, Jennifer; Seehra, Jasbir S; Marazzi, Giovanna; Sassoon, David A

2018-01-01

Degenerative myopathies typically display a decline in satellite cells coupled with a replacement of muscle fibers by fat and fibrosis. During this pathological remodeling, satellite cells are present at lower numbers and do not display a proper regenerative function. Whether a decline in satellite cells directly contributes to disease progression or is a secondary result is unknown. In order to dissect these processes, we used a genetic model to reduce the satellite cell population by ~70-80% which leads to a nearly complete loss of regenerative potential. We observe that while no overt tissue damage is observed following satellite cell depletion, muscle fibers atrophy accompanied by changes in the stem cell niche cellular composition. Treatment of these mice with an Activin receptor type-2B (AcvR2B) pathway blocker reverses muscle fiber atrophy as expected, but also restores regenerative potential of the remaining satellite cells. These findings demonstrate that in addition to controlling fiber size, the AcvR2B pathway acts to regulate the muscle stem cell niche providing a more favorable environment for muscle regeneration.

Emerging Roles for Extracellular Vesicles in Tissue Engineering and Regenerative Medicine

PubMed Central

Lamichhane, Tek N.; Sokic, Sonja; Schardt, John S.; Raiker, Rahul S.; Lin, Jennifer W.

2015-01-01

Extracellular vesicles (EVs)—comprising a heterogeneous population of cell-derived lipid vesicles including exosomes, microvesicles, and others—have recently emerged as both mediators of intercellular information transfer in numerous biological systems and vehicles for drug delivery. In both roles, EVs have immense potential to impact tissue engineering and regenerative medicine applications. For example, the therapeutic effects of several progenitor and stem cell-based therapies have been attributed primarily to EVs secreted by these cells, and EVs have been recently reported to play direct roles in injury-induced tissue regeneration processes in multiple physiological systems. In addition, EVs have been utilized for targeted drug delivery in regenerative applications and possess unique potential to be harnessed as patient-derived drug delivery vehicles for personalized medicine. This review discusses EVs in the context of tissue repair and regeneration, including their utilization as drug carriers and their crucial role in cell-based therapies. Furthermore, the article highlights the growing need for bioengineers to understand, consider, and ultimately design and specifically control the activity of EVs to maximize the efficacy of tissue engineering and regenerative therapies. PMID:24957510

NASA's Advanced Life Support Systems Human-Rated Test Facility

NASA Technical Reports Server (NTRS)

Henninger, D. L.; Tri, T. O.; Packham, N. J.

1996-01-01

Future NASA missions to explore the solar system will be long-duration missions, requiring human life support systems which must operate with very high reliability over long periods of time. Such systems must be highly regenerative, requiring minimum resupply, to enable the crews to be largely self-sufficient. These regenerative life support systems will use a combination of higher plants, microorganisms, and physicochemical processes to recycle air and water, produce food, and process wastes. A key step in the development of these systems is establishment of a human-rated test facility specifically tailored to evaluation of closed, regenerative life supports systems--one in which long-duration, large-scale testing involving human test crews can be performed. Construction of such a facility, the Advanced Life Support Program's (ALS) Human-Rated Test Facility (HRTF), has begun at NASA's Johnson Space Center, and definition of systems and development of initial outfitting concepts for the facility are underway. This paper will provide an overview of the HRTF project plan, an explanation of baseline configurations, and descriptive illustrations of facility outfitting concepts.

Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential.

PubMed

Ng, Tsz Kin; Carballosa, Carlos M; Pelaez, Daniel; Wong, Hoi Kin; Choy, Kwong Wai; Pang, Chi Pui; Cheung, Herman S

2013-03-01

Adult stem cells are critical for the healing process in regenerative medicine. However, cigarette smoking inhibits stem cell recruitment to tissues and delays the wound-healing process. This study investigated the effect of nicotine, a major constituent in the cigarette smoke, on the regenerative potentials of human mesenchymal stem cells (MSC) and periodontal ligament-derived stem cells (PDLSC). The cell proliferation of 1.0 μM nicotine-treated MSC and PDLSC was significantly reduced when compared to the untreated control. Moreover, nicotine also retarded the locomotion of these adult stem cells. Furthermore, their osteogenic differentiation capabilities were reduced in the presence of nicotine as evidenced by gene expression (RUNX2, ALPL, BGLAP, COL1A1, and COL1A2), calcium deposition, and alkaline phosphatase activity analyses. In addition, the microRNA (miRNA) profile of nicotine-treated PDLSC was altered; suggesting miRNAs might play an important role in the nicotine effects on stem cells. This study provided the possible mechanistic explanations on stem cell-associated healing delay in cigarette smoking.

Biomimetics of Bone Implants: The Regenerative Road.

PubMed

Brett, Elizabeth; Flacco, John; Blackshear, Charles; Longaker, Michael T; Wan, Derrick C

2017-01-01

The current strategies for healing bone defects are numerous and varied. At the core of each bone healing therapy is a biomimetic mechanism, which works to enhance bone growth. These range from porous scaffolds, bone mineral usage, collagen, and glycosaminoglycan substitutes to transplanted cell populations. Bone defects face a range of difficulty in their healing, given the composite of dense outer compact bone and blood-rich inner trabecular bone. As such, the tissue possesses a number of inherent characteristics, which may be clinically harnessed as promoters of bone healing. These include mechanical characteristics, mineral composition, native collagen content, and cellular fraction of bone. This review charts multiple biomimetic strategies to help heal bony defects in large and small osseous injury sites, with a special focus on cell transplantation.

Measurement uncertainty evaluation of cellular spheroids surface tension in compressing tests using Young-Laplace equation

NASA Astrophysics Data System (ADS)

Beatrici, Anderson; Santos Baptista, Leandra; Mauro Granjeiro, José

2018-03-01

Regenerative Medicine comprises the Biotechnology, Tissue Engineering and Biometrology for stem cell therapy. Starting from stem cells extracted from the patient, autologous implant, these cells are cultured and differentiated into other tissues, for example, articular cartilage. These cells are reorganized into microspheres (cell spheroids). Such tissue units are recombined into functional tissues constructs that can be implanted in the injured region for regeneration. It is necessary the biomechanical characterization of these constructed to determine if their properties are similar to native tissue. In this study was carried out the modeling of the calculation of uncertainty of the surface tension of cellular spheroids with the use of the Young-Laplace equation. We obtained relative uncertainties about 10%.

Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress.

PubMed

Zaborin, Alexander; Krezalek, Monika; Hyoju, Sanjiv; Defazio, Jennifer R; Setia, Namrata; Belogortseva, Natalia; Bindokas, Vytautas P; Guo, Qiti; Zaborina, Olga; Alverdy, John C

2017-02-01

Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts' microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery. This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts. Copyright © 2017 the American Physiological Society.

Chemokine Involvement in Fetal and Adult Wound Healing

PubMed Central

Balaji, Swathi; Watson, Carey L.; Ranjan, Rajeev; King, Alice; Bollyky, Paul L.; Keswani, Sundeep G.

2015-01-01

Significance: Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a roadmap to recapitulating regenerative repair in adult wounds. Reduced leukocyte infiltration, likely mediated, in part, through changes in the chemokine milieu, is a fundamental feature of fetal wound healing. Recent Advances: The contributions of chemokines to wound healing are a topic of active investigation. Recent discoveries have opened the possibility of targeting chemokines therapeutically to treat disease processes and improve healing capability, including the possibility of achieving a scarless phenotype in postnatal wounds. Critical Issues: Successful wound healing is a complex process, in which there is a significant interplay between multiple cell types, signaling molecules, growth factors, and extracellular matrix. Chemokines play a crucial role in this interplay and have been shown to have different effects in various stages of the healing process. Understanding how these chemokines are locally produced and regulated during wound healing and how the chemokine milieu differs in fetal versus postnatal wounds may help us identify ways in which we can target chemokine pathways. Future Directions: Further studies on the role of chemokines and their role in the healing process will greatly advance the potential for using these molecules as therapeutic targets. PMID:26543680

Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

PubMed Central

Sundelacruz, Sarah; Kaplan, David L.

2009-01-01

In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System

PubMed Central

Fraser, John K.; Hicok, Kevin C.; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M.

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing. PMID:24761343

Investigation of bypass fluid flow in an active magnetic regenerative liquefier

DOE PAGES

Holladay, Jamelyn; Teyber, Reed; Meinhardt, Kerry; ...

2018-05-19

Active magnetic regenerators (AMR) with second order magnetocaloric materials operating below the Curie temperature have a unique property where the magnetized specific heat is lower than the demagnetized specific heat. The associated thermal mass imbalance allows a fraction of heat transfer fluid in the cold heat exchanger to bypass the magnetized regenerator. This cold bypassed fluid can precool a process stream as it returns to the hot side, thereby increasing the efficiency of liquefaction and reducing the cost of liquid cryogens. In the present work, the net cooling power of an active magnetic regenerative liquefier is investigated as a functionmore » of the bypass flow fraction. In conclusion, experiments are performed at a fixed temperature span yielding a 30% improvement in net cooling power, affirming the potential of bypass flow in active magnetic regenerative liquefiers.« less

Investigation of bypass fluid flow in an active magnetic regenerative liquefier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holladay, Jamelyn; Teyber, Reed; Meinhardt, Kerry

Active magnetic regenerators (AMR) with second order magnetocaloric materials operating below the Curie temperature have a unique property where the magnetized specific heat is lower than the demagnetized specific heat. The associated thermal mass imbalance allows a fraction of heat transfer fluid in the cold heat exchanger to bypass the magnetized regenerator. This cold bypassed fluid can precool a process stream as it returns to the hot side, thereby increasing the efficiency of liquefaction and reducing the cost of liquid cryogens. In the present work, the net cooling power of an active magnetic regenerative liquefier is investigated as a functionmore » of the bypass flow fraction. Experiments are performed at a fixed temperature span yielding a 30% improvement in net cooling power, affirming the potential of bypass flow in active magnetic regenerative liquefiers.« less

Investigation of bypass fluid flow in an active magnetic regenerative liquefier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holladay, Jamelyn; Teyber, Reed; Meinhardt, Kerry

Active magnetic regenerators (AMR) with second order magnetocaloric materials operating below the Curie temperature have a unique property where the magnetized specific heat is lower than the demagnetized specific heat. The associated thermal mass imbalance allows a fraction of heat transfer fluid in the cold heat exchanger to bypass the magnetized regenerator. This cold bypassed fluid can precool a process stream as it returns to the hot side, thereby increasing the efficiency of liquefaction and reducing the cost of liquid cryogens. In the present work, the net cooling power of an active magnetic regenerative liquefier is investigated as a functionmore » of the bypass flow fraction. In conclusion, experiments are performed at a fixed temperature span yielding a 30% improvement in net cooling power, affirming the potential of bypass flow in active magnetic regenerative liquefiers.« less

Autologous Bone Marrow Concentrate in a Sheep Model of Osteoarthritis: New Perspectives for Cartilage and Meniscus Repair.

PubMed

Desando, Giovanna; Giavaresi, Gianluca; Cavallo, Carola; Bartolotti, Isabella; Sartoni, Federica; Nicoli Aldini, Nicolò; Martini, Lucia; Parrilli, Annapaola; Mariani, Erminia; Fini, Milena; Grigolo, Brunella

2016-06-01

Cell-based therapies are becoming a valuable tool to treat osteoarthritis (OA). This study investigated and compared the regenerative potential of bone marrow concentrate (BMC) and mesenchymal stem cells (MSC), both engineered with Hyaff(®)-11 (HA) for OA treatment in a sheep model. OA was induced via unilateral medial meniscectomy. Bone marrow was aspirated from the iliac crest, followed by concentration processes or cell isolation and expansion to obtain BMC and MSC, respectively. Treatments consisted of autologous BMC and MSC seeded onto HA. The regenerative potential of bone, cartilage, menisci, and synovia was monitored using macroscopy, histology, immunohistochemistry, and micro-computed tomography at 12 weeks post-op. Data were analyzed using the general linear model with adjusted Sidak's multiple comparison and Spearman's tests. BMC-HA treatment showed a greater repair ability in inhibiting OA progression compared to MSC-HA, leading to a reduction of inflammation in cartilage, meniscus, and synovium. Indeed, the decrease of inflammation positively contributed to counteract the progression of fibrotic and hypertrophic processes, known to be involved in tissue failure. Moreover, the treatment with BMC-HA showed the best results in allowing meniscus regeneration. Minor healing effects were noticed at bone level for both cell strategies; however, a downregulation of subchondral bone thickness (Cs.Th) was found in both cell treatments compared to the OA group in the femur. The transplantation of BMC-HA provided the best effects in supporting regenerative processes in cartilage, meniscus, and synovium and at less extent in bone. On the whole, both MSC and BMC combined with HA reduced inflammation and contributed to switch off fibrotic and hypertrophic processes. The observed regenerative potential by BMC-HA on meniscus could open new perspectives, suggesting its use not only for OA care but also for the treatment of meniscal lesions, even if further analyses are necessary to confirm its healing potential at long-term follow-up.

New Japanese Regulatory Frameworks for Clinical Research and Marketing Authorization of Gene Therapy and Cellular Therapy Products.

PubMed

Nagai, Sumimasa; Ozawa, Keiya

2017-01-01

In Japan, the Pharmaceuticals and Medical Devices Law was passed in 2014. In this new law, regenerative medical products were defined, and a conditional and term-limited approval system only for regenerative medical products was instituted. Therefore, regenerative medical products can be approved based on phase I and/or II trials. Gene therapy and adoptive cellular therapy are categorized as regenerative medical products. This law is intended for registration trials for marketing authorization. The Act on the Safety of Regenerative Medicine was also implemented in 2014. This act is intended for clinical research and medical practice involving processed cells other than registration trials. Under this act, a review of plans on medical treatments or clinical studies by a certified committee and submission of the plans to the Ministry of Health, Labour and Welfare (MHLW) are mandatory. The MHLW instituted the SAKIGAKE (meaning a pioneer or forerunner in Japanese) designation system in 2015. This designation is similar to the breakthrough therapy designation in the US and PRIME in the EU. In addition, the MHLW started the "Project for Enhanced Practical Application of Innovative Drugs, Medical Devices and Regenerative Medical Products" to promote personnel exchange and cooperation in writing of guidelines on the evaluation of innovative medical products between the Pharmaceuticals and Medical Devices Agency and academia. Some new guidelines regarding gene and cellular therapy were published. In this review, we comprehensively described these complicated regulations and problems to be solved in order to facilitate global readers' understanding of Japanese regulatory frameworks. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Engineering a collagen matrix that replicates the biological properties of native extracellular matrix.

PubMed

Nam, Kwangwoo; Sakai, Yuuki; Funamoto, Seiichi; Kimura, Tsuyoshi; Kishida, Akio

2011-01-01

In this study, we aimed to replicate the function of native tissues that can be used in tissue engineering and regenerative medicine. The key to such replication is the preparation of an artificial collagen matrix that possesses a structure resembling that of the extracellular matrix. We, therefore, prepared a collagen matrix by fibrillogenesis in a NaCl/Na(2)HPO(4) aqueous solution using a dialysis cassette and investigated its biological behavior in vitro and in vivo. The in vitro cell adhesion and proliferation did not show any significant differences. The degradation rate in the living body could be controlled according to the preparation condition, where the collagen matrix with high water content (F-collagen matrix, >98%) showed fast degradation and collagen matrix with lower water content (T-collagen matrix, >80%) showed no degradation for 8 weeks. The degradation did not affect the inflammatory response at all and relatively faster wound healing response was observed. Comparing this result with that of collagen gel and decellularized cornea, it can be concluded that the structural factor is very important and no cell abnormal behavior would be observed for quaternary structured collagen matrix.

Bioreactor Expansion of Skin-Derived Precursor Schwann Cells.

PubMed

Walsh, Tylor; Biernaskie, Jeff; Midha, Rajiv; Kallos, Michael S

2016-01-01

Scaling up the production of cells in a culture process is a critical step when trying to develop cell-based regenerative therapies. Static cultures often cannot be easily scaled up to clinically relevant cell numbers. Alternatively, bioreactors offer a highly valuable means to develop a clinical-ready process. To culture adherent cells in suspension, such as skin-derived precursor Schwann cells (SKP-SCs), microcarriers need to be used. Microcarriers are small spherical beads suspended within the vessel that allow for higher growth surface area to volume ratio. Here we describe the procedure of combining microcarriers with the controllability of bioreactors to generate higher cell densities in smaller reactor volumes leading to a more efficient and cost-effective cell production for applications in regenerative medicine.

An overview: recycling nutrients from crop residues for space applications.

PubMed

Strayer, R F; Atkinson, C F

1997-01-01

Without some form of regenerative life support system, long duration space habitation or travel will be limited severely by the prohibitive costs of resupplying air, water, and food from Earth. Components under consideration for inclusion in a regenerative life support system are based on either physicochemical or biological processes. Physicochemical systems would use filtration and elemental phase changes to convert waste materials into usable products, while biological systems would use higher plants and bioreactors to supply crew needs. Neither a purely biological nor strictly a physicochemical approach can supply all crew needs, thus, the best each approach can offer will be combined into a hybrid regenerative life support system. Researchers at Kennedy Space Center (KSC) Advanced Life Support Breadboard Project have taken the lead on bioregenerative aspects of space life support. The major focus has been on utilization of higher plants for production of food, oxygen, and clean water. However, a key to any regenerative life support system is recycling and recovery of resources (wastes). In keeping with the emphasis at KSC on bioregenerative systems and with the focus on plants, this paper focuses on research with biologically-based options for resource recovery from inedible crop residues.

From stem to roots: Tissue engineering in endodontics

PubMed Central

Kala, M.; Banthia, Priyank; Banthia, Ruchi

2012-01-01

The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such ‘test tube teeth’ requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold. PMID:24558528

Inhibition of the Activin Receptor Type-2B Pathway Restores Regenerative Capacity in Satellite Cell-Depleted Skeletal Muscle

PubMed Central

Formicola, Luigi; Pannérec, Alice; Correra, Rosa Maria; Gayraud-Morel, Barbara; Ollitrault, David; Besson, Vanessa; Tajbakhsh, Shahragim; Lachey, Jennifer; Seehra, Jasbir S.; Marazzi, Giovanna; Sassoon, David A.

2018-01-01

Degenerative myopathies typically display a decline in satellite cells coupled with a replacement of muscle fibers by fat and fibrosis. During this pathological remodeling, satellite cells are present at lower numbers and do not display a proper regenerative function. Whether a decline in satellite cells directly contributes to disease progression or is a secondary result is unknown. In order to dissect these processes, we used a genetic model to reduce the satellite cell population by ~70–80% which leads to a nearly complete loss of regenerative potential. We observe that while no overt tissue damage is observed following satellite cell depletion, muscle fibers atrophy accompanied by changes in the stem cell niche cellular composition. Treatment of these mice with an Activin receptor type-2B (AcvR2B) pathway blocker reverses muscle fiber atrophy as expected, but also restores regenerative potential of the remaining satellite cells. These findings demonstrate that in addition to controlling fiber size, the AcvR2B pathway acts to regulate the muscle stem cell niche providing a more favorable environment for muscle regeneration. PMID:29881353

An overview: recycling nutrients from crop residues for space applications

NASA Technical Reports Server (NTRS)

Strayer, R. F.; Atkinson, C. F.

1997-01-01

Without some form of regenerative life support system, long duration space habitation or travel will be limited severely by the prohibitive costs of resupplying air, water, and food from Earth. Components under consideration for inclusion in a regenerative life support system are based on either physicochemical or biological processes. Physicochemical systems would use filtration and elemental phase changes to convert waste materials into usable products, while biological systems would use higher plants and bioreactors to supply crew needs. Neither a purely biological nor strictly a physicochemical approach can supply all crew needs, thus, the best each approach can offer will be combined into a hybrid regenerative life support system. Researchers at Kennedy Space Center (KSC) Advanced Life Support Breadboard Project have taken the lead on bioregenerative aspects of space life support. The major focus has been on utilization of higher plants for production of food, oxygen, and clean water. However, a key to any regenerative life support system is recycling and recovery of resources (wastes). In keeping with the emphasis at KSC on bioregenerative systems and with the focus on plants, this paper focuses on research with biologically-based options for resource recovery from inedible crop residues.

Tissue engineering and regenerative medicine: recent innovations and the transition to translation.

PubMed

Fisher, Matthew B; Mauck, Robert L

2013-02-01

The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent "hot topics" and transformative publications within the field. Through this process, several key themes emerged: (1) tissue engineering: grafts and materials, (2) regenerative medicine: scaffolds and factors that control endogenous tissue formation, (3) clinical trials, and (4) novel cell sources: induced pluripotent stem cells. Within these focus areas, we summarize the highly impactful articles that emerged from our objective analysis and review additional recent publications to augment and expand upon these key themes. Finally, we discuss where the TERM field may be headed and how to monitor such a broad-based and ever-expanding community.

The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

PubMed Central

Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

2009-01-01

Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

Tissue Engineering and Regenerative Medicine: Recent Innovations and the Transition to Translation

PubMed Central

Fisher, Matthew B.

2013-01-01

The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent “hot topics” and transformative publications within the field. Through this process, several key themes emerged: (1) tissue engineering: grafts and materials, (2) regenerative medicine: scaffolds and factors that control endogenous tissue formation, (3) clinical trials, and (4) novel cell sources: induced pluripotent stem cells. Within these focus areas, we summarize the highly impactful articles that emerged from our objective analysis and review additional recent publications to augment and expand upon these key themes. Finally, we discuss where the TERM field may be headed and how to monitor such a broad-based and ever-expanding community. PMID:23253031

40 CFR 63.1562 - What parts of my plant are covered by this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... regeneration of the catalyst used in the unit (i.e., the catalyst regeneration flue gas vent). (2) The process...-regenerative, cyclic, or continuous processes) that are associated with regeneration of the catalyst used in...

40 CFR 63.1562 - What parts of my plant are covered by this subpart?

Code of Federal Regulations, 2013 CFR

2013-07-01

... regeneration of the catalyst used in the unit (i.e., the catalyst regeneration flue gas vent). (2) The process...-regenerative, cyclic, or continuous processes) that are associated with regeneration of the catalyst used in...

40 CFR 63.1562 - What parts of my plant are covered by this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... regeneration of the catalyst used in the unit (i.e., the catalyst regeneration flue gas vent). (2) The process...-regenerative, cyclic, or continuous processes) that are associated with regeneration of the catalyst used in...

40 CFR 63.1562 - What parts of my plant are covered by this subpart?

Code of Federal Regulations, 2014 CFR

2014-07-01

... regeneration of the catalyst used in the unit (i.e., the catalyst regeneration flue gas vent). (2) The process...-regenerative, cyclic, or continuous processes) that are associated with regeneration of the catalyst used in...

40 CFR 63.1562 - What parts of my plant are covered by this subpart?

Code of Federal Regulations, 2010 CFR

2010-07-01

... regeneration of the catalyst used in the unit (i.e., the catalyst regeneration flue gas vent). (2) The process...-regenerative, cyclic, or continuous processes) that are associated with regeneration of the catalyst used in...

Effect of fiber orientation of collagen-based electrospun meshes on human fibroblasts for ligament tissue engineering applications.

PubMed

Full, Sean Michael; Delman, Connor; Gluck, Jessica M; Abdmaulen, Raushan; Shemin, Richard J; Heydarkhan-Hagvall, Sepideh

2015-01-01

Within the past two decades polylactic-co-glycolic acid (PLGA) has gained considerable attention as a biocompatible and biodegradable polymer that is suitable for tissue engineering and regenerative medicine. In this present study, we have investigated the potential of PLGA, collagen I (ColI), and polyurethane (PU) scaffolds for ligament tissue regeneration. Two different ratios of PLGA (50:50 and 85:15) were used to determine the effects on mechanical tensile properties and cell adhesion. The Young's modulus, tensile stress at yield, and ultimate tensile strain of PLGA(50:50)-ColI-PU scaffolds demonstrated similar tensile properties to that of ligaments found in the knee. Whereas, scaffolds composed of PLGA(85:15)-ColI-PU had lower tensile properties than that of ligaments. Furthermore, we investigated the effect of fiber orientation on mechanical properties and our results indicate that aligned fiber scaffolds demonstrate higher tensile properties than scaffolds with random fiber orientation. Also, human fibroblasts attached and proliferated with no need for additional surface modifications to the presented electrospun scaffolds in both categories. Collectively, our investigation demonstrates the effectiveness of electrospun PLGA scaffolds as a suitable candidate for regenerative medicine, capable of being manipulated and combined with other polymers to create three-dimensional microenvironments with adjustable tensile properties to mimic native tissues. © 2014 Wiley Periodicals, Inc.

Auditory detection of non-speech and speech stimuli in noise: Effects of listeners' native language background.

PubMed

Liu, Chang; Jin, Su-Hyun

2015-11-01

This study investigated whether native listeners processed speech differently from non-native listeners in a speech detection task. Detection thresholds of Mandarin Chinese and Korean vowels and non-speech sounds in noise, frequency selectivity, and the nativeness of Mandarin Chinese and Korean vowels were measured for Mandarin Chinese- and Korean-native listeners. The two groups of listeners exhibited similar non-speech sound detection and frequency selectivity; however, the Korean listeners had better detection thresholds of Korean vowels than Chinese listeners, while the Chinese listeners performed no better at Chinese vowel detection than the Korean listeners. Moreover, thresholds predicted from an auditory model highly correlated with behavioral thresholds of the two groups of listeners, suggesting that detection of speech sounds not only depended on listeners' frequency selectivity, but also might be affected by their native language experience. Listeners evaluated their native vowels with higher nativeness scores than non-native listeners. Native listeners may have advantages over non-native listeners when processing speech sounds in noise, even without the required phonetic processing; however, such native speech advantages might be offset by Chinese listeners' lower sensitivity to vowel sounds, a characteristic possibly resulting from their sparse vowel system and their greater cognitive and attentional demands for vowel processing.

Analysis of the rate of maturogenesis of a traumatized Cvek's stage 3 anterior tooth treated with platelet-rich fibrin as a regenerative tool using three-dimensional cone-beam computed tomography: an original case report.

PubMed

Solomon, Raji Viola; Faizuddin, Umrana; Guniganti, Sushma Shravani; Waghray, Shefali

2015-01-01

Regenerative endodontic procedures are biologically based procedures which deal with the regeneration of pulp-like tissue, more idealistically the pulp-dentin complex. The regeneration of this pulp-dentin complex in an infected necrotic tooth with an open apex is possible only when the canal is effectively disinfected. Though there are various procedures for treating open apex ranging from Ca(OH) 2 apexification, mineral trioxide aggregate apexification and surgical approach, regeneration of tissues has always taken superior hand over the repair of tissues. The mechanics behind the regenerative endodontic procedures is that despite the tooth being necrotic, some pulp tissue can survive apically which under favorable conditions proliferate to aid in the process of regeneration. In the past 2 decades, an increased understanding of the physiological roles of platelets in wound healing and after tissue injury has led to the idea of using platelets as therapeutic tools in the field regenerative endodontics. In the present case report with an open apex, high sterilization protocol is followed using triple antibiotic paste as intra-canal medicament, followed which platelet rich fibrin is used as the regenerative material of choice. Over an 18-month follow-up period, clinically patient is asymptomatic and radiographically there is complete regression of the periapical lesion and initiation of the root end closure.

Gradient biomaterials and their influences on cell migration

PubMed Central

Wu, Jindan; Mao, Zhengwei; Tan, Huaping; Han, Lulu; Ren, Tanchen; Gao, Changyou

2012-01-01

Cell migration participates in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. The cells specifically migrate to destiny sites induced by the gradually varying concentration (gradient) of soluble signal factors and the ligands bound with the extracellular matrix in the body during a wound healing process. Therefore, regulation of the cell migration behaviours is of paramount importance in regenerative medicine. One important way is to create a microenvironment that mimics the in vivo cellular and tissue complexity by incorporating physical, chemical and biological signal gradients into engineered biomaterials. In this review, the gradients existing in vivo and their influences on cell migration are briefly described. Recent developments in the fabrication of gradient biomaterials for controlling cellular behaviours, especially the cell migration, are summarized, highlighting the importance of the intrinsic driving mechanism for tissue regeneration and the design principle of complicated and advanced tissue regenerative materials. The potential uses of the gradient biomaterials in regenerative medicine are introduced. The current and future trends in gradient biomaterials and programmed cell migration in terms of the long-term goals of tissue regeneration are prospected. PMID:23741610

Side population cells in the human vocal fold.

PubMed

Yamashita, Masaru; Hirano, Shigeru; Kanemaru, Shin-ichi; Tsuji, Shunichiro; Suehiro, Atsushi; Ito, Juichi

2007-11-01

The regenerative processes of the vocal fold, or the existence of stem cells in the folds, are unknown. Side population (SP) cells are defined as cells that have the ability to exclude the DNA binding dye, Hoechst 33342. They are regarded as a cell population enriched with stem cells and can be isolated from non-SP cells by a fluorescence-activated cell sorter. This study was designed to determine whether SP cells exist in the human vocal fold, as a first step in elucidating the regenerative mechanisms of the vocal fold. Seven human excised larynges were used in this study. Two were used for fluorescence-activated cell sorter analysis, and 5 were subjected to immunohistochemical analysis with antibodies against an adenosine triphosphate binding cassette transporter family member, ABCG2, which is expressed in SP cells. The number of SP cells in the human vocal fold was about 0.2% of the total number of cells. ABCG2-positive cells were identified in both the epithelium and subepithelial tissue throughout the entire vocal fold. This preliminary study demonstrated the existence of SP cells in the human vocal fold. Further studies are warranted to clarify how these cells work in the vocal fold, particularly in the regenerative process.

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

Cyclosporin A reduces matrix metalloproteinases and collagen expression in dermal fibroblasts from regenerative FOXN1 deficient (nude) mice

PubMed Central

2013-01-01

Background Cyclosporin A (CsA), an immunosuppressive agent modifies the wound healing process through an influence on extracellular matrix metabolism. We have compared the effects of CsA on dermal fibroblasts from nude (FOXN1 deficient) mice, a genetic model of skin scarless healing, and from control (C57BL/6 J (B6) mice to evaluate metabolic pathways that appear to have important roles in the process of scarless healing/regeneration. Results High levels of matrix metalloproteinases (MMPs) and collagen III expression in dermal fibroblasts from nude (regenerative) mice were down-regulated by CsA treatment to the levels observed in dermal fibroblasts from B6 (non-regenerative) mice. In contrast, dermal fibroblasts from control mice respond to CsA treatment with a minor reduction of Mmps mRNA and 2.5-fold increase expression of collagen I mRNA. An in vitro migratory assay revealed that CsA treatment profoundly delayed the migratory behavior of dermal fibroblasts from both nude and control mice. Conclusion The data suggest that by alternation of the accumulation of extracellular matrix components CsA treatment stimulates the transition from a scarless to a scar healing. PMID:23547542

Activating human genes with zinc finger proteins, transcription activator-like effectors and CRISPR/Cas9 for gene therapy and regenerative medicine.

PubMed

Gersbach, Charles A; Perez-Pinera, Pablo

2014-08-01

New technologies have recently been developed to control the expression of human genes in their native genomic context by engineering synthetic transcription factors that can be targeted to any DNA sequence. The ability to precisely regulate any gene as it occurs naturally in the genome provides a means to address a variety of diseases and disorders. This approach also circumvents some of the traditional challenges of gene therapy. In this editorial, we review the technologies that have enabled targeted human gene activation, including the engineering of transcription factors based on zinc finger proteins, transcription activator-like effectors and the CRISPR/Cas9 system. Additionally, we highlight examples in which these methods have been developed for therapeutic applications and discuss challenges and opportunities.

Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration

PubMed Central

Cao, Hung; Kang, Bong Jin; Lee, Chia-An; Shung, K. Kirk; Hsiai, Tzung K.

2015-01-01

Inadequate replacement of lost ventricular myocardium from myocardial infarction leads to heart failure. Investigating the regenerative capacity of mammalian hearts represents an emerging direction for tissue engineering and cell-based therapy. Recent advances in stem cells hold promise to restore cardiac functions. However, embryonic or induced pluripotent stem cell-derived cardiomyocytes lack functional phenotypes of the native myocardium, and transplanted tissues are not fully integrated for synchronized electrical and mechanical coupling with the host. In this context, this review highlights the mechanical and electrical strategies to promote cardiomyocyte maturation and integration, and to assess the functional phenotypes of regenerating myocardium. Simultaneous micro-electrocardiogram and high-frequency ultrasound techniques will also be introduced to assess electrical and mechanical coupling for small animal models of heart regeneration. PMID:25974948

Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration

NASA Astrophysics Data System (ADS)

Wang, Dong-An; Varghese, Shyni; Sharma, Blanka; Strehin, Iossif; Fermanian, Sara; Gorham, Justin; Fairbrother, D. Howard; Cascio, Brett; Elisseeff, Jennifer H.

2007-05-01

A biologically active, high-strength tissue adhesive is needed for numerous medical applications in tissue engineering and regenerative medicine. Integration of biomaterials or implants with surrounding native tissue is crucial for both immediate functionality and long-term performance of the tissue. Here, we use the biopolymer chondroitin sulphate (CS), one of the major components of cartilage extracellular matrix, to develop a novel bioadhesive that is readily applied and acts quickly. CS was chemically functionalized with methacrylate and aldehyde groups on the polysaccharide backbone to chemically bridge biomaterials and tissue proteins via a twofold covalent link. Three-dimensional hydrogels (with and without cells) bonded to articular cartilage defects. In in vitro and in vivo functional studies this approach led to mechanical stability of the hydrogel and tissue repair in cartilage defects.

Elements of the niche for adult stem cell expansion

PubMed Central

Redondo, Patricia A; Pavlou, Marina; Loizidou, Marilena; Cheema, Umber

2017-01-01

Adult stem cells are crucial for tissue homeostasis. These cells reside within exclusive locations in tissues, termed niches, which protect adult stem cell fidelity and regulate their many functions through biophysical-, biochemical- and cellular-mediated mechanisms. There is a growing understanding of how these mechanisms and their components contribute towards maintaining stem cell quiescence, self-renewal, expansion and differentiation patterns. In vitro expansion of adult stem cells is a powerful tool for understanding stem cell biology, and for tissue engineering and regenerative medicine applications. However, it is technically challenging, since adult stem cell removal from their native microenvironment has negative repercussions on their sustainability. In this review, we overview specific elements of the biomimetic niche and how recreating such elements can help in vitro propagation of adult stem cells. PMID:28890779

Elements of the niche for adult stem cell expansion.

PubMed

Redondo, Patricia A; Pavlou, Marina; Loizidou, Marilena; Cheema, Umber

2017-01-01

Adult stem cells are crucial for tissue homeostasis. These cells reside within exclusive locations in tissues, termed niches, which protect adult stem cell fidelity and regulate their many functions through biophysical-, biochemical- and cellular-mediated mechanisms. There is a growing understanding of how these mechanisms and their components contribute towards maintaining stem cell quiescence, self-renewal, expansion and differentiation patterns. In vitro expansion of adult stem cells is a powerful tool for understanding stem cell biology, and for tissue engineering and regenerative medicine applications. However, it is technically challenging, since adult stem cell removal from their native microenvironment has negative repercussions on their sustainability. In this review, we overview specific elements of the biomimetic niche and how recreating such elements can help in vitro propagation of adult stem cells.

Biomimetic strategies for engineering composite tissues.

PubMed

Lee, Nancy; Robinson, Jennifer; Lu, Helen

2016-08-01

The formation of multiple tissue types and their integration into composite tissue units presents a frontier challenge in regenerative engineering. Tissue-tissue synchrony is crucial in providing structural support for internal organs and enabling daily activities. This review highlights the state-of-the-art in composite tissue scaffold design, and explores how biomimicry can be strategically applied to avoid over-engineering the scaffold. Given the complexity of biological tissues, determining the most relevant parameters for recapitulating native structure-function relationships through strategic biomimicry will reduce the burden for clinical translation. It is anticipated that these exciting efforts in composite tissue engineering will enable integrative and functional repair of common soft tissue injuries and lay the foundation for total joint or limb regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiscale Poly-(ϵ-caprolactone) Scaffold Mimicking Nonlinearity in Tendon Tissue Mechanics

PubMed Central

Banik, Brittany L.; Lewis, Gregory S.; Brown, Justin L.

2016-01-01

Regenerative medicine plays a critical role in the future of medicine. However, challenges remain to balance stem cells, biomaterial scaffolds, and biochemical factors to create successful and effective scaffold designs. This project analyzes scaffold architecture with respect to mechanical capability and preliminary mesenchymal stem cell response for tendon regeneration. An electrospun fiber scaffold with tailorable properties based on a “Chinese-fingertrap” design is presented. The unique criss-crossed fiber structures demonstrate non-linear mechanical response similar to that observed in native tendon. Mechanical testing revealed that optimizing the fiber orientation resulted in the characteristic “S”-shaped curve, demonstrating a toe region and linear elastic region. This project has promising research potential across various disciplines: vascular engineering, nerve regeneration, and ligament and tendon tissue engineering. PMID:27141530

Native-language N400 and P600 predict dissociable language-learning abilities in adults

PubMed Central

Qi, Zhenghan; Beach, Sara D.; Finn, Amy S.; Minas, Jennifer; Goetz, Calvin; Chan, Brian; Gabrieli, John D.E.

2018-01-01

Language learning aptitude during adulthood varies markedly across individuals. An individual’s native-language ability has been associated with success in learning a new language as an adult. However, little is known about how native-language processing affects learning success and what neural markers of native-language processing, if any, are related to success in learning. We therefore related variation in electrophysiology during native-language processing to success in learning a novel artificial language. Event-related potentials (ERPs) were recorded while native English speakers judged the acceptability of English sentences prior to learning an artificial language. There was a trend towards a double dissociation between native-language ERPs and their relationships to novel syntax and vocabulary learning. Individuals who exhibited a greater N400 effect when processing English semantics showed better future learning of the artificial language overall. The N400 effect was related to syntax learning via its specific relationship to vocabulary learning. In contrast, the P600 effect size when processing English syntax predicted future syntax learning but not vocabulary learning. These findings show that distinct neural signatures of native-language processing relate to dissociable abilities for learning novel semantic and syntactic information. PMID:27737775

microRNA expression in the neural retina: Focus on Müller glia.

PubMed

Quintero, Heberto; Lamas, Mónica

2018-03-01

The neural retina hosts a unique specialized type of macroglial cell that not only preserves retinal homeostasis, function, and integrity but also may serve as a source of new neurons during regenerative processes: the Müller cell. Precise microRNA-driven mechanisms of gene regulation impel and direct the processes of Müller glia lineage acquisition from retinal progenitors during development, the triggering of their response to retinal degeneration and, in some cases, Müller cell reprogramming and regenerative events. In this review we survey the recent reports describing, through functional assays, the regulatory role of microRNAs in Müller cell physiology, differentiation potential, and retinal pathology. We discuss also the evidence based on expression analysis that points out the relevance of a Müller glia-specific microRNA signature that would orchestrate these processes. © 2017 Wiley Periodicals, Inc.

The early fracture hematoma and its potential role in fracture healing.

PubMed

Kolar, Paula; Schmidt-Bleek, Katharina; Schell, Hanna; Gaber, Timo; Toben, Daniel; Schmidmaier, Gerhard; Perka, Carsten; Buttgereit, Frank; Duda, Georg N

2010-08-01

Research regarding the potency and potential of the fracture hematoma has begun to receive increasing attention. However, currently there is a paucity of relevant literature on the capability and composition of the fracture hematoma. This review briefly summarizes the regenerative fracture healing process and the close interplay between the skeletal and immune systems. The role of immune cells in wound healing is also discussed to clarify their involvement in immunological processes during regeneration. We attempt to describe the current state of knowledge regarding the fracture hematoma as the initial stage of the regenerative process of fracture healing. The review discusses how a better understanding of immune reactions in the hematoma may have implications for bone tissue engineering strategies. We conclude the review by emphasizing how additional investigations of the initial phase of healing will allow us to better differentiate between deleterious and beneficial aspects of inflammation, thereby facilitating improved fracture treatment strategies.

Memory for non-native language: the role of lexical processing in the retention of surface form.

PubMed

Sampaio, Cristina; Konopka, Agnieszka E

2013-01-01

Research on memory for native language (L1) has consistently shown that retention of surface form is inferior to that of gist (e.g., Sachs, 1967). This paper investigates whether the same pattern is found in memory for non-native language (L2). We apply a model of bilingual word processing to more complex linguistic structures and predict that memory for L2 sentences ought to contain more surface information than L1 sentences. Native and non-native speakers of English were tested on a set of sentence pairs with different surface forms but the same meaning (e.g., "The bullet hit/struck the bull's eye"). Memory for these sentences was assessed with a cued recall procedure. Responses showed that native and non-native speakers did not differ in the accuracy of gist-based recall but that non-native speakers outperformed native speakers in the retention of surface form. The results suggest that L2 processing involves more intensive encoding of lexical level information than L1 processing.

When one person's mistake is another's standard usage: the effect of foreign accent on syntactic processing.

PubMed

Hanulíková, Adriana; van Alphen, Petra M; van Goch, Merel M; Weber, Andrea

2012-04-01

How do native listeners process grammatical errors that are frequent in non-native speech? We investigated whether the neural correlates of syntactic processing are modulated by speaker identity. ERPs to gender agreement errors in sentences spoken by a native speaker were compared with the same errors spoken by a non-native speaker. In line with previous research, gender violations in native speech resulted in a P600 effect (larger P600 for violations in comparison with correct sentences), but when the same violations were produced by the non-native speaker with a foreign accent, no P600 effect was observed. Control sentences with semantic violations elicited comparable N400 effects for both the native and the non-native speaker, confirming no general integration problem in foreign-accented speech. The results demonstrate that the P600 is modulated by speaker identity, extending our knowledge about the role of speaker's characteristics on neural correlates of speech processing.

Transcriptome dynamics along axolotl regenerative development are consistent with an extensive reduction in gene expression heterogeneity in dedifferentiated cells

PubMed Central

2017-01-01

Although in recent years the study of gene expression variation in the absence of genetic or environmental cues or gene expression heterogeneity has intensified considerably, many basic and applied biological fields still remain unaware of how useful the study of gene expression heterogeneity patterns might be for the characterization of biological systems and/or processes. Largely based on the modulator effect chromatin compaction has for gene expression heterogeneity and the extensive changes in chromatin compaction known to occur for specialized cells that are naturally or artificially induced to revert to less specialized states or dedifferentiate, I recently hypothesized that processes that concur with cell dedifferentiation would show an extensive reduction in gene expression heterogeneity. The confirmation of the existence of such trend could be of wide interest because of the biomedical and biotechnological relevance of cell dedifferentiation-based processes, i.e., regenerative development, cancer, human induced pluripotent stem cells, or plant somatic embryogenesis. Here, I report the first empirical evidence consistent with the existence of an extensive reduction in gene expression heterogeneity for processes that concur with cell dedifferentiation by analyzing transcriptome dynamics along forearm regenerative development in Ambystoma mexicanum or axolotl. Also, I briefly discuss on the utility of the study of gene expression heterogeneity dynamics might have for the characterization of cell dedifferentiation-based processes, and the engineering of tools that afforded better monitoring and modulating such processes. Finally, I reflect on how a transitional reduction in gene expression heterogeneity for dedifferentiated cells can promote a long-term increase in phenotypic heterogeneity following cell dedifferentiation with potential adverse effects for biomedical and biotechnological applications. PMID:29134148

Processing of Materials for Regenerative Medicine Using Supercritical Fluid Technology.

PubMed

García-González, Carlos A; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2015-07-15

The increase in the world demand of bone and cartilage replacement therapies urges the development of advanced synthetic scaffolds for regenerative purposes, not only providing mechanical support for tissue formation, but also promoting and guiding the tissue growth. Conventional manufacturing techniques have severe restrictions for designing these upgraded scaffolds, namely, regarding the use of organic solvents, shearing forces, and high operating temperatures. In this context, the use of supercritical fluid technology has emerged as an attractive solution to design solvent-free scaffolds and ingredients for scaffolds under mild processing conditions. The state-of-the-art on the technological endeavors for scaffold production using supercritical fluids is presented in this work with a critical review on the key processing parameters as well as the main advantages and limitations of each technique. A special stress is focused on the strategies suitable for the incorporation of bioactive agents (drugs, bioactive glasses, and growth factors) and the in vitro and in vivo performance of supercritical CO2-processed scaffolds.

Purity and the dangers of regenerative medicine: regulatory innovation of human tissue-engineered technology.

PubMed

Faulkner, Alex; Kent, Julie; Geesink, Ingrid; FitzPatrick, David

2006-11-01

This paper examines the development of innovation in human tissue technologies as a form of regenerative medicine, firstly by applying 'pollution ideas' to contemporary trends in its risk regulation and to the processes of regulatory policy formation, and secondly by analysing the classificatory processes deployed in regulatory policy. The analysis draws upon data from fieldwork and documentary materials with a focus on the UK and EU (2002-05) and explores four arenas: governance and regulatory policy; commercialisation and the market; 'evidentiality' manifest in evidence-based policy; and publics' and technology users' values and ethics. The analysis suggests that there is a trend toward 'purification' across these arenas, both material and socio-political. A common process of partitioning is found in stakeholders' attempts to define a clear terrain, which the field of tissue-engineered technology might occupy. We conclude that pollution ideas and partitioning processes are useful in understanding regulatory ordering and innovation in the emerging technological zone of human tissue engineering.

Entropy Generation in Regenerative Systems

NASA Technical Reports Server (NTRS)

Kittel, Peter

1995-01-01

Heat exchange to the oscillating flows in regenerative coolers generates entropy. These flows are characterized by oscillating mass flows and oscillating temperatures. Heat is transferred between the flow and heat exchangers and regenerators. In the former case, there is a steady temperature difference between the flow and the heat exchangers. In the latter case, there is no mean temperature difference. In this paper a mathematical model of the entropy generated is developed for both cases. Estimates of the entropy generated by this process are given for oscillating flows in heat exchangers and in regenerators. The practical significance of this entropy is also discussed.

Fuels from renewable resources

NASA Astrophysics Data System (ADS)

Hoffmann, L.; Schnell, C.; Gieseler, G.

Consideration is given to fuel substitution based on regenerative plants. Methanol can be produced from regenerative plants by gasification followed by the catalytic hydration of carbon oxides. Ethanol can be used as a replacement fuel in gasoline and diesel engines and its high-knock rating allows it to be mixed with lead-free gasoline. Due to the depletion of oil and gas reserves, fermentation alcohol is being considered. The raw materials for the fermentation process can potentially include: (1) sugar (such as yeasts, beet or cane sugar); (2) starch (from potatoes or grain) and (3) cellulose which can be hydrolized into glucose for fermentation.

ERP evidence for different strategies in the processing of case markers in native speakers and non-native learners

PubMed Central

Mueller, Jutta L; Hirotani, Masako; Friederici, Angela D

2007-01-01

Background The present experiments were designed to test how the linguistic feature of case is processed in Japanese by native and non-native listeners. We used a miniature version of Japanese as a model to compare sentence comprehension mechanisms in native speakers and non-native learners who had received training until they had mastered the system. In the first experiment we auditorily presented native Japanese speakers with sentences containing incorrect double nominatives and incorrect double accusatives, and with correct sentences. In the second experiment we tested trained non-natives with the same material. Based on previous research in German we expected an N400-P600 biphasic ERP response with specific modulations depending on the violated case and whether the listeners were native or non-native. Results For native Japanese participants the general ERP response to the case violations was an N400-P600 pattern. Double accusatives led to an additional enhancement of the P600 amplitude. For the learners a native-like P600 was present for double accusatives and for double nominatives. The additional negativity, however, was present in learners only for double nominative violations, and it was characterized by a different topographical distribution. Conclusion The results indicate that native listeners use case markers for thematic as well as syntactic structure building during incremental sentence interpretation. The modulation of the P600 component for double accusatives possibly reflects case specific syntactic restrictions in Japanese. For adult language learners later processes, as reflected in the P600, seem to be more native-like compared to earlier processes. The anterior distribution of the negativity and its selective emergence for canonical sentences were taken to suggest that the non-native learners resorted to a rather formal processing strategy whereby they relied to a large degree on the phonologically salient nominative case marker. PMID:17331265

Smart Dressings Based on Nanostructured Fibers Containing Natural Origin Antimicrobial, Anti-Inflammatory, and Regenerative Compounds

PubMed Central

Andreu, Vanesa; Mendoza, Gracia; Arruebo, Manuel; Irusta, Silvia

2015-01-01

A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients’ quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies). The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory properties together with nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about the beneficial or inert effects of those natural origin occurring materials, the scientific community leads towards the identification of the main active components involved and their mechanism of action during the corresponding healing, antimicrobial, or regenerative processes and in carrying out systematic and comparative controlled tests. Once those natural origin components have been identified and their efficacy validated through solid clinical trials, their combination within nanostructured dressings can open up new avenues in the fabrication of bioactive dressings with outstanding characteristics for wound care. The motivation of this work is to analyze the state of the art in the use of different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring materials as antimicrobial, anti-inflammatory and regenerative components with the aim of clarifying their potential clinical use in bioactive dressings. We conclude that, for those natural occurring materials, more clinical trials are needed to reach a sufficient level of evidence as therapeutic agents for wound healing management. PMID:28793497

Infant diet-related changes in syllable processing between 4 and 5 months: Implications for developing native language sensitivity

USDA-ARS?s Scientific Manuscript database

Since maturational processes triggering increased attunement to native language features in early infancy are sensitive to dietary factors, infant-diet related differences in brain processing of native-language speech stimuli might indicate variations in onset of this tuning process. We measured cor...

Native-language N400 and P600 predict dissociable language-learning abilities in adults.

PubMed

Qi, Zhenghan; Beach, Sara D; Finn, Amy S; Minas, Jennifer; Goetz, Calvin; Chan, Brian; Gabrieli, John D E

2017-04-01

Language learning aptitude during adulthood varies markedly across individuals. An individual's native-language ability has been associated with success in learning a new language as an adult. However, little is known about how native-language processing affects learning success and what neural markers of native-language processing, if any, are related to success in learning. We therefore related variation in electrophysiology during native-language processing to success in learning a novel artificial language. Event-related potentials (ERPs) were recorded while native English speakers judged the acceptability of English sentences prior to learning an artificial language. There was a trend towards a double dissociation between native-language ERPs and their relationships to novel syntax and vocabulary learning. Individuals who exhibited a greater N400 effect when processing English semantics showed better future learning of the artificial language overall. The N400 effect was related to syntax learning via its specific relationship to vocabulary learning. In contrast, the P600 effect size when processing English syntax predicted future syntax learning but not vocabulary learning. These findings show that distinct neural signatures of native-language processing relate to dissociable abilities for learning novel semantic and syntactic information. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stem cell research and regenerative medicine in 2014: first year of regenerative medicine in Japan.

PubMed

Okano, Hideyuki

2014-09-15

It is my great pleasure to announce that we were able to publish the Japan Issue in Stem Cells and Development, especially in this year 2014. This year, 2014, is said to be the First Year of Regenerative Medicine in Japan. This movement is likely to be based on the establishment of a new law system regarding regenerative medicine (an Act for Ensuring the Safety of Regenerative Medicine or the so-called Regenerative Medicine Law) and the partial revision of the Pharmaceutical Affairs Law (PAL). Both laws will come into effect in 2014 in this country. These new law systems are expected to have a great impact on the facilitation of R&D related to regenerative medicine and stem cell biology. In the present Japan Issue, some excellent stem cell research in this country will be introduced to celebrate the First Year of Regenerative Medicine in Japan.

Analysis of expression profiles of selected genes associated with the regenerative property and the receptivity to gene transfer during somatic embryogenesis in Triticum aestivum L.

PubMed

Delporte, Fabienne; Muhovski, Yordan; Pretova, Anna; Watillon, Bernard

2013-10-01

The physiological, biochemical and molecular mechanisms regulating the initiation of a regenerative pathway remain partially unknown. Efforts to identify the biological features that confer transformation ability, or the tendency of some cells to induce transgene silencing, would help to improve plant genetic engineering. The objective of our study was to monitor the evolution of plant cell competencies in relation to both in vitro tissue culture regeneration and the genetic transformation properties. We used a simple wheat regeneration procedure as an experimental model for studying the regenerative capacity of plant cells and their receptivity to direct gene transfer over the successive steps of the regenerative pathway. Target gene profiling studies and biochemical assays were conducted to follow some of the mechanisms triggered during the somatic-to-embryogenic transition (i.e. dedifferentiation, cell division activation, redifferentiation) and affecting the accessibility of plant cells to receive and stably express the exogenous DNA introduced by bombardment. Our results seem to indicate that the control of cell-cycle (S-phase) and host defense strategies can be crucial determinants of genetic transformation efficiency. The results from studies conducted at macro-, micro- and molecular scales are then integrated into a holistic approach that addresses the question of tissue culture and transgenesis competencies more broadly. Through this multilevel analysis we try to establish functional links between both regenerative capacity and transformation receptiveness, and thereby to provide a more global and integrated vision of both processes, at the core of defense/adaptive mechanisms and survival, between undifferentiated cell proliferation and organization.

Regenerative endodontics: A way forward.

PubMed

Diogenes, Anibal; Ruparel, Nikita B; Shiloah, Yoav; Hargreaves, Kenneth M

2016-05-01

Immature teeth are susceptible to infections due to trauma, anatomic anomalies, and caries. Traditional endodontic therapies for immature teeth, such as apexification procedures, promote resolution of the disease and prevent future infections. However, these procedures fail to promote continued root development, leaving teeth susceptible to fractures. Regenerative endodontic procedures (REPs) have evolved in the past decade, being incorporated into endodontic practice and becoming a viable treatment alternative for immature teeth. The authors have summarized the status of regenerative endodontics on the basis of the available published studies and provide insight into the different levels of clinical outcomes expected from these procedures. Substantial advances in regenerative endodontics are allowing a better understanding of a multitude of factors that govern stem cell-mediated regeneration and repair of the damaged pulp-dentin complex. REPs promote healing of apical periodontitis, continued radiographic root development, and, in certain cases, vitality responses. Despite the clinical success of these procedures, they appear to promote a guided endodontic repair process rather than a true regeneration of physiological-like tissue. Immature teeth with pulpal necrosis with otherwise poor prognosis can be treated with REPs. These procedures do not preclude the possibility of apexification procedures if attempts are unsuccessful. Therefore, REPs may be considered first treatment options for immature teeth with pulpal necrosis. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Tissue Engineering and Regenerative Medicine 2017: A Year in Review.

PubMed

Park, Kyung Min; Shin, Young Min; Kim, Kyobum; Shin, Heungsoo

2018-04-26

In 2017, a new paradigm change caused by artificial intelligence and big data analysis resulted in innovation in each field of science and technology, and also significantly influenced progress in tissue engineering and regenerative medicine (TERM). TERM has continued to make technological advances based on interdisciplinary approaches and has contributed to the overall field of biomedical technology, including cancer biology, personalized medicine, development biology, and cell-based therapeutics. While researchers are aware that there is still a long way to go until TERM reaches the ultimate goal of patient treatment through clinical translation, the rapid progress in convergence studies led by technological improvements in TERM has been encouraging. In this review, we highlighted the significant advances made in TERM in 2017 (with an overlap of 5 months in 2016). We identified major progress in TERM in a manner similar to previous reviews published in the last few years. In addition, we carefully considered all four previous reviews during the selection process and chose main themes that minimize the duplication of the topics. Therefore, we have identified three areas that have been the focus of most journal publications in the TERM community in 2017: (i) advanced biomaterials and three-dimensional (3D) cell printing, (ii) exosomes as bioactive agents for regenerative medicine, and (iii) 3D culture in regenerative medicine.

Employment of the Triple Helix concept for development of regenerative medicine applications based on human pluripotent stem cells

PubMed Central

2014-01-01

Using human pluripotent stem cells as a source to generate differentiated progenies for regenerative medicine applications has attracted substantial interest during recent years. Having the capability to produce large quantities of human cells that can replace damaged tissue due to disease or injury opens novel avenues for relieving symptoms and also potentially offers cures for many severe human diseases. Although tremendous advancements have been made, there is still much research and development left before human pluripotent stem cell derived products can be made available for cell therapy applications. In order to speed up the development processes, we argue strongly in favor of cross-disciplinary collaborative efforts which have many advantages, especially in a relatively new field such as regenerative medicine based on human pluripotent stem cells. In this review, we aim to illustrate how some of the hurdles for bringing human pluripotent stem cell derivatives from bench-to-bed can be effectively addressed through the establishment of collaborative programs involving academic institutions, biotech industries, and pharmaceutical companies. By taking advantage of the strengths from each organization, innovation and productivity can be maximized from a resource perspective and thus, the chances of successfully bringing novel regenerative medicine treatment options to patients increase. PMID:24872863

Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4.

PubMed

Chen, Chih-Chiang; Murray, Philip J; Jiang, Ting Xin; Plikus, Maksim V; Chang, Yun-Ting; Lee, Oscar K; Widelitz, Randall B; Chuong, Cheng-Ming

2014-08-01

Hair cycling is modulated by factors both intrinsic and extrinsic to hair follicles. Cycling defects lead to conditions such as aging-associated alopecia. Recently, we demonstrated that mouse skin exhibits regenerative hair waves, reflecting a coordinated regenerative behavior in follicle populations. Here, we use this model to explore the regenerative behavior of aging mouse skin. Old mice (>18 months) tracked over several months show that with progressing age, hair waves slow down, wave propagation becomes restricted, and hair cycle domains fragment into smaller domains. Transplanting aged donor mouse skin to a young host can restore donor cycling within a 3 mm range of the interface, suggesting that changes are due to extracellular factors. Therefore, hair stem cells in aged skin can be reactivated. Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen. Further, we identify follistatin as an extra-follicular modulator, which is highly expressed in late telogen and early anagen. Indeed, follistatin induces hair wave propagation and its level decreases in aging mice. We present an excitable medium model to simulate the cycling behavior in aging mice and illustrate how the interorgan macroenvironment can regulate the aging process by integrating both "activator" and "inhibitor" signals.

Adding More Fuel to the Fire: An Eye-Tracking Study of Idiom Processing by Native and Non-Native Speakers

ERIC Educational Resources Information Center

Siyanova-Chanturia, Anna; Conklin, Kathy; Schmitt, Norbert

2011-01-01

Using eye-tracking, we investigate on-line processing of idioms in a biasing story context by native and non-native speakers of English. The stimuli are idioms used figuratively ("at the end of the day"--"eventually"), literally ("at the end of the day"--"in the evening"), and novel phrases ("at the end of the war"). Native speaker results…

Decellularized Tendon Extracellular Matrix—A Valuable Approach for Tendon Reconstruction?

PubMed Central

Schulze-Tanzil, Gundula; Al-Sadi, Onays; Ertel, Wolfgang; Lohan, Anke

2012-01-01

Tendon healing is generally a time-consuming process and often leads to a functionally altered reparative tissue. Using degradable scaffolds for tendon reconstruction still remains a compromise in view of the required high mechanical strength of tendons. Regenerative approaches based on natural decellularized allo- or xenogenic tendon extracellular matrix (ECM) have recently started to attract interest. This ECM combines the advantages of its intrinsic mechanical competence with that of providing tenogenic stimuli for immigrating cells mediated, for example, by the growth factors and other mediators entrapped within the natural ECM. A major restriction for their therapeutic application is the mainly cell-associated immunogenicity of xenogenic or allogenic tissues and, in the case of allogenic tissues, also the risk of disease transmission. A survey of approaches for tendon reconstruction using cell-free tendon ECM is presented here, whereby the problems associated with the decellularization procedures, the success of various recellularization strategies, and the applicable cell types will be thoroughly discussed. Encouraging in vivo results using cell-free ECM, as, for instance, in rabbit models, have already been reported. However, in comparison to native tendon, cells remain mostly inhomogeneously distributed in the reseeded ECM and do not align. Hence, future work should focus on the optimization of tendon ECM decellularization and recolonization strategies to restore tendon functionality. PMID:24710540

Fibrinogen and fibrin based micro and nano scaffolds incorporated with drugs, proteins, cells and genes for therapeutic biomedical applications

PubMed Central

Rajangam, Thanavel; An, Seong Soo A

2013-01-01

Over the past two decades, many types of natural and synthetic polymer-based micro- and nanocarriers, with exciting properties and applications, have been developed for application in various types of tissue regeneration, including bone, cartilage, nerve, blood vessels, and skin. The development of suitable polymers scaffold designs to aid the repair of specific cell types have created diverse and important potentials in tissue restoration. Fibrinogen (Fbg)- and fibrin (Fbn)-based micro- and nanostructures can provide suitable natural matrix environments. Since these primary materials are abundantly available in blood as the main coagulation proteins, they can easily interact with damaged tissues and cells through native biochemical interactions. Fbg- and Fbn-based micro and nanostructures can also be consecutively furnished/or encapsulated and specifically delivered, with multiple growth factors, proteins, and stem cells, in structures designed to aid in specific phases of the tissue regeneration process. The present review has been carried out to demonstrate the progress made with micro and nanoscaffold applications and features a number of applications of Fbg- and Fbn-based carriers in the field of biomaterials, including the delivery of drugs, active biomolecules, cells, and genes, that have been effectively used in tissue engineering and regenerative medicine. PMID:24106425

Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration

PubMed Central

Phipps, Matthew C.; Clem, William C.; Grunda, Jessica M.; Clines, Gregory A.; Bellis, Susan L.

2012-01-01

Bone-mimetic electrospun scaffolds consisting of polycaprolactone (PCL), collagen I and nanoparticulate hydroxyapatite (HA) have previously been shown to support the adhesion, integrin-related signaling and proliferation of mesenchymal stem cells (MSCs), suggesting these matrices serve as promising degradable substrates for osteoregeneration. However, the small pore sizes in electrospun scaffolds hinder cell infiltration in vitro and tissue-ingrowth into the scaffold in vivo, limiting their clinical potential. In this study, three separate techniques were evaluated for their capability to increase the pore size of the PCL/col I/nanoHA scaffolds: limited protease digestion, decreasing the fiber packing density during electro-spinning, and inclusion of sacrificial fibers of the water-soluble polymer PEO. The PEO sacrificial fiber approach was found to be the most effective in increasing scaffold pore size. Furthermore, the use of sacrificial fibers promoted increased MSC infiltration into the scaffolds, as well as greater infiltration of endogenous cells within bone upon placement of scaffolds within calvarial organ cultures. These collective findings support the use of sacrificial PEO fibers as a means to increase the porosity of complex, bone-mimicking electrospun scaffolds, thereby enhancing tissue regenerative processes that depend upon cell infiltration, such as vascularization and replacement of the scaffold with native bone tissue. PMID:22014462

International Space Station Water Balance Operations

NASA Technical Reports Server (NTRS)

Tobias, Barry; Garr, John D., II; Erne, Meghan

2011-01-01

In November 2008, the Water Regenerative System racks were launched aboard Space Shuttle flight, STS-126 (ULF2) and installed and activated on the International Space Station (ISS). These racks, consisting of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA), completed the installation of the Regenerative (Regen) Environmental Control and Life Support Systems (ECLSS), which includes the Oxygen Generation Assembly (OGA) that was launched 2 years prior. With the onset of active water management on the US segment of the ISS, a new operational concept was required, that of water balance . In November of 2010, the Sabatier system, which converts H2 and CO2 into water and methane, was brought on line. The Regen ECLSS systems accept condensation from the atmosphere, urine from crew, and processes that fluid via various means into potable water, which is used for crew drinking, building up skip-cycle water inventory, and water for electrolysis to produce oxygen. Specification (spec) rates of crew urine output, condensate output, O2 requirements, toilet flush water, and drinking needs are well documented and used as the best guess planning rates when Regen ECLSS came online. Spec rates are useful in long term planning, however, daily or weekly rates are dependent upon a number of variables. The constantly changing rates created a new challenge for the ECLSS flight controllers, who are responsible for operating the ECLSS systems onboard ISS from Mission Control in Houston. This paper reviews the various inputs to water planning, rate changes, and dynamic events, including but not limited to: crew personnel makeup, Regen ECLSS system operability, vehicle traffic, water storage availability, and Carbon Dioxide Removal Assembly (CDRA), Sabatier, and OGA capability. Along with the inputs that change the various rates, the paper will review the different systems, their constraints, and finally the operational challenges and means by which flight controllers manage this new concept of "water balance."

Innovative regenerative medicines in the EU: a better future in evidence?

PubMed

Corbett, Mark S; Webster, Andrew; Hawkins, Robert; Woolacott, Nerys

2017-03-08

Despite a steady stream of headlines suggesting they will transform the future of healthcare, high-tech regenerative medicines have, to date, been quite inaccessible to patients, with only eight having been granted an EU marketing licence in the last 7 years. Here, we outline some of the historical reasons for this paucity of licensed innovative regenerative medicines. We discuss the challenges to be overcome to expedite the development of this complex and rapidly changing area of medicine, together with possible reasons to be more optimistic for the future. Several factors have contributed to the scarcity of cutting-edge regenerative medicines in clinical practice. These include the great expense and difficulties involved in planning how individual therapies will be developed, manufactured to commercial levels and ultimately successfully delivered to patients. Specific challenges also exist when evaluating the safety, efficacy and cost-effectiveness of these therapies. Furthermore, many treatments are used without a licence from the European Medicines Agency, under "Hospital Exemption" from the EC legislation. For products which are licensed, alternative financing approaches by healthcare providers may be needed, since many therapies will have significant up-front costs but uncertain benefits and harms in the long-term. However, increasing political interest and more flexible mechanisms for licensing and financing of therapies are now evident; these could be key to the future growth and development of regenerative medicine in clinical practice. Recent developments in regulatory processes, coupled with increasing political interest, may offer some hope for improvements to the long and often difficult routes from laboratory to marketplace for leading-edge cell or tissue therapies. Collaboration between publicly-funded researchers and the pharmaceutical industry could be key to the future development of regenerative medicine in clinical practice; such collaborations might also offer a possible antidote to the innovation crisis in the pharmaceutical industry.

Connective Tissue Fibroblast Properties Are Position-Dependent during Mouse Digit Tip Regeneration

PubMed Central

Wu, Yuanyuan; Wang, Karen; Karapetyan, Adrine; Fernando, Warnakulusuriya Akash; Simkin, Jennifer; Han, Manjong; Rugg, Elizabeth L.; Muneoka, Ken

2013-01-01

A key factor that contributes to the regenerative ability of regeneration-competent animals such as the salamander is their use of innate positional cues that guide the regeneration process. The limbs of mammals has severe regenerative limitations, however the distal most portion of the terminal phalange is regeneration competent. This regenerative ability of the adult mouse digit is level dependent: amputation through the distal half of the terminal phalanx (P3) leads to successful regeneration, whereas amputation through a more proximal location, e.g. the subterminal phalangeal element (P2), fails to regenerate. Do the connective tissue cells of the mammalian digit play a role similar to that of the salamander limb in controlling the regenerative response? To begin to address this question, we isolated and cultured cells of the connective tissue surrounding the phalangeal bones of regeneration competent (P3) and incompetent (P2) levels. Despite their close proximity and localization, these cells show very distinctive profiles when characterized in vitro and in vivo. In vitro studies comparing their proliferation and position-specific interactions reveal that cells isolated from the P3 and P2 are both capable of organizing and differentiating epithelial progenitors, but with different outcomes. The difference in interactions are further characterized with three-dimension cultures, in which P3 regenerative cells are shown to lack a contractile response that is seen in other fibroblast cultures, including the P2 cultures. In in vivo engraftment studies, the difference between these two cell lines is made more apparent. While both P2 and P3 cells participated in the regeneration of the terminal phalanx, their survival and proliferative indices were distinct, thus suggesting a key difference in their ability to interact within a regeneration permissive environment. These studies are the first to demonstrate distinct positional characteristics of connective tissue cells that are associated with their regenerative capabilities. PMID:23349966

Additive Manufacturing of Low Cost Upper Stage Propulsion Components

NASA Technical Reports Server (NTRS)

Protz, Christopher; Bowman, Randy; Cooper, Ken; Fikes, John; Taminger, Karen; Wright, Belinda

2014-01-01

NASA is currently developing Additive Manufacturing (AM) technologies and design tools aimed at reducing the costs and manufacturing time of regeneratively cooled rocket engine components. These Low Cost Upper Stage Propulsion (LCUSP) tasks are funded through NASA's Game Changing Development Program in the Space Technology Mission Directorate. The LCUSP project will develop a copper alloy additive manufacturing design process and develop and optimize the Electron Beam Freeform Fabrication (EBF3) manufacturing process to direct deposit a nickel alloy structural jacket and manifolds onto an SLM manufactured GRCop chamber and Ni-alloy nozzle. In order to develop these processes, the project will characterize both the microstructural and mechanical properties of the SLMproduced GRCop-84, and will explore and document novel design techniques specific to AM combustion devices components. These manufacturing technologies will be used to build a 25K-class regenerative chamber and nozzle (to be used with tested DMLS injectors) that will be tested individually and as a system in hot fire tests to demonstrate the applicability of the technologies. These tasks are expected to bring costs and manufacturing time down as spacecraft propulsion systems typically comprise more than 70% of the total vehicle cost and account for a significant portion of the development schedule. Additionally, high pressure/high temperature combustion chambers and nozzles must be regeneratively cooled to survive their operating environment, causing their design to be time consuming and costly to build. LCUSP presents an opportunity to develop and demonstrate a process that can infuse these technologies into industry, build competition, and drive down costs of future engines.

Adsorptive removal of organics from aqueous phase by acid-activated coal fly ash: preparation, adsorption, and Fenton regenerative valorization of "spent" adsorbent.

PubMed

Wang, Nannan; Hao, Linlin; Chen, Jiaqing; Zhao, Qiang; Xu, Han

2018-05-01

Raw coal fly ash was activated to an adsorbent by sulfuric acid impregnation. The activation condition, the adsorption capacity, and the regenerative valorization of the adsorbent were studied. The results show that the optimal preparation conditions of the adsorbent are [H 2 SO 4 ] = 1 mol L -1 , activation time = 30 min, the ratio of coal fly ash to acid = 1:20 (g:mL), calcination temperature = 100 °C. The adsorption of p-nitrophenol on the adsorbent accords with the pseudo-second-order kinetic equation and the adsorption rate constant is 0.089 g mg -1  min -1 . The adsorption on this adsorbent can be considered enough after 35 min, when the corresponding adsorption capacity is 1.07 mg g -1 (85.6% of p-nitrophenol removal). Compared with raw coal fly ash, the adsorbent has a stable adsorption performance at low pH range (pH = 1-6) and the adsorption of p-nitrophenol is an exothermic process. Ninety minutes is required for the regenerative valorization of saturated adsorbent by Fenton process. The regenerative valorization for this saturated adsorbent can reach 89% under the optimal proposed conditions (30 °C, pH = 3, [H 2 O 2 ] = 5.0 mmol L -1 , [Fe 2+ ] = 5.5 mmol L -1 ). Within 15 experimental runs, the adsorbent has a better and better stability with the increase of experimental runs. Finally, the mechanism of activating coal fly ash is proposed, being verified by the results of the SEM and BET test.

Regenerative Engineering and Bionic Limbs.

PubMed

James, Roshan; Laurencin, Cato T

2015-03-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades.

Regenerative Engineering and Bionic Limbs

PubMed Central

James, Roshan; Laurencin, Cato T.

2015-01-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades. PMID:25983525

Cytoskeletal Regulation of Dermal Regeneration

PubMed Central

Strudwick, Xanthe L.; Cowin, Allison J.

2012-01-01

Wound healing results in the repair of injured tissues however fibrosis and scar formation are, more often than not the unfortunate consequence of this process. The ability of lower order vertebrates and invertebrates to regenerate limbs and tissues has been all but lost in mammals; however, there are some instances where glimpses of mammalian regenerative capacity do exist. Here we describe the unlocked potential that exists in mammals that may help us understand the process of regeneration post-injury and highlight the potential role of the actin cytoskeleton in this process. The precise function and regulation of the cytoskeleton is critical to the success of the healing process and its manipulation may therefore facilitate regenerative healing. The gelsolin family of actin remodelling proteins in particular has been shown to have important functions in wound healing and family member Flightless I (Flii) is involved in both regeneration and repair. Understanding the interactions between different cytoskeletal proteins and their dynamic control of processes including cellular adhesion, contraction and motility may assist the development of therapeutics that will stimulate regeneration rather than repair. PMID:24710556

Researches on regenerative medicine-current state and prospect.

PubMed

Wang, Zheng-Guo; Xiao, Kai

2012-01-01

Since 1980s, the rapid development of tissue engineering and stem cell research has pushed regenerative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine. The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine. In accord with this strategy, the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD) for the research on regenerative medicine. In order to push the translation of regenerative medicine forward-from bench to bedside, a strategic alliance has been established, and it includes 27 top-level research institutes, medical institutes, colleges, universities and enterprises in the field of stem cell and regeneration medicine. Recently the journal, Science, has published a special issue-Regenerative Medicine in China, consisting of 35 papers dealing with stem cell and regeneration, tissue engineering and regeneration, trauma and regeneration and bases for tissue repair and regenerative medicine. It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years).

Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

PubMed Central

2012-01-01

Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

Additively Manufactured Low Cost Upper Stage Combustion Chamber

NASA Technical Reports Server (NTRS)

Protz, Christopher; Cooper, Ken; Ellis, David; Fikes, John; Jones, Zachary; Kim, Tony; Medina, Cory; Taminger, Karen; Willingham, Derek

2016-01-01

Over the past two years NASA's Low Cost Upper Stage Propulsion (LCUSP) project has developed Additive Manufacturing (AM) technologies and design tools aimed at reducing the costs and manufacturing time of regeneratively cooled rocket engine components. High pressure/high temperature combustion chambers and nozzles must be regeneratively cooled to survive their operating environment, causing their design fabrication to be costly and time consuming due to the number of individual steps and different processes required. Under LCUSP, AM technologies in Sintered Laser Melting (SLM) GRCop-84 and Electron Beam Freeform Fabrication (EBF3) Inconel 625 have been significantly advanced, allowing the team to successfully fabricate a 25k-class regenerative chamber. Estimates of the costs and schedule of future builds indicate cost reductions and significant schedule reductions will be enabled by this technology. Characterization of the microstructural and mechanical properties of the SLM-produced GRCop-84, EBF3 Inconel 625 and the interface layer between the two has been performed and indicates the properties will meet the design requirements. The LCUSP chamber is to be tested with a previously demonstrated SLM injector in order to advance the Technology Readiness Level (TRL) and demonstrate the capability of the application of these processes. NASA is advancing these technologies to reduce cost and schedule for future engine applications and commercial needs.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish.

PubMed

Cacialli, Pietro; Palladino, Antonio; Lucini, Carla

2018-06-01

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

Bioactive Molecule Delivery Systems for Dentin-pulp Tissue Engineering.

PubMed

Shrestha, Suja; Kishen, Anil

2017-05-01

Regenerative endodontic procedures use bioactive molecules (BMs), which are active signaling molecules that initiate and maintain cell responses and interactions. When applied in a bolus form, they may undergo rapid diffusion and denaturation resulting in failure to induce the desired effects on target cells. The controlled release of BMs from a biomaterial carrier is expected to enhance and accelerate functional tissue engineering during regenerative endodontic procedures. This narrative review presents a comprehensive review of different polymeric BM release strategies with relevance to dentin-pulp engineering. Carrier systems designed to allow the preprogrammed release of BMs in a spatial- and temporal-controlled manner would aid in mimicking the natural wound healing process while overcoming some of the challenges faced in clinical translation of regenerative endodontic procedures. Spatial- and temporal-controlled BM release systems have become an exciting option in dentin-pulp tissue engineering; nonetheless, further validation of this concept and knowledge is required for their potential clinical translation. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Resetting the epigenome for heart regeneration.

PubMed

Quaife-Ryan, Gregory A; Sim, Choon Boon; Porrello, Enzo R; Hudson, James E

2016-10-01

In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyocytes following modulation of these factors rarely reaches neonatal levels. The inefficient re-induction of proliferation in adult cardiomyocytes may be due to the epigenetic landscape, which drastically changes during cardiac development and maturation. In this review, we provide an overview of the role of epigenetic modifiers in developmental processes related to cardiac regeneration. We propose an epigenetic framework for heart regeneration whereby adult cardiomyocyte identity requires resetting to a neonatal-like state to facilitate cell cycle re-entry and regeneration following cardiac injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

Skin bioengineering: preclinical and clinical applications.

PubMed

Martínez-Santamaría, L; Guerrero-Aspizua, S; Del Río, M

2012-01-01

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

Stem cell therapy clinical research: A regulatory conundrum for academia.

PubMed

Nagpal, Anjali; Juttner, Chris; Hamilton-Bruce, Monica Anne; Rolan, Paul; Koblar, Simon A

2017-12-01

The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Artificial organs versus regenerative medicine: is it true?

PubMed

Nosé, Yukihiko; Okubo, Hisashi

2003-09-01

Individuals engaged in the fields of artificial kidney and artificial heart have often mistakenly stated that "the era of artificial organs is over; regenerative medicine is the future." Contrarily, we do not believe artificial organs and regenerative medicine are different medical technologies. As a matter of fact, artificial organs developed during the last 50 years have been used as a bridge to regeneration. The only difference between regenerative medicine and artificial organs is that artificial organs for the bridge to regeneration promote tissue regeneration in situ, instead of outside the body (for example, vascular prostheses, neuroprostheses, bladder substitutes, skin prostheses, bone prostheses, cartilage prostheses, ligament prostheses, etc.). All of these artificial organs are successful because tissue regeneration over a man-made prosthesis is established inside the patient's body (artificial organs to support regeneration). Another usage of the group of artificial organs for the bridge to regeneration is to sustain the functions of the patient's diseased organs during the regeneration process of the body's healthy tissues and/or organs. This particular group includes artificial kidney, hepatic assist, respiratory assist, and circulatory assist. Proof of regeneration of these healthy tissues and/or organs is demonstrated in the short-term recovery of end-stage organ failure patients (artificial organs for bridge to regeneration). A third group of artificial organs for the bridge to regeneration accelerates the regenerating process of the patient's healthy tissues and organs. This group includes neurostimulators, artificial blood (red cells) blood oxygenators, and plasmapheresis devices, including hemodiafiltrators. So-called "therapeutic artificial organs" fall into this category (artificial organs to accelerate regeneration). Thus, almost all of today's artificial organs are useful in the bridge to regeneration of healthy natural tissues and organs. It does not matter whether these tissues are cultivated inside or outside the patient's body. Thus, we strongly believe in the need for joint development programs between artificial organ technologies and regenerative medicine technologies. In particular, the importance of using both man-made substitute organ technologies and natural tissue-derived substitute organ technologies is stressed for improved medical care in the future.

Real-Time Processing of Gender-Marked Articles by Native and Non-Native Spanish Speakers

ERIC Educational Resources Information Center

Lew-Williams, Casey; Fernald, Anne

2010-01-01

Three experiments using online-processing measures explored whether native and non-native Spanish-speaking adults use gender-marked articles to identify referents of target nouns more rapidly, as shown previously with 3-year-old children learning Spanish as L1 (Lew-Williams & Fernald, 2007). In Experiment 1, participants viewed familiar objects…

The Processing of Subject-Object Ambiguities in Native and Near-Native Mexican Spanish

ERIC Educational Resources Information Center

Jegerski, Jill

2012-01-01

This self-paced reading study first tested the prediction that the garden path effect previously observed during the processing of subject-object ambiguities in native English would not obtain in a null subject language like Spanish. The investigation then further explored whether the effect would be evident among near-native readers of Spanish…

Tissue engineering of urinary bladder - current state of art and future perspectives.

PubMed

Adamowicz, Jan; Kowalczyk, Tomasz; Drewa, Tomasz

2013-01-01

Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary blad- der based on tissue engineering methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells. Numerous studies to develop a substitute for the native urinary bladder wall us- ing the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application. Before tissue engineering techniques could be recognize as effective and safe for patients, more research stud- ies performed on large animal models and with long follow-up are needed to carry on in the future.

Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche.

PubMed

Madl, Christopher M; Heilshorn, Sarah C

2018-06-04

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell-cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.

Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

PubMed Central

Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

2012-01-01

The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

SAM-based Cell Transfer to Photopatterned Hydrogels for Microengineering Vascular-Like Structures

PubMed Central

Sadr, Nasser; Zhu, Mojun; Osaki, Tatsuya; Kakegawa, Takahiro; Yang, Yunzhi; Moretti, Matteo; Fukuda, Junji; Khademhosseini, Ali

2011-01-01

A major challenge in tissue engineering is to reproduce the native 3D microvascular architecture fundamental for in vivo functions. Current approaches still lack a network of perfusable vessels with native 3D structural organization. Here we present a new method combining self-assembled monolayer (SAM)-based cell transfer and gelatin methacrylate hydrogel photopatterning techniques for microengineering vascular structures. Human umbilical vein cell (HUVEC) transfer from oligopeptide SAM-coated surfaces to the hydrogel revealed two SAM desorption mechanisms: photoinduced and electrochemically triggered. The former, occurs concomitantly to hydrogel photocrosslinking, and resulted in efficient (>97%) monolayer transfer. The latter, prompted by additional potential application, preserved cell morphology and maintained high transfer efficiency of VE-cadherin positive monolayers over longer culture periods. This approach was also applied to transfer HUVECs to 3D geometrically defined vascular-like structures in hydrogels, which were then maintained in perfusion culture for 15 days. As a step toward more complex constructs, a cell-laden hydrogel layer was photopatterned around the endothelialized channel to mimic the vascular smooth muscle structure of distal arterioles. This study shows that the coupling of the SAM-based cell transfer and hydrogel photocrosslinking could potentially open up new avenues in engineering more complex, vascularized tissue constructs for regenerative medicine and tissue engineering applications. PMID:21802723

Musical ability and non-native speech-sound processing are linked through sensitivity to pitch and spectral information.

PubMed

Kempe, Vera; Bublitz, Dennis; Brooks, Patricia J

2015-05-01

Is the observed link between musical ability and non-native speech-sound processing due to enhanced sensitivity to acoustic features underlying both musical and linguistic processing? To address this question, native English speakers (N = 118) discriminated Norwegian tonal contrasts and Norwegian vowels. Short tones differing in temporal, pitch, and spectral characteristics were used to measure sensitivity to the various acoustic features implicated in musical and speech processing. Musical ability was measured using Gordon's Advanced Measures of Musical Audiation. Results showed that sensitivity to specific acoustic features played a role in non-native speech-sound processing: Controlling for non-verbal intelligence, prior foreign language-learning experience, and sex, sensitivity to pitch and spectral information partially mediated the link between musical ability and discrimination of non-native vowels and lexical tones. The findings suggest that while sensitivity to certain acoustic features partially mediates the relationship between musical ability and non-native speech-sound processing, complex tests of musical ability also tap into other shared mechanisms. © 2014 The British Psychological Society.

Native and Non-Native Speakers' Brain Responses to Filled Indirect Object Gaps

ERIC Educational Resources Information Center

Jessen, Anna; Festman, Julia; Boxell, Oliver; Felser, Claudia

2017-01-01

We examined native and non-native English speakers' processing of indirect object "wh"-dependencies using a filled-gap paradigm while recording event-related potentials (ERPs). The non-native group was comprised of native German-speaking, proficient non-native speakers of English. Both participant groups showed evidence of linking…

“Ins” and “Outs” of mesenchymal stem cell osteogenesis in regenerative medicine

PubMed Central

Yamaguchi, Dean T

2014-01-01

Repair and regeneration of bone requires mesenchymal stem cells that by self-renewal, are able to generate a critical mass of cells with the ability to differentiate into osteoblasts that can produce bone protein matrix (osteoid) and enable its mineralization. The number of human mesenchymal stem cells (hMSCs) diminishes with age and ex vivo replication of hMSCs has limited potential. While propagating hMSCs under hypoxic conditions may maintain their ability to self-renew, the strategy of using human telomerase reverse transcriptase (hTERT) to allow for hMSCs to prolong their replicative lifespan is an attractive means of ensuring a critical mass of cells with the potential to differentiate into various mesodermal structural tissues including bone. However, this strategy must be tempered by the oncogenic potential of TERT-transformed cells, or their ability to enhance already established cancers, the unknown differentiating potential of high population doubling hMSCs and the source of hMSCs (e.g., bone marrow, adipose-derived, muscle-derived, umbilical cord blood, etc.) that may provide peculiarities to self-renewal, differentiation, and physiologic function that may differ from non-transformed native cells. Tissue engineering approaches to use hMSCs to repair bone defects utilize the growth of hMSCs on three-dimensional scaffolds that can either be a base on which hMSCs can attach and grow or as a means of sequestering growth factors to assist in the chemoattraction and differentiation of native hMSCs. The use of whole native extracellular matrix (ECM) produced by hMSCs, rather than individual ECM components, appear to be advantageous in not only being utilized as a three-dimensional attachment base but also in appropriate orientation of cells and their differentiation through the growth factors that native ECM harbor or in simulating growth factor motifs. The origin of native ECM, whether from hMSCs from young or old individuals is a critical factor in “rejuvenating” hMSCs from older individuals grown on ECM from younger individuals. PMID:24772237

In vitro characterization of MG-63 osteoblast-like cells cultured on organic-inorganic lyophilized gelatin sponges for early bone healing.

PubMed

Rodriguez, Isaac A; Saxena, Gunjan; Hixon, Katherine R; Sell, Scott A; Bowlin, Gary L

2016-08-01

The development of three-dimensional porous scaffolds with enhanced osteogenic and angiogenic potential would be beneficial for inducing early-stage bone regeneration. Previous studies have demonstrated the advantages of mineralized and nonmineralized acellular 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers. In this study, those same scaffolds were mineralized and dynamically seeded with MG-63 cells. Cell proliferation, protein/cytokine secretion, and compressive mechanical properties of scaffolds were evaluated. It was found that mineralization and the addition of growth factors increased cell proliferation compared to gelatin controls. Cells on all scaffolds responded in an appropriate bone regenerative fashion as shown through osteocalcin secretion and little to no secretion of bone resorbing markers. However, compressive mechanical properties of cellularized scaffolds were not significantly different from acellular scaffolds. The combined results of increased cellular attachment, infiltration, and bone regenerative protein/cytokine secretion on scaffolds support the need for the addition of a bone-like mineral surface. Cellularized scaffolds containing growth factors reported similar advantages and mechanical values in the range of native tissues present in the early stages of bone healing. These results suggest that the developed composite sponges exhibited cellular responses and mechanical properties appropriate for promoting early bone healing in various applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2011-2019, 2016. © 2016 Wiley Periodicals, Inc.

Regenerative Medicine Strategies for Esophageal Repair

PubMed Central

Londono, Ricardo

2015-01-01

Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

Induced Pluripotent Stem Cells from Nonhuman Primates.

PubMed

Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

2016-01-01

Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

Regenerative Rehabilitation: Applied Biophysics Meets Stem Cell Therapeutics.

PubMed

Rando, Thomas A; Ambrosio, Fabrisia

2018-03-01

The emerging field of regenerative rehabilitation integrates biological and bioengineering advances in regenerative medicine with rehabilitative sciences. Here we highlight recent stem cell-based examples of the regenerative rehabilitation paradigm to promote tissue repair and regeneration, and we discuss remaining challenges and future directions for the field. Published by Elsevier Inc.

Stylistic Change in Classroom Native Music.

ERIC Educational Resources Information Center

Johnston, Thomas F.

1981-01-01

Discusses the teaching of native music in classes for Native Americans. Highlights the ways in which changes in musical style evolve and the disparities between the teaching process and the music itself. Suggests methods for successfully uniting process and product. (MK)

Word order processing in a second language: from VO to OV.

PubMed

Erdocia, Kepa; Zawiszewski, Adam; Laka, Itziar

2014-12-01

Event-related potential studies on second language processing reveal that L1/L2 differences are due either to proficiency, age of acquisition or grammatical differences between L1 and L2 (Kotz in Brain Lang 109(2-3):68-74, 2009). However, the relative impact of these and other factors in second language processing is still not well understood. Here we present evidence from behavioral and ERP experiments on Basque sentence word order processing by L1Spanish-L2Basque early bilinguals (Age of Aquisition [Formula: see text] 3 years) with very high proficiency in their L2. Results reveal that these L2 speakers have a preference towards canonical Subject-Object-Verb word order, which they processed faster and with greater ease than non-canonical Object-Subject-Verb. This result converges with the processing preferences shown by natives and reported in Erdocia et al. (Brain Lang 109(1):1-17, 2009). However, electrophysiological measures associated to canonical (SOV) and non-canonical (OSV) sentences revealed a different pattern in the non-natives, as compared to that reported previously for natives. The non-native group elicited a P600 component that native group did not show when comparing S and O at sentence's second position. This pattern of results suggests that, despite high proficiency, non-native language processing recruits neural resources that are different from those employed in native languages.

The erythropoietin and regenerative medicine: a lesson from fish.

PubMed

Buemi, M; Lacquaniti, A; Bolignano, D; Maricchiolo, G; Favaloro, A; Buemi, A; Grasso, G; Donato, V; Giorgianni, G; Genovese, L; Coppolino, G; Sfacteria, A

2009-11-01

Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties. In this study, we aimed to test the regenerative effects of EPO administration in an experimental model of Sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin. Erythropoietin-treated fishes (3000 UI of human recombinant EPO-alpha immediately after cutting and after 15 days) showed an increased growth rate of their fins compared with those untreated (anova variance: P: 0.01 vs. P: 0.04). By analysing fin length at established times (15 and 30 days after cut), EPO-treated fishes always showed an increased length compared with untreated ones (T-15: 1.1 +/- 0.2 vs. 0.7 +/- 0.2 cm, P: 0.03; T-30: 1.9 +/- 0.3 vs. 1.2 +/- 0.2 cm, P: 0.01). Moreover, exogenous EPO administration induced an enormous increase in EPO-blood levels at each observation time (T-15: 2240 +/- 210 vs. 16.7 +/- 1.8 mU mL(-1), P < 0.001; T-30: 2340 +/- 190 vs. 17.1 +/- 1.9 mU mL(-1), P < 0.001), whereas these levels remained quite unmodified in untreated fishes. Immunochemical analyses performed by confocal laser scanning microscopic observations showed an increased expression of EPO-receptors and PECAM-1 (an endothelial surface marker of vessels sprout) in the regenerating tissue, whereas no signs of inflammation or fibrosis were recognisable. All these findings confirm EPO as a new factor involved in regenerative processes, also suggesting a potential, future utility for new therapeutical applications in the field of human regenerative medicine.

Investigation of Bio-Regenerative Life Support and Trash-To-Gas Experiment on a 4 Month Mars Simulation Mission

NASA Technical Reports Server (NTRS)

Caraccio, Anne; Poulet, Lucie; Hintze, Paul E.; Miles, John D.

2014-01-01

Future crewed missions to other planets or deep space locations will require regenerative Life Support Systems (LSS) as well as recycling processes for mission waste. Constant resupply of many commodity materials will not be a sustainable option for deep space missions, nor will storing trash on board a vehicle or at a lunar or Martian outpost. The habitable volume will decline as the volume of waste increases. A complete regenerative environmentally controlled life support system (ECLSS) on an extra-terrestrial outpost will likely include physico-chemical and biological technologies, such as bioreactors and greenhouse modules. Physico-chemical LSS do not enable food production and bio-regenerative LSS are not stable enough to be used alone in space. Mission waste that cannot be recycled into the bio-regenerative ECLSS can include excess food, food packaging, clothing, tape, urine and fecal waste. This waste will be sent to a system for converting the trash into the high value products. Two crew members on a 120 day Mars analog simulation, in collaboration with Kennedy Space Centers (KSC) Trash to Gas (TtG) project investigated a semi-closed loop system that treated non-edible biomass and other logistical waste for volume reduction and conversion into useful commodities. The purposes of this study are to show the how plant growth affects the amount of resources required by the habitat and how spent plant material can be recycled. Real-time data was sent to the reactor at KSC in Florida for replicating the analog mission waste for laboratory operation. This paper discusses the 120 day mission plant growth activity, logistical and plant waste management, power and water consumption effects of the plant and logistical waste, and potential energy conversion techniques using KSCs TtG reactor technology.

Investigation of Bio-Regenerative Life Support and Trash-to-Gas Experiment on a 4-Month Mars Simulation Mission

NASA Technical Reports Server (NTRS)

Caraccio, Anne; Poulet, Lucie; Hintze, Paul E.; Miles, John D.

2014-01-01

Future crewed missions to other planets or deep space locations will require regenerative Life Support Systems (LSS) as well as recycling processes for mission waste. Constant resupply of many commodity materials will not be a sustainable option for deep space missions, nor will stowing trash on board a vehicle or at a lunar or Martian outpost. The habitable volume will decline as the volume of waste increases. A complete regenerative environmentally controlled life support system (ECLSS) on an extra-terrestrial outpost will likely include physico-chemical and biological technologies, such as bioreactors and greenhouse modules. Physico-chemical LSS do not enable food production and bio-regenerative LSS are not stable enough to be used alone in space. Mission waste that cannot be recycled into the bio-regenerative ECLSS can include excess food, food packaging, clothing, tape, urine and fecal waste. This waste will be sent to a system for converting the trash into high value products. Two crew members on a 120 day Mars analog simulation, in collaboration with Kennedy Space Centers (KSC) Trash to Gas (TtG) project investigated a semi-closed loop system that treated non-edible biomass and other logistical waste for volume reduction and conversion into useful commodities. The purpose of this study is to show how plant growth affects the amount of resources required by the habitat and how spent plant material can be recycled. Real-time data was sent to the reactor at KSC in Florida for replicating the analog mission waste for laboratory operation. This paper discusses the 120 day mission plant growth activity, logistical and plant waste management, power and water consumption effects of the plant and logistical waste, and potential energy conversion techniques using KSCs TtG technology.

Concise Review: The U.S. Food and Drug Administration and Regenerative Medicine.

PubMed

Witten, Celia M; McFarland, Richard D; Simek, Stephanie L

2015-12-01

Regenerative medicine (RM) is a popular term for a field of scientific and medical research. There is not one universally accepted definition of RM, but it is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. RM products have the potential to provide treatments for a number of unmet needs but have substantial scientific and regulatory challenges that need to be addressed for this potential to be fully realized. FDA has established formal regulatory definitions for biologics, medical devices, and combination products, as well as human cells and tissues. Regenerative medicine products regulated by FDA are classified on the basis of these definitions, and the classification forms the basis for determining the regulatory requirements to each specific product. FDA regulations are generally written to allow the agency flexibility to accommodate new scientific questions raised by novel and evolving technologies. FDA efforts to facilitate product development in this novel and promising area include working with individual sponsors, interacting with the scientific and industry communities, participating in standards development, and developing policy and guidance. Regenerative medicine is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. This article provides an overview of the efforts of the U.S. Food and Drug Administration (FDA) to facilitate product development in the field commonly known was regenerative medicine. It provides an introduction to the processes by which FDA works with individual sponsors, interacts with the scientific and industry communities, participates in standards development, and develops formal FDA policy and guidance. ©AlphaMed Press.

Regenerative Rehabilitation: Combining Stem Cell Therapies and Activity-Dependent Stimulation.

PubMed

Moritz, Chet T; Ambrosio, Fabrisia

2017-07-01

The number of clinical trials in regenerative medicine is burgeoning, and stem cell/tissue engineering technologies hold the possibility of becoming the standard of care for a multitude of diseases and injuries. Advances in regenerative biology reveal novel molecular and cellular targets, with potential to optimize tissue healing and functional recovery, thereby refining rehabilitation clinical practice. The purpose of this review is to (1) highlight the potential for synergy between the fields of regenerative medicine and rehabilitation, a convergence of disciplines known as regenerative rehabilitation; (2) provide translational examples of regenerative rehabilitation within the context of neuromuscular injuries and diseases; and (3) offer recommendations for ways to leverage activity dependence via combined therapy and technology, with the goal of enhancing long-term recovery. The potential clinical benefits of regenerative rehabilitation will likely become a critical aspect in the standard of care for many neurological and musculoskeletal disorders.

A review of the regenerative endodontic treatment procedure

PubMed Central

Lee, Bin-Na; Moon, Jong-Wook; Chang, Hoon-Sang; Hwang, In-Nam; Oh, Won-Mann

2015-01-01

Traditionally, apexification has been used to treat immature permanent teeth that have lost pulp vitality. This technique promotes the formation of an apical barrier to close the open apex so that the filling materials can be confined to the root canal. Because tissue regeneration cannot be achieved with apexification, a new technique called regenerative endodontic treatment was presented recently to treat immature permanent teeth. Regenerative endodontic treatment is a treatment procedure designed to replace damaged pulp tissue with viable tissue which restores the normal function of the pulp-dentin structure. After regenerative endodontic treatment, continued root development and hard tissue deposition on the dentinal wall can occur under ideal circumstances. However, it is difficult to predict the result of regenerative endodontic treatment. Therefore, the purpose of this study was to summarize multiple factors effects on the result of regenerative endodontic treatment in order to achieve more predictable results. In this study, we investigated the features of regenerative endodontic treatment in comparison with those of other pulp treatment procedures and analyzed the factors that have an effect on regenerative endodontic treatment. PMID:26295020

China's landscape in regenerative medicine.

PubMed

Tang, Xin; Qin, Hua; Gu, Xiaosong; Fu, Xiaobing

2017-04-01

Regenerative medicine is a burgeoning interdisciplinary research field that can impact healthcare by offering new therapeutic strategies to replace or regenerate human cells, tissues, or organs with the ultimate goal of restoring or establishing normal human functions. The past decade has seen significant progress of regenerative medicine in China, the world's most populous developing country. With government backing, the progress in regenerative medicine is driven by increasing medical demands of people, accompanied by the economic growth, population aging, and lifestyle change in China. Although regenerative medicine encompasses many components, tissue engineering and stem cell technology are generally considered the two key players. In this review article, we outline the representative achievements in the research and application of tissue engineering, stem cell technology, and other regenerative medical strategies attained by various research groups in China, and highlight the major contributions and features of several outstanding studies made by leading Chinese researchers. Where possible, we discuss the unique opportunities and challenges for advancement of regenerative medicine in China. It is our hope that this review will stimulate new research directions for regenerative medicine in general, and encourage strategic collaborations between the east and the west in particular, so that the clinical translation of regenerative medicine can be accelerated to benefit mankind. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-Time Processing of Gender-Marked Articles by Native and Non-Native Spanish-Speaking Children and Adults

ERIC Educational Resources Information Center

Lew-Williams, Casey

2009-01-01

Six experiments explored how native and non-native Spanish speakers process article-noun sequences in real time, using eye movements as a response measure. Can listeners use gender-marked articles ("la" and "el", the feminine and masculine forms of "the") to rapidly identify familiar and novel nouns? In Experiment 1, adults who learned Spanish as…

Emerging trends and new developments in regenerative medicine: a scientometric update (2000 - 2014).

PubMed

Chen, Chaomei; Dubin, Rachael; Kim, Meen Chul

2014-09-01

Our previous scientometric review of regenerative medicine provides a snapshot of the fast-growing field up to the end of 2011. The new review identifies emerging trends and new developments appearing in the literature of regenerative medicine based on relevant articles and reviews published between 2000 and the first month of 2014. Multiple datasets of publications relevant to regenerative medicine are constructed through topic search and citation expansion to ensure adequate coverage of the field. Networks of co-cited references representing the literature of regenerative medicine are constructed and visualized based on a combined dataset of 71,393 articles published between 2000 and 2014. Structural and temporal dynamics are identified in terms of most active topical areas and cited references. New developments are identified in terms of newly emerged clusters and research areas. Disciplinary-level patterns are visualized in dual-map overlays. While research in induced pluripotent stem cells remains the most prominent area in the field of regenerative medicine, research related to clinical and therapeutic applications in regenerative medicine has experienced a considerable growth. In addition, clinical and therapeutic developments in regenerative medicine have demonstrated profound connections with the induced pluripotent stem cell research and stem cell research in general. A rapid adaptation of graphene-based nanomaterials in regenerative medicine is evident. Both basic research represented by stem cell research and application-oriented research typically found in tissue engineering are now increasingly integrated in the scientometric landscape of regenerative medicine. Tissue engineering is an interdisciplinary field in its own right. Advances in multiple disciplines such as stem cell research and graphene research have strengthened the connections between tissue engineering and regenerative medicine.

Tissue engineering: current strategies and future directions.

PubMed

Olson, Jennifer L; Atala, Anthony; Yoo, James J

2011-04-01

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future.

Electrophysiological Correlates of Second-Language Syntactic Processes Are Related to Native and Second Language Distance Regardless of Age of Acquisition

PubMed Central

Díaz, Begoña; Erdocia, Kepa; de Menezes, Robert F.; Mueller, Jutta L.; Sebastián-Gallés, Núria; Laka, Itziar

2016-01-01

In the present study, we investigate how early and late L2 learners process L2 grammatical traits that are either present or absent in their native language (L1). Thirteen early (AoA = 4 years old) and 13 late (AoA = 18 years old) Spanish learners of Basque performed a grammatical judgment task on auditory Basque sentences while their event-related brain potentials (ERPs) were recorded. The sentences contained violations of a syntactic property specific to participants' L2, i.e., ergative case, or violations of a syntactic property present in both of the participants' languages, i.e., verb agreement. Two forms of verb agreement were tested: subject agreement, found in participants' L1 and L2, and object agreement, present only in participants' L2. Behaviorally, early bilinguals were more accurate in the judgment task than late L2 learners. Early bilinguals showed native-like ERPs for verb agreement, which differed from the late learners' ERP pattern. Nonetheless, approximation to native-likeness was greater for the subject-verb agreement processing, the type of verb-agreement present in participants' L1, compared to object-verb agreement, the type of verb-agreement present only in participants' L2. For the ergative argument alignment, unique to L2, the two non-native groups showed similar ERP patterns which did not correspond to the natives' ERP pattern. We conclude that non-native syntactic processing approximates native processing for early L2 acquisition and high proficiency levels when the syntactic property is common to the L1 and L2. However, syntactic traits that are not present in the L1 do not rely on native-like processing, despite early AoA and high proficiency. PMID:26903930

The Fallacy of the Longevity Elixir: Negligible Senescence May be Achieved, but Not by Using Something Physical.

PubMed

Kyriazis, Marios; Apostolides, Andreas

2015-01-01

The process of aging is a continuum of degeneration which eventually leads to loss of function and clinically manifest disease. Yet, in the purely therapeutic sense, there is a distinct clinical and practical separation between age-related degenerative diseases and the background process of aging itself. It is quite possible that biomedical technologies will prove invaluable in treating or alleviating the impact of distinct age-related degenerative diseases such as cardiovascular disease, arthritis or dementia. However, when it comes to addressing the fundamental, background stochastic nature of aging, it is unlikely that regenerative biotechnologies will have any appreciable impact in continually counteracting the process. In this paper we discuss some essential conceptual obstacles, both functional and translational, which will prove overwhelming and which preclude the notion that aging can be eliminated by using physical therapies. Our reasoning is two-fold: 1. Disruptive regenerative biotechnologies interfere with the complex, dynamic topological architecture of the human organism, in a manner that will render them unsuitable for clinical use against all age-related degeneration. 2. Even if some regenerative biotechnological treatments are developed in the laboratory, the translational issues will be insurmountable, and the treatments will thus be practically unusable by the general public at large. Predictions about the near or mid-term development of rejuvenating biotechnologies are not sufficiently grounded, and do not provide a framework for effective practical achievement of negligible senescence. Instead, the answer must lie in more global and abstract methods which align well with evolutionary mechanisms based on techno-cultural societal necessities. These are likely to operate in a way which ultimately may downgrade the importance of human aging and make it an evolutionarily unnecessary process.

Narrative Comprehension Processes: A Study of Native and Non-Native Readers of Japanese.

ERIC Educational Resources Information Center

Horiba, Yukie

1990-01-01

Comparison of the reading strategies and resulting reading comprehension and recall of native and advanced non-native adult speakers of Japanese found that reading strategy significantly affected comprehension and recall, with non-native readers with limited language command paying more attention to vocabulary and grammar than native readers, who…

Advances in Decoding Axolotl Limb Regeneration.

PubMed

Haas, Brian J; Whited, Jessica L

2017-08-01

Humans and other mammals are limited in their natural abilities to regenerate lost body parts. By contrast, many salamanders are highly regenerative and can spontaneously replace lost limbs even as adults. Because salamander limbs are anatomically similar to human limbs, knowing how they regenerate should provide important clues for regenerative medicine. Although interest in understanding the mechanics of this process has never wavered, until recently researchers have been vexed by seemingly impenetrable logistics of working with these creatures at a molecular level. Chief among the problems has been the very large size of salamander genomes, and not a single salamander genome has been fully sequenced to date. Recently the enormous gap in sequence information has been bridged by approaches that leverage mRNA as the starting point. Together with functional experimentation, these data are rapidly enabling researchers to finally uncover the molecular mechanisms underpinning the astonishing biological process of limb regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Women finding the way: American Indian women leading intervention research in Native communities.

PubMed

Brave Heart, Maria Yellow Horse; Chase, Josephine; Elkins, Jennifer; Martin, Jennifer; Nanez, Jennifer; Mootz, Jennifer

2016-01-01

Although there is literature concentrating on cross-cultural approaches to academic and community partnerships with Native communities, few address the process and experiences of American Indian women leading federally funded and culturally grounded behavioral health intervention research in Native communities. This paper summarizes relevant literature on community-engaged research with Native communities, examines traditional roles and modern challenges for American Indian women, describes the culturally grounded collaborative process for the authors' behavioral health intervention development with Native communities, and considers emergent themes from our own research experiences navigating competing demands from mainstream and Native communities. It concludes with recommendations for supporting and enhancing resilience.

WOMEN FINDING THE WAY: AMERICAN INDIAN WOMEN LEADING INTERVENTION RESEARCH IN NATIVE COMMUNITIES

PubMed Central

Brave Heart, Maria Yellow Horse; Chase, Josephine; Elkins, Jennifer; Martin, Jennifer; Nanez, Jennifer S.; Mootz, Jennifer J.

2017-01-01

Although there is literature concentrating on cross-cultural approaches to academic and community partnerships with Native communities, few address the process and experiences of American Indian women leading federally funded and culturally grounded behavioral health intervention research in Native communities. This paper summarizes relevant literature on community-engaged research with Native communities, examines traditional roles and modern challenges for American Indian women, describes the culturally grounded collaborative process for the authors’ behavioral health intervention development with Native communities, and considers emergent themes from our own research experiences navigating competing demands from mainstream and Native communities. It concludes with recommendations for supporting and enhancing resilience. PMID:27383085

Fully relayed regenerative amplifier

DOEpatents

Glass, Alexander J.

1981-01-01

A regenerative laser apparatus and method using the optical relay concept to maintain high fill factors, to suppress diffraction effects, and to minimize phase distortions in a regenerative amplifier.

Syntactic learning by mere exposure - An ERP study in adult learners

PubMed Central

Mueller, Jutta L; Oberecker, Regine; Friederici, Angela D

2009-01-01

Background Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation. Results The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect. Conclusion The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers. PMID:19640301

Syntactic learning by mere exposure--an ERP study in adult learners.

PubMed

Mueller, Jutta L; Oberecker, Regine; Friederici, Angela D

2009-07-29

Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation. The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect. The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers.

Allogeneic transplantation of programmable cells of monocytic origin (PCMO) improves angiogenesis and tissue recovery in critical limb ischemia (CLI): a translational approach.

PubMed

Berndt, Rouven; Hummitzsch, Lars; Heß, Katharina; Albrecht, Martin; Zitta, Karina; Rusch, Rene; Sarras, Beke; Bayer, Andreas; Cremer, Jochen; Faendrich, Fred; Groß, Justus

2018-04-27

Employing growth factor-induced partial reprogramming in vitro, peripheral human blood monocytes can acquire a state of plasticity along with expression of various markers of pluripotency. These so-called programmable cells of monocytic origin (PCMO) hold great promise in regenerative therapies. The aim of this translational study was to explore and exploit the functional properties of PCMO for allogeneic cell transplantation therapy in critical limb ischemia (CLI). Using our previously described differentiation protocol, murine and human monocytes were differentiated into PCMO. We examined paracrine secretion of pro-angiogenic and tissue recovery-associated proteins under hypoxia and induction of angiogenesis by PCMO in vitro. Allogeneic cell transplantation of PCMO was performed in a hind limb ischemia mouse model in comparison to cell transplantation of native monocytes and a placebo group. Moreover, we analyzed retrospectively four healing attempts with PCMO in patients with peripheral artery disease (PAD; Rutherford classification, stage 5 and 6). Statistical analysis was performed by using one-way ANOVA, Tukey's test or the Student's t test, p < 0.05. Cell culture experiments revealed good resilience of PCMO under hypoxia, enhanced paracrine release of pro-angiogenic and tissue recovery-associated proteins and induction of angiogenesis in vitro by PCMO. Animal experiments demonstrated significantly enhanced SO 2 saturation, blood flow, neoangiogenesis and tissue recovery after treatment with PCMO compared to treatment with native monocytes and placebo. Finally, first therapeutic application of PCMO in humans demonstrated increased vascular collaterals and improved wound healing in patients with chronic CLI without exaggerated immune response, malignant processes or extended infection after 12 months. In all patients minor and/or major amputations of the lower extremity could be avoided. In summary, PCMO improve angiogenesis and tissue recovery in chronic ischemic muscle and first clinical results promise to provide an effective and safe treatment of CLI.

Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities

PubMed Central

Bukowiecki, Anne; Hos, Deniz; Cursiefen, Claus; Eming, Sabine A.

2017-01-01

The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea. PMID:28604651

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

PubMed Central

Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S.; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J.; Benowitz, Larry

2017-01-01

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn2+) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn2+ accumulation in amacrine cell processes involves the Zn2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn2+ chelation extends for several days after nerve injury. These results show that retinal Zn2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration. PMID:28049831

[Algorithm for the differential diagnosis of precancerous and regenerative changes in the cervix uteri].

PubMed

Sazonova, V Iu; Fedorova, V E; Danilova, N V

2013-01-01

Pretumoral changes in the epithelium of the cervix uteri include cervical intraepithelial neoplasia (CIN). CIN III should be differentiated with regenerative changes during epidermization of endocervicoses. Epidermization is proliferation of undifferentiated reserve cells that differentiate towards the squamous epithelium, by superseding the ectopic endocervical glandular epithelium. This process was called immature squamous metaplasia (ISM). The objective of the investigation was to define the significance of different morphological signs in the differential diagnosis of CIN III and ISM. One hundred and twelve cervical, CIN III, and immature squamous metaplasia biopsies were selected for examination. The selected cervical specimens were divided into 2 groups according to the presence or absence of p16 and CK17 expression. The p16+, CK17- cases were taken as true CIN III and the pl 6-, CK17+ as a regenerative process. The basis for this investigation is the signs included by O.K. Khmelnitsky into an algorithm for the differential diagnosis of epidermizing pseudoerosion and intraepithelial cancer of the cervix uteri. The algorithm was reconsidered to objectify. The investigation established great differences in the number of significant mitoses in the study groups. A clear trend was found for differences in the number of acanthotic strands. A new differential diagnostic algorithm for CIN III and ISM, which included the number of significant mitoses and acanthotic strands and p16 and CK17 expression, was proposed.

Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities.

PubMed

Bukowiecki, Anne; Hos, Deniz; Cursiefen, Claus; Eming, Sabine A

2017-06-12

The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

PubMed

Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J; Rosenberg, Paul A; Benowitz, Larry

2017-01-10

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn 2+ ) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn 2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn 2+ accumulation in amacrine cell processes involves the Zn 2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn 2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn 2+ chelation extends for several days after nerve injury. These results show that retinal Zn 2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn 2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

Molecular Determinants of Cephalopod Muscles and Their Implication in Muscle Regeneration

PubMed Central

Zullo, Letizia; Fossati, Sara M.; Imperadore, Pamela; Nödl, Marie-Therese

2017-01-01

The ability to regenerate whole-body structures has been studied for many decades and is of particular interest for stem cell research due to its therapeutic potential. Several vertebrate and invertebrate species have been used as model systems to study pathways involved in regeneration in the past. Among invertebrates, cephalopods are considered as highly evolved organisms, which exhibit elaborate behavioral characteristics when compared to other mollusks including active predation, extraordinary manipulation, and learning abilities. These are enabled by a complex nervous system and a number of adaptations of their body plan, which were acquired over evolutionary time. Some of these novel features show similarities to structures present in vertebrates and seem to have evolved through a convergent evolutionary process. Octopus vulgaris (the common octopus) is a representative of modern cephalopods and is characterized by a sophisticated motor and sensory system as well as highly developed cognitive capabilities. Due to its phylogenetic position and its high regenerative power the octopus has become of increasing interest for studies on regenerative processes. In this paper we provide an overview over the current knowledge of cephalopod muscle types and structures and present a possible link between these characteristics and their high regenerative potential. This may help identify conserved molecular pathways underlying regeneration in invertebrate and vertebrate animal species as well as discover new leads for targeted tissue treatments in humans. PMID:28555185

Group C. Initiator paper. Periodontal regeneration--fact or fiction?

PubMed

Bartold, P M

2015-01-01

Numerous techniques have been tried and tested to regenerate tissues lost to periodontal disease. While there has been some success to date, more work is required to move this to a reliable and clinically predictable procedure. Much of the future success for such treatments will rely largely on our understanding of the biology of both developmental and regenerative processes. Nonetheless, despite the noble goal of periodontal regeneration, the relevance of re-creation of a connective tissue attachment has been questioned. Since formation of a long junctional epithelial attachment to the tooth following a variety of periodontal treatment procedures has been shown to be no more susceptible to further breakdown than a non-diseased site, the question arises as to what purpose do we seek the ultimate outcome of periodontal regeneration? The answer lies in the "fact and fiction" of periodontal regeneration. There is no doubt that the regenerative procedures that have been developed can be shown to be biologically successful at the histological level. Furthermore, the results of periodontal regeneration (particularly guided tissue regeneration) have been stable over the long term (at least up to 10 years). However, the techniques currently under use which show the greatest promise (guided tissue regeneration and growth factors) are still clinically unpredictable because of their highly technique-sensitive nature. In addition, whether the slight clinical improvements offered by these procedures over routine open flap debridement procedures are of cost or patient benefit with regards to improved periodontal health and retention of teeth remains to be established. The next phase in regenerative technologies will undoubtedly involve a deeper understanding of the molecular signaling (both intra- and extra-cellular) and cellular differentiation processes involved in the regenerative processes. So in answer to the question of whether periodontal regeneration is fact or fiction, the answer clearly is that it is both. However, with more work it will become established fact with little fiction and the desired clinical endpoint of predictable regeneration of the periodontal tissues damaged by inflammation to their original form and function will be achieved.

Micro RNAs are involved in activation of epicardium during zebrafish heart regeneration.

PubMed

Ceci, Marcello; Carlantoni, Claudia; Missinato, Maria Azzurra; Bonvissuto, Davide; Di Giacomo, Bruna; Contu, Riccardo; Romano, Nicla

2018-01-01

Zebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in humans. The adult zebrafish is able to regenerate efficiently after resecting nearly 20% of the ventricular apex. This process requires the concert activation of the epicardium and endocardium, as well as trans-differentiation of pre-existing cardiomyocytes that together replace the lost tissue. The molecular mechanisms involved in this activation process are not completely clarified. In this work, in order to investigate if the downregulation of these miRNAs (miRs) are linked with the activation of epicardium, the expressions of miR-133a, b and miR-1 during regeneration were analysed. qPCR analyses in whole-heart, or from distinct dissected epicardial cells comparing to regenerative clot (containing cardiomyocytes, fibroblasts and endocardial cells) by a laser-micro-dissector, have indicated that already at 24 h there is a downregulation of miRs: (1) miR-133a and miR-1 in the epicardium and (2) miR-133b and miR-1 in the regenerative clot. All the miRs remain downregulated until 7 days post-surgery. With the aim to visualize the activations of heart component in combination with miRs, we developed immunohistochemistry using antibodies directed against common markers in mammals as well as zebrafish: Wilms tumour 1 (WT1), a marker of epicardium; heat-shock protein 70 (HSP70), a chaperon activated during regeneration; and the Cardiac Troponin T (cTnT), a marker of differentiated cardiomyocytes. All these markers are directly or indirectly linked to the investigated miRs. WT1 and HSP70 strongly marked the regeneration site just at 2-3 days postventricular resection. In coherence, cTnT intensively marked the regenerative portion from 7 days onwards. miRs-1 and -133 (a,b) have been strongly involved in the activation of epicardium and regenerative clot during the regeneration process in zebrafish. This study can be a useful translational model to understand the early epicardial activation in which miRs-133a and miR-1 seem to play a central role as observed in the human heart.

Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents.

PubMed

Giacomelli, Chiara; Natali, Letizia; Nisi, Marco; De Leo, Marinella; Daniele, Simona; Costa, Barbara; Graziani, Filippo; Gabriele, Mario; Braca, Alessandra; Trincavelli, M Letizia; Martini, Claudia

2018-05-11

Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs.

Early Orthodontic Tooth Movement into Regenerative Bony Defects: A Case Report.

PubMed

Tsai, Hui-Chen; Yao, Chung-Chen Jane; Wong, Man-Ying

Early orthodontic tooth movement following regenerative surgery is controversial. In this case, during protraction of the maxillary right first premolar to substitute for the long-term missing maxillary right canine, Bio-Oss and Bio-Gide were used for lateral ridge augmentation at the area of the maxillary right lateral incisor and to cover the denuded surface at the buccal side of the first premolar. Orthodontic tooth movement (OTM) commenced 2 weeks after regenerative surgery. After 8 months, new bone formation was observed on the root surface of the first premolar during implant surgery. A cone beam computed tomography scan taken 1.5 years postsurgery revealed good maintenance of regenerative bone at the same site. This satisfactory outcome of early OTM following regenerative surgery suggests biomechanical stimulation may not jeopardize the regenerative effect.

Regenerative medicine blueprint.

PubMed

Terzic, Andre; Harper, C Michel; Gores, Gregory J; Pfenning, Michael A

2013-12-01

Regenerative medicine, a paragon of future healthcare, holds unprecedented potential in extending the reach of treatment modalities for individuals across diseases and lifespan. Emerging regenerative technologies, focused on structural repair and functional restoration, signal a radical transformation in medical and surgical practice. Regenerative medicine is poised to provide innovative solutions in addressing major unmet needs for patients, ranging from congenital disease and trauma to degenerative conditions. Realization of the regenerative model of care predicates a stringent interdisciplinary paradigm that will drive validated science into standardized clinical options. Designed as a catalyst in advancing rigorous new knowledge on disease causes and cures into informed delivery of quality care, the Mayo Clinic regenerative medicine blueprint offers a patient-centered, team-based strategy that optimizes the discovery-translation-application roadmap for the express purpose of science-supported practice advancement.

Nativization Processes in L1 Esperanto.

ERIC Educational Resources Information Center

Bergen, Benjamin K.

2001-01-01

Describes characteristics of the Native Esperanto of eight speakers, ranging from age 6 to 14 years. Found bilingualism and nativization effects, differentiating native from non-native Esperanto speech. Among these effects are loss or modification of the accusative case, phonological reduction, attrition of tense/aspect system, and pronominal…

Comparison of Analytical and Numerical Performance Predictions for an International Space Station Node 3 Internal Active Thermal Control System Regenerative Heat Exchanger

NASA Technical Reports Server (NTRS)

Wise, Stephen A.; Holt, James M.

2002-01-01

The complexity of International Space Station (ISS) systems modeling often necessitates the concurrence of various dissimilar, parallel analysis techniques to validate modeling. This was the case with a feasibility and performance study of the ISS Node 3 Regenerative Heat Exchanger (RHX). A thermo-hydraulic network model was created and analyzed in SINDA/FLUINT. A less complex, closed form solution of the systems dynamics was created using an Excel Spreadsheet. The purpose of this paper is to provide a brief description of the modeling processes utilized, the results and benefits of each to the ISS Node 3 RHX study.

Comparison of Analytical and Numerical Performance Predictions for a Regenerative Heat Exchanger in the International Space Station Node 3 Internal Active Thermal Control System

NASA Technical Reports Server (NTRS)

Wise, Stephen A.; Holt, James M.; Turner, Larry D. (Technical Monitor)

2001-01-01

The complexity of International Space Station (ISS) systems modeling often necessitates the concurrence of various dissimilar, parallel analysis techniques to validate modeling. This was the case with a feasibility and performance study of the ISS Node 3 Regenerative Heat Exchanger (RHX). A thermo-hydraulic network model was created and analyzed in SINDA/FLUINT. A less complex, closed form solution of the system dynamics was created using Excel. The purpose of this paper is to provide a brief description of the modeling processes utilized, the results and benefits of each to the ISS Node 3 RHX study.

Hepatic Regeneration and Reno-Protection by Fish oil, Nigella sativa Oil and Combined Fish Oil/Nigella sativa Volatiles in CCl4 Treated Rats.

PubMed

Al-Okbi, Sahar Y; Mohamed, Doha A; Hamed, Thanaa E; Edris, Amr E; Fouda, Karem

2018-03-01

The aim of the present research was to investigate the effect of fish oil, crude Nigella sative oil and combined fish oil/Nigella sative volatile oil as hepato-regenerative and renal protective supplements. The oils were administered as emulsions to rat model with liver injury induced by CCl 4 . Plasma activities of transaminases (AST and ALT) were evaluated as liver function indicators, while plasma creatinine and urea and creatinine clearance were determined as markers of kidney function. Plasma malondialdehyde (MDA), nitrite (NO) and tumor necrosis factor-α (TNF-α) were estimated to assess the exposure to oxidative stress and subsequent inflammation. Liver fat was extracted and their fatty acids´ methyl esters were determined using gas chromatography. Results showed that plasma activities of AST and ALT were significantly higher in CCl 4 control group compared to control healthy group. Plasma levels of creatinine and urea increased significantly in CCl 4 control, while creatinine clearance was reduced significantly in the same group. All rat treated groups given the three oil emulsions showed improvement in liver function pointing to the initiation of liver regeneration. The combination of fish oil/Nigella sative volatiles showed the most promising regenerative activity. Oxidative stress and inflammation which were increased significantly in CCl 4 control group showed improvement on administration of the three different oil emulsions. Fatty acids methyl ester of liver fat revealed that rats treated with fish oil/Nigella sative volatile oil presented the highest content of unsaturated fatty acids (45.52% ± 0.81) while fish oil showed the highest saturated fatty acids (53.28% ± 1.68). Conclusion; Oral administration of oil emulsions of native fish oil, Nigella sative crude oil and combined fish oil/Nigella sative volatile oil reduced liver and kidney injury in rat model of CCl 4 through exerting anti-inflammatory and antioxidant activity. Fish oil/Nigella sative volatile oil emulsion was the most promising hepato-regenerative and reno-protective formula among the different groups.

The potential role of bioengineering and three-dimensional printing in curing global corneal blindness.

PubMed

Ludwig, Parker E; Huff, Trevor J; Zuniga, Jorge M

2018-01-01

An insufficiency of accessible allograft tissue for corneal transplantation leaves many impaired by untreated corneal disease. There is promise in the field of regenerative medicine for the development of autologous corneal tissue grafts or collagen-based scaffolds. Another approach is to create a suitable corneal implant that meets the refractive needs of the cornea and is integrated into the surrounding tissue but does not attempt to perfectly mimic the native cornea on a cellular level. Materials that have been investigated for use in the latter concept include natural polymers such as gelatin, semisynthetic polymers like gelatin methacrylate, and synthetic polymers. There are advantages and disadvantages inherent in natural and synthetic polymers: natural polymers are generally more biodegradable and biocompatible, while synthetic polymers typically provide greater control over the characteristics or property adjustment of the materials. Additive manufacturing could aid in the precision production of keratoprostheses and the personalization of implants.

Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.

PubMed

Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Ohashi, Toya; Sado, Yoshikazu; Suzuki, Hideaki; Kawamura, Tetsuya; Okabe, Masataka; Hosoya, Tatsuo; Kobayashi, Eiji

2008-06-15

Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.

Synthetic Hydrogels for Human Intestinal Organoid Generation and Colonic Wound Repair

PubMed Central

Cruz-Acuña, Ricardo; Quirós, Miguel; Farkas, Attila E.; Dedhia, Priya H.; Huang, Sha; Siuda, Dorothée; García-Hernández, Vicky; Miller, Alyssa J.; Spence, Jason R.; Nusrat, Asma; García, Andrés J.

2017-01-01

In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multi-cellular 3D structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumor-derived extracellular matrix (ECM), which severely limits use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs such that 3D structures are never embedded in tumor-derived ECM. We also demonstrate that the hydrogel serves as an injectable HIO vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury. PMID:29058719

The potential role of bioengineering and three-dimensional printing in curing global corneal blindness

PubMed Central

Ludwig, Parker E; Huff, Trevor J; Zuniga, Jorge M

2018-01-01

An insufficiency of accessible allograft tissue for corneal transplantation leaves many impaired by untreated corneal disease. There is promise in the field of regenerative medicine for the development of autologous corneal tissue grafts or collagen-based scaffolds. Another approach is to create a suitable corneal implant that meets the refractive needs of the cornea and is integrated into the surrounding tissue but does not attempt to perfectly mimic the native cornea on a cellular level. Materials that have been investigated for use in the latter concept include natural polymers such as gelatin, semisynthetic polymers like gelatin methacrylate, and synthetic polymers. There are advantages and disadvantages inherent in natural and synthetic polymers: natural polymers are generally more biodegradable and biocompatible, while synthetic polymers typically provide greater control over the characteristics or property adjustment of the materials. Additive manufacturing could aid in the precision production of keratoprostheses and the personalization of implants. PMID:29686829

Lampreys as Diverse Model Organisms in the Genomics Era.

PubMed

McCauley, David W; Docker, Margaret F; Whyard, Steve; Li, Weiming

2015-11-01

Lampreys, one of the two surviving groups of ancient vertebrates, have become important models for study in diverse fields of biology. Lampreys (of which there are approximately 40 species) are being studied, for example, (a) to control pest sea lamprey in the North American Great Lakes and to restore declining populations of native species elsewhere; (b) in biomedical research, focusing particularly on the regenerative capability of lampreys; and (c) by developmental biologists studying the evolution of key vertebrate characters. Although a lack of genetic resources has hindered research on the mechanisms regulating many aspects of lamprey life history and development, formerly intractable questions are now amenable to investigation following the recent publication of the sea lamprey genome. Here, we provide an overview of the ways in which genomic tools are currently being deployed to tackle diverse research questions and suggest several areas that may benefit from the availability of the sea lamprey genome.

Lampreys as Diverse Model Organisms in the Genomics Era

PubMed Central

McCauley, David W.; Docker, Margaret F.; Whyard, Steve; Li, Weiming

2015-01-01

Lampreys, one of the two surviving groups of ancient vertebrates, have become important models for study in diverse fields of biology. Lampreys (of which there are approximately 40 species) are being studied, for example, (a) to control pest sea lamprey in the North American Great Lakes and to restore declining populations of native species elsewhere; (b) in biomedical research, focusing particularly on the regenerative capability of lampreys; and (c) by developmental biologists studying the evolution of key vertebrate characters. Although a lack of genetic resources has hindered research on the mechanisms regulating many aspects of lamprey life history and development, formerly intractable questions are now amenable to investigation following the recent publication of the sea lamprey genome. Here, we provide an overview of the ways in which genomic tools are currently being deployed to tackle diverse research questions and suggest several areas that may benefit from the availability of the sea lamprey genome. PMID:26951616

Combinatorial biomatrix/cell-based therapies for restoration of host tissue architecture and function

PubMed Central

Cantu, David Antonio; Kao, W. John

2014-01-01

This Progress Report reviews recent advances in the utility of extracellular matrix (ECM)-mimic biomaterials in presenting and delivering therapeutic cells to promote tissue healing. This overview gives a brief introduction of different cell types being used in regenerative medicine and tissue engineering while addressing critical issues that must be overcome before cell-based approaches can be routinely employed in the clinic. A selection of 5 commonly used cell-associated, biomaterial platforms (collagen, hyaluronic acid, fibrin, alginate, and poly(ethylene glycol)) are reviewed for treatment of a number of acute injury or diseases with emphasis on animal models and clinical trials. This article concludes with current challenges and future perspectives regarding foreign body host response to biomaterials and immunological reactions to allogeneic or xenogeneic cells, vascularization and angiogenesis, matching mechanical strength and anisotropy of native tissues, as well as other non-technical issues regarding the clinical translation of biomatrix/cell-based therapies. PMID:23828863

Multicenter Cell Processing for Cardiovascular Regenerative Medicine Applications - The Cardiovascular Cell Therapy Research Network (CCTRN) Experience

PubMed Central

Gee, Adrian P.; Richman, Sara; Durett, April; McKenna, David; Traverse, Jay; Henry, Timothy; Fisk, Diann; Pepine, Carl; Bloom, Jeannette; Willerson, James; Prater, Karen; Zhao, David; Koç, Jane Reese; Ellis, Steven; Taylor, Doris; Cogle, Christopher; Moyé, Lemuel; Simari, Robert; Skarlatos, Sonia

2013-01-01

Background Aims Multi-center cellular therapy clinical trials require the establishment and implementation of standardized cell processing protocols and associated quality control mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients. Methods Standardized cell preparations, consisting of autologous bone marrow mononuclear cells, prepared using the Sepax device were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central quality control program that included product evaluation by the CCTRN biorepositories. Results Data from the first 60 procedures demonstrate that uniform products, that met all release criteria, could be manufactured at all five sites within 7 hours of receipt of the bone marrow. Uniformity was facilitated by use of the automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized quality control. Conclusions Complex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training, and quality control. PMID:20524773

Technology Of Controlled-Environment Agriculture

NASA Technical Reports Server (NTRS)

Bubenheim, David L.; Bates, Maynard E.

1995-01-01

Report discusses controlled-environment agriculture (CEA) for commercial production of organisms, whether plants or animals. Practiced in greenhouses to produce food on nonarable lands. Describes conceptual regenerative system that incorporates biological, physical, and chemical processes to support humans in extraterrestrial environments.

Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

PubMed Central

Hinderer, Svenja; Brauchle, Eva

2015-01-01

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel.

PubMed

Wang, Zheng; Zhang, Yeshun; Zhang, Jinxiang; Huang, Lei; Liu, Jia; Li, Yongkui; Zhang, Guozheng; Kundu, Subhas C; Wang, Lin

2014-11-20

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel

PubMed Central

Wang, Zheng; Zhang, Yeshun; Zhang, Jinxiang; Huang, Lei; Liu, Jia; Li, Yongkui; Zhang, Guozheng; Kundu, Subhas C.; Wang, Lin

2014-01-01

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine. PMID:25412301

Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel

NASA Astrophysics Data System (ADS)

Wang, Zheng; Zhang, Yeshun; Zhang, Jinxiang; Huang, Lei; Liu, Jia; Li, Yongkui; Zhang, Guozheng; Kundu, Subhas C.; Wang, Lin

2014-11-01

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff.

PubMed

Meyer, Gretchen A; Ward, Samuel R

2016-05-01

Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in developmental biology combined with the novel tools and strategies emerging in regenerative medicine provide new avenues to combat the vexing problem of muscle atrophy in the rotator cuff. Moving these treatment strategies forward likely will involve the combination of surgery, biologic/cellular agents, and physical interventions, as increasing experimental evidence points to the beneficial interaction between biologic therapies and physiologic stresses. Thus, the physical therapy profession is poised to play a significant role in defining the success of these combinatorial therapies. This perspective article will provide an overview of the developmental biology and regenerative medicine strategies currently under investigation to combat muscle atrophy and how they may integrate into the current and future practice of physical therapy. © 2016 American Physical Therapy Association.

Hydrogen-Oxygen PEM Regenerative Fuel Cell Development at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Bents, David J.; Scullin, Vincent J.; Chang, B. J.; Johnson, Donald W.; Garcia, Christopher P.; Jakupca, Ian J.

2006-01-01

The closed-cycle hydrogen-oxygen PEM regenerative fuel cell (RFC) at NASA Glenn Research Center has demonstrated multiple back to back contiguous cycles at rated power, and round trip efficiencies up to 52 percent. It is the first fully closed cycle regenerative fuel cell ever demonstrated (entire system is sealed: nothing enters or escapes the system other than electrical power and heat). During FY2006 the system has undergone numerous modifications and internal improvements aimed at reducing parasitic power, heat loss and noise signature, increasing its functionality as an unattended automated energy storage device, and in-service reliability. It also serves as testbed towards development of a 600 W-hr/kg flight configuration, through the successful demonstration of lightweight fuel cell and electrolyser stacks and supporting components. The RFC has demonstrated its potential as an energy storage device for aerospace solar power systems such as solar electric aircraft, lunar and planetary surface installations; any airless environment where minimum system weight is critical. Its development process continues on a path of risk reduction for the flight system NASA will eventually need for the manned lunar outpost.

Naturally Engineered Maturation of Cardiomyocytes

PubMed Central

Scuderi, Gaetano J.; Butcher, Jonathan

2017-01-01

Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration. PMID:28529939

A review of techniques for visualising soft tissue microstructure deformation and quantifying strain Ex Vivo.

PubMed

Disney, C M; Lee, P D; Hoyland, J A; Sherratt, M J; Bay, B K

2018-04-14

Many biological tissues have a complex hierarchical structure allowing them to function under demanding physiological loading conditions. Structural changes caused by ageing or disease can lead to loss of mechanical function. Therefore, it is necessary to characterise tissue structure to understand normal tissue function and the progression of disease. Ideally intact native tissues should be imaged in 3D and under physiological loading conditions. The current published in situ imaging methodologies demonstrate a compromise between imaging limitations and maintaining the samples native mechanical function. This review gives an overview of in situ imaging techniques used to visualise microstructural deformation of soft tissue, including three case studies of different tissues (tendon, intervertebral disc and artery). Some of the imaging techniques restricted analysis to observational mechanics or discrete strain measurement from invasive markers. Full-field local surface strain measurement has been achieved using digital image correlation. Volumetric strain fields have successfully been quantified from in situ X-ray microtomography (micro-CT) studies of bone using digital volume correlation but not in soft tissue due to low X-ray transmission contrast. With the latest developments in micro-CT showing in-line phase contrast capability to resolve native soft tissue microstructure, there is potential for future soft tissue mechanics research where 3D local strain can be quantified. These methods will provide information on the local 3D micromechanical environment experienced by cells in healthy, aged and diseased tissues. It is hoped that future applications of in situ imaging techniques will impact positively on the design and testing of potential tissue replacements or regenerative therapies. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Quantitative Analysis of a Hybrid Electric HMMWV for Fuel Economy Improvement

DTIC Science & Technology

2012-05-01

HMMWV of equivalent size. Hybrid vehicle powertrains show improved fuel economy gains due to optimized engine operation and regenerative braking . In... regenerative braking . Validated vehicle models as well as data collected on test tracks are used in the quantitative analysis. The regenerative braking ...hybrid electric vehicle, drive cycle, fuel economy, engine efficiency, regenerative braking . 1 Introduction The US Army (Tank Automotive

Spring Ankle with Regenerative Kinetics to Build a New Generation of Transtibial Prostheses

DTIC Science & Technology

2008-07-31

form factor that is portable to the wearer. The objective is to build a transtibial prosthesis that will support a Military amputee’s return to...active duty. 15. SUBJECT TERMS Transtibial Prosthesis , regenerative, spring, wearable robot 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...Regenerative Kinetics” to build a new generation of transtibial prostheses Keywords: Transtibial Prosthesis , regenerative, spring, wearable robot

SPE (tm) regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications

NASA Technical Reports Server (NTRS)

Mcelroy, J. F.

1990-01-01

Viewgraphs on SPE regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications are presented. Topics covered include: hydrogen-oxygen regenerative fuel cell energy storage system; electrochemical cell reactions; SPE cell voltage stability; passive water removal SPE fuel cell; fuel cell performance; SPE water electrolyzers; hydrophobic oxygen phase separator; hydrophilic/electrochemical hydrogen phase separator; and unitized regenerative fuel cell.

Dissociating Cortical Activity during Processing of Native and Non-Native Audiovisual Speech from Early to Late Infancy

PubMed Central

Fava, Eswen; Hull, Rachel; Bortfeld, Heather

2014-01-01

Initially, infants are capable of discriminating phonetic contrasts across the world’s languages. Starting between seven and ten months of age, they gradually lose this ability through a process of perceptual narrowing. Although traditionally investigated with isolated speech sounds, such narrowing occurs in a variety of perceptual domains (e.g., faces, visual speech). Thus far, tracking the developmental trajectory of this tuning process has been focused primarily on auditory speech alone, and generally using isolated sounds. But infants learn from speech produced by people talking to them, meaning they learn from a complex audiovisual signal. Here, we use near-infrared spectroscopy to measure blood concentration changes in the bilateral temporal cortices of infants in three different age groups: 3-to-6 months, 7-to-10 months, and 11-to-14-months. Critically, all three groups of infants were tested with continuous audiovisual speech in both their native and another, unfamiliar language. We found that at each age range, infants showed different patterns of cortical activity in response to the native and non-native stimuli. Infants in the youngest group showed bilateral cortical activity that was greater overall in response to non-native relative to native speech; the oldest group showed left lateralized activity in response to native relative to non-native speech. These results highlight perceptual tuning as a dynamic process that happens across modalities and at different levels of stimulus complexity. PMID:25116572

Speech-sound duration processing in a second language is specific to phonetic categories.

PubMed

Nenonen, Sari; Shestakova, Anna; Huotilainen, Minna; Näätänen, Risto

2005-01-01

The mismatch negativity (MMN) component of the auditory event-related potential was used to determine the effect of native language, Russian, on the processing of speech-sound duration in a second language, Finnish, that uses duration as a cue for phonological distinction. The native-language effect was compared with Finnish vowels that either can or cannot be categorized using the Russian phonological system. The results showed that the duration-change MMN for the Finnish sounds that could be categorized through Russian was reduced in comparison with that for the Finnish sounds having no Russian equivalent. In the Finnish sounds that can be mapped through the Russian phonological system, the facilitation of the duration processing may be inhibited by the native Russian language. However, for the sounds that have no Russian equivalent, new vowel categories independent of the native Russian language have apparently been established, enabling a native-like duration processing of Finnish.

State of the art: stem cells in equine regenerative medicine.

PubMed

Lopez, M J; Jarazo, J

2015-03-01

According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano- and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no 'one-size-fits-all' regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine. © 2014 EVJ Ltd.

Exposure to microgravity for 30 days onboard Bion M1 caused muscle atrophy and impaired regeneration in murine femoral Quadriceps

NASA Astrophysics Data System (ADS)

Radugina, E. A.; Almeida, E. A. C.; Blaber, E.; Poplinskaya, V. A.; Markitantova, Y. V.; Grigoryan, E. N.

2018-02-01

Mechanical unloading in microgravity during spaceflight is known to cause muscular atrophy, changes in muscle fiber composition, gene expression, and reduction in regenerative muscle growth. Although some limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how long-term (30-day long) mechanical unloading in microgravity affects murine muscles of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 microgravity mice, in comparison to habitat (7), and vivarium (14) ground control mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle histomorphology from microgravity specimens showed signs of extensive atrophy and regenerative hypoplasia relative to ground controls. Specifically, we observed a two-fold decrease in the number of myonuclei, compared to vivarium and ground controls, and central location of myonuclei, low density of myofibers in the tissue, and of myofibrils within a fiber, as well as fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appeared to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them, however, showed evidence of apoptotic cells and myofibril degradation, suggesting that long-term unloading in microgravity may affect late stages of myofiber differentiation. Ground asynchronous and vivarium control animals demonstrated normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Regenerative activity of satellite cells in muscles was observed both in microgravity and ground control groups, using Pax7 and Myogenin immunolocalization, as well as Myogenin expression analysis. In addition, we have detected positive nuclear immunolocalization of c-Jun and c-Myc proteins indicating their sensitivity to changes in gravitational loading in a given model. In summary, long-term spaceflight in microgravity caused significant atrophy and degeneration of the femoral Quadriceps muscle group, and it may interfere with muscle regenerative processes by inducing apoptosis in newly-formed myofibrils during their differentiation phase.

A survey of dental residents' expectations for regenerative endodontics.

PubMed

Manguno, Christine; Murray, Peter E; Howard, Cameron; Madras, Jonathan; Mangan, Stephen; Namerow, Kenneth N

2012-02-01

The objective was to survey a group of dental residents regarding their expectations for using regenerative endodontic procedures as part of future dental treatments. After institutional review board approval, the opinions of 32 dentists who were having postgraduate residency training to become specialists in a dental school were surveyed. The survey had 40 questions about professional status, ethical beliefs, judgment, and clinical practice. It was found that 83.9% of dentists had no continuing education or training in stem cells or regenerative endodontic procedures. Results showed that 96.8% of dentists are willing to receive training to be able to provide regenerative endodontic procedures for their patients. Of the total group, 49.1% of dentists already use membranes, scaffolds, or bioactive materials to provide dental treatment. It was determined that 47.3% of dentists agree that the costs of regenerative procedures should be comparable with current treatments. It was also found that 55.1% of dentists were unsure whether regenerative procedures would be successful. Dentists are supportive of using regenerative endodontic procedures in their dental practice, and they are willing to undergo extra training and to buy new technology to provide new procedures. Nevertheless, dentists also need more evidence for the effectiveness and safety of regenerative treatments before they will be recommended for most patients. Copyright © 2012. Published by Elsevier Inc.

Regenerative Rehabilitation – a New Future?

PubMed Central

Perez-Terzic, Carmen; Childers, Martin K.

2014-01-01

Modern rehabilitation medicine is propelled by newfound knowledge aimed at offering solutions for an increasingly aging population afflicted by chronic debilitating conditions. Considered a core component of future healthcare, the roll-out of regenerative medicine underscores a paradigm shift in patient management targeted at restoring physiologic function and restituting normative impact. Nascent regenerative technologies offer unprecedented prospects in achieving repair of degenerated, diseased or damaged tissues. In this context, principles of regenerative science are increasingly integrated in rehabilitation practices as illustrated in the present Supplement. Encompassing a growing multidisciplinary domain, the emergent era of “regenerative rehabilitation” brings radical innovations at the forefront of healthcare blueprints. PMID:25310603

Regenerative braking system of PM synchronous motor

NASA Astrophysics Data System (ADS)

Gao, Qian; Lv, Chengxing; Zhao, Na; Zang, Hechao; Jiang, Huilue; Zhang, Zhaowen; Zhang, Fengli

2018-04-01

Permanent-magnet synchronous motor is widely adopted in many fields with the advantage of a high efficiency and a high torque density. Regenerative Braking Systems (RBS) provide an efficient method to assist PMSM system achieve better fuel economy and lowering exhaust emissions. This paper describes the design and testing of the regenerative braking systems of PMSM. The mode of PWM duty has been adjusted to control regenerative braking of PMSM using energy controller for the port-controlled Hamiltonian model. The simulation analysis indicates that a smooth control could be realized and the highest efficiency and the smallest current ripple could be achieved by Regenerative Braking Systems.

Semantic and phonetic enhancements for speech-in-noise recognition by native and non-native listeners.

PubMed

Bradlow, Ann R; Alexander, Jennifer A

2007-04-01

Previous research has shown that speech recognition differences between native and proficient non-native listeners emerge under suboptimal conditions. Current evidence has suggested that the key deficit that underlies this disproportionate effect of unfavorable listening conditions for non-native listeners is their less effective use of compensatory information at higher levels of processing to recover from information loss at the phoneme identification level. The present study investigated whether this non-native disadvantage could be overcome if enhancements at various levels of processing were presented in combination. Native and non-native listeners were presented with English sentences in which the final word varied in predictability and which were produced in either plain or clear speech. Results showed that, relative to the low-predictability-plain-speech baseline condition, non-native listener final word recognition improved only when both semantic and acoustic enhancements were available (high-predictability-clear-speech). In contrast, the native listeners benefited from each source of enhancement separately and in combination. These results suggests that native and non-native listeners apply similar strategies for speech-in-noise perception: The crucial difference is in the signal clarity required for contextual information to be effective, rather than in an inability of non-native listeners to take advantage of this contextual information per se.

Characterization of a low frequency magnetic noise from a two-stage pulse tube cryocooler

NASA Astrophysics Data System (ADS)

Eshraghi, M. J.; Sasada, I.; Kim, J. M.; Lee, Y. H.

2009-07-01

Magnetic noise of a two-stage pulse tube cryocooler (PT) was measured by a fundamental mode orthogonal fluxgate magnetometer and by a LTS Double Relaxation Oscillation SQUID (DROS) first-order planar gradiometer. The magnetometer was installed in a dewar made of aluminum at 12 cm distance from a section containing magnetic regenerative materials of the second pulse tube. The magnetic noise spectrum showed a clear peak at 1.8 Hz, which is the fundamental frequency of the He gas pumping rate. The 1.8 Hz magnetic noise registered a peak, during the cooling down process, when the second cold-stage temperature was around 12 K, which is well correlated with the 1.8 Hz variation of the temperature of the second cold stage. Hence, we attributed the main source of this magnetic noise to the temperature variation of the magnetic moments resulting from magnetic regenerative materials, Er 3Ni and HoCu 2, in the presence of background static magnetic fields. We have also pointed out that the superconducting magnetic shield of lead sheets reduced the low frequency magnetic noise generated from the magnetic regenerative materials. With this arrangement, the magnetic noise amplitude measured with the LTS DROS gradiometer, mounted at 7 cm horizontal distance from the magnetic regenerative materials, in the optimum condition, was lower than 500 pT peak-to-peak, whereas the noise level without lead shielding was higher than the dynamic range of DROS instrumentations which was around ±10nT.

The potential role of telocytes in Tissue Engineering and Regenerative Medicine.

PubMed

Boos, Anja M; Weigand, Annika; Brodbeck, Rebekka; Beier, Justus P; Arkudas, Andreas; Horch, Raymund E

2016-07-01

Research and ideas for potential applications in the field of Tissue Engineering (TE) and Regenerative Medicine (RM) have been constantly increasing over recent years, basically driven by the fundamental human dream of repairing and regenerating lost tissue and organ functions. The basic idea of TE is to combine cells with putative stem cell properties with extracellular matrix components, growth factors and supporting matrices to achieve independently growing tissue. As a side effect, in the past years, more insights have been gained into cell-cell interaction and how to manipulate cell behavior. However, to date the ideal cell source has still to be found. Apart from commonly known various stem cell sources, telocytes (TC) have recently attracted increasing attention because they might play a potential role for TE and RM. It becomes increasingly evident that TC provide a regenerative potential and act in cellular communication through their network-forming telopodes. While TE in vitro experiments can be the first step, the key for elucidating their regenerative role will be the investigation of the interaction of TC with the surrounding tissue. For later clinical applications further steps have to include an upscaling process of vascularization of engineered tissue. Arteriovenous loop models to vascularize such constructs provide an ideal platform for preclinical testing of future therapeutic concepts in RM. The following review article should give an overview of what is known so far about the potential role of TC in TE and RM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue-specific composite cell aggregates drive periodontium tissue regeneration by reconstructing a regenerative microenvironment.

PubMed

Zhu, Bin; Liu, Wenjia; Zhang, Hao; Zhao, Xicong; Duan, Yan; Li, Dehua; Jin, Yan

2017-06-01

Periodontitis is the most common cause of periodontium destruction. Regeneration of damaged tissue is the expected treatment goal. However, the regeneration of a functional periodontal ligament (PDL) insertion remains a difficulty, due to complicated factors. Recently, periodontal ligament stem cells (PDLSCs) and bone marrow-derived mesenchymal stem cells (BMMSCs) have been shown to participate in PDL regeneration, both pathologically and physiologically. Besides, interactions affect the biofunctions of different derived cells during the regenerative process. Therefore, the purpose of this study was to discuss the different derived composite cell aggregate (CA) systems of PDLSCs and BMMSCs (iliac-derived or jaw-derived) for periodontium regeneration under regenerative microenvironment reconstruction. Our results showed although all three mono-MSC CAs were compacted and the cells arranged regularly in them, jaw-derived BMMSC (JBMMSC) CAs secreted more extracellular matrix than the others. Furthermore, PDLSC/JBMMSC compound CAs highly expressed ALP, Col-I, fibronectin, integrin-β1 and periostin, suggesting that their biofunction is more appropriate for periodontal structure regeneration. Inspiringly, PDLSC/JBMMSC compound CAs regenerated more functional PDL-like tissue insertions in both nude mice ectopic and minipig orthotopic transplantation. The results indicated that the different derived CAs of PDLSCs/JBMMSCs provided an appropriate regenerative microenvironment facilitating a more stable and regular regeneration of functional periodontium tissue. This method may provide a possible strategy to solve periodontium defects in periodontitis and powerful experimental evidence for clinical applications in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Cell interactions in bone tissue engineering.

PubMed

Pirraco, R P; Marques, A P; Reis, R L

2010-01-01

Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering.

PubMed

Duarte Campos, Daniela Filipa; Blaeser, Andreas; Buellesbach, Kate; Sen, Kshama Shree; Xun, Weiwei; Tillmann, Walter; Fischer, Horst

2016-06-01

3D-manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). 3D-bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D-bioprinted polysaccharide-based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo-responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D-bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D-bioprinted agarose-collagen hydrogels with high-collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low-collagen blends, as proved by two-photon microscopy, Alizarin Red staining, and real-time polymerase chain reaction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stress-resistant neural stem cells positively influence regional energy metabolism after spinal cord injury in mice.

PubMed

Schwerdtfeger, Karsten; Mautes, Angelika E M; Bernreuther, Christian; Cui, Yifang; Manville, Jérôme; Dihné, Marcel; Blank, Simon; Schachner, Melitta

2012-02-01

The importance of stem cells to ameliorate the devastating consequences of traumatic injuries in the adult mammalian central nervous system calls for improvements in the capacity of these cells to cope, in particular, with the host response to the injury. We have previously shown, however, that in the acutely traumatized spinal cord local energy metabolism led to decreased ATP levels after neural stem cell (NSC) transplantation. As this might counteract NSC-mediated regenerative processes, we investigated if NSC selected for increased oxidative stress resistance are better suited to preserve local energy content. For this purpose, we exposed wild-type (WT) NSC to hydrogen peroxide prior to transplantation. We demonstrate here that transplantation of WT-NSC into a complete spinal cord compression injury model even lowers the ATP content beyond the level detected in spinal cord injury-control animals. Compared to WT-NSC, stress-resistant (SR) NSC did not lead to a further decrease in ATP content. These differences between WT- and SR-NSC were observed 4 h after the lesion with subsequent transplantation. At 24 h after lesioning, these differences were no more as obvious. Thus, in contrast to native NSC, transplantation of NSC selected for oxidative stress resistance can positively influence local energy metabolism in the first hours after spinal cord compression. The functional relevance of this observation has to be tested in further experiments.

Process gas hear recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, W.M.; Thurner, R.P.

1977-01-01

In considering the use of regenerative and recuperative heat exchangers for process-gas heat recovery general information regarding heat-exchanger effectiveness versus initial capital investment and operating costs is discussed. Specific examples for preheating combustion air for process furnaces and for using primary and secondary heat exchangers in conjunction with an air-pollution-control system for drying and curing ovens cover basic heat-exchanger design and application considerations as well as investment-payback factors.

Applicability of different onboard routing and processing techniques to mobile satellite systems

NASA Technical Reports Server (NTRS)

Craig, A. D.; Marston, P. C.; Bakken, P. M.; Vernucci, A.; Benedicto, J.

1993-01-01

The paper summarizes a study contract recently undertaken for ESA. The study compared the effectiveness of several processing architectures applied to multiple beam, geostationary global and European regional missions. The paper discusses architectures based on transparent SS-FDMA analog, transparent DSP and regenerative processing. Quantitative comparisons are presented and general conclusions are given with respect to suitability of the architectures to different mission requirements.

Fleshy fruit removal and nutritional composition of winter-fruiting plants: a comparison of non-native invasive and native species

Treesearch

Cathryn H. Greenberg; Scott T. Walter

2010-01-01

Invasive, non-native plants threaten forest ecosystems by reducing native plant species richness and potentially altering ecosystem processes. Seed dispersal is critical for successful invasion and range expansion by non-native plants; dispersal is likely to be enhanced if they can successfully compete with native plants for disperser services. Fruit production by non-...

[Development of guidance for the approval process of brand-new medical products and regenerative medicine products].

PubMed

Niimi, Shingo

2015-01-01

Ministry of Health, Labour and Weltare has been conducting development of guidance for the approval process of brand-new medical products/development of guidance for medical devices in collaboration with Ministry of Economy, Trade and Industry as part of measures to promote practical use of brand-new medical products since 2005. The objective of this project is to expedite the processes from developmental process of medical devices to approval review and to introduce the medical devices to medical front quickly.. Ministry of Health, Labour and Welfare side has been making guidance for the guide in approval process of brand-new medical products and regeneration medicine products to aim at acceleration and facilitation of development and approval process of innovative medical products. Twenty-two of the guidance have been issued as director of the evaluation and licensing division. The evaluation index about safety and efficacy required for medical devices and regenerative medicine products in progress were put together in these guidance and useful for medical devices developer to understand the point at the approved review. Therefore, I think that the evaluation index could also contribute to the efficient product development. The guidance about implantable artificial heart is issued as the representative example which was useful in the approved review.

Effects of Fiber Orientation on the Frictional Properties and Damage of Regenerative Articular Cartilage Surfaces

PubMed Central

Accardi, Mario Alberto; McCullen, Seth D.; Callanan, Anthony; Chung, Sangwon; Cann, Philippa M.

2013-01-01

Articular cartilage provides a low-friction, wear-resistant surface for diarthrodial joints. Due to overloading and overuse, articular cartilage is known to undergo significant wear and degeneration potentially resulting in osteoarthritis (OA). Regenerative medicine strategies offer a promising solution for the treatment of articular cartilage defects and potentially localized early OA. Such strategies rely on the development of materials to restore some aspects of cartilage. In this study, microfibrous poly(ɛ-caprolactone) scaffolds of varying fiber orientations (random and aligned) were cultured with bovine chondrocytes for 4 weeks in vitro, and the mechanical and frictional properties were evaluated. Mechanical properties were quantified using unconfined compression and tensile testing techniques. Frictional properties were investigated at physiological compressive strains occurring in native articular cartilage. Scaffolds were sheared along the fiber direction, perpendicular to the fiber direction and in random orientation. The evolution of damage as a result of shear was evaluated via white light interferometry and scanning electron microscopy. As expected, the fiber orientation strongly affected the tensile properties as well as the compressive modulus of the scaffolds. Fiber orientation did not significantly affect the equilibrium frictional coefficient, but it was, however, a key factor in dictating the evolution of surface damage on the surface. Scaffolds shear tested perpendicular to the fiber orientation displayed the highest surface damage. Our results suggest that the fiber orientation of the scaffold implanted in the joint could strongly affect its resistance to damage due to shear. Scaffold fiber orientation should thus be carefully considered when using microfibrous scaffolds. PMID:23688110

Morphosyntactic Processing in Advanced Second Language (L2) Learners: An Event-Related Potential Investigation of the Effects of L1-l2 Similarity and Structural Distance

ERIC Educational Resources Information Center

Alemán Bañón, José; Fiorentino, Robert; Gabriele, Alison

2014-01-01

Different theoretical accounts of second language (L2) acquisition differ with respect to whether or not advanced learners are predicted to show native-like processing for features not instantiated in the native language (L1). We examined how native speakers of English, a language with number but not gender agreement, process number and gender…

Regenerative Simulation of Harris Recurrent Markov Chains.

DTIC Science & Technology

1982-07-01

Sutijle) S. TYPE OF REPORT A PERIOD COVERED REGENERATIVE SIMULATION OF HARRIS RECURRENT Technical Report MARKOV CHAINS 14. PERFORMING ORG. REPORT NUMBER...7 AD-Ag 251 STANFORD UNIV CA DEPT OF OPERATIONS RESEARCH /s i2/ REGENERATIVE SIMULATION OF HARRIS RECURRENT MARKOV CHAINS,(U) JUL 82 P W GLYNN N0001...76-C-0578 UNtLASSIFIED TR-62 NL EhhhIhEEEEEEI EEEEEIIIIIII REGENERATIVE SIMULATION OF HARRIS RECURRENT MARKOV CHAINS by Peter W. Glynn TECHNICAL

Engineering model system study for a regenerative fuel cell: Study report

NASA Technical Reports Server (NTRS)

Chang, B. J.; Schubert, F. H.; Kovach, A. J.; Wynveen, R. A.

1984-01-01

Key design issues of the regenerative fuel cell system concept were studied and a design definition of an alkaline electrolyte based engineering model system or low Earth orbit missions was completed. Definition of key design issues for a regenerative fuel cell system include gaseous reactant storage, shared heat exchangers and high pressure pumps. A power flow diagram for the 75 kW initial space station and the impact of different regenerative fuel cell modular sizes on the total 5 year to orbit weight and volume are determined. System characteristics, an isometric drawing, component sizes and mass and energy balances are determined for the 10 kW engineering model system. An open loop regenerative fuel cell concept is considered for integration of the energy storage system with the life support system of the space station. Technical problems and their solutions, pacing technologies and required developments and demonstrations for the regenerative fuel cell system are defined.

SAM-based cell transfer to photopatterned hydrogels for microengineering vascular-like structures.

PubMed

Sadr, Nasser; Zhu, Mojun; Osaki, Tatsuya; Kakegawa, Takahiro; Yang, Yunzhi; Moretti, Matteo; Fukuda, Junji; Khademhosseini, Ali

2011-10-01

A major challenge in tissue engineering is to reproduce the native 3D microvascular architecture fundamental for in vivo functions. Current approaches still lack a network of perfusable vessels with native 3D structural organization. Here we present a new method combining self-assembled monolayer (SAM)-based cell transfer and gelatin methacrylate hydrogel photopatterning techniques for microengineering vascular structures. Human umbilical vein cell (HUVEC) transfer from oligopeptide SAM-coated surfaces to the hydrogel revealed two SAM desorption mechanisms: photoinduced and electrochemically triggered. The former, occurs concomitantly to hydrogel photocrosslinking, and resulted in efficient (>97%) monolayer transfer. The latter, prompted by additional potential application, preserved cell morphology and maintained high transfer efficiency of VE-cadherin positive monolayers over longer culture periods. This approach was also applied to transfer HUVECs to 3D geometrically defined vascular-like structures in hydrogels, which were then maintained in perfusion culture for 15 days. As a step toward more complex constructs, a cell-laden hydrogel layer was photopatterned around the endothelialized channel to mimic the vascular smooth muscle structure of distal arterioles. This study shows that the coupling of the SAM-based cell transfer and hydrogel photocrosslinking could potentially open up new avenues in engineering more complex, vascularized tissue constructs for regenerative medicine and tissue engineering applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Advances in biomimetic regeneration of elastic matrix structures

PubMed Central

Sivaraman, Balakrishnan; Bashur, Chris A.

2012-01-01

Elastin is a vital component of the extracellular matrix, providing soft connective tissues with the property of elastic recoil following deformation and regulating the cellular response via biomechanical transduction to maintain tissue homeostasis. The limited ability of most adult cells to synthesize elastin precursors and assemble them into mature crosslinked structures has hindered the development of functional tissue-engineered constructs that exhibit the structure and biomechanics of normal native elastic tissues in the body. In diseased tissues, the chronic overexpression of proteolytic enzymes can cause significant matrix degradation, to further limit the accumulation and quality (e.g., fiber formation) of newly deposited elastic matrix. This review provides an overview of the role and importance of elastin and elastic matrix in soft tissues, the challenges to elastic matrix generation in vitro and to regenerative elastic matrix repair in vivo, current biomolecular strategies to enhance elastin deposition and matrix assembly, and the need to concurrently inhibit proteolytic matrix disruption for improving the quantity and quality of elastogenesis. The review further presents biomaterial-based options using scaffolds and nanocarriers for spatio-temporal control over the presentation and release of these biomolecules, to enable biomimetic assembly of clinically relevant native elastic matrix-like superstructures. Finally, this review provides an overview of recent advances and prospects for the application of these strategies to regenerating tissue-type specific elastic matrix structures and superstructures. PMID:23355960

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?

PubMed

Gilissen, L P L; Derijks, L J J; Driessen, A; Bos, L P; Hooymans, P M; Stockbrügger, R W; Engels, L G J B

2007-02-01

6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging. Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine. 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity.

Age of Acquisition and Proficiency in a Second Language Independently Influence the Perception of Non-Native Speech

ERIC Educational Resources Information Center

Archila-Suerte, Pilar; Zevin, Jason; Bunta, Ferenc; Hernandez, Arturo E.

2012-01-01

Sensorimotor processing in children and higher-cognitive processing in adults could determine how non-native phonemes are acquired. This study investigates how age-of-acquisition (AOA) and proficiency-level (PL) predict native-like perception of statistically dissociated L2 categories, i.e., within-category and between-category. In a similarity…

Native and L2 Processing of Homonyms in Sentential Context

ERIC Educational Resources Information Center

Elston-Guttler, K.E.; Friederici, A.D.

2005-01-01

We compare native and non-native processing of homonyms in sentence context whose two most frequent meanings are nouns (e.g., sentence) or a noun and a verb (e.g., trip). With both participant groups, we conducted a combined reaction time (RT)/event-related brain potential (ERP) lexical decision experiment with two stimulus-onset asynchronies…

Nature's Electric Potential: A Systematic Review of the Role of Bioelectricity in Wound Healing and Regenerative Processes in Animals, Humans, and Plants.

PubMed

Tyler, Sheena E B

2017-01-01

Natural endogenous voltage gradients not only predict and correlate with growth and development but also drive wound healing and regeneration processes. This review summarizes the existing literature for the nature, sources, and transmission of information-bearing bioelectric signals involved in controlling wound healing and regeneration in animals, humans, and plants. It emerges that some bioelectric characteristics occur ubiquitously in a range of animal and plant species. However, the limits of similarities are probed to give a realistic assessment of future areas to be explored. Major gaps remain in our knowledge of the mechanistic basis for these processes, on which regenerative therapies ultimately depend. In relation to this, it is concluded that the mapping of voltage patterns and the processes generating them is a promising future research focus, to probe three aspects: the role of wound/regeneration currents in relation to morphology; the role of endogenous flux changes in driving wound healing and regeneration; and the mapping of patterns in organisms of extreme longevity, in contrast with the aberrant voltage patterns underlying impaired healing, to inform interventions aimed at restoring them.

Nature's Electric Potential: A Systematic Review of the Role of Bioelectricity in Wound Healing and Regenerative Processes in Animals, Humans, and Plants

PubMed Central

Tyler, Sheena E. B.

2017-01-01

Natural endogenous voltage gradients not only predict and correlate with growth and development but also drive wound healing and regeneration processes. This review summarizes the existing literature for the nature, sources, and transmission of information-bearing bioelectric signals involved in controlling wound healing and regeneration in animals, humans, and plants. It emerges that some bioelectric characteristics occur ubiquitously in a range of animal and plant species. However, the limits of similarities are probed to give a realistic assessment of future areas to be explored. Major gaps remain in our knowledge of the mechanistic basis for these processes, on which regenerative therapies ultimately depend. In relation to this, it is concluded that the mapping of voltage patterns and the processes generating them is a promising future research focus, to probe three aspects: the role of wound/regeneration currents in relation to morphology; the role of endogenous flux changes in driving wound healing and regeneration; and the mapping of patterns in organisms of extreme longevity, in contrast with the aberrant voltage patterns underlying impaired healing, to inform interventions aimed at restoring them. PMID:28928669

Widening the Circle: Culturally Relevant Pedagogy for American Indian Children.

ERIC Educational Resources Information Center

Klug, Beverly J.; Whitfield, Patricia T.

This book provides non-Native teachers with information about Native American cultures and offers a pedagogical model that blends Native and non-Native worldviews and methodologies. The book aims to describe the process of becoming bicultural as it relates to success in teaching Native students; provide a short history of American Indian nations,…

Germination responses of an invasive species in native and non-native ranges

Treesearch

Jose L. Hierro; Ozkan Eren; Liana Khetsuriani; Alecu Diaconu; Katalin Torok; Daniel Montesinos; Krikor Andonian; David Kikodze; Levan Janoian; Diego Villarreal; Maria Estanga-Mollica; Ragan M. Callaway

2009-01-01

Studying germination in the native and non-native range of a species can provide unique insights into processes of range expansion and adaptation; however, traits related to germination have rarely been compared between native and nonnative populations. In a series of common garden experiments, we explored whether differences in the seasonality of precipitation,...

Syntactic Constraints and Individual Differences in Native and Non-Native Processing of Wh-Movement

PubMed Central

Johnson, Adrienne; Fiorentino, Robert; Gabriele, Alison

2016-01-01

There is a debate as to whether second language (L2) learners show qualitatively similar processing profiles as native speakers or whether L2 learners are restricted in their ability to use syntactic information during online processing. In the realm of wh-dependency resolution, research has examined whether learners, similar to native speakers, attempt to resolve wh-dependencies in grammatically licensed contexts but avoid positing gaps in illicit contexts such as islands. Also at issue is whether the avoidance of gap filling in islands is due to adherence to syntactic constraints or whether islands simply present processing bottlenecks. One approach has been to examine the relationship between processing abilities and the establishment of wh-dependencies in islands. Grammatical accounts of islands do not predict such a relationship as the parser should simply not predict gaps in illicit contexts. In contrast, a pattern of results showing that individuals with more processing resources are better able to establish wh-dependencies in islands could conceivably be compatible with certain processing accounts. In a self-paced reading experiment which examines the processing of wh-dependencies, we address both questions, examining whether native English speakers and Korean learners of English show qualitatively similar patterns and whether there is a relationship between working memory, as measured by counting span and reading span, and processing in both island and non-island contexts. The results of the self-paced reading experiment suggest that learners can use syntactic information on the same timecourse as native speakers, showing qualitative similarity between the two groups. Results of regression analyses did not reveal a significant relationship between working memory and the establishment of wh-dependencies in islands but we did observe significant relationships between working memory and the processing of licit wh-dependencies. As the contexts in which these relationships emerged differed for learners and native speakers, our results call for further research examining individual differences in dependency resolution in both populations. PMID:27148152

Syntactic Constraints and Individual Differences in Native and Non-Native Processing of Wh-Movement.

PubMed

Johnson, Adrienne; Fiorentino, Robert; Gabriele, Alison

2016-01-01

There is a debate as to whether second language (L2) learners show qualitatively similar processing profiles as native speakers or whether L2 learners are restricted in their ability to use syntactic information during online processing. In the realm of wh-dependency resolution, research has examined whether learners, similar to native speakers, attempt to resolve wh-dependencies in grammatically licensed contexts but avoid positing gaps in illicit contexts such as islands. Also at issue is whether the avoidance of gap filling in islands is due to adherence to syntactic constraints or whether islands simply present processing bottlenecks. One approach has been to examine the relationship between processing abilities and the establishment of wh-dependencies in islands. Grammatical accounts of islands do not predict such a relationship as the parser should simply not predict gaps in illicit contexts. In contrast, a pattern of results showing that individuals with more processing resources are better able to establish wh-dependencies in islands could conceivably be compatible with certain processing accounts. In a self-paced reading experiment which examines the processing of wh-dependencies, we address both questions, examining whether native English speakers and Korean learners of English show qualitatively similar patterns and whether there is a relationship between working memory, as measured by counting span and reading span, and processing in both island and non-island contexts. The results of the self-paced reading experiment suggest that learners can use syntactic information on the same timecourse as native speakers, showing qualitative similarity between the two groups. Results of regression analyses did not reveal a significant relationship between working memory and the establishment of wh-dependencies in islands but we did observe significant relationships between working memory and the processing of licit wh-dependencies. As the contexts in which these relationships emerged differed for learners and native speakers, our results call for further research examining individual differences in dependency resolution in both populations.

Nitrogen dioxide produced by self-sustained pyrolysis of nitrous oxide

NASA Technical Reports Server (NTRS)

Sabol, A. P.

1965-01-01

Apparatus is developed for achieving continuous self-sustaining pyrolysis reaction in the production of nitrogen dioxide from nitrous oxide. The process becomes self-sustaining because of the exothermic reaction and the regenerative heating of the gases in the pyrolysis chamber.

Run-Curve Design for Energy Saving Operation in a Modern DC-Electrification

NASA Astrophysics Data System (ADS)

Koseki, Takafumi; Noda, Takashi

Mechanical brakes are often used by electric trains. These brakes have a few problems like response speed, coefficient of friction, maintenance cost and so on. As a result, methods for actively using regenerative brakes are required. In this paper, we propose the useful pure electric braking, which would involve ordinary brakes by only regenerative brakes without any mechanical brakes at high speed. Benefits of our proposal include a DC-electrification system with regenerative substations that can return powers to the commercial power system and a train that can use the full regenerative braking force. We furthermore evaluate the effects on running time and energies saved by regenerative substations in the proposed method.

Conference Report: 6th Annual International Symposium on Regenerative Rehabilitation.

PubMed

Loghmani, M Terry; Roche, Joseph A

2018-04-03

The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR 3 T), included a preconference meeting of institutional representatives of the International Consortium of Regenerative Rehabilitation, keynote talks from distinguished scientists, platform and poster presentations from experts and trainees, panel discussions and postconference workshops. The following priorities were identified: increasing rigor in basic, preclinical and clinical studies, especially the use of better controls; developing better outcome measures for preclinical and clinical trials; focusing on developing more tissue-based interventions versus cell-based interventions; including regenerative rehabilitation in curricula of professional programs like occupational and physical therapy; and developing better instruments to quantify rehabilitative interventions.

Semantic processing in native and second language: evidence from hemispheric differences in fine and coarse semantic coding.

PubMed

Faust, Miriam; Ben-Artzi, Elisheva; Vardi, Nili

2012-12-01

Previous studies suggest that whereas the left hemisphere (LH) is involved in fine semantic processing, the right hemisphere (RH) is uniquely engaged in coarse semantic coding including the comprehension of distinct types of language such as figurative language, lexical ambiguity and verbal humor (e.g., Chiarello, 2003; Faust, 2012). The present study examined the patterns of hemispheric involvement in fine/coarse semantic processing in native and non-native languages using a split visual field priming paradigm. Thirty native Hebrew speaking students made lexical decision judgments of Hebrew and English target words preceded by strongly, weakly, or unrelated primes. Results indicated that whereas for Hebrew pairs, priming effect for the weakly-related word pairs was obtained only for RH presented target words, for English pairs, no priming effect for the weakly-related pairs emerged for either LH or RH presented targets, suggesting that coarse semantic coding is much weaker for a non-native than native language. Copyright © 2012 Elsevier Inc. All rights reserved.

Cost Analysis of Utilizing Electric Vehicles and Photovoltaic Solar Energy in the United States Marine Corps Commercial Vehicle Fleet

DTIC Science & Technology

2009-12-01

vehicles so do some electric vehicle braking systems (MIT, 2008). e. Brakes Regenerative braking on electric vehicles recoups some of the energy lost...engine is required to replace the energy lost by braking . Regenerative braking takes some of the lost energy during braking and turns it into...Motors and Tesla Motors offer regenerative breaking in their respective electric vehicles. Tesla explains regenerative braking as “engine braking

Modeling and Demonstrating Regenerative Braking of a Squirrel Cage Induction Motor with Various Deceleration Rates Using V by F Control

DTIC Science & Technology

2010-06-01

DEMONSTRATING REGENERATIVE BRAKING OF A SQUIRREL CAGE INDUCTION MOTOR WITH VARIOUS DECELERATION RATES USING V BY F CONTROL by Billy J. Nytko...Regenerative Braking of a Squirrel Cage Induction Motor with Various Deceleration Rates Using V by F Control 6. AUTHOR(S) Billy J. Nytko 5. FUNDING...Naval Postgraduate School (NPS) to model regenerative braking to support energy conservation technologies and to improve the efficiencies within the

Introduced birds incompletely replace seed dispersal by a native frugivore

PubMed Central

Pejchar, Liba

2015-01-01

The widespread loss of native species and the introduction of non-native species has important consequences for island ecosystems. Non-native species may or may not functionally replace the role of native species in ecological processes such as seed dispersal. Although the majority of Hawaii's native plants require bird-mediated seed dispersal, only one native frugivore, Omao (Myadestes obscurus), persists in sufficient numbers to fill this functional role. Omao are restricted to less than half their original range, but two introduced frugivores are abundant throughout Hawaii. Given large-scale extinctions on islands, it is important to understand whether introduced birds serve as functional replacements or whether the absence of native frugivores alters plant communities. To assess seed dispersal by native and introduced birds, seed rain, vegetation characteristics, bird diet, density and habitat use were measured at three sites with Omao and three sites without Omao on Hawaii Island. The diet of native and introduced birds overlapped substantially, but Omao dispersed a variety of native species (n = 6) relatively evenly. In contrast, introduced birds dispersed an invasive species and fewer native species (n = 4), and >90 % of seeds dispersed by introduced birds were from two ubiquitous small-seeded species. Seed rain was significantly greater and more species rich at sites with Omao. These findings suggest that patterns of seed dispersal are altered following the local extinction of a native island frugivore. To more directly evaluate the relative roles of native and introduced frugivores in ecological processes, future studies could include reintroducing Omao to a suitable habitat within its historic range, or novel introductions to nearby islands where closely related species are now extinct. In an era of widespread extinction and invasion of island ecosystems, understanding the consequences of novel animal assemblages for processes like seed dispersal will be critical for maintaining diverse and self-regenerating plant communities. PMID:26139183

Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions

PubMed Central

Furusho, M; Roulois, A; Franklin, RJM; Bansal, R

2015-01-01

Remyelination is a potent regenerative process in demyelinating diseases, such as multiple sclerosis, the effective therapeutic promotion of which will fill an unmet clinical need. The development of pro-regenerative therapies requires the identification of key regulatory targets that are likely to be involved in the integration of multiple signaling mechanisms. Fibroblast growth factor (FGF) signaling system, which comprises multiple ligands and receptors, potentially provides one such target. Since the FGF/FGF receptor (FGFR) interactions are complex and regulate multiple diverse functions of oligodendrocyte lineage cells, it is difficult to predict their overall therapeutic potential in the regeneration of oligodendrocytes and myelin. Therefore, to assess the integrated effects of FGFR signaling on this process, we simultaneously inactivated both FGFR1 and FGFR2 in oligodendrocytes and their precursors using two Cre-driver mouse lines. Acute and chronic cuprizone-induced or lysolecithin-induced demyelination was established in Fgfr1/Fgfr2 double knockout mice (dKO). We found that in the acute cuprizone model, there was normal differentiation of oligodendrocytes and recovery of myelin in the corpus callosum of both control and dKO mice. Similarly, in the spinal cord, lysolecithin-induced demyelinated lesions regenerated similarly in the dKO and control mice. In contrast, in the chronic cuprizone model, fewer differentiated oligodendrocytes and less efficient myelin recovery were observed in the dKO compared to control mice. These data suggest that while cell-autonomous FGF signaling is redundant during recovery of acute demyelinated lesions, it facilitates regenerative processes in chronic demyelination. Thus, FGF-based therapies have potential value in stimulating oligodendrocyte and myelin regeneration in late-stage disease. PMID:25913734

Differential expression of myogenic regulatory genes and Msx-1 during dedifferentiation and redifferentiation of regenerating amphibian limbs.

PubMed

Simon, H G; Nelson, C; Goff, D; Laufer, E; Morgan, B A; Tabin, C

1995-01-01

An amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to derive from differentiated tissues of the adult limb. However, the exact source of these cells and the process by which they undergo dedifferentiation are poorly understood. In order to elucidate the molecular and cellular basis for dedifferentiation we isolated a number of genes which are potential regulators of the process. These include Msx-1, which is believed to support the undifferentiated and proliferative state of cells in the embryonic limb bud; and two members of the myogenic regulatory gene family, MRF-4 and Myf-5, which are expressed in differentiated muscle and regulate muscle-specific gene activity. As anticipated, we find that Msx-1 is strongly up-regulated during the initiation of regeneration. It remains expressed throughout regeneration but is not found in the fully regenerated limb. The myogenic gene MRF-4 has the reverse expression pattern. It is expressed in adult limb muscle, is rapidly shut off in early regenerative blastemas, and is only reexpressed at the completion of regeneration. These kinetics are paralleled by those of a muscle-specific Myosin gene. In contrast Myf-5, a second member of the myogenic gene family, continues to be expressed throughout the regenerative process. Thus, MRF-4 and Myf-5 are likely to play distinct roles during regeneration. MRF-4 may directly regulate muscle phenotype and as such its repression may be a key event in dedifferentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemisphericity and information processing in North American Native (Ojibwa) and non-native adolescents.

PubMed

Morton, L L; Allen, J D; Williams, N H

1994-04-01

Thirty-two male and female adolescents of native ancestry (Ojibwa) and 32 controls were tested using (1) four WISC-R subtests and (2) two dichotic listening tasks which employed a focused-attention paradigm for processing consonant-vowel combinations (CVs) and musical melodies. On the WISC-R, natives scored higher than controls on Block Design and Picture Completion subtests but lower on Vocabulary and Similarities subtests. On laterality measures more native males showed a left ear advantage on the CV task and the melody task. For CVs the left ear advantage was due to native males' lower right ear (i.e., left hemisphere) involvement. For melodies, the laterality index pointed to less left hemisphere involvement for native males, however, the raw scores showed that natives were performing lower overall. The findings are consistent with culturally-based strategy differences, possibly linked to "hemisphericity," but additional clarifying research regarding the cause and extent of such differences is warranted. Thus, implications for education are premature but a focus on teaching "left hemisphere type" strategies to all individuals not utilizing such skills, including many native males, may prove beneficial.

Design of An Energy Efficient Hydraulic Regenerative circuit

NASA Astrophysics Data System (ADS)

Ramesh, S.; Ashok, S. Denis; Nagaraj, Shanmukha; Adithyakumar, C. R.; Reddy, M. Lohith Kumar; Naulakha, Niranjan Kumar

2018-02-01

Increasing cost and power demand, leads to evaluation of new method to increase through productivity and help to solve the power demands. Many researchers have break through to increase the efficiency of a hydraulic power pack, one of the promising methods is the concept of regenerative. The objective of this research work is to increase the efficiency of a hydraulic circuit by introducing a concept of regenerative circuit. A Regenerative circuit is a system that is used to speed up the extension stroke of the double acting single rod hydraulic cylinder. The output is connected to the input in the directional control value. By this concept, increase in velocity of the piston and decrease the cycle time. For the research, a basic hydraulic circuit and a regenerative circuit are designated and compared both with their results. The analysis was based on their time taken for extension and retraction of the piston. From the detailed analysis of both the hydraulic circuits, it is found that the efficiency by introducing hydraulic regenerative circuit increased by is 5.3%. The obtained results conclude that, implementing hydraulic regenerative circuit in a hydraulic power pack decreases power consumption, reduces cycle time and increases productivity in a longer run.

Mesenchymal Stem and Progenitor Cells in Regeneration: Tissue Specificity and Regenerative Potential

PubMed Central

Pieber, Thomas Rudolf

2017-01-01

It has always been an ambitious goal in medicine to repair or replace morbid tissues for regaining the organ functionality. This challenge has recently gained momentum through considerable progress in understanding the biological concept of the regenerative potential of stem cells. Routine therapeutic procedures are about to shift towards the use of biological and molecular armamentarium. The potential use of embryonic stem cells and invention of induced pluripotent stem cells raised hope for clinical regenerative purposes; however, the use of these interventions for regenerative therapy showed its dark side, as many health concerns and ethical issues arose in terms of using these cells in clinical applications. In this regard, adult stem cells climbed up to the top list of regenerative tools and mesenchymal stem cells (MSC) showed promise for regenerative cell therapy with a rather limited level of risk. MSC have been successfully isolated from various human tissues and they have been shown to offer the possibility to establish novel therapeutic interventions for a variety of hard-to-noncurable diseases. There have been many elegant studies investigating the impact of MSC in regenerative medicine. This review provides compact information on the role of stem cells, in particular, MSC in regeneration. PMID:28286525

Literacy achievement of children with intellectual disabilities and differing linguistic backgrounds.

PubMed

Verhoeven, L; Vermeer, A

2006-10-01

The aim of the present study was to examine the literacy achievement of 10- to 12-year-old native and non-native children with intellectual disabilities (ID) living in the Netherlands. An intriguing question within this context was whether the second language learning non-native children with ID would show a double disadvantage when compared with their monolingual Dutch peers with no ID. Dutch literacy scores in the domains of word decoding, vocabulary, syntax and text were therefore compared for: (1) intellectually disabled native Dutch children; (2) intellectually disabled non-native children; (3) normally developing native Dutch children; and (4) normally developing non-native children. The interrelations between literacy subskills were also compared for native vs. non-native children with ID. The native and non-native students diagnosed as intellectually disabled produced substantially lower literacy scores than their non-disabled peers. The differences between the native (L1) and non-native (L2) children in regular vs. special education were found to depend on the aspect of literacy considered. Word decoding and language skills turned out to significantly predict the children's reading comprehension, although some differences in the strength of relationships could also be evidenced. The literacy achievement of intellectually disabled children with differing linguistic backgrounds generally falls behind that of their non-disabled peers. For word decoding, the non-native children in regular and special education were generally able to keep up with their native peers. For higher-order literacy abilities closely related to the mental lexicon, sentence processing and text processing, however, significant differences in the performances of the native (L1) and non-native (L2) children in regular vs. special education were found, suggesting a double disadvantage for the non-native children in special education.

Maynard Participation in Alaska Forum on the Environment Panel Discussion on Increasing Input to the US National Climate Assessment (NCA) and the Intergovernmental Panel on Climate Change (IPCC) Processes from Alaska, with Emphasis on Indigenous Peoples Issues

NASA Technical Reports Server (NTRS)

Maynard, Nancy G.

2012-01-01

Dr. Nancy Maynard was invited by the Alaska Forum on the Environment to participate in a Panel Discussion to discuss (1) background about what the US NCA and International IPCC assessments are, (2) the impact the assessments have on policy-making, (3) the process for participation in both assessments, (4) how we can increase participation by Indigenous Peoples such as Native Americans and Alaska Natives, (5) How we can increase historical and current impacts input from Native communities through stories, oral history, "grey" literature, etc. The session will be chaired by Dr. Bull Bennett, a cochair of the US NCA's chapter on "Native and Tribal Lands and Resources" and Dr. Maynard is the other co-chair of that chapter and they will discuss the latest activities under the NCA process relevant to Native Americans and Alaska Natives. Dr. Maynard is also a Lead Author of the "Polar Regions" chapter of the IPCC WG2 (5th Assessment) and she will describes some of the latest approaches by the IPCC to entrain more Indigenous peoples into the IPCC process.

Reanalysis and semantic persistence in native and non-native garden-path recovery.

PubMed

Jacob, Gunnar; Felser, Claudia

2016-01-01

We report the results from an eye-movement monitoring study investigating how native and non-native speakers of English process temporarily ambiguous sentences such as While the gentleman was eating the burgers were still being reheated in the microwave, in which an initially plausible direct-object analysis is first ruled out by a syntactic disambiguation (were) and also later on by semantic information (being reheated). Both participant groups showed garden-path effects at the syntactic disambiguation, with native speakers showing significantly stronger effects of ambiguity than non-native speakers in later eye-movement measures but equally strong effects in first-pass reading times. Ambiguity effects at the semantic disambiguation and in participants' end-of-trial responses revealed that for both participant groups, the incorrect direct-object analysis was frequently maintained beyond the syntactic disambiguation. The non-native group showed weaker reanalysis effects at the syntactic disambiguation and was more likely to misinterpret the experimental sentences than the native group. Our results suggest that native language (L1) and non-native language (L2) parsing are similar with regard to sensitivity to syntactic and semantic error signals, but different with regard to processes of reanalysis.

[Ethical aspects of regenerative medicine, with special reference to embryonic stem cells and therapeutic cloning].

PubMed

Imura, Hiroo

2003-03-01

Regenerative medicine is expected to be new therapeutic means for treating incurable diseases but requires serious bioethical consideration. Embryonic stem(ES) cells, that are pleuripotent cells suitable to regenerative medicine, can be used in Japan for investigative use under a strict control by guide-lines. On the other hand, use of embryo produced by nuclear transfer has not been allowed in Japan and further serious consideration is required. Some other ethical aspects of regenerative medicine are also discussed.

Strategies for Stabilizing Nitrogenous Compounds in ECLSS Wastewater: Top-Down System Design and Unit Operation Selection with Focus on Bio-Regenerative Processes for Short and Long Term Scenarios

NASA Technical Reports Server (NTRS)

Lunn, Griffin M.

2011-01-01

Water recycling and eventual nutrient recovery is crucial for surviving in or past low earth orbit. New approaches and syste.m architecture considerations need to be addressed to meet current and future system requirements. This paper proposes a flexible system architecture that breaks down pretreatment , steps into discrete areas where multiple unit operations can be considered. An overview focusing on the urea and ammonia conversion steps allows an analysis on each process's strengths and weaknesses and synergy with upstream and downstream processing. Process technologies to be covered include chemical pretreatment, biological urea hydrolysis, chemical urea hydrolysis, combined nitrification-denitrification, nitrate nitrification, anammox denitrification, and regenerative ammonia absorption through struvite formation. Biological processes are considered mainly for their ability to both maximize water recovery and to produce nutrients for future plant systems. Unit operations can be considered for traditional equivalent system mass requirements in the near term or what they can provide downstream in the form of usable chemicals or nutrients for the long term closed-loop ecological control and life support system. Optimally this would allow a system to meet the former but to support the latter without major modification.

Delivery of growth factors for tissue regeneration and wound healing.

PubMed

Koria, Piyush

2012-06-01

Growth factors are soluble secreted proteins capable of affecting a variety of cellular processes important for tissue regeneration. Consequently, the self-healing capacity of patients can be augmented by artificially enhancing one or more processes important for healing through the application of growth factors. However, their application in clinics remains limited due to lack of robust delivery systems and biomaterial carriers. Interestingly, all clinically approved therapies involving growth factors utilize some sort of a biomaterial carrier for growth factor delivery. This suggests that biomaterial delivery systems are extremely important for successful usage of growth factors in regenerative medicine. This review outlines the role of growth factors in tissue regeneration, and their application in both pre-clinical animal models of regeneration and clinical trials is discussed. Additionally, current status of biomaterial substrates and sophisticated delivery systems such as nanoparticles for delivery of exogenous growth factors and peptides in humans are reviewed. Finally, issues and possible future research directions for growth factor therapy in regenerative medicine are discussed.

[The ultrastructural manifestations of the regenerative processes in the Sertoli cells under the action of low-intensity electromagnetic radiation in the rats subjected to stress].

PubMed

Korolev, Iu N; Geniatulina, M S; Nikulina, L A; Mikhaĭlik, L V

2015-01-01

The experiments on the outbred female rats using the electron microscopic technique have demonstrated that the application of ultrahigh frequency low-intensity electromagnetic radiation (LIEMR) with a flux density below 1 mCW/Cm2 and a frequency of approximately 1,000 MHz in the regime of primary prophylaxis and therapeutic-preventive action suppressed the development of the post-stress pathological ultrastructural changes and increased the activity of the regenerative processes in the Sertoli cells. It was shown that the developing adaptive and compensatory changes in the Sertoli cells most frequently involve the energy-producing structures (mitochondria) that undergo the enlargement of their average and total dimensions. Simultaneously, the amount of granular endoplasmic reticulum and the number of ribosomes increased while the intracellular links between the organelles strengthened and the reserve potential of the cells improved. It is concluded that the observed effects may be due to the action of both local and systemic regulation mechanisms.

Simulation of energy buildups in solid-state regenerative amplifiers for 2-μm emitting lasers

NASA Astrophysics Data System (ADS)

Springer, Ramon; Alexeev, Ilya; Heberle, Johannes; Pflaum, Christoph

2018-02-01

A numerical model for solid-state regenerative amplifiers is presented, which is able to precisely simulate the quantitative energy buildup of stretched femtosecond pulses over passed roundtrips in the cavity. In detail, this model is experimentally validated with a Ti:Sapphire regenerative amplifier. Additionally, the simulation of a Ho:YAG based regenerative amplifier is conducted and compared to experimental data from literature. Furthermore, a bifurcation study of the investigated Ho:YAG system is performed, which leads to the identification of stable and instable operation regimes. The presented numerical model exhibits a well agreement to the experimental results from the Ti:Sapphire regenerative amplifier. Also, the gained pulse energy from the Ho:YAG system could be approximated closely, while the mismatch is explained with the monochromatic calculation of pulse amplification. Since the model is applicable to other solid-state gain media, it allows for the efficient design of future amplification systems based on regenerative amplification.

Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

PubMed Central

2016-01-01

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

The influence of language deprivation in early childhood on L2 processing: An ERP comparison of deaf native signers and deaf signers with a delayed language acquisition.

PubMed

Skotara, Nils; Salden, Uta; Kügow, Monique; Hänel-Faulhaber, Barbara; Röder, Brigitte

2012-05-03

To examine which language function depends on early experience, the present study compared deaf native signers, deaf non-native signers and hearing German native speakers while processing German sentences. The participants watched simple written sentences while event-related potentials (ERPs) were recorded. At the end of each sentence they were asked to judge whether the sentence was correct or not. Two types of violations were introduced in the middle of the sentence: a semantically implausible noun or a violation of subject-verb number agreement. The results showed a similar ERP pattern after semantic violations (an N400 followed by a positivity) in all three groups. After syntactic violations, native German speakers and native signers of German sign language (DGS) with German as second language (L2) showed a left anterior negativity (LAN) followed by a P600, whereas no LAN but a negativity over the right hemisphere instead was found in deaf participants with a delayed onset of first language (L1) acquisition. The P600 of this group had a smaller amplitude and a different scalp distribution as compared to German native speakers. The results of the present study suggest that language deprivation in early childhood alters the cerebral organization of syntactic language processing mechanisms for L2. Semantic language processing instead was unaffected.

Native American Indians and the Counseling Process: Culture, Adaptation, and Style.

ERIC Educational Resources Information Center

Skouras, Thomas J.

Native Americans constitute a significant population that is growing and has great need for mental health and counseling services. Social problems in Native communities include high rates of alcoholism, alcohol-related deaths, drug use, youth suicide, and sexually transmitted diseases. Despite their mental health needs, Native Americans are…

Application of stem cell/growth factor system, as a multimodal therapy approach in regenerative medicine to improve cell therapy yields.

PubMed

Pourrajab, Fatemeh; Babaei Zarch, Mojtaba; Baghi Yazdi, Mohammad; Rahimi Zarchi, Abolfazl; Vakili Zarch, Abbas

2014-04-15

Stem cells hold a great promise for regenerative medicine, especially for replacing cells in infarcted organ that hardly have any intrinsic renewal capacity, including heart and brain. Signaling pathways that regulate pluripotency or lineage-specific gene and protein expression have been the major focus of stem cell research. Between them, there are some well known signaling pathways such as GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines may regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes or accentuate synergistic compliance. For example, contributing factors in the progression of heart failure are both the loss of cardiomyocytes after myocardial infarction, and the absence of an adequate endogenous repair signaling. Combining cell engraftment with therapeutic signaling factor delivery is more exciting in terms of host progenitor/donor stem cell survival and proliferation. Thus stem cell-based therapy, besides triggering signaling pathways through GF/GFR systems can become a realistic option in regenerative processes for replacing lost cells and reconstituting the damaged organ, as before. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials

PubMed Central

Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S.

2015-01-01

Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells. PMID:25591783

Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials.

PubMed

Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S

2015-01-16

Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells.

Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine.

PubMed

Hinderer, Svenja; Brauchle, Eva; Schenke-Layland, Katja

2015-11-18

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug-free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus-free vascular substitutes that are smaller than 6 mm, and stem cell-recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off-the-shelf biomaterials as well as automatable and up-scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact- and marker-free biomaterial and extracellular matrix assessment methods are highlighted. © 2015 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Secretome within the bone marrow microenvironment: A basis for mesenchymal stem cell treatment and role in cancer dormancy.

PubMed

Eltoukhy, Hussam S; Sinha, Garima; Moore, Caitlyn; Gergues, Marina; Rameshwar, Pranela

2018-05-31

The secretome produced by cells within the bone marrow is significant to homeostasis. The bone marrow, a well-studied organ, has multiple niches with distinct roles for supporting stem cell functions. Thus, an understanding of mediators involved in the regulation of stem cells could serve as a model for clinical problems and solutions such as tissue repair and regeneration. The exosome secretome of bone marrow stem cells is a developing area of research with respect to the regenerative potential by bone marrow cell, particularly the mesenchymal stem cells. The bone marrow niche regulates endogenous processes such as hematopoiesis but could also support the survival of tumors such as facilitating the cancer stem cells to exist in dormancy for decades. The bone marrow-derived secretome will be critical to future development of therapeutic strategies for oncologic diseases, in addition to regenerative medicine. This article discusses the importance for parallel studies to determine how the same secretome may compromise safety during the use of stem cells in regenerative medicine. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The Pharmacology of Regenerative Medicine

PubMed Central

Saul, Justin M.; Furth, Mark E.; Andersson, Karl-Erik

2013-01-01

Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase “regenerative pharmacology” to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is “the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues.” As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all. PMID:23818131

Understanding Mechanobiology: Physical Therapists as a Force in Mechanotherapy and Musculoskeletal Regenerative Rehabilitation

PubMed Central

Thompson, William R.; Scott, Alexander; Loghmani, M. Terry; Ward, Samuel R.

2016-01-01

Achieving functional restoration of diseased or injured tissues is the ultimate goal of both regenerative medicine approaches and physical therapy interventions. Proper integration and healing of the surrogate cells, tissues, or organs introduced using regenerative medicine techniques are often dependent on the co-introduction of therapeutic physical stimuli. Thus, regenerative rehabilitation represents a collaborative approach whereby rehabilitation specialists, basic scientists, physicians, and surgeons work closely to enhance tissue restoration by creating tailored rehabilitation treatments. One of the primary treatment regimens that physical therapists use to promote tissue healing is the introduction of mechanical forces, or mechanotherapies. These mechanotherapies in regenerative rehabilitation activate specific biological responses in musculoskeletal tissues to enhance the integration, healing, and restorative capacity of implanted cells, tissues, or synthetic scaffolds. To become future leaders in the field of regenerative rehabilitation, physical therapists must understand the principles of mechanobiology and how mechanotherapies augment tissue responses. This perspective article provides an overview of mechanotherapy and discusses how mechanical signals are transmitted at the tissue, cellular, and molecular levels. The synergistic effects of physical interventions and pharmacological agents also are discussed. The goals are to highlight the critical importance of mechanical signals on biological tissue healing and to emphasize the need for collaboration within the field of regenerative rehabilitation. As this field continues to emerge, physical therapists are poised to provide a critical contribution by integrating mechanotherapies with regenerative medicine to restore musculoskeletal function. PMID:26637643

Does the speaker matter? Online processing of semantic and pragmatic information in L2 speech comprehension.

PubMed

Foucart, Alice; Garcia, Xavier; Ayguasanosa, Meritxell; Thierry, Guillaume; Martin, Clara; Costa, Albert

2015-08-01

The present study investigated how pragmatic information is integrated during L2 sentence comprehension. We put forward that the differences often observed between L1 and L2 sentence processing may reflect differences on how various types of information are used to process a sentence, and not necessarily differences between native and non-native linguistic systems. Based on the idea that when a cue is missing or distorted, one relies more on other cues available, we hypothesised that late bilinguals favour the cues that they master during sentence processing. To verify this hypothesis we investigated whether late bilinguals take the speaker's identity (inferred by the voice) into account when incrementally processing speech and whether this affects their online interpretation of the sentence. To do so, we adapted Van Berkum, J.J.A., Van den Brink, D., Tesink, C.M.J.Y., Kos, M., Hagoort, P., 2008. J. Cogn. Neurosci. 20(4), 580-591, study in which sentences with either semantic violations or pragmatic inconsistencies were presented. While both the native and the non-native groups showed a similar response to semantic violations (N400), their response to speakers' inconsistencies slightly diverged; late bilinguals showed a positivity much earlier than native speakers (LPP). These results suggest that, like native speakers, late bilinguals process semantic and pragmatic information incrementally; however, what seems to differ between L1 and L2 processing is the time-course of the different processes. We propose that this difference may originate from late bilinguals' sensitivity to pragmatic information and/or their ability to efficiently make use of the information provided by the sentence context to generate expectations in relation to pragmatic information during L2 sentence comprehension. In other words, late bilinguals may rely more on speaker identity than native speakers when they face semantic integration difficulties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electrophysiological correlates of cross-linguistic semantic integration in hearing signers: N400 and LPC.

PubMed

Zachau, Swantje; Korpilahti, Pirjo; Hämäläinen, Jarmo A; Ervast, Leena; Heinänen, Kaisu; Suominen, Kalervo; Lehtihalmes, Matti; Leppänen, Paavo H T

2014-07-01

We explored semantic integration mechanisms in native and non-native hearing users of sign language and non-signing controls. Event-related brain potentials (ERPs) were recorded while participants performed a semantic decision task for priming lexeme pairs. Pairs were presented either within speech or across speech and sign language. Target-related ERP responses were subjected to principal component analyses (PCA), and neurocognitive basis of semantic integration processes were assessed by analyzing the N400 and the late positive complex (LPC) components in response to spoken (auditory) and signed (visual) antonymic and unrelated targets. Semantically-related effects triggered across modalities would indicate a similar tight interconnection between the signers׳ two languages like that described for spoken language bilinguals. Remarkable structural similarity of the N400 and LPC components with varying group differences between the spoken and signed targets were found. The LPC was the dominant response. The controls׳ LPC differed from the LPC of the two signing groups. It was reduced to the auditory unrelated targets and was less frontal for all the visual targets. The visual LPC was more broadly distributed in native than non-native signers and was left-lateralized for the unrelated targets in the native hearing signers only. Semantic priming effects were found for the auditory N400 in all groups, but only native hearing signers revealed a clear N400 effect to the visual targets. Surprisingly, the non-native signers revealed no semantically-related processing effect to the visual targets reflected in the N400 or the LPC; instead they appeared to rely more on visual post-lexical analyzing stages than native signers. We conclude that native and non-native signers employed different processing strategies to integrate signed and spoken semantic content. It appeared that the signers׳ semantic processing system was affected by group-specific factors like language background and/or usage. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Theory of Indian Controlled Schools.

ERIC Educational Resources Information Center

Clifford, Gerald M.

American Indian rejection of the assimilation process coupled with recent positive Office of Educational Opportunity (OEO) experiences have given birth to new Indian ideologies which encompass regeneration of the internal forces in the Indian community. Local control of education provides the key to regenerative action and total development,…

Gene expression profiling of intestinal regeneration in the sea cucumber

PubMed Central

Ortiz-Pineda, Pablo A; Ramírez-Gómez, Francisco; Pérez-Ortiz, Judit; González-Díaz, Sebastián; Santiago-De Jesús, Francisco; Hernández-Pasos, Josue; Del Valle-Avila, Cristina; Rojas-Cartagena, Carmencita; Suárez-Castillo, Edna C; Tossas, Karen; Méndez-Merced, Ana T; Roig-López, José L; Ortiz-Zuazaga, Humberto; García-Arrarás, José E

2009-01-01

Background Among deuterostomes, the regenerative potential is maximally expressed in echinoderms, animals that can quickly replace most injured organs. In particular, sea cucumbers are excellent models for studying organ regeneration since they regenerate their digestive tract after evisceration. However, echinoderms have been sidelined in modern regeneration studies partially because of the lack of genome-wide profiling approaches afforded by modern genomic tools. For the last decade, our laboratory has been using the sea cucumber Holothuria glaberrima to dissect the cellular and molecular events that allow for such amazing regenerative processes. We have already established an EST database obtained from cDNA libraries of normal and regenerating intestine at two different regeneration stages. This database now has over 7000 sequences. Results In the present work we used a custom-made microchip from Agilent with 60-mer probes for these ESTs, to determine the gene expression profile during intestinal regeneration. Here we compared the expression profile of animals at three different intestinal regeneration stages (3-, 7- and 14-days post evisceration) against the profile from normal (uneviscerated) intestines. The number of differentially expressed probes ranged from 70% at p < 0.05 to 39% at p < 0.001. Clustering analyses show specific profiles of expression for early (first week) and late (second week) regeneration stages. We used semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) to validate the expression profile of fifteen microarray detected differentially expressed genes which resulted in over 86% concordance between both techniques. Most of the differentially expressed ESTs showed no clear similarity to sequences in the databases and might represent novel genes associated with regeneration. However, other ESTs were similar to genes known to be involved in regeneration-related processes, wound healing, cell proliferation, differentiation, morphological plasticity, cell survival, stress response, immune challenge, and neoplastic transformation. Among those that have been validated, cytoskeletal genes, such as actins, and developmental genes, such as Wnt and Hox genes, show interesting expression profiles during regeneration. Conclusion Our findings set the base for future studies into the molecular basis of intestinal regeneration. Moreover, it advances the use of echinoderms in regenerative biology, animals that because of their amazing properties and their key evolutionary position, might provide important clues to the genetic basis of regenerative processes. PMID:19505337

Periosteum mechanobiology and mechanistic insights for regenerative medicine

PubMed Central

Knothe Tate, Melissa L; Yu, Nicole Y C; Jalilian, Iman; Pereira, André F; Knothe, Ulf R

2016-01-01

Periosteum is a smart mechanobiological material that serves as a habitat and delivery vehicle for stem cells as well as biological factors that modulate tissue genesis and healing. Periosteum's remarkable regenerative capacity has been harnessed clinically for over two hundred years. Scientific studies over the past decade have begun to decipher the mechanobiology of periosteum, which has a significant role in its regenerative capacity. This integrative review outlines recent mechanobiological insights that are key to modulating and translating periosteum and its resident stem cells in a regenerative medicine context. PMID:27974968

Platelet-rich fibrin: a boon in regenerative endodontics.

PubMed

Rebentish, Priyanka D; Umashetty, Girish; Kaur, Harpreet; Doizode, Trupthi; Kaslekar, Mithun; Chowdhury, Shouvik

2016-12-01

Research into regenerative dentistry has contributed momentum to the field of molecular biology. Periapical surgery aims at removing periapical pathology to achieve complete wound healing and regeneration of bone and periodontal tissue. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. Platelet-rich fibrin (PRF) is a wonderful tissue-engineering product and has recently gained much popularity due its promising results in wound healing bone induction. The features of this product are an attribute of platelets which, after cellular interactions, release growth factors and have shown application in diverse disciplines of dentistry. This paper is intended to shed light onto the various prospects of PRF and to provide clinical insight into regenerative endodontic therapy.

Science and Ethics: Bridge to the Future for Regenerative Medicine

PubMed Central

Patricio, Ventura-Juncá

2011-01-01

The objective of this article is to reflect on the relationship between regenerative medicine and ethics, using as references the Aristotelian concept of what is ethical and that of Raessler Van Potter about bioethics. To do this, I will briefly describe the advances in regenerative medicine with stem cells, the strategies for producing pluripotential cells without destroying human embryos, and the great potential of stem cells to improve life for Humanity, noting that for this to be possible, it is necessary to locate the role of regenerative medicine in the context of human values and well being. In this way, this article has a real perspective of the role that regenerative medicine can play in benefitting human beings and engendering respect for human and natural environments. PMID:24298338

Current overview on challenges in regenerative endodontics

PubMed Central

Bansal, Ramta; Jain, Aditya; Mittal, Sunandan

2015-01-01

Introduction: Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment. Aim: The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice. Materials and Methods: A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were “regenerative endodontics,” “dental stem cells,” “growth factor regeneration,” “scaffolds,” and “challenges in regeneration.” This review article screened about 150 articles and then the relevant information was compiled. Results: Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes. Conclusion: Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth. PMID:25657518

Concise Review: Translating Regenerative Biology into Clinically Relevant Therapies: Are We on the Right Path?

PubMed Central

2017-01-01

Abstract Despite approaches in regenerative medicine using stem cells, bio‐engineered scaffolds, and targeted drug delivery to enhance human tissue repair, clinicians remain unable to regenerate large‐scale, multi‐tissue defects in situ. The study of regenerative biology using mammalian models of complex tissue regeneration offers an opportunity to discover key factors that stimulate a regenerative rather than fibrotic response to injury. For example, although primates and rodents can regenerate their distal digit tips, they heal more proximal amputations with scar tissue. Rabbits and African spiny mice re‐grow tissue to fill large musculoskeletal defects through their ear pinna, while other mammals fail to regenerate identical defects and instead heal ear holes through fibrotic repair. This Review explores the utility of these comparative healing models using the spiny mouse ear pinna and the mouse digit tip to consider how mechanistic insight into reparative regeneration might serve to advance regenerative medicine. Specifically, we consider how inflammation and immunity, extracellular matrix composition, and controlled cell proliferation intersect to establish a pro‐regenerative microenvironment in response to injuries. Understanding how some mammals naturally regenerate complex tissue can provide a blueprint for how we might manipulate the injury microenvironment to enhance regenerative abilities in humans. Stem Cells Translational Medicine 2018;7:220–231 PMID:29271610

Assessing Competence in ESL: Reading.

ERIC Educational Resources Information Center

Oller, John W., Jr.

Results from research with eye movement photography (EMP) are discussed with a view to defining differences between native-speaker and non-native reading processes. The greatest contrast is in terms of the duration of eye fixations; non-native speakers at the college level require about as much time for a fixation as an average native-speaker at…

Making it stick: chasing the optimal stem cells for cardiac regeneration

PubMed Central

Quijada, Pearl; Sussman, Mark A

2014-01-01

Despite the increasing use of stem cells for regenerative-based cardiac therapy, the optimal stem cell population(s) remains in a cloud of uncertainty. In the past decade, the field has witnessed a surge of researchers discovering stem cell populations reported to directly and/or indirectly contribute to cardiac regeneration through processes of cardiomyogenic commitment and/or release of cardioprotective paracrine factors. This review centers upon defining basic biological characteristics of stem cells used for sustaining cardiac integrity during disease and maintenance of communication between the cardiac environment and stem cells. Given the limited successes achieved so far in regenerative therapy, the future requires development of unprecedented concepts involving combinatorial approaches to create and deliver the optimal stem cell(s) that will enhance myocardial healing. PMID:25340282

Tissue Engineering and Regenerative Repair in Wound Healing

PubMed Central

Hu, Michael S.; Maan, Zeshaan N.; Wu, Jen-Chieh; Rennert, Robert C.; Hong, Wan Xing; Lai, Tiffany S.; Cheung, Alexander T. M.; Walmsley, Graham G.; Chung, Michael T.; McArdle, Adrian; Longaker, Michael T.; Lorenz, H. Peter

2014-01-01

Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration. PMID:24788648

Development of sputtering process to deposit stoichiometric zirconia coatings for the inside wall of regeneratively cooled rocket thrust chambers

NASA Technical Reports Server (NTRS)

Busch, R.

1978-01-01

Thermal barrier coatings of yttria stabilized zirconia and zirconia-ceria mixtures were deposited by RF reactive sputtering. Coatings were 1-2 mils thick, and were deposited on copper cylinders intended to simulate the inner wall of a regeneratively cooled thrust chamber. Coating stoichiometry and adherence were investigated as functions of deposition parameters. Modest deposition rates (approximately 0.15 mil/hr) and subambient sustrate temperatures (-80 C) resulted in nearly stoichiometric coatings which remained adherent through thermal cycles between -196 and 400 C. Coatings deposited at higher rates or substrates temperatures exhibited greater oxygen deficiences, while coatings deposited at lower temperatures were not adherent. Substrate bias resulted in structural changes in the coating and high krypton contents; no clear effect on stoichiometry was observed.

A journey from basic stem cell discovery to clinical application: the case of adventitial progenitor cells.

PubMed

Spencer, Helen L; Slater, Sadie C; Rowlinson, Jonathan; Morgan, Tom; Culliford, Lucy A; Guttridge, Martin; Emanueli, Costanza; Angelini, Gianni; Madeddu, Paolo

2015-01-01

Ischemia is a leading cause of death in the western world. Regenerative medicine aims to improve healing of ischemic injury by complementing pharmacologic/interventional treatments. Navigating regenerative therapies from 'bench-to-bedside' is a multistep time-consuming process, balancing cell expansion, purity, safety and efficacy while complying with regulatory guidelines. Studies started in academic laboratories unused to long-term planning often fail because of poor strategy design, lack of contingency plans or funding. We provide a strategic insight into our translation of saphenous vein-derived adventitial progenitor cells into a clinical grade product to treat angina. We discuss discovery phases, introduction of standard operating procedures and upgrade to clinical standards. We also examine contractual aspects of transferring to GMP-accredited facilities for clinical production and unexpected hurdles.

Community-based participatory research with Native American communities: the Chronic Disease Self-Management Program.

PubMed

Jernigan, Valarie Blue Bird

2010-11-01

Health disparities among Native Americans persist despite efforts to translate evidence-based programs from research to practice. Few evidence-based, theory-driven prevention and management interventions have been successfully translated within Native American communities. The use of community-based participatory research (CBPR) has shown promise in this process. This article provides an overview of the use of CBPR with Native American communities and discusses the translation of the Stanford Chronic Disease Self-Management Program, using a CBPR approach, with an urban Native American community. This article highlights not only how the CBPR process facilitates the successful translation of the Stanford program but also how CBPR is used within this community to build community capacity.

Initiating a regenerative response; cellular and molecular features of wound healing in the cnidarian Nematostella vectensis.

PubMed

DuBuc, Timothy Q; Traylor-Knowles, Nikki; Martindale, Mark Q

2014-03-26

Wound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response. Defective wound healing can block regeneration even in animals with a high regenerative capacity. Understanding how signals generated during wound healing promote regeneration of lost structures is highly important, considering that virtually all animals have the ability to heal but many lack the ability to regenerate missing structures. Cnidarians are the phylogenetic sister taxa to bilaterians and are highly regenerative animals. To gain a greater understanding of how early animals generate a regenerative response, we examined the cellular and molecular components involved during wound healing in the anthozoan cnidarian Nematostella vectensis. Pharmacological inhibition of extracellular signal-regulated kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. We characterized early and late wound healing events through genome-wide microarray analysis, quantitative PCR, and in situ hybridization to identify potential wound healing targets. We identified a number of genes directly related to the wound healing response in other animals (metalloproteinases, growth factors, transcription factors) and suggest that glycoproteins (mucins and uromodulin) play a key role in early wound healing events. This study also identified a novel cnidarian-specific gene, for a thiamine biosynthesis enzyme (vitamin B synthesis), that may have been incorporated into the genome by lateral gene transfer from bacteria and now functions during wound healing. Lastly, we suggest that ERK signaling is a shared element of the early wound response for animals with a high regenerative capacity. This research describes the temporal events involved during Nematostella wound healing, and provides a foundation for comparative analysis with other regenerative and non-regenerative species. We have shown that the same genes that heal puncture wounds are also activated after oral-aboral bisection, indicating a clear link with the initiation of regenerative healing. This study demonstrates the strength of using a forward approach (microarray) to characterize a developmental phenomenon (wound healing) at a phylogenetically important crossroad of animal evolution (cnidarian-bilaterian ancestor). Accumulation of data on the early wound healing events across numerous systems may provide clues as to why some animals have limited regenerative abilities.

Initiating a regenerative response; cellular and molecular features of wound healing in the cnidarian Nematostella vectensis

PubMed Central

2014-01-01

Background Wound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response. Defective wound healing can block regeneration even in animals with a high regenerative capacity. Understanding how signals generated during wound healing promote regeneration of lost structures is highly important, considering that virtually all animals have the ability to heal but many lack the ability to regenerate missing structures. Cnidarians are the phylogenetic sister taxa to bilaterians and are highly regenerative animals. To gain a greater understanding of how early animals generate a regenerative response, we examined the cellular and molecular components involved during wound healing in the anthozoan cnidarian Nematostella vectensis. Results Pharmacological inhibition of extracellular signal-regulated kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. We characterized early and late wound healing events through genome-wide microarray analysis, quantitative PCR, and in situ hybridization to identify potential wound healing targets. We identified a number of genes directly related to the wound healing response in other animals (metalloproteinases, growth factors, transcription factors) and suggest that glycoproteins (mucins and uromodulin) play a key role in early wound healing events. This study also identified a novel cnidarian-specific gene, for a thiamine biosynthesis enzyme (vitamin B synthesis), that may have been incorporated into the genome by lateral gene transfer from bacteria and now functions during wound healing. Lastly, we suggest that ERK signaling is a shared element of the early wound response for animals with a high regenerative capacity. Conclusions This research describes the temporal events involved during Nematostella wound healing, and provides a foundation for comparative analysis with other regenerative and non-regenerative species. We have shown that the same genes that heal puncture wounds are also activated after oral-aboral bisection, indicating a clear link with the initiation of regenerative healing. This study demonstrates the strength of using a forward approach (microarray) to characterize a developmental phenomenon (wound healing) at a phylogenetically important crossroad of animal evolution (cnidarian-bilaterian ancestor). Accumulation of data on the early wound healing events across numerous systems may provide clues as to why some animals have limited regenerative abilities. PMID:24670243

The Role of Native-Language Knowledge in the Perception of Casual Speech in a Second Language

PubMed Central

Mitterer, Holger; Tuinman, Annelie

2012-01-01

Casual speech processes, such as /t/-reduction, make word recognition harder. Additionally, word recognition is also harder in a second language (L2). Combining these challenges, we investigated whether L2 learners have recourse to knowledge from their native language (L1) when dealing with casual speech processes in their L2. In three experiments, production and perception of /t/-reduction was investigated. An initial production experiment showed that /t/-reduction occurred in both languages and patterned similarly in proper nouns but differed when /t/ was a verbal inflection. Two perception experiments compared the performance of German learners of Dutch with that of native speakers for nouns and verbs. Mirroring the production patterns, German learners’ performance strongly resembled that of native Dutch listeners when the reduced /t/ was part of a word stem, but deviated where /t/ was a verbal inflection. These results suggest that a casual speech process in a second language is problematic for learners when the process is not known from the leaner’s native language, similar to what has been observed for phoneme contrasts. PMID:22811675

Processing changes when listening to foreign-accented speech

PubMed Central

Romero-Rivas, Carlos; Martin, Clara D.; Costa, Albert

2015-01-01

This study investigates the mechanisms responsible for fast changes in processing foreign-accented speech. Event Related brain Potentials (ERPs) were obtained while native speakers of Spanish listened to native and foreign-accented speakers of Spanish. We observed a less positive P200 component for foreign-accented speech relative to native speech comprehension. This suggests that the extraction of spectral information and other important acoustic features was hampered during foreign-accented speech comprehension. However, the amplitude of the N400 component for foreign-accented speech comprehension decreased across the experiment, suggesting the use of a higher level, lexical mechanism. Furthermore, during native speech comprehension, semantic violations in the critical words elicited an N400 effect followed by a late positivity. During foreign-accented speech comprehension, semantic violations only elicited an N400 effect. Overall, our results suggest that, despite a lack of improvement in phonetic discrimination, native listeners experience changes at lexical-semantic levels of processing after brief exposure to foreign-accented speech. Moreover, these results suggest that lexical access, semantic integration and linguistic re-analysis processes are permeable to external factors, such as the accent of the speaker. PMID:25859209

Umyuangcaryaraq "Reflecting": multidimensional assessment of reflective processes on the consequences of alcohol use among rural Yup'ik Alaska Native youth.

PubMed

Allen, James; Fok, Carlotta Ching Ting; Henry, David; Skewes, Monica

2012-09-01

Concerns in some settings regarding the accuracy and ethics of employing direct questions about alcohol use suggest need for alternative assessment approaches with youth. Umyuangcaryaraq is a Yup'ik Alaska Native word meaning "Reflecting." The Reflective Processes Scale was developed as a youth measure tapping awareness and thinking over potential negative consequences of alcohol misuse as a protective factor that includes cultural elements often shared by many other Alaska Native and American Indian cultures. This study assessed multidimensional structure, item functioning, and validity. Responses from 284 rural Alaska Native youth allowed bifactor analysis to assess structure, estimates of location and discrimination parameters, and convergent and discriminant validity. A bifactor model of the scale items with three content factors provided excellent fit to observed data. Item response theory analysis suggested a binary response format as optimal. Evidence of convergent and discriminant validity was established. The measure provides an assessment of reflective processes about alcohol that Alaska Native youth engage in when thinking about reasons not to drink. The concept of reflective processes has potential to extend understandings of cultural variation in mindfulness, alcohol expectancies research, and culturally mediated protective factors in Alaska Native and American Indian youth.

Hemispheric asymmetry of emotion words in a non-native mind: a divided visual field study.

PubMed

Jończyk, Rafał

2015-05-01

This study investigates hemispheric specialization for emotional words among proficient non-native speakers of English by means of the divided visual field paradigm. The motivation behind the study is to extend the monolingual hemifield research to the non-native context and see how emotion words are processed in a non-native mind. Sixty eight females participated in the study, all highly proficient in English. The stimuli comprised 12 positive nouns, 12 negative nouns, 12 non-emotional nouns and 36 pseudo-words. To examine the lateralization of emotion, stimuli were presented unilaterally in a random fashion for 180 ms in a go/no-go lexical decision task. The perceptual data showed a right hemispheric advantage for processing speed of negative words and a complementary role of the two hemispheres in the recognition accuracy of experimental stimuli. The data indicate that processing of emotion words in non-native language may require greater interhemispheric communication, but at the same time demonstrates a specific role of the right hemisphere in the processing of negative relative to positive valence. The results of the study are discussed in light of the methodological inconsistencies in the hemifield research as well as the non-native context in which the study was conducted.

Regenerative peripheral nerve interface viability and signal transduction with an implanted electrode.

PubMed

Kung, Theodore A; Langhals, Nicholas B; Martin, David C; Johnson, Philip J; Cederna, Paul S; Urbanchek, Melanie G

2014-06-01

The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer. In a rat model, the extensor digitorum longus muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided peroneal nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was implanted on the muscle transfer and secured with an encircling acellular extracellular matrix. The contralateral muscle served as the control. The free muscle transfers were successfully revascularized and over time reinnervated as evidenced by serial insertional needle electromyography. Compound muscle action potentials were successfully transduced through the regenerative peripheral nerve interface. The conductive polymer coating on the implanted electrode resulted in increased recorded signal amplitude that was observed throughout the course of the study. Histologic examination confirmed axonal sprouting, elongation, and synaptogenesis within regenerative peripheral nerve interface regardless of electrode type. The regenerative peripheral nerve interface remains viable over seven months in the presence of an implanted electrode. Electrodes with and without conductive polymer reliably transduced signals from the regenerative peripheral nerve interface. Electrodes with a conductive polymer coating resulted in recording more of the regenerative peripheral nerve interface signal.

Regenerative agriculture: merging farming and natural resource conservation profitably.

PubMed

LaCanne, Claire E; Lundgren, Jonathan G

2018-01-01

Most cropland in the United States is characterized by large monocultures, whose productivity is maintained through a strong reliance on costly tillage, external fertilizers, and pesticides (Schipanski et al., 2016). Despite this, farmers have developed a regenerative model of farm production that promotes soil health and biodiversity, while producing nutrient-dense farm products profitably. Little work has focused on the relative costs and benefits of novel regenerative farming operations, which necessitates studying in situ , farmer-defined best management practices. Here, we evaluate the relative effects of regenerative and conventional corn production systems on pest management services, soil conservation, and farmer profitability and productivity throughout the Northern Plains of the United States. Regenerative farming systems provided greater ecosystem services and profitability for farmers than an input-intensive model of corn production. Pests were 10-fold more abundant in insecticide-treated corn fields than on insecticide-free regenerative farms, indicating that farmers who proactively design pest-resilient food systems outperform farmers that react to pests chemically. Regenerative fields had 29% lower grain production but 78% higher profits over traditional corn production systems. Profit was positively correlated with the particulate organic matter of the soil, not yield. These results provide the basis for dialogue on ecologically based farming systems that could be used to simultaneously produce food while conserving our natural resource base: two factors that are pitted against one another in simplified food production systems. To attain this requires a systems-level shift on the farm; simply applying individual regenerative practices within the current production model will not likely produce the documented results.

A novel regenerative shock absorber with a speed doubling mechanism and its Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Zhang, Ran; Wang, Xu; Liu, Zhenwei

2018-03-01

A novel regenerative shock absorber has been designed and fabricated. The novelty of the presented work is the application of the double speed regenerative shock absorber that utilizes the rack and pinion mechanism to increase the magnet speed with respect to the coils for higher power output. The simulation models with parameters identified from finite element analysis and the experiments are developed. The proposed regenerative shock absorber is compared with the regenerative shock absorber without the rack and pinion mechanism, when they are integrated into the same quarter vehicle suspension system. The sinusoidal wave road profile displacement excitation and the random road profile displacement excitation with peak amplitude of 0.035 m are applied as the inputs in the frequency range of 0-25 Hz. It is found that with the sinusoidal and random road profile displacement input, the proposed innovative design can increase the output power by 4 times comparing to the baseline design. The proposed double speed regenerative shock absorber also presents to be more sensitive to the road profile irregularity than the single speed regenerative shock absorber as suggested by Monte Carlo simulation. Lastly the coil mass and amplification factor are studied for sensitivity analysis and performance optimization, which provides a general design method of the regenerative shock absorbers. It shows that for the system power output, the proposed design becomes more sensitive to either the coil mass or amplification factor depending on the amount of the coil mass. With the specifically selected combination of the coil mass and amplification factor, the optimized energy harvesting performance can be achieved.

The Perception and Representation of Segmental and Prosodic Mandarin Contrasts in Native Speakers of Cantonese

PubMed Central

Zhang, Xujin; Samuel, Arthur G.; Liu, Siyun

2011-01-01

Previous research has found that a speaker’s native phonological system has a great influence on perception of another language. In three experiments, we tested the perception and representation of Mandarin phonological contrasts by Guangzhou Cantonese speakers, and compared their performance to that of native Mandarin speakers. Despite their rich experience using Mandarin Chinese, the Cantonese speakers had problems distinguishing specific Mandarin segmental and tonal contrasts that do not exist in Guangzhou Cantonese. However, we found evidence that the subtle differences between two members of a contrast were nonetheless represented in the lexicon. We also found different processing patterns for non-native segmental versus non-native tonal contrasts. The results provide substantial new information about the representation and processing of segmental and prosodic information by individuals listening to a closely-related, very well-learned, but still non-native language. PMID:22707849

Photochemical Upconversion: A Physical or Inorganic Chemistry Experiment for Undergraduates Using a Conventional Fluorimeter

ERIC Educational Resources Information Center

Wilke, Bryn M.; Castellano, Felix N.

2013-01-01

Photochemical upconversion is a regenerative process that transforms lower-energy photons into higher-energy light through two sequential bimolecular reactions, triplet sensitization of an appropriate acceptor followed by singlet fluorescence producing triplet-triplet annihilation derived from two energized acceptors. This laboratory directly…

Stem cells: intellectual property issues in regenerative medicine.

PubMed

Zachariades, Nicholas A

2013-12-01

The topic of stem cells for use in regenerative medicine, especially embryonic stem cells, inspires much debate, discussion, and outrage as it slices through the very core moral values of society. These social and moral issues have, in turn, resulted in government policies that have influenced the study of stem cells in regenerative medicine.

Calculating Electrical Requirements for Direct Current Electric Actuators

DTIC Science & Technology

2017-11-29

These requirements lead to the determination of multiple design decisions such as: operating voltage, regenerative energy capture/dissipation, and...15. SUBJECT TERMS Electro-mechanical actuation Regenerative energy Electrical power Servo control Direct current (DC...Method 6 Power Supply Requirements 7 Approaches to Handling Regenerative Energy 8 Conductor Selection 10 Results and Discussions 10 Example

Are Local Filters Blind to Provenance? Ant Seed Predation Suppresses Exotic Plants More than Natives

PubMed Central

Pearson, Dean E.; Icasatti, Nadia S.; Hierro, Jose L.; Bird, Benjamin J.

2014-01-01

The question of whether species’ origins influence invasion outcomes has been a point of substantial debate in invasion ecology. Theoretically, colonization outcomes can be predicted based on how species’ traits interact with community filters, a process presumably blind to species’ origins. Yet, exotic plant introductions commonly result in monospecific plant densities not commonly seen in native assemblages, suggesting that exotic species may respond to community filters differently than natives. Here, we tested whether exotic and native species differed in their responses to a local community filter by examining how ant seed predation affected recruitment of eighteen native and exotic plant species in central Argentina. Ant seed predation proved to be an important local filter that strongly suppressed plant recruitment, but ants suppressed exotic recruitment far more than natives (89% of exotic species vs. 22% of natives). Seed size predicted ant impacts on recruitment independent of origins, with ant preference for smaller seeds resulting in smaller seeded plant species being heavily suppressed. The disproportionate effects of provenance arose because exotics had generally smaller seeds than natives. Exotics also exhibited greater emergence and earlier peak emergence than natives in the absence of ants. However, when ants had access to seeds, these potential advantages of exotics were negated due to the filtering bias against exotics. The differences in traits we observed between exotics and natives suggest that higher-order introduction filters or regional processes preselected for certain exotic traits that then interacted with the local seed predation filter. Our results suggest that the interactions between local filters and species traits can predict invasion outcomes, but understanding the role of provenance will require quantifying filtering processes at multiple hierarchical scales and evaluating interactions between filters. PMID:25099535

Repairing quite swimmingly: advances in regenerative medicine using zebrafish.

PubMed

Goessling, Wolfram; North, Trista E

2014-07-01

Regenerative medicine has the promise to alleviate morbidity and mortality caused by organ dysfunction, longstanding injury and trauma. Although regenerative approaches for a few diseases have been highly successful, some organs either do not regenerate well or have no current treatment approach to harness their intrinsic regenerative potential. In this Review, we describe the modeling of human disease and tissue repair in zebrafish, through the discovery of disease-causing genes using classical forward-genetic screens and by modulating clinically relevant phenotypes through chemical genetic screening approaches. Furthermore, we present an overview of those organ systems that regenerate well in zebrafish in contrast to mammalian tissue, as well as those organs in which the regenerative potential is conserved from fish to mammals, enabling drug discovery in preclinical disease-relevant models. We provide two examples from our own work in which the clinical translation of zebrafish findings is either imminent or has already proven successful. The promising results in multiple organs suggest that further insight into regenerative mechanisms and novel clinically relevant therapeutic approaches will emerge from zebrafish research in the future. © 2014. Published by The Company of Biologists Ltd.

An Efficient Power Regeneration and Drive Method of an Induction Motor by Means of an Optimal Torque Derived by Variational Method

NASA Astrophysics Data System (ADS)

Inoue, Kaoru; Ogata, Kenji; Kato, Toshiji

When the motor speed is reduced by using a regenerative brake, the mechanical energy of rotation is converted to the electrical energy. When the regenerative torque is large, the corresponding current increases so that the copper loss also becomes large. On the other hand, the damping effect of rotation increases according to the time elapse when the regenerative torque is small. In order to use the limited energy effectively, an optimal regenerative torque should be discussed in order to regenerate electrical energy as much as possible. This paper proposes a design methodology of a regenerative torque for an induction motor to maximize the regenerative electric energy by means of the variational method. Similarly, an optimal torque for acceleration is derived in order to minimize the energy to drive. Finally, an efficient motor drive system with the proposed optimal torque and the power storage system stabilizing the DC link voltage will be proposed. The effectiveness of the proposed methods are illustrated by both simulations and experiments.

Cultivating regenerative medicine innovation in China.

PubMed

McMahon, Dominique S; Thorsteinsdóttir, Halla; Singer, Peter A; Daar, Abdallah S

2010-01-01

While China has become a significant contributor and prolific publisher in regenerative medicine, its role in the field is not well understood. We analyze how capacity in regenerative medicine was built in China to identify some of its main strengths and challenges. This case study of regenerative medicine in China is primarily based on interviews with experts in China, including researchers, policy makers, clinicians, representatives of firms and regulators. Our analysis shows that diverse groups are active in this field in China. Leading research groups are contributing extensively to international peer-reviewed journals. Strong governmental support and recruitment of highly trained Chinese scientists from abroad has made it possible for China to rapidly build up capacity in regenerative medicine. However, some hospitals in China are offering stem cell therapies with limited scientific evidence supporting their efficacy/safety, and international skepticism of medical research in China presents a challenge to the development of the field. China has been able to catapult itself into the forefront of regenerative medicine but needs to address current regulatory challenges in order to secure its position in this emerging field.

Reciprocal Effects of Litter from Exotic and Congeneric Native Plant Species via Soil Nutrients

PubMed Central

Meisner, Annelein; de Boer, Wietse; Cornelissen, Johannes H. C.; van der Putten, Wim H.

2012-01-01

Invasive exotic plant species are often expected to benefit exclusively from legacy effects of their litter inputs on soil processes and nutrient availability. However, there are relatively few experimental tests determining how litter of exotic plants affects their own growth conditions compared to congeneric native plant species. Here, we test how the legacy of litter from three exotic plant species affects their own performance in comparison to their congeneric natives that co-occur in the invaded habitat. We also analyzed litter effects on soil processes. In all three comparisons, soil with litter from exotic plant species had the highest respiration rates. In two out of the three exotic-native species comparisons, soil with litter from exotic plant species had higher inorganic nitrogen concentrations than their native congener, which was likely due to higher initial litter quality of the exotics. When litter from an exotic plant species had a positive effect on itself, it also had a positive effect on its native congener. We conclude that exotic plant species develop a legacy effect in soil from the invaded range through their litter inputs. This litter legacy effect results in altered soil processes that can promote both the exotic plant species and their native congener. PMID:22359604

Second Language Processing in Reading and Translation

ERIC Educational Resources Information Center

Lim, Jung Hyun

2011-01-01

The purpose of this dissertation is to investigate the processing mechanisms of non-native English speakers at both the sentence level and the morphological level, addressing the issue of whether adult second language (L2) learners qualitatively differ from native speakers in processing linguistic input. Using psycholinguistic on-line techniques…

Fuzzy logic electric vehicle regenerative antiskid braking and traction control system

DOEpatents

Cikanek, S.R.

1994-10-25

An regenerative antiskid braking and traction control system using fuzzy logic for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensor and determining if regenerative antiskid braking control, requiring hydraulic braking control, and requiring traction control are required. The processor then employs fuzzy logic based on the determined vehicle state and provides command signals to a motor controller to control operation of the electric traction motor and to the brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative braking control, hydraulic braking control, and traction control. 123 figs.

Fuzzy logic electric vehicle regenerative antiskid braking and traction control system

DOEpatents

Cikanek, Susan R.

1994-01-01

An regenerative antiskid braking and traction control system using fuzzy logic for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensor and determining if regenerative antiskid braking control, requiring hydraulic braking control, and requiring traction control are required. The processor then employs fuzzy logic based on the determined vehicle state and provides command signals to a motor controller to control operation of the electric traction motor and to the brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative braking control, hydraulic braking control, and traction control.

Electrical power production from low-grade waste heat using a thermally regenerative ethylenediamine battery

NASA Astrophysics Data System (ADS)

Rahimi, Mohammad; D'Angelo, Adriana; Gorski, Christopher A.; Scialdone, Onofrio; Logan, Bruce E.

2017-05-01

Thermally regenerative ammonia-based batteries (TRABs) have been developed to harvest low-grade waste heat as electricity. To improve the power production and anodic coulombic efficiency, the use of ethylenediamine as an alternative ligand to ammonia was explored here. The power density of the ethylenediamine-based battery (TRENB) was 85 ± 3 W m-2-electrode area with 2 M ethylenediamine, and 119 ± 4 W m-2 with 3 M ethylenediamine. This power density was 68% higher than that of TRAB. The energy density was 478 Wh m-3-anolyte, which was ∼50% higher than that produced by TRAB. The anodic coulombic efficiency of the TRENB was 77 ± 2%, which was more than twice that obtained using ammonia in a TRAB (35%). The higher anodic efficiency reduced the difference between the anode dissolution and cathode deposition rates, resulting in a process more suitable for closed loop operation. The thermal-electric efficiency based on ethylenediamine separation using waste heat was estimated to be 0.52%, which was lower than that of TRAB (0.86%), mainly due to the more complex separation process. However, this energy recovery could likely be improved through optimization of the ethylenediamine separation process.

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

Lexical Encoding of L2 Tones: The Role of L1 Stress, Pitch Accent and Intonation

ERIC Educational Resources Information Center

Braun, Bettina; Galts, Tobias; Kabak, Baris

2014-01-01

Native language prosodic structure is known to modulate the processing of non-native suprasegmental information. It has been shown that native speakers of French, a language without lexical stress, have difficulties storing non-native stress contrasts. We investigated whether the ability to store lexical tone (as in Mandarin Chinese) also depends…

An Authentic Voice in the Technocratic Wilderness: Alaskan Natives and the "Tundra Times."

ERIC Educational Resources Information Center

Daley, Patrick; James, Beverly

1986-01-01

Examines a pair of critical challenges to the cultural integrity of Alaskan Natives around 1960 as pivotal episodes in the process of native resistance to U. S. dominance. Historically evaluates the fragility of native culture in terms of the political, scientific, and economic interests expressed in the mainstream Alaskan press, particularly the…

Mathematics and Science Curricula in Elementary and Secondary Education for American Indian and Alaska Native Students.

ERIC Educational Resources Information Center

Preston, Vera

Issues related to the improvement of mathematics and science education pertain to Native students as well as to the general population. Native students are most successful at tasks that use visual and spatial abilities and that involve simultaneous processing. Instruction should build on Native students' strengths. Experiential learning and…

Cell electrospinning: a novel tool for functionalising fibres, scaffolds and membranes with living cells and other advanced materials for regenerative biology and medicine.

PubMed

Jayasinghe, Suwan N

2013-04-21

Recent years have seen interest in approaches for directly generating fibers and scaffolds following a rising trend for their exploration in the health sciences. In this review the author wishes to briefly highlight the many approaches explored to date for generating such structures, while underlining their advantages and disadvantages, and their contribution in particular to the biomedical sciences. Such structures have been demonstrated as having implications in both the laboratory and the clinic, as they mimic the native extra cellular matrix. Interestingly the only materials investigated until very recently for generating fibrous architectures employed either natural or synthetic polymers with or without the addition of functional molecule(s). Arguably although such constructs have been demonstrated to have many applications, they lack the one unit most important for carrying out the ability to directly reconstruct a three-dimensional functional tissue, namely living cells. Therefore recent findings have demonstrated the ability to directly form cell-laden fibers and scaffolds in useful quantities from which functional three-dimensional living tissues can be conceived. These recent developments have far-reaching ramifications to many areas of research and development, a few of which range from tissue engineering and regenerative medicine, a novel approach to analyzing cell behavior and function in real time in three-dimensions, to the advanced controlled and targeted delivery of experimental and/or medical cells and/or genes for localized treatment. At present these developments have passed all in vitro and in vivo mouse model based challenge trials and are now spearheading their journey towards initiating human clinical trials.

Three-dimensional assembly of tissue-engineered cartilage constructs results in cartilaginous tissue formation without retainment of zonal characteristics.

PubMed

Schuurman, W; Harimulyo, E B; Gawlitta, D; Woodfield, T B F; Dhert, W J A; van Weeren, P R; Malda, J

2016-04-01

Articular cartilage has limited regenerative capabilities. Chondrocytes from different layers of cartilage have specific properties, and regenerative approaches using zonal chondrocytes may yield better replication of the architecture of native cartilage than when using a single cell population. To obtain high seeding efficiency while still mimicking zonal architecture, cell pellets of expanded deep zone and superficial zone equine chondrocytes were seeded and cultured in two layers on poly(ethylene glycol)-terephthalate-poly(butylene terephthalate) (PEGT-PBT) scaffolds. Scaffolds seeded with cell pellets consisting of a 1:1 mixture of both cell sources served as controls. Parallel to this, pellets of superficial or deep zone chondrocytes, and combinations of the two cell populations, were cultured without the scaffold. Pellet cultures of zonal chondrocytes in scaffolds resulted in a high seeding efficiency and abundant cartilaginous tissue formation, containing collagen type II and glycosaminoglycans (GAGs) in all groups, irrespective of the donor (n = 3), zonal population or stratified scaffold-seeding approach used. However, whereas total GAG production was similar, the constructs retained significantly more GAG compared to pellet cultures, in which a high percentage of the produced GAGs were secreted into the culture medium. Immunohistochemistry for zonal markers did not show any differences between the conditions. We conclude that spatially defined pellet culture in 3D scaffolds is associated with high seeding efficiency and supports cartilaginous tissue formation, but did not result in the maintenance or restoration of the original zonal phenotype. The use of pellet-assembled constructs leads to a better retainment of newly produced GAGs than the use of pellet cultures alone. Copyright © 2013 John Wiley & Sons, Ltd.

Rheological characterization of human fibrin and fibrin-agarose oral mucosa substitutes generated by tissue engineering.

PubMed

Rodríguez, I A; López-López, M T; Oliveira, A C X; Sánchez-Quevedo, M C; Campos, A; Alaminos, M; Durán, J D G

2012-08-01

In regenerative medicine, the generation of biocompatible substitutes of tissues by in vitro tissue engineering must fulfil certain requirements. In the case of human oral mucosa, the rheological properties of tissues deserve special attention because of their influence in the acoustics and biomechanics of voice production. This work is devoted to the rheological characterization of substitutes of the connective tissue of the human oral mucosa. Two substitutes, composed of fibrin and fibrin-agarose, were prepared in cell culture for periods in the range 1-21 days. The time evolution of the rheological properties of both substitutes was studied by two different experimental procedures: steady-state and oscillatory measurements. The former allows the plastic behaviour of the substitutes to be characterized by estimating their yield stress; the latter is employed to quantify their viscoelastic responses by obtaining the elastic (G') and viscous (G'') moduli. The results demonstrate that both substitutes are characterized by a predominant elastic response, in which G' (order 100 Pa) is roughly one order of magnitude larger than G'' (order 10 Pa). But the most relevant insight is the stability, throughout the 21 days of culture time, of the rheological quantities in the case of fibrin-agarose, whereas the fibrin substitute shows a significant hardening. This result provides evidence that the addition to fibrin of a small amount of agarose allows the rheological stability of the oral mucosa substitute to be maintained. This feature, together with its viscoelastic similitude with native tissues, makes this biomaterial appropriate for potential use as a scaffold in regenerative therapies of human oral mucosa. Copyright © 2011 John Wiley & Sons, Ltd.

Conversion of native terrestrial ecosystems in Hawai‘i to novel grazing systems: a review

USGS Publications Warehouse

Leopold, Christina R.; Hess, Steven C.

2017-01-01

The remote oceanic islands of Hawai‘i exemplify the transformative effects that non-native herbivorous mammals can bring to isolated terrestrial ecosystems. We reviewed published literature containing systematically collected, analyzed, and peer-reviewed original data specifically addressing direct effects of non-native hoofed mammals (ungulates) on terrestrial ecosystems, and indirect effects and interactions on ecosystem processes in Hawai‘i. The effects of ungulates on native vegetation and ecosystems were addressed in 58 original studies and mostly showed strong short-term regeneration of dominant native trees and understory ferns after ungulate removal, but unassisted recovery was dependent on the extent of previous degradation. Ungulates were associated with herbivory, bark-stripping, disturbance by hoof action, soil erosion, enhanced nutrient cycling from the interaction of herbivory and grasses, and increased pyrogenicity and competition between native plants and pasture grasses. No studies demonstrated that ungulates benefitted native ecosystems except in short-term fire-risk reduction. However, non-native plants became problematic and continued to proliferate after release from herbivory, including at least 11 species of non-native pasture grasses that had become established prior to ungulate removal. Competition from non-native grasses inhibited native species regeneration where degradation was extensive. These processes have created novel grazing systems which, in some cases, have irreversibly altered Hawaii’s terrestrial ecology. Non-native plant control and outplanting of rarer native species will be necessary for recovery where degradation has been extensive. Lack of unassisted recovery in some locations should not be construed as a reason to not attempt restoration of other ecosystems.

Modeling invasive alien plant species in river systems: Interaction with native ecosystem engineers and effects on hydro-morphodynamic processes

NASA Astrophysics Data System (ADS)

van Oorschot, M.; Kleinhans, M. G.; Geerling, G. W.; Egger, G.; Leuven, R. S. E. W.; Middelkoop, H.

2017-08-01

Invasive alien plant species negatively impact native plant communities by out-competing species or changing abiotic and biotic conditions in their introduced range. River systems are especially vulnerable to biological invasions, because waterways can function as invasion corridors. Understanding interactions of invasive and native species and their combined effects on river dynamics is essential for developing cost-effective management strategies. However, numerical models for simulating long-term effects of these processes are lacking. This paper investigates how an invasive alien plant species affects native riparian vegetation and hydro-morphodynamics. A morphodynamic model has been coupled to a dynamic vegetation model that predicts establishment, growth and mortality of riparian trees. We introduced an invasive alien species with life-history traits based on Japanese Knotweed (Fallopia japonica), and investigated effects of low- and high propagule pressure on invasion speed, native vegetation and hydro-morphodynamic processes. Results show that high propagule pressure leads to a decline in native species cover due to competition and the creation of unfavorable native colonization sites. With low propagule pressure the invader facilitates native seedling survival by creating favorable hydro-morphodynamic conditions at colonization sites. With high invader abundance, water levels are raised and sediment transport is reduced during the growing season. In winter, when the above-ground invader biomass is gone, results are reversed and the floodplain is more prone to erosion. Invasion effects thus depend on seasonal above- and below ground dynamic vegetation properties and persistence of the invader, on the characteristics of native species it replaces, and the combined interactions with hydro-morphodynamics.

Non-invasive quality evaluation of confluent cells by image-based orientation heterogeneity analysis.

PubMed

Sasaki, Kei; Sasaki, Hiroto; Takahashi, Atsuki; Kang, Siu; Yuasa, Tetsuya; Kato, Ryuji

2016-02-01

In recent years, cell and tissue therapy in regenerative medicine have advanced rapidly towards commercialization. However, conventional invasive cell quality assessment is incompatible with direct evaluation of the cells produced for such therapies, especially in the case of regenerative medicine products. Our group has demonstrated the potential of quantitative assessment of cell quality, using information obtained from cell images, for non-invasive real-time evaluation of regenerative medicine products. However, image of cells in the confluent state are often difficult to evaluate, because accurate recognition of cells is technically difficult and the morphological features of confluent cells are non-characteristic. To overcome these challenges, we developed a new image-processing algorithm, heterogeneity of orientation (H-Orient) processing, to describe the heterogeneous density of cells in the confluent state. In this algorithm, we introduced a Hessian calculation that converts pixel intensity data to orientation data and a statistical profiling calculation that evaluates the heterogeneity of orientations within an image, generating novel parameters that yield a quantitative profile of an image. Using such parameters, we tested the algorithm's performance in discriminating different qualities of cellular images with three types of clinically important cell quality check (QC) models: remaining lifespan check (QC1), manipulation error check (QC2), and differentiation potential check (QC3). Our results show that our orientation analysis algorithm could predict with high accuracy the outcomes of all types of cellular quality checks (>84% average accuracy with cross-validation). Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Adaptive controller for regenerative and friction braking system

DOEpatents

Davis, R.I.

1990-10-16

A regenerative and friction braking system for a vehicle having one or more road wheels driven by an electric traction motor includes a driver responsive device for producing a brake demand signal having a magnitude corresponding to the level of braking force selected by the driver and friction and regenerative brakes operatively connected with the road wheels of the vehicle. A system according to this invention further includes control means for operating the friction and regenerative braking subsystems so that maximum brake torques sustainable by the road wheels of the vehicle without skidding or slipping will not be exceeded. 8 figs.

Adaptive controller for regenerative and friction braking system

DOEpatents

Davis, Roy I.

1990-01-01

A regenerative and friction braking system for a vehicle having one or more roadwheels driven by an electric traction motor includes a driver responsive device for producing a brake demand signal having a magnitude corresponding to the level of braking force selected by the driver and friction and regenerative brakes operatively connected with the roadwheels of the vehicle. A system according to this invention further includes control means for operating the friction and regenerative braking subsystems so that maximum brake torques sustainable by the roadwheels of the vehicle without skidding or slipping will not be exceeded.

Operator interface for vehicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bissontz, Jay E

2015-03-10

A control interface for drivetrain braking provided by a regenerative brake and a non-regenerative brake is implemented using a combination of switches and graphic interface elements. The control interface comprises a control system for allocating drivetrain braking effort between the regenerative brake and the non-regenerative brake, a first operator actuated control for enabling operation of the drivetrain braking, and a second operator actuated control for selecting a target braking effort for drivetrain braking. A graphic display displays to an operator the selected target braking effort and can be used to further display actual braking effort achieved by drivetrain braking.

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

Regenerative braking systems with torsional springs made of carbon nanotube yarn

NASA Astrophysics Data System (ADS)

Liu, S.; Martin, C.; Lashmore, D.; Schauer, M.; Livermore, C.

2014-11-01

The demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as an energy-storing actuator for regenerative braking systems. Originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing until failure. The maximum extractable energy density is measured to be as high as 6.13 kJ/kg. The tests also reveal structural reorganization and hysteresis in the torsional loading curves. A regenerative braking system is built to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yam's twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking system are up to 4.69 kJ/kg and 1.21 kW/kg, respectively. A slightly lower energy density of up to 1.23 kJ/kg and a 0.29 kW/kg mean power density are measured for the CNT yarns in a more complex system that mimics a unidirectional rotating regenerative braking mechanism. The lower energy densities for CNT yarns in the regenerative braking systems as compared with the yarns themselves reflect the frictional losses of the regenerative systems.

Collective Framework and Performance Optimizations to Open MPI for Cray XT Platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ladd, Joshua S; Gorentla Venkata, Manjunath; Shamis, Pavel

2011-01-01

The performance and scalability of collective operations plays a key role in the performance and scalability of many scientific applications. Within the Open MPI code base we have developed a general purpose hierarchical collective operations framework called Cheetah, and applied it at large scale on the Oak Ridge Leadership Computing Facility's Jaguar (OLCF) platform, obtaining better performance and scalability than the native MPI implementation. This paper discuss Cheetah's design and implementation, and optimizations to the framework for Cray XT 5 platforms. Our results show that the Cheetah's Broadcast and Barrier perform better than the native MPI implementation. For medium data,more » the Cheetah's Broadcast outperforms the native MPI implementation by 93% for 49,152 processes problem size. For small and large data, it out performs the native MPI implementation by 10% and 9%, respectively, at 24,576 processes problem size. The Cheetah's Barrier performs 10% better than the native MPI implementation for 12,288 processes problem size.« less

Software For Design Of Life-Support Systems

NASA Technical Reports Server (NTRS)

Rudokas, Mary R.; Cantwell, Elizabeth R.; Robinson, Peter I.; Shenk, Timothy W.

1991-01-01

Design Assistant Workstation (DAWN) computer program is prototype of expert software system for analysis and design of regenerative, physical/chemical life-support systems that revitalize air, reclaim water, produce food, and treat waste. Incorporates both conventional software for quantitative mathematical modeling of physical, chemical, and biological processes and expert system offering user stored knowledge about materials and processes. Constructs task tree as it leads user through simulated process, offers alternatives, and indicates where alternative not feasible. Also enables user to jump from one design level to another.

Predicting Forest Regeneration in the Central Appalachians Using the REGEN Expert System

Treesearch

Lance A. Vickers; Thomas R. Fox; David L. Loftis; David A. Boucugnani

2011-01-01

REGEN is an expert system designed by David Loftis to predict the future species composition of dominant and codominant stems in forest stands at the onset of stem exclusion following a proposed harvest. REGEN predictions are generated using competitive rankings for advance reproduction along with other existing stand conditions. These parameters are contained within...

Adaptation and validation of the REGEN expert system for the Central Appalachians

Treesearch

Lance A. Vickers; Thomas R. Fox; David L. Loftis; David A. Boucugnani

2011-01-01

REGEN is an expert system that predicts future species composition at the onset of stem exclusion using preharvest stand conditions. To extend coverage into hardwood stands of the Central Appalachians, we developed REGEN knowledge bases for four site qualities (xeric, subxeric, submesic, mesic) based on relevant literature and expert opinion. Data were collected from...

Emerging Technologies for Assembly of Microscale Hydrogels

PubMed Central

Kavaz, Doga; Demirel, Melik C.; Demirci, Utkan

2013-01-01

Assembly of cell encapsulating building blocks (i.e., microscale hydrogels) has significant applications in areas including regenerative medicine, tissue engineering, and cell-based in vitro assays for pharmaceutical research and drug discovery. Inspired by the repeating functional units observed in native tissues and biological systems (e.g., the lobule in liver, the nephron in kidney), assembly technologies aim to generate complex tissue structures by organizing microscale building blocks. Novel assembly technologies enable fabrication of engineered tissue constructs with controlled properties including tunable microarchitectural and predefined compositional features. Recent advances in micro- and nano-scale technologies have enabled engineering of microgel based three dimensional (3D) constructs. There is a need for high-throughput and scalable methods to assemble microscale units with a complex 3D micro-architecture. Emerging assembly methods include novel technologies based on microfluidics, acoustic and magnetic fields, nanotextured surfaces, and surface tension. In this review, we survey emerging microscale hydrogel assembly methods offering rapid, scalable microgel assembly in 3D, and provide future perspectives and discuss potential applications. PMID:23184717

Three-dimensional printing and pediatric liver disease.

PubMed

Alkhouri, Naim; Zein, Nizar N

2016-10-01

Enthusiastic physicians and medical researchers are investigating the role of three-dimensional printing in medicine. The purpose of the current review is to provide a concise summary of the role of three-dimensional printing technology as it relates to the field of pediatric hepatology and liver transplantation. Our group and others have recently demonstrated the feasibility of printing three-dimensional livers with identical anatomical and geometrical landmarks to the native liver to facilitate presurgical planning of complex liver surgeries. Medical educators are exploring the use of three-dimensional printed organs in anatomy classes and surgical residencies. Moreover, mini-livers are being developed by regenerative medicine scientist as a way to test new drugs and, eventually, whole livers will be grown in the laboratory to replace organs with end-stage disease solving the organ shortage problem. From presurgical planning to medical education to ultimately the bioprinting of whole organs for transplantation, three-dimensional printing will change medicine as we know in the next few years.

Design of electrospun nanofibrous mats for osteogenic differentiation of mesenchymal stem cells.

PubMed

Wang, Shige; Hu, Fei; Li, Jingchao; Zhang, Shuping; Shen, Mingwu; Huang, Mingxian; Shi, Xiangyang

2017-05-26

The clinical translation potential of mesenchymal stem cells (MSCs) in regenerative medicine has been greatly exploited. With the merits of high surface area to volume ratio, facile control of components, well retained topography, and the capacity to mimic the native extracellular matrix (ECM), nanofibers have received a great deal of attention as bone tissue engineering scaffolds. Electrospinning has been considered as an efficient approach for scale-up fabrication of nanofibrous materials. Electrospun nanofibers are capable of stimulating cell-matrix interaction to form a cell niche, directing cellular behavior, and promoting the MSCs adhesion and proliferation. In this review, we give a comprehensive literature survey on the mechanisms of electrospun nanofibers in supporting the MSCs differentiation. Specifically, the influences of biological and physical osteogenic inductive cues on the MSCs osteogenic differentiation are reviewed. Along with the significant advances in the field, current research challenges and future perspectives are also discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

PubMed

van Kogelenberg, Sylvia; Yue, Zhilian; Dinoro, Jeremy N; Baker, Christopher S; Wallace, Gordon G

2018-05-01

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Nanotopographic Substrates of Poly (Methyl Methacrylate) Do Not Strongly Influence the Osteogenic Phenotype of Mesenchymal Stem Cells In Vitro

PubMed Central

Janson, Isaac A.; Kong, Yen P.; Putnam, Andrew J.

2014-01-01

The chemical, mechanical, and topographical features of the extracellular matrix (ECM) have all been documented to influence cell adhesion, gene expression, migration, proliferation, and differentiation. Topography plays a key role in the architecture and functionality of various tissues in vivo, thus raising the possibility that topographic cues can be instructive when incorporated into biomaterials for regenerative applications. In the literature, there are discrepancies regarding the potential roles of nanotopography to enhance the osteogenic phenotype of mesenchymal stem cells (MSC). In this study, we used thin film substrates of poly(methyl methacrylate) (PMMA) with nanoscale gratings to investigate the influence of nanotopography on the osteogenic phenotype of MSCs, focusing in particular on their ability to produce mineral similar to native bone. Topography influenced focal adhesion size and MSC alignment, and enhanced MSC proliferation after 14 days of culture. However, the osteogenic phenotype was minimally influenced by surface topography. Specifically, alkaline phosphatase (ALP) expression was not increased on nanotopographic films, nor was calcium deposition improved after 21 days in culture. Ca: P ratios were similar to native mouse bone on films with gratings of 415 nm width and 200 nm depth (G415) and 303 nm width and 190 nm depth (G303). Notably, all surfaces had Ca∶P ratios significantly lower than G415 films. Collectively, these data suggest that, PMMA films with nanogratings are poor drivers of an osteogenic phenotype. PMID:24594848

Translational Challenges in Cardiovascular Tissue Engineering.

PubMed

Emmert, Maximilian Y; Fioretta, Emanuela S; Hoerstrup, Simon P

2017-04-01

Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. They do not promote regeneration, physiological remodeling, or growth (particularly important aspects for children) as their native counterparts. This results in the continuous degeneration and subsequent failure of these prostheses which is often associated with an increased morbidity and mortality as well as the need for multiple re-interventions. To overcome this problem, the concept of tissue engineering (TE) has been repeatedly suggested as a potential technology to enable native-like cardiovascular replacements with regenerative and growth capacities, suitable for young adults and children. However, despite promising data from pre-clinical and first clinical pilot trials, the translation and clinical relevance of such TE technologies is still very limited. The reasons that currently limit broad clinical adoption are multifaceted and comprise of scientific, clinical, logistical, technical, and regulatory challenges which need to be overcome. The aim of this review is to provide an overview about the translational problems and challenges in current TE approaches. It further suggests directions and potential solutions on how these issues may be efficiently addressed in the future to accelerate clinical translation. In addition, a particular focus is put on the current regulatory guidelines and the associated challenges for these promising TE technologies.

Biomimicry in biomedical research

PubMed Central

Zhang, Ge

2012-01-01

Biomimicry (literally defined as the imitation of life or nature) has sparked a variety of human innovations and inspired countless cutting-edge designs. From spider silk-made artificial skin to lotus leaf-inspired self-cleaning materials, biomimicry endeavors to solve human problems. Biomimetic approaches have contributed significantly to advances biomedical research during recent years. Using polyacrylamide gels to mimic the elastic modulus of different biological tissues, Disher’s lab has directed meschymal stem cell differentiation into specific lineages.1 They have shown that soft substrates mimicking the elastic modulus of brain tissues (0.1~1 kPa) were neurogenic, substrates of intermediate elastic modulus mimicking muscle (8 ~17 kPa) were myogenic, and substrates with bone-like elastic modulus (25~40 kPa) were osteogenic. This work represents a novel way to regulate the fate of stem cells and exerts profound influence on stem cell research. Biomimcry also drives improvements in tissue engineering. Novel scaffolds have been designed to capture extracellular matrix-like structures, binding of ligands, sustained release of cytokines, and mechanical properties intrinsic to specific tissues for tissue engineering applications.2,3 For example, tissue engineering skin grafts have been designed to mimic the cell composition and layered structure of native skin.4 Similarly, in the field of regenerative medicine, researchers aim to create biomimetic scaffolds to mimic the properties of a native stem cell environment (niche) to dynamically interact with the entrapped stem cells and direct their response.5 PMID:23275257

Design and experiment study of a semi-active energy-regenerative suspension system

NASA Astrophysics Data System (ADS)

Shi, Dehua; Chen, Long; Wang, Ruochen; Jiang, Haobin; Shen, Yujie

2015-01-01

A new kind of semi-active energy-regenerative suspension system is proposed to recover suspension vibration energy, as well as to reduce the suspension cost and demands for the motor-rated capacity. The system consists of an energy-regenerative damper and a DC-DC converter-based energy-regenerative circuit. The energy-regenerative damper is composed of an electromagnetic linear motor and an adjustable shock absorber with three regulating levels. The linear motor just works as the generator to harvest the suspension vibration energy. The circuit can be used to improve the system’s energy-regenerative performance and to continuously regulate the motor’s electromagnetic damping force. Therefore, although the motor works as a generator and damps the isolation without an external power source, the motor damping force is controllable. The damping characteristics of the system are studied based on a two degrees of freedom vehicle vibration model. By further analyzing the circuit operation characteristics under different working modes, the double-loop controller is designed to track the desired damping force. The external-loop is a fuzzy controller that offers the desired equivalent damping. The inner-loop controller, on one hand, is used to generate the pulse number and the frequency to control the angle and the rotational speed of the step motor; on the other hand, the inner-loop is used to offer the duty cycle of the energy-regenerative circuit. Simulations and experiments are conducted to validate such a new suspension system. The results show that the semi-active energy-regenerative suspension can improve vehicle ride comfort with the controllable damping characteristics of the linear motor. Meanwhile, it also ensures energy regeneration.

Investigation on thermo-acoustic instability dynamic characteristics of hydrocarbon fuel flowing in scramjet cooling channel based on wavelet entropy method

NASA Astrophysics Data System (ADS)

Zan, Hao; Li, Haowei; Jiang, Yuguang; Wu, Meng; Zhou, Weixing; Bao, Wen

2018-06-01

As part of our efforts to find ways and means to further improve the regenerative cooling technology in scramjet, the experiments of thermo-acoustic instability dynamic characteristics of hydrocarbon fuel flowing have been conducted in horizontal circular tubes at different conditions. The experimental results indicate that there is a developing process from thermo-acoustic stability to instability. In order to have a deep understanding on the developing process of thermo-acoustic instability, the method of Multi-scale Shannon Wavelet Entropy (MSWE) based on Wavelet Transform Correlation Filter (WTCF) and Multi-Scale Shannon Entropy (MSE) is adopted in this paper. The results demonstrate that the developing process of thermo-acoustic instability from noise and weak signals is well detected by MSWE method and the differences among the stability, the developing process and the instability can be identified. These properties render the method particularly powerful for warning thermo-acoustic instability of hydrocarbon fuel flowing in scramjet cooling channels. The mass flow rate and the inlet pressure will make an influence on the developing process of the thermo-acoustic instability. The investigation on thermo-acoustic instability dynamic characteristics at supercritical pressure based on wavelet entropy method offers guidance on the control of scramjet fuel supply, which can secure stable fuel flowing in regenerative cooling system.

Incorporation of an invasive plant into a native insect herbivore food web

PubMed Central

Santos Pimenta, Lúcia P.; Lammers, Youri; Steenbergen, Peter J.; Flohil, Marco; Beveridge, Nils G.P.; van Duijn, Pieter T.; Meulblok, Marjolein M.; Sosef, Nils; van de Ven, Robin; Werring, Ralf; Beentjes, Kevin K.; Meijer, Kim; Vos, Rutger A.; Vrieling, Klaas; Gravendeel, Barbara; Choi, Young; Verpoorte, Robert; Smit, Chris; Beukeboom, Leo W.

2016-01-01

The integration of invasive species into native food webs represent multifarious dynamics of ecological and evolutionary processes. We document incorporation of Prunus serotina (black cherry) into native insect food webs. We find that P. serotina harbours a herbivore community less dense but more diverse than its native relative, P. padus (bird cherry), with similar proportions of specialists and generalists. While herbivory on P. padus remained stable over the past century, that on P. serotina gradually doubled. We show that P. serotina may have evolved changes in investment in cyanogenic glycosides compared with its native range. In the leaf beetle Gonioctena quinquepunctata, recently shifted from native Sorbus aucuparia to P. serotina, we find divergent host preferences on Sorbus- versus Prunus-derived populations, and weak host-specific differentiation among 380 individuals genotyped for 119 SNP loci. We conclude that evolutionary processes may generate a specialized herbivore community on an invasive plant, allowing prognoses of reduced invasiveness over time. On the basis of the results presented here, we would like to caution that manual control might have the adverse effect of a slowing down of processes of adaptation, and a delay in the decline of the invasive character of P. serotina. PMID:27190702

Influences of Native American land use on the Colonial Euro-American settlement of the South Carolina Piedmont

PubMed Central

Nelson, Donald R.

2018-01-01

We test the hypothesis that prehistoric Native American land use influenced the Euro-American settlement process in a South Carolina Piedmont landscape. Long term ecological studies demonstrate that land use legacies influence processes and trajectories in complex, coupled social and ecological systems. Native American land use likely altered the ecological and evolutionary feedback and trajectories of many North American landscapes. Yet, considerable debate revolves around the scale and extent of land use legacies of prehistoric Native Americans. At the core of this debate is the question of whether or not European colonists settled a mostly “wild” landscape or an already “humanized” landscape. We use statistical event analysis to model the effects of prehistoric Native American settlement on the rate of Colonial land grants (1749–1775). Our results reveal how abandoned Native American settlements were among the first areas claimed and homesteaded by Euro-Americans. We suggest that prehistoric land use legacies served as key focal nodes in the Colonial era settlement process. As a consequence, localized prehistoric land use legacies likely helped structure the long term, landscape- to regional-level ecological inheritances that resulted from Euro-American settlement. PMID:29596504

Influences of Native American land use on the Colonial Euro-American settlement of the South Carolina Piedmont.

PubMed

Coughlan, Michael R; Nelson, Donald R

2018-01-01

We test the hypothesis that prehistoric Native American land use influenced the Euro-American settlement process in a South Carolina Piedmont landscape. Long term ecological studies demonstrate that land use legacies influence processes and trajectories in complex, coupled social and ecological systems. Native American land use likely altered the ecological and evolutionary feedback and trajectories of many North American landscapes. Yet, considerable debate revolves around the scale and extent of land use legacies of prehistoric Native Americans. At the core of this debate is the question of whether or not European colonists settled a mostly "wild" landscape or an already "humanized" landscape. We use statistical event analysis to model the effects of prehistoric Native American settlement on the rate of Colonial land grants (1749-1775). Our results reveal how abandoned Native American settlements were among the first areas claimed and homesteaded by Euro-Americans. We suggest that prehistoric land use legacies served as key focal nodes in the Colonial era settlement process. As a consequence, localized prehistoric land use legacies likely helped structure the long term, landscape- to regional-level ecological inheritances that resulted from Euro-American settlement.

Advancing pig cloning technologies towards application in regenerative medicine.

PubMed

Nagashima, H; Matsunari, H; Nakano, K; Watanabe, M; Umeyama, K; Nagaya, M

2012-08-01

Regenerative medicine is expected to make a significant contribution by development of novel therapeutic treatments for intractable diseases and for improving the quality of life of patients. Many advances in regenerative medicine, including basic and translational research, have been developed and tested in experimental animals; pigs have played an important role in various aspects of this work. The value of pigs as a model species is being enhanced by the generation of specially designed animals through cloning and genetic modifications, enabling more sophisticated research to be performed and thus accelerating the clinical application of regenerative medicine. This article reviews the significant aspects of the creation and application of cloned and genetically modified pigs in regenerative medicine research and considers the possible future directions of the technology. We also discuss the importance of reproductive biology as an interface between basic science and clinical medicine. © 2012 Blackwell Verlag GmbH.

Exploring the Digital Natives among Pre-Service Teachers in Turkey: A Cross-Cultural Validation of the Digital Native Assessment Scale

ERIC Educational Resources Information Center

Teo, Timothy; Kabakçi Yurdakul, Isil; Ursavas, Ömer Faruk

2016-01-01

This study aims to explore the digital natives among a sample of pre-service teachers and in the process, examine the validity of a Turkish adaptation of the digital native assessment scale (DNAS) [Teo, T., & Fan, X. (2013). "Coefficient alpha and beyond: Issues and alternatives for educational research." "The Asia-Pacific…

Can native annual forbs reduce Bromus tectorum biomass and indirectly facilitate establishment of a native perennial grass?

Treesearch

Elizabeth A. Leger; Erin M. Goergen; Tara Forbis de Queiroz

2014-01-01

Restoration is challenging in systems invaded by competitive, disturbance oriented plants, but greater success may be achieved by mimicking natural successional processes and including disturbanceoriented natives in a seed mix. We asked whether seven native annual forbs from the Great Basin Desert, USA, were capable of reducing biomass of the invasive annual grass...

Advances in Regenerative Orthopaedics

PubMed Central

Evans, Christopher H.

2013-01-01

Orthopaedic injuries are very common and a source of much misery and economic stress. Several relevant tissues, such as cartilage, meniscus and intra-articular ligaments, do not heal. And even bone, which normally regenerates spontaneously, can fail to mend. The regeneration of orthopaedic tissues requires four key components: cells, morphogenetic signals, scaffolds and an appropriate mechanical environment. Although differentiated cells from the tissue in question can be used, most cellular research focuses on the use mesenchymal stem cells (MSCs). These can be retrieved from many different tissues, and one unresolved question is the degree to which the origin of the cells matters. Embryonic and induced, pluripotential stem cells are also under investigation. Morphogenetic signals are most frequently supplied by individual, recombinant growth factors or native mixtures provided by, for instance, platelet-rich plasma; MSCs are also a rich source of trophic factors. Obstacles to the sustained delivery of individual growth factors can be addressed by gene transfer or smart scaffolds, but we still lack detailed, necessary information on which delivery profiles are needed. Scaffolds may be based upon natural products, synthetic materials, or devitalized extracellular matrix. Strategies to combine these components to regenerate tissue can follow traditional tissue engineering practices, but these are costly, cumbersome and not well suited to treating large numbers of individuals. More expeditious approaches make full use of intrinsic biological processes in vivo to avoid the need for ex vivo expansion of autologous cells and multiple procedures. Clinical translation remains a bottleneck. PMID:24182709

Regeneration in the Pituitary After Cell-Ablation Injury: Time-Related Aspects and Molecular Analysis.

PubMed

Willems, Christophe; Fu, Qiuli; Roose, Heleen; Mertens, Freya; Cox, Benoit; Chen, Jianghai; Vankelecom, Hugo

2016-02-01

We recently showed that the mouse pituitary holds regenerative competence. Young-adult GHCre/iDTR mice, expressing diphtheria toxin (DT) receptor in GH-producing cells, regenerate the GH(+) cells, as ablated by 3-day DT treatment (3DT), up to 60% after 5 months. The pituitary's stem cells participate in this restoration process. Here, we characterized this regenerative capacity in relation to age and recovery period and started to search for underlying molecular mechanisms. Extending the recovery period (up to 19 mo) does not result in higher regeneration levels. In addition, the regenerative competence disappears at older age, coinciding with a reduction in pituitary stem cell number and fitness. Surprisingly, prolonging DT treatment of young-adult mice to 10 days (10DT) completely blocks the regeneration, although the stem cell compartment still reacts by promptly expanding, and retains in vitro stem cell functionality. To obtain a first broad view on molecular grounds underlying reparative capacity and/or failure, the stem cell-clustering side population was analyzed by whole-genome expression analysis. A number of stemness factors and components of embryonic, epithelial-mesenchymal transition, growth factor and Hippo pathways are higher expressed in the stem cell-clustering side population of the regenerating pituitary (after 3DT) when compared with the basal gland and to the nonregenerating pituitary (after 10DT). Together, the regenerative capacity of the pituitary is limited both in age-related terms and final efficacy, and appears to rely on stem cell-associated pathway activation. Dissection of the molecular profiles may eventually identify targets to induce or boost regeneration in situations of (injury-related) pituitary deficiency.

Periodontal regeneration around natural teeth.

PubMed

Garrett, S

1996-11-01

1. Evidence is conclusive (Table 2) that periodontal regeneration in humans is possible following the use of bone grafts, guided tissue regeneration procedures, both without and in combination with bone grafts, and root demineralization procedures. 2. Clinically guided tissue regeneration procedures have demonstrated significant positive clinical change beyond that achieved with debridement alone in treating mandibular and maxillary (buccal only) Class II furcations. Similar data exist for intraosseous defects. Evidence suggests that the use of bone grafts or GTR procedures produce equal clinical benefit in treating intraosseous defects. Further research is necessary to evaluate GTR procedures compared to, or combined with, bone grafts in treating intraosseous defects. 3. Although there are some data suggesting hopeful results in Class II furcations, the clinical advantage of procedures combining present regenerative techniques remains to be demonstrated. Additional randomized controlled trials with sufficient power are needed to demonstrate the potential usefulness of these techniques. 4. Outcomes following regenerative attempts remain somewhat variable with differences in results between studies and individual subjects. Some of this variability is likely patient related in terms of compliance with plaque control and maintenance procedures, as well as personal habits; e.g., smoking. Variations in the defects selected for study may also affect predictability of outcomes along with other factors. 5. There is evidence to suggest that present regenerative techniques lead to significant amounts of regeneration at localized sites on specific teeth. However, if complete regeneration is to become a reality, additional stimuli to enhance the regenerative process are likely needed. Perhaps this will be accomplished in the future, with combined procedures that include appropriate polypeptide growth factors or tissue factors to provide additional stimulus.

The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment.

PubMed

Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

2013-05-01

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

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

Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

PubMed Central

Van houcke, Jessie

2017-01-01

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies. PMID:28203046

Electrolyte for batteries with regenerative solid electrolyte interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Jie; Lu, Dongping; Shao, Yuyan

2017-08-01

An energy storage device comprising: an anode; and a solute-containing electrolyte composition wherein the solute concentration in the electrolyte composition is sufficiently high to form a regenerative solid electrolyte interface layer on a surface of the anode only during charging of the energy storage device, wherein the regenerative layer comprises at least one solute or solvated solute from the electrolyte composition.

New glossary of terms used in regenerative medicine: standardization continues to emerge as regenerative medicine matures.

PubMed

Sheridan, Ben; Harris, Neil

2009-07-01

Regenerative medicine is an evolving, cross-disciplinary, international field that, as a result, uses terms that are either not widely understood, or may have a number of different meanings. Many stakeholders have identified this lack of clarity as a potential barrier to effective communication within the field. To address this, BSI British Standards, supported by the UK Department for Innovation, Universities and Skills (DIUS), was commissioned to develop guidance on the definitions of terms used within regenerative medicine. The resulting document aims to provide clear consensus terminology to improve communication and facilitate a common understanding for a broad range of potential users.

Regenerative endodontics: barriers and strategies for clinical translation.

PubMed

Mao, Jeremy J; Kim, Sahng G; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y; Yang, Rujing; Zhou, Xuedong

2012-07-01

Regenerative endodontics has encountered substantial challenges toward clinical translation. The adoption by the American Dental Association of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for most endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation. Copyright © 2012 Elsevier Inc. All rights reserved.

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

PubMed

Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W; Wolf, Matthew T; Fan, Hongni; Tam, Ada J; Patel, Chirag H; Luber, Brandon S; Wang, Hao; Wagner, Kathryn R; Powell, Jonathan D; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

2016-04-15

Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. Copyright © 2016, American Association for the Advancement of Science.

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells

PubMed Central

Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W.; Wolf, Matthew T.; Fan, Hongni; Tam, Ada J.; Patel, Chirag H.; Luber, Brandon S.; Wang, Hao; Wagner, Kathryn R.; Powell, Jonathan D.; Housseau, Franck; Pardoll, Drew M.

2016-01-01

Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4–dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. PMID:27081073

The continued promise of stem cell therapy in regenerative medicine.

PubMed

Eve, David J

2011-12-01

The use of stem cells is galvanizing regenerative medicine research. An analysis of recent trends as typified by articles published between 2009 and 2010 in the journals Cell Transplantation--The Regenerative Medicine Journal and Medical Science Monitor demonstrate the increasing importance of stem cell research as being on the cutting edge of regenerative medicine research. The analysis revealed an even split between transplantation and non-transplantation studies, showing that both the applicability and general research is being pursued. New methods and tissue engineering are also highly important components of regenerative medicine as demonstrated by a number of the stem cell studies being involved with either ex vivo manipulation, or cotransplantation with other cells or biomaterials. This suggests that the best results may be achieved with adjuvant therapies. The non-transplantation studies were more focused on manipulation of transplantable agents including cells and scaffold systems, as well as the use of medicines and dietary supplements. The further elucidation of disease mechanisms was a major contribution. This analysis suggests that regenerative medicine is proceeding at a rapid pace and the next few years should be of considerable interest with the initial results of pioneering stem cell therapies being announced.

Industry perceptions of barriers to commercialization of regenerative medicine products in the UK.

PubMed

Plagnol, Anke C; Rowley, Emma; Martin, Paul; Livesey, Finbarr

2009-07-01

Regenerative medicine is an emerging field with the potential to provide widespread improvement in healthcare and patient wellbeing via the delivery of therapies that can restore, regenerate or repair damaged tissue. As an industry, it could significantly contribute to economic growth if products are successfully commercialized. However, to date, relatively few products have reached the market owing to a variety of barriers, including a lack of funding and regulatory hurdles. The present study analyzes industry perceptions of the barriers to commercialization that currently impede the success of the regenerative medicine industry in the UK. The analysis is based on 20 interviews with leading industrialists in the field. The study revealed that scientific research in regenerative medicine is thriving in the UK. Unfortunately, lack of access to capital, regulatory hurdles, lack of clinical evidence leading to problems with reimbursement, as well as the culture of the NHS do not provide a good environment for the commercialization of regenerative medicine products. Policy interventions, including increased translational government funding, a change in NHS and NICE organization and policies, and regulatory clarity, would likely improve the general outcomes for the regenerative medicine industry in the UK.

Detection of micronuclei formation and nuclear anomalies in regenerative nodules of human cirrhotic livers and relationship to hepatocellular carcinoma.

PubMed

de Almeida, Terezinha M B; Leitão, Regina C; Andrade, Joyce D; Beçak, Willy; Carrilho, Flair J; Sonohara, Shigueko

2004-04-01

Human cirrhosis is considered an important factor in hepatocarcinogenesis. The lack of substantial genetics and cytogenetics data in human cirrhosis led us to investigate spontaneous micronuclei formation, as an indicator of chromosomal damage. The analysis was performed in hepatocytes of regenerative, macroregenerative, and tumoral nodules from 30 cases of cirrhosis (paraffin-embedded archival material), retrospectively selected: cryptogenic, hepatitis C virus, and hepatitis C virus associated with hepatocellular carcinoma (HCC). Thirteen control liver samples of healthy organ donors were included. Micronucleated hepatocytes were analyzed with Feulgen-fast-green dyeing techniques. The spontaneous frequency of micronucleated hepatocytes in both regenerative and macroregenerative nodules of all cirrhotic patients was significantly higher than for the normal control group. There was no significant difference in frequency of micronucleated hepatocytes in regenerative nodules compared with macroregenerative nodules for all cases analyzed, whereas a significantly higher frequency of micronucleated hepatocytes was detected in tumoral nodules, compared with cirrhotic regenerative nodules and normal parenchyma. A higher frequency of the nuclear anomalies termed broken-eggs was observed in hepatitis C virus-related samples. Chromatinic losses and genotoxicity already existed in the cirrhotic regenerative nodules, which might predispose to development of HCC.

Impacts of Carpobrotus edulis (L.) N.E.Br. on the Germination, Establishment and Survival of Native Plants: A Clue for Assessing Its Competitive Strength

PubMed Central

Novoa, Ana; González, Luís

2014-01-01

Does Carpobrotus edulis have an impact on native plants? How do C. edulis’ soil residual effects affect the maintenance of native populations? What is the extent of interspecific competition in its invasion process? In order to answer those questions, we established pure and mixed cultures of native species and C. edulis on soil collected from invaded and native areas of Mediterranean coastal dunes in the Iberian Peninsula. We examined the impact of the invader on the germination, growth and survival of seeds and adult plants of two native plant species (Malcolmia littorea (L.) R.Br, and Scabiosa atropurpurea L.) growing with ramets or seeds of C. edulis. Residual effects of C. edulis on soils affected the germination process and early growth of native plants in different ways, depending on plant species and density. Interspecific competition significantly reduced the germination and early growth of native plants but this result was soil, density, timing and plant species dependent. Also, at any density of adult individuals of C. edulis, established native adult plants were not competitive. Moreover, ramets of C. edulis had a lethal effect on native plants, which died in a short period of time. Even the presence of C. edulis seedlings prevents the recruitment of native species. In conclusion, C. edulis have strong negative impacts on the germination, growth and survival of the native species M. littorea and S. atropurpurea. These impacts were highly depended on the development stages of native and invasive plants. Our findings are crucial for new strategies of biodiversity conservation in coastal habitats. PMID:25210924

Impacts of Carpobrotus edulis (L.) N.E.Br. on the germination, establishment and survival of native plants: a clue for assessing its competitive strength.

PubMed

Novoa, Ana; González, Luís

2014-01-01

Does Carpobrotus edulis have an impact on native plants? How do C. edulis' soil residual effects affect the maintenance of native populations? What is the extent of interspecific competition in its invasion process? In order to answer those questions, we established pure and mixed cultures of native species and C. edulis on soil collected from invaded and native areas of Mediterranean coastal dunes in the Iberian Peninsula. We examined the impact of the invader on the germination, growth and survival of seeds and adult plants of two native plant species (Malcolmia littorea (L.) R.Br, and Scabiosa atropurpurea L.) growing with ramets or seeds of C. edulis. Residual effects of C. edulis on soils affected the germination process and early growth of native plants in different ways, depending on plant species and density. Interspecific competition significantly reduced the germination and early growth of native plants but this result was soil, density, timing and plant species dependent. Also, at any density of adult individuals of C. edulis, established native adult plants were not competitive. Moreover, ramets of C. edulis had a lethal effect on native plants, which died in a short period of time. Even the presence of C. edulis seedlings prevents the recruitment of native species. In conclusion, C. edulis have strong negative impacts on the germination, growth and survival of the native species M. littorea and S. atropurpurea. These impacts were highly depended on the development stages of native and invasive plants. Our findings are crucial for new strategies of biodiversity conservation in coastal habitats.

Clitic pronouns reveal the time course of processing gender and number in a second language

PubMed Central

Rossi, Eleonora; Kroll, Judith F.; Dussias, Paola E.

2014-01-01

This study investigates grammatical gender and number processing marked on clitic pronouns in native Spanish speakers and in late English-Spanish bilinguals using ERPs. Spanish clitic pronouns were chosen as a critical grammatical structure which is absent in English, and which encodes both grammatical gender and number. Number, but not grammatical gender, is present in English, making this structure a prime one to investigate second language processing. Results reveal a P600 effect in native speakers for violations of both gender and number. Late but relatively proficient English-Spanish bilinguals show a P600 effect only for number violations occurring at the clitic pronoun, but not for gender violations. However a post-hoc analysis reveals that a subset of highly proficient late bilinguals does reveal sensitivity to violations of grammatical gender marked on clitic pronouns. Taken together these results suggest that native-like processing is possible for highly proficient late second language learners for grammatical features that are not present in the speakers' native language, even when those features are encoded on a grammatical morpheme which itself is absent in the speakers' native language. PMID:25036762

Honey: an effective regenerative medicine product in wound management.

PubMed

Martinotti, Simona; Bucekova, Marcela; Majtan, Juraj; Ranzato, Elia

2018-05-10

Honey has successfully been used in treatment of a broad spectrum of injuries including burns and non-healing wounds. It acts as antibacterial and anti-biofilm agent with anti/pro-inflammatory properties. However, besides these traditional properties, recent evidence suggests that honey is also an immunomodulator in wound healing and contains several bee and plant-derived components that may speed up the wound healing and tissue regeneration process. Identifying their exact mechanism of action allows better understanding of honey healing properties and promotes its wider translation into clinical practice. This review will discuss the physiological basis for the use of honey in wound management, its current clinical uses, as well as the potential role of honey bioactive compounds in dermal regenerative medicine and tissue re-modelling. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modified Confidence Intervals for the Mean of an Autoregressive Process.

DTIC Science & Technology

1985-08-01

Validity of the method 45 3.6 Theorem 47 4 Derivation of corrections 48 Introduction 48 The zero order pivot 50 4.1 Algorithm 50 CONTENTS The first...of standard confidence intervals. There are several standard methods of setting confidence intervals in simulations, including the regener- ative... method , batch means, and time series methods . We-will focus-s on improved confidence intervals for the mean of an autoregressive process, and as such our

Tools for Regeneration: Specific Ways To Help an Economy Thrive.

ERIC Educational Resources Information Center

Rodale Press, Inc., Emmaus, PA.

This paper describes some of the tools that The Regeneration Project, in Emmaus, Pennsylvania, has developed for use in the process of local economic improvement. One or more of these may be of interest to other individuals in communities that wish to undertake similar projects. Regenerative development provides markets for locally produced goods…

Macrophages are required to coordinate mouse digit tip regeneration.

PubMed

Simkin, Jennifer; Sammarco, Mimi C; Marrero, Luis; Dawson, Lindsay A; Yan, Mingquan; Tucker, Catherine; Cammack, Alex; Muneoka, Ken

2017-11-01

In mammals, macrophages are known to play a major role in tissue regeneration. They contribute to inflammation, histolysis, re-epithelialization, revascularization and cell proliferation. Macrophages have been shown to be essential for regeneration in salamanders and fish, but their role has not been elucidated in mammalian epimorphic regeneration. Here, using the regenerating mouse digit tip as a mammalian model, we demonstrate that macrophages are essential for the regeneration process. Using cell-depletion strategies, we show that regeneration is completely inhibited; bone histolysis does not occur, wound re-epithelialization is inhibited and the blastema does not form. Although rescue of epidermal wound closure in the absence of macrophages promotes blastema accumulation, it does not rescue cell differentiation, indicating that macrophages play a key role in the redifferentiation of the blastema. We provide additional evidence that although bone degradation is a component, it is not essential to the overall regenerative process. These findings show that macrophages play an essential role in coordinating the epimorphic regenerative response in mammals. © 2017. Published by The Company of Biologists Ltd.

Does autophagy in the midgut epithelium of centipedes depend on the day/night cycle?

PubMed

Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K; Kszuk-Jendrysik, M

2015-01-01

The midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata, is composed of digestive, secretory and regenerative cells. In L. forficatus, the autophagy occurred only in the cytoplasm of the digestive cells as a sporadic process, while in S. cingulata, it occurred intensively in the digestive, secretory and regenerative cells of the midgut epithelium. In both of the species that were analyzed, this process proceeded in a continuous manner and did not depend on the day/night cycle. Ultrastructural analysis showed that the autophagosomes and autolysosomes were located mainly in the apical and perinuclear cytoplasm of the digestive cells in L. forficatus. However, in S. cingulata, the entire cytoplasm was filled with autophagosomes and autolysosomes. Initially the membranes of phagophores surround organelles during autophagosome formation. Autolysosomes result from the fusion of autophagosomes and lysosomes. Residual bodies which are the last stage of autophagy were released into the midgut lumen due to necrosis. Autophagy in the midgut epithelia that were analyzed was confirmed using acid phosphatase and mono-dansyl-cadaverine stainings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Consequences of Neurite Transection In Vitro

PubMed Central

Cengiz, Nurettin; Erdoğan, Ender; Him, Aydın; Oğuz, Elif Kaval

2012-01-01

Abstract In order to quantify degenerative and regenerative changes and analyze the contribution of multiple factors to the outcome after neurite transection, we cultured adult mouse dorsal root ganglion neurons, and with a precise laser beam, we transected the nerve fibers they extended. Cell preparations were continuously visualized for 24 h with time-lapse microscopy. More distal cuts caused a more elongated field of degeneration, while thicker neurites degenerated faster than thinner ones. Transected neurites degenerated more if the uncut neurites of the same neuron simultaneously degenerated. If any of these uncut processes regenerated, the transected neurites underwent less degeneration. Regeneration of neurites was limited to distal cuts. Unipolar neurons had shorter regeneration than multipolar ones. Branching slowed the regenerative process, while simultaneous degeneration of uncut neurites increased it. Proximal lesions, small neuronal size, and extensive and rapid neurite degeneration were predictive of death of an injured neuron, which typically displayed necrotic rather than apoptotic form. In conclusion, this in vitro model proved useful in unmasking many new aspects and correlates of mechanically-induced neurite injury. PMID:20121423

Refurbishment of one-person regenerative air revitalization system

NASA Technical Reports Server (NTRS)

Powell, Ferolyn T.

1989-01-01

Regenerative processes for the revitalization of spacecraft atmospheres and reclamation of waste waters are essential for making long-term manned space missions a reality. Processes studied include: static feed water electrolysis for oxygen generation, Bosch carbon dioxide reduction, electrochemical carbon dioxide concentration, vapor compression distillation water recovery, and iodine monitoring. The objectives were to: provide engineering support to Marshall Space Flight Center personnel throughout all phases of the test program, e.g., planning through data analysis; fabricate, test, and deliver to Marshall Space Flight Center an electrochemical carbon dioxide module and test stand; fabricate and deliver an iodine monitor; evaluate the electrochemical carbon dioxide concentrator subsystem configuration and its ability to ensure safe utilization of hydrogen gas; evaluate techniques for recovering oxygen from a product oxygen and carbon dioxide stream; and evaluate the performance of an electrochemical carbon dioxide concentrator module to operate without hydrogen as a method of safe haven operation. Each of the tasks were related in that all focused on providing a better understanding of the function, operation, and performance of developmental pieces of environmental control and life support system hardware.

Manufacturing Process Developments for Regeneratively-Cooled Channel Wall Rocket Nozzles

NASA Technical Reports Server (NTRS)

Gradl, Paul; Brandsmeier, Will

2016-01-01

Regeneratively cooled channel wall nozzles incorporate a series of integral coolant channels to contain the coolant to maintain adequate wall temperatures and expand hot gas providing engine thrust and specific impulse. NASA has been evaluating manufacturing techniques targeting large scale channel wall nozzles to support affordability of current and future liquid rocket engine nozzles and thrust chamber assemblies. The development of these large scale manufacturing techniques focus on the liner formation, channel slotting with advanced abrasive water-jet milling techniques and closeout of the coolant channels to replace or augment other cost reduction techniques being evaluated for nozzles. NASA is developing a series of channel closeout techniques including large scale additive manufacturing laser deposition and explosively bonded closeouts. A series of subscale nozzles were completed evaluating these processes. Fabrication of mechanical test and metallography samples, in addition to subscale hardware has focused on Inconel 625, 300 series stainless, aluminum alloys as well as other candidate materials. Evaluations of these techniques are demonstrating potential for significant cost reductions for large scale nozzles and chambers. Hot fire testing is planned using these techniques in the future.

Rational Deletion Cloze Processing Strategies: ESL and Native English.

ERIC Educational Resources Information Center

Markham, Paul L.

1987-01-01

Explores cloze sensitivity to global comprehension by means of retrospective interview techniques. No significant differences were found between English as a second language (ESL) college students (N=14) and native English-speaking students (N=14) in their processing strategies. (Author/CB)

Bidirectional clear speech perception benefit for native and high-proficiency non-native talkers and listeners: Intelligibility and accentednessa

PubMed Central

Smiljanić, Rajka; Bradlow, Ann R.

2011-01-01

This study investigated how native language background interacts with speaking style adaptations in determining levels of speech intelligibility. The aim was to explore whether native and high proficiency non-native listeners benefit similarly from native and non-native clear speech adjustments. The sentence-in-noise perception results revealed that fluent non-native listeners gained a large clear speech benefit from native clear speech modifications. Furthermore, proficient non-native talkers in this study implemented conversational-to-clear speaking style modifications in their second language (L2) that resulted in significant intelligibility gain for both native and non-native listeners. The results of the accentedness ratings obtained for native and non-native conversational and clear speech sentences showed that while intelligibility was improved, the presence of foreign accent remained constant in both speaking styles. This suggests that objective intelligibility and subjective accentedness are two independent dimensions of non-native speech. Overall, these results provide strong evidence that greater experience in L2 processing leads to improved intelligibility in both production and perception domains. These results also demonstrated that speaking style adaptations along with less signal distortion can contribute significantly towards successful native and non-native interactions. PMID:22225056

Words and pictures: An electrophysiological investigation of domain specific processing in native Chinese and English speakers

PubMed Central

Yum, Yen Na; Holcomb, Phillip J.; Grainger, Jonathan

2011-01-01

Comparisons of word and picture processing using Event-Related Potentials (ERPs) are contaminated by gross physical differences between the two types of stimuli. In the present study, we tackle this problem by comparing picture processing with word processing in an alphabetic and a logographic script, that are also characterized by gross physical differences. Native Mandarin Chinese speakers viewed pictures (line drawings) and Chinese characters (Experiment 1), native English speakers viewed pictures and English words (Experiment 2), and naïve Chinese readers (native English speakers) viewed pictures and Chinese characters (Experiment 3) in a semantic categorization task. The varying pattern of differences in the ERPs elicited by pictures and words across the three experiments provided evidence for i) script-specific processing arising between 150–200 ms post-stimulus onset, ii) domain-specific but script-independent processing arising between 200–300 ms post-stimulus onset, and iii) processing that depended on stimulus meaningfulness in the N400 time window. The results are interpreted in terms of differences in the way visual features are mapped onto higher-level representations for pictures and words in alphabetic and logographic writing systems. PMID:21439991

Vibration control of an energy regenerative seat suspension with variable external resistance

NASA Astrophysics Data System (ADS)

Ning, Donghong; Sun, Shuaishuai; Du, Haiping; Li, Weihua; Zhang, Nong

2018-06-01

In this paper, an energy regenerative seat suspension with a variable external resistance is proposed and built, and a semi-active controller for its vibration control is also designed and validated. The energy regenerative seat suspension is built with a three-phase generator and a gear reducer, which are installed in the scissors structure centre of the seat suspension, and the vibration energy is directly harvested from the rotary movement of suspension's scissors structure. The electromagnetic torque of the semi-active seat suspension actuator is controlled by an external variable resistor. An integrated model including the seat suspension's kinematics and the generator is built and proven to match the test result very well. A simplified experimental phenomenon model is also built based on the test results for the controller design. A state feedback H∞ controller is proposed for the regenerative seat suspension's semi-active vibration control. The proposed regenerative seat suspension and its controller are validated with both simulations and experiments. A well-tuned passive seat suspension is applied to evaluate the regenerative seat's performance. Based on ISO 2631-1, the frequency-weighted root mean square (FW-RMS) acceleration of the proposed seat suspension has a 22.84% reduction when compared with the passive one, which indicates the improvement of ride comfort. At the same time, the generated RMS power is 1.21 W. The proposed regenerative seat suspension can greatly improve the driver's ride comfort and has the potential to be developed to a self-powered semi-active system.

A survey of attitude and opinions of endodontic residents towards regenerative endodontics

PubMed Central

Utneja, Shivani; Nawal, Ruchika Roongta; Ansari, Mohammed Irfan; Talwar, Sangeeta; Verma, Mahesh

2013-01-01

Aim: The objective of this survey was to study the level of awareness, current state of knowledge and opinions towards regenerative endodontic treatments amongst the endodontic residents of India. Settings and Design: Questionnaire based survey was designed. Materials and Methods: After approval from the organizing committee of 26th Federation of Operative Dentistry of India and 19th Indian Endodontic Society National conference 2011, 200 copies of the questionnaire were circulated amongst the endodontic residents in conservative dentistry and endodontics at various colleges across the country about regenerative endodontic procedures. The survey included profile of the respondents and consisted of 23 questions about their knowledge, attitude and opinions regarding use of these procedures as part of future dental treatment. Results: The survey showed that half the participants (50.6%) had received continued education in stem cells and/or regenerative dental treatments. The majority of participants were of the opinion (86.6%) that regenerative therapy should be incorporated into dentistry, and most of them (88%) were willing to acquire training in learning this new treatment strategy. The results indicated that half of the participants (52.6%) were already using some type of regenerative therapy in their clinical practice; however, with a majority of these limited to use of membranes, scaffolds or bioactive materials. Conclusions: These results reflect that endodontic residents are optimistic about the use of regenerative endodontic procedures; however, a need for more research and training was felt. PMID:23956532

Investigating Auditory Processing of Syntactic Gaps with L2 Speakers Using Pupillometry

ERIC Educational Resources Information Center

Fernandez, Leigh; Höhle, Barbara; Brock, Jon; Nickels, Lyndsey

2018-01-01

According to the Shallow Structure Hypothesis (SSH), second language (L2) speakers, unlike native speakers, build shallow syntactic representations during sentence processing. In order to test the SSH, this study investigated the processing of a syntactic movement in both native speakers of English and proficient late L2 speakers of English using…

Analysis of Non-Tactical Vehicle Utilization at Fort Carson Colorado

DTIC Science & Technology

2012-01-01

regenerative braking energy recovery. The mass of the vehicles monitored in this study was not known. However, some useful information may be... regenerative energy recovery potential for specific duty cycles was also quantified through a cumulative assessment of the number and severity of deceleration...extracted on usage time, distance, vehicle speed and geographic location in order to compare vehicle driving profiles. The regenerative energy recovery

Analysis of Non-Tactical Vehicle Utilization at Fort Carson

DTIC Science & Technology

2012-03-30

regenerative braking energy recovery. The mass of the vehicles monitored in this study was not known. However, some useful information may be...regeneration to add braking action when the driver demand for deceleration rate exceeds the power absorption capability of the regenerative energy...recovery efficiency. However, the VSquareLoss calculation can be easily adapted to take into account the clipping of regenerative braking at high speeds

Empirical Knowledge Transfer and Collaboration with Self-Regenerative Systems

DTIC Science & Technology

2007-06-01

SYSTEMS Raytheon Company Sponsored by Defense Advanced Research Projects Agency DARPA Order No. T120 APPROVED FOR PUBLIC RELEASE...FA8750-04-C-0286 5b. GRANT NUMBER 4. TITLE AND SUBTITLE EMPIRICAL KNOWLEDGE TRANSFER AND COLLABORATION WITH SELF-REGENERATIVE SYSTEMS 5c...Self-Regenerative Systems program to develop new technologies supporting granular scalable redundancy. The key focus of Raytheon’s effort was to

Native language shapes automatic neural processing of speech.

PubMed

Intartaglia, Bastien; White-Schwoch, Travis; Meunier, Christine; Roman, Stéphane; Kraus, Nina; Schön, Daniele

2016-08-01

The development of the phoneme inventory is driven by the acoustic-phonetic properties of one's native language. Neural representation of speech is known to be shaped by language experience, as indexed by cortical responses, and recent studies suggest that subcortical processing also exhibits this attunement to native language. However, most work to date has focused on the differences between tonal and non-tonal languages that use pitch variations to convey phonemic categories. The aim of this cross-language study is to determine whether subcortical encoding of speech sounds is sensitive to language experience by comparing native speakers of two non-tonal languages (French and English). We hypothesized that neural representations would be more robust and fine-grained for speech sounds that belong to the native phonemic inventory of the listener, and especially for the dimensions that are phonetically relevant to the listener such as high frequency components. We recorded neural responses of American English and French native speakers, listening to natural syllables of both languages. Results showed that, independently of the stimulus, American participants exhibited greater neural representation of the fundamental frequency compared to French participants, consistent with the importance of the fundamental frequency to convey stress patterns in English. Furthermore, participants showed more robust encoding and more precise spectral representations of the first formant when listening to the syllable of their native language as compared to non-native language. These results align with the hypothesis that language experience shapes sensory processing of speech and that this plasticity occurs as a function of what is meaningful to a listener. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regeneration experiments below 10K in a regenerative-cycle cryocooler

NASA Technical Reports Server (NTRS)

Sager, R. E.; Paulson, D. N.

1983-01-01

At temperatures below 10K, regenerative cycle cryocoolers are limited by regeneration losses in the helium working fluid which result from the decreasing heat capacity of the regenerating material and the increasing density of helium. Experiments examining several approaches to improving the low-temperature regeneration in a four-stage regenerative cycle cooler constructed primarily of fiberglass materials are discussed. Using an interchangeable fourth stage, the experiments included configurations with multiple regeneration passages, and a static helium volume for increased heat capacity. Experiments using helium-3 as the working fluid and a Malone stage are planned. Results indicate that, using these techniques, it should be possible to construct a regenerative cycle cooler which will operate below 6K.

The past, present and future of ligament regenerative engineering

PubMed Central

Mengsteab, Paulos Y; Nair, Lakshmi S; Laurencin, Cato T

2016-01-01

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes. PMID:27879170

Regenerative Life Support Evaluation

NASA Technical Reports Server (NTRS)

Kleiner, G. N.; Thompson, C. D.

1977-01-01

This paper describes the development plan and design concept of the Regenerative Life Support Evaluation (RLSE) planned for flight testing in the European Space Agency Spacelab. The development plan encompasses the ongoing advanced life support subsystem and a systems integration effort to evolve concurrently subsystem concepts that perform their function and can be integrated with other subsystems in a flight demonstration of a regenerative life support system. The design concept for RLSE comprises water-electrolysis O2 generation, electrochemically depolarized CO2 removal, and Sabatier CO2 reduction for atmosphere regeneration, urine vapor-compression distillation, and wash-water hyperfiltration for waste-water recovery. The flight demonstration by RLSE is an important step in qualifying the regenerative concepts for life support in space stations.

The past, present and future of ligament regenerative engineering.

PubMed

Mengsteab, Paulos Y; Nair, Lakshmi S; Laurencin, Cato T

2016-12-01

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes.

Repetition Suppression in the Left Inferior Frontal Gyrus Predicts Tone Learning Performance.

PubMed

Asaridou, Salomi S; Takashima, Atsuko; Dediu, Dan; Hagoort, Peter; McQueen, James M

2016-06-01

Do individuals differ in how efficiently they process non-native sounds? To what extent do these differences relate to individual variability in sound-learning aptitude? We addressed these questions by assessing the sound-learning abilities of Dutch native speakers as they were trained on non-native tone contrasts. We used fMRI repetition suppression to the non-native tones to measure participants' neuronal processing efficiency before and after training. Although all participants improved in tone identification with training, there was large individual variability in learning performance. A repetition suppression effect to tone was found in the bilateral inferior frontal gyri (IFGs) before training. No whole-brain effect was found after training; a region-of-interest analysis, however, showed that, after training, repetition suppression to tone in the left IFG correlated positively with learning. That is, individuals who were better in learning the non-native tones showed larger repetition suppression in this area. Crucially, this was true even before training. These findings add to existing evidence that the left IFG plays an important role in sound learning and indicate that individual differences in learning aptitude stem from differences in the neuronal efficiency with which non-native sounds are processed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Japanese artificial organs scene: current status.

PubMed

Mitamura, Yoshinori; Murabayashi, Shun

2005-08-01

Artificial organs and regenerative medicine are the subjects of very active research and development (R&D) in Japan and various artificial organs are widely used in patients. Results of the R&D are presented at the annual conference of the Japanese Society for Artificial Organs (JSAO). Progress in the fields of artificial organs and regenerative medicine are reviewed annually in the Japanese Journal of Artificial Organs. The official English-language journal of JSAO, Journal of Artificial Organs, also publishes many original articles by Japanese researchers. Although the annual conference and the publications of JSAO provide the world with update information on artificial organs and regenerative medicine in Japan, the information is not always understood appropriately in the rest of the world, mainly due to language problems. This article therefore introduces the current status of artificial organs and regenerative medicine in Japan. Artificial hearts and metabolic support systems are reviewed here and other interesting areas such as regenerative medicine can be found elsewhere.

Power Management in Regenerative Life Support Systems

NASA Technical Reports Server (NTRS)

Crawford, Sekou; Pawlowski, Christopher; Finn, Cory; Mead, Susan C. (Technical Monitor)

1999-01-01

Effective management of power can reduce the cost of launch and operation of regenerative life support systems. Variations in power may be quite severe and may manifest as surges or spikes, While the power plant may have some ability to deal with these variations, with batteries for example, over-capacity is expensive and does nothing to address the fundamental issue of excessive demand. Because the power unit must be sized to accommodate the largest demand, avoiding power spikes has the potential to reduce the required size of the power plant while at the same time increasing the dependability of the system. Scheduling of processors can help to reduce potential power spikes. However, not all power-consuming equipment is easily scheduled. Therefore, active power management is needed to further decrease the risk of surges or spikes. We investigate the use of a hierarchical scheme to actively manage power for a model of a regenerative life support system. Local level controllers individually determine subsystem power usage. A higher level controller monitors overall system power and detects surges or spikes. When a surge condition is detected, the higher level controller conducts an 'auction' and describes subsystem power usage to re-allocate power. The result is an overall reduction in total power during a power surge. The auction involves each subsystem making a 'bid' to buy or sell power based on local needs. However, this re-allocation cannot come at the expense of life support function. To this end, participation in the auction is restricted to those processes meeting certain tolerance constraints. These tolerances represent acceptable limits within which system processes can be operated. We present a simulation model and discuss some of our results.

Re-membering the body: applications of computational neuroscience to the top-down control of regeneration of limbs and other complex organs.

PubMed

Pezzulo, G; Levin, M

2015-12-01

A major goal of regenerative medicine and bioengineering is the regeneration of complex organs, such as limbs, and the capability to create artificial constructs (so-called biobots) with defined morphologies and robust self-repair capabilities. Developmental biology presents remarkable examples of systems that self-assemble and regenerate complex structures toward their correct shape despite significant perturbations. A fundamental challenge is to translate progress in molecular genetics into control of large-scale organismal anatomy, and the field is still searching for an appropriate theoretical paradigm for facilitating control of pattern homeostasis. However, computational neuroscience provides many examples in which cell networks - brains - store memories (e.g., of geometric configurations, rules, and patterns) and coordinate their activity towards proximal and distant goals. In this Perspective, we propose that programming large-scale morphogenesis requires exploiting the information processing by which cellular structures work toward specific shapes. In non-neural cells, as in the brain, bioelectric signaling implements information processing, decision-making, and memory in regulating pattern and its remodeling. Thus, approaches used in computational neuroscience to understand goal-seeking neural systems offer a toolbox of techniques to model and control regenerative pattern formation. Here, we review recent data on developmental bioelectricity as a regulator of patterning, and propose that target morphology could be encoded within tissues as a kind of memory, using the same molecular mechanisms and algorithms so successfully exploited by the brain. We highlight the next steps of an unconventional research program, which may allow top-down control of growth and form for numerous applications in regenerative medicine and synthetic bioengineering.

Modulating macrophage polarization with divalent cations in nanostructured titanium implant surfaces

NASA Astrophysics Data System (ADS)

Lee, Chung-Ho; Kim, Youn-Jeong; Jang, Je-Hee; Park, Jin-Woo

2016-02-01

Nanoscale topographical modification and surface chemistry alteration using bioactive ions are centrally important processes in the current design of the surface of titanium (Ti) bone implants with enhanced bone healing capacity. Macrophages play a central role in the early tissue healing stage and their activity in response to the implant surface is known to affect the subsequent healing outcome. Thus, the positive modulation of macrophage phenotype polarization (i.e. towards the regenerative M2 rather than the inflammatory M1 phenotype) with a modified surface is essential for the osteogenesis funtion of Ti bone implants. However, relatively few advances have been made in terms of modulating the macrophage-centered early healing capacity in the surface design of Ti bone implants for the two important surface properties of nanotopography and and bioactive ion chemistry. We investigated whether surface bioactive ion modification exerts a definite beneficial effect on inducing regenerative M2 macrophage polarization when combined with the surface nanotopography of Ti. Our results indicate that nanoscale topographical modification and surface bioactive ion chemistry can positively modulate the macrophage phenotype in a Ti implant surface. To the best of our knowledge, this is the first demonstration that chemical surface modification using divalent cations (Ca and Sr) dramatically induces the regenerative M2 macrophage phenotype of J774.A1 cells in nanostructured Ti surfaces. In this study, divalent cation chemistry regulated the cell shape of adherent macrophages and markedly up-regulated M2 macrophage phenotype expression when combined with the nanostructured Ti surface. These results provide insight into the surface engineering of future Ti bone implants that are harmonized between the macrophage-governed early wound healing process and subsequent mesenchymal stem cell-centered osteogenesis function.

Non-pathogenic microflora of a spring water with regenerative properties.

PubMed

Nicoletti, Giovanni; Corbella, Marta; Jaber, Omar; Marone, Piero; Scevola, Daniele; Faga, Angela

2015-11-01

The Comano spring water (Comano, Italy) has been demonstrated to improve skin regeneration, not only by increasing keratinocyte proliferation and migration, but also by modulating the regenerated collagen and elastic fibers in the dermis. However, such biological properties may not be entirely explained by its mineral composition only. As the non-pathogenic bacterial populations have demonstrated an active role in different biological processes, the potential presence of non-pathogenic bacterial species within the Comano spring water was investigated in order to identify any possible correlation between these bacterial populations and the demonstrated biological properties of this water. The water was collected at the spring using an aseptic procedure and multiple cultures were carried out. A total of 9 different strains were isolated, which were Aeromonas hydrophila , Brevundimonas vesicularis , Chromobacterium violaceum , Citrobacter youngae , Empedobacter brevis , Pantoea agglomerans , Pseudomonas putida , Pseudomonas stutzeri and Streptococcus mitis . All the isolated bacterial strains, although showing a rare potential virulence, demonstrated peculiar and favorable metabolic attitudes in controlling environmental pollution. The therapeutical effects of certain spring waters are currently being proven as correlated not only to their peculiar mineral composition, but also to the complex activity of their resident non-pathogenic bacterial populations. Although the present study provided only preliminary data, some of the non-pathogenic bacterial populations that were identified in the Comano spring water are likely to produce molecular mediators with a role in the wound healing process that, thus far, remain unknown. Numerous other unknown bacterial species, comprehensively termed DNA-rich 'dark matter', are likely to contribute to the Comano water regenerative properties as well. Therefore, the non-pathogenic bacterial populations of the Comano spring water are possibly credited for its demonstrated regenerative properties.

New frontier in regenerative medicine: site-specific gene correction in patient-specific induced pluripotent stem cells.

PubMed

Garate, Zita; Davis, Brian R; Quintana-Bustamante, Oscar; Segovia, Jose C

2013-06-01

Advances in cell and gene therapy are opening up new avenues for regenerative medicine. Because of their acquired pluripotency, human induced pluripotent stem cells (hiPSCs) are a promising source of autologous cells for regenerative medicine. They show unlimited self-renewal while retaining the ability, in principle, to differentiate into any cell type of the human body. Since Yamanaka and colleagues first reported the generation of hiPSCs in 2007, significant efforts have been made to understand the reprogramming process and to generate hiPSCs with potential for clinical use. On the other hand, the development of gene-editing platforms to increase homologous recombination efficiency, namely DNA nucleases (zinc finger nucleases, TAL effector nucleases, and meganucleases), is making the application of locus-specific gene therapy in human cells an achievable goal. The generation of patient-specific hiPSC, together with gene correction by homologous recombination, will potentially allow for their clinical application in the near future. In fact, reports have shown targeted gene correction through DNA-Nucleases in patient-specific hiPSCs. Various technologies have been described to reprogram patient cells and to correct these patient hiPSCs. However, no approach has been clearly more efficient and safer than the others. In addition, there are still significant challenges for the clinical application of these technologies, such as inefficient differentiation protocols, genetic instability resulting from the reprogramming process and hiPSC culture itself, the efficacy and specificity of the engineered DNA nucleases, and the overall homologous recombination efficiency. To summarize advances in the generation of gene corrected patient-specific hiPSCs, this review focuses on the available technological platforms, including their strengths and limitations regarding future therapeutic use of gene-corrected hiPSCs.

Dissociation of working memory processing associated with native and second languages: PET investigation.

PubMed

Kim, Jae-Jin; Kim, Myung Sun; Lee, Jae Sung; Lee, Dong Soo; Lee, Myung Chul; Kwon, Jun Soo

2002-04-01

Verbal working memory plays a significant role in language comprehension and problem-solving. The prefrontal cortex has been suggested as a critical area in working memory. Given that domain-specific dissociations of working memory may exist within the prefrontal cortex, it is possible that there may also be further functional divisions within the verbal working memory processing. While differences in the areas of the brain engaged in native and second languages have been demonstrated, little is known about the dissociation of verbal working memory associated with native and second languages. We have used H2(15)O positron emission tomography in 14 normal subjects in order to identify the neural correlates selectively involved in working memory of native (Korean) and second (English) languages. All subjects were highly proficient in the native language but poorly proficient in the second language. Cognitive tasks were a two-back task for three kinds of visually presented objects: simple pictures, English words, and Korean words. The anterior portion of the right dorsolateral prefrontal cortex and the left superior temporal gyrus were activated in working memory for the native language, whereas the posterior portion of the right dorsolateral prefrontal cortex and the left inferior temporal gyrus were activated in working memory for the second language. The results suggest that the right dorsolateral prefrontal cortex and left temporal lobe may be organized into two discrete, language-related functional systems. Internal phonological processing seems to play a predominant role in working memory processing for the native language with a high proficiency, whereas visual higher order control does so for the second language with a low proficiency. (C)2002 Elsevier Science (USA).

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal.

PubMed

Hettle, Robert; Corbett, Mark; Hinde, Sebastian; Hodgson, Robert; Jones-Diette, Julie; Woolacott, Nerys; Palmer, Stephen

2017-02-01

The National Institute for Health and Care Excellence (NICE) commissioned a 'mock technology appraisal' to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal. Our research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia. An assessment of previous evaluations of regenerative medicines found that, although there were a number of evidential challenges, none was unique to regenerative medicines or was beyond the scope of existing methods used to conceptualise decision uncertainty. Regarding the clinical evidence for regenerative medicines, the issues were those associated with a limited evidence base but were not unique to regenerative medicines: small non-randomised studies, high variation in response and the intervention subject to continuing development. The relative treatment effects generated from single-arm trials are likely to be optimistic unless it is certain that the historical data have accurately estimated the efficacy of the control agent. Pivotal trials may use surrogate end points, which, on average, overestimate treatment effects. To reduce overall uncertainty, multivariate meta-analysis of all available data should be considered. Incorporating indirectly relevant but more reliable (more mature) data into the analysis can also be considered; such data may become available as a result of the evolving regulatory pathways being developed by the European Medicines Agency. For the exemplar case of CAR T-cell therapy, target product profiles (TPPs) were developed, which considered the 'curative' and 'bridging to stem-cell transplantation' treatment approaches separately. Within each TPP, three 'hypothetical' evidence sets (minimum, intermediate and mature) were generated to simulate the impact of alternative levels of precision and maturity in the clinical evidence. Subsequent assessments of cost-effectiveness were undertaken, employing the existing NICE reference case alongside additional analyses suggested within alternative frameworks. The additional exploratory analyses were undertaken to demonstrate how assessments of cost-effectiveness and uncertainty could be impacted by alternative managed entry agreements (MEAs), including price discounts, performance-related schemes and technology leasing. The panel deliberated on the range of TPPs, evidence sets and MEAs, commenting on the likely recommendations for each scenario. The panel discussed the challenges associated with the exemplar and regenerative medicines more broadly, focusing on the need for a robust quantification of the level of uncertainty in the cost-effective estimates and the potential value of MEAs in limiting the exposure of the NHS to high upfront costs and loss associated with a wrong decision. It is to be expected that there will be a significant level of uncertainty in determining the clinical effectiveness of regenerative medicines and their long-term costs and benefits, but the existing methods available to estimate the implications of this uncertainty are sufficient. The use of risk sharing and MEAs between the NHS and manufacturers of regenerative medicines should be investigated further. The National Institute for Health Research Health Technology Assessment programme.

7 CFR 1780.49 - Rural or Native Alaskan villages.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Rural or Native Alaskan villages. 1780.49 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE LOANS AND GRANTS Loan and Grant Application Processing § 1780.49 Rural or Native Alaskan villages. (a) General. (1) This section contains regulations for...

Education and the Native American.

ERIC Educational Resources Information Center

Iannucilli, Mary V.

Traditionally, Native Americans educated their children through the oral transmission of beliefs and values. Christian missions dominated Indian education from the 16th to the 19th century and began the process of erasing Native American identity and culture. After the Civil War, control of 73 Indian agencies was assigned to 13 religious…

A Novel Unitized Regenerative Proton Exchange Membrane Fuel Cell

NASA Technical Reports Server (NTRS)

Murphy, O. J.; Cisar, A. J.; Gonzalez-Martin, A.; Salinas, C. E.; Simpson, S. F.

1996-01-01

A difficulty encountered in designing a unitized regenerative proton exchange membrane (PEM) fuel cell lies in the incompatibility of electrode structures and electrocatalyst materials optimized for either of the two functions (fuel cell or electrolyzer) with the needs of the other function. This difficulty is compounded in previous regenerative fuel cell designs by the fact that water, which is needed for proton conduction in the PEM during both modes of operation, is the reactant supplied to the anode in the electrolyzer mode of operation and the product formed at the cathode in the fuel cell mode. Drawbacks associated with existing regenerative fuel cells have been addressed. In a first innovation, electrodes function either as oxidation electrodes (hydrogen ionization or oxygen evolution) or as reduction electrodes (oxygen reduction or hydrogen evolution) in the fuel cell and electrolyzer modes, respectively. Control of liquid water within the regenerative fuel cell has been brought about by a second innovation. A novel PEM has been developed with internal channels that permit the direct access of water along the length of the membrane. Lateral diffusion of water along the polymer chains of the PEM provides the water needed at electrode/PEM interfaces. Fabrication of the novel single cell unitized regenerative fuel cell and results obtained on testing it are presented.

A novel unitized regenerative proton exchange membrane fuel cell

NASA Technical Reports Server (NTRS)

Murphy, O. J.; Cisar, A. J.; Gonzalez-Martin, A.; Salinas, C. E.; Simpson, S. F.

1995-01-01

A difficulty encountered in designing a unitized regenerative proton exchange membrane (PEM) fuel cell lies in the incompatibility of electrode structures and electrocatalyst materials optimized for either of the two functions (fuel cell or electrolyzer) with the needs of the other function. This difficulty is compounded in previous regenerative fuel cell designs by the fact that water, which is needed for proton conduction in the PEM during both modes of operation, is the reactant supplied to the anode in the electrolyzer mode of operation and the product formed at the cathode in the fuel cell mode. Drawbacks associated with existing regenerative fuel cells have been addressed in work performed at Lynntech. In a first innovation, electrodes function either as oxidation electrodes (hydrogen ionization or oxygen evolution) or as reduction electrodes (oxygen reduction or hydrogen evolution) in the fuel cell and electrolyzer modes, respectively. Control of liquid water within the regenerative fuel cell has been brought about by a second innovation. A novel PEM has been developed with internal channels that permit the direct access of water along the length of the membrane. Lateral diffusion of water along the polymer chains of the PEM provides the water needed at electrode/PEM interfaces. Fabrication of the novel unitized regenerative fuel cell and results obtained on testing it will be presented.

Regenerative endodontics: a true paradigm shift or a bandwagon about to be derailed?

PubMed

Nazzal, H; Duggal, M S

2017-02-01

Regenerative endodontic techniques (RETs) have been hailed as a paradigm shift for the management of traumatised non-vital immature permanent anterior teeth. In this article the aim was to critically appraise the literature with regards to the outcome of regenerative endodontics on root development. Critical review of the literature where regenerative endodontic techniques have been used in the management of immature non-vital teeth with continuation of root development as the main outcome reported. Most studies published were in the form of case reports and series with very few randomised controlled trials with a high risk of bias. Continuation of root development following the use of RET has been shown to be unpredictable at best with lower success in those teeth losing vitality as a result of dental trauma. Despite the high success of regenerative endodontics in terms of periodontal healing including resolution of clinical and radiographic signs and symptoms of infection, continuation of root development remains an unpredictable outcome. The use of a blood clot as a scaffold in regenerative endodontics should be reviewed carefully as that might offer an environment for repair rather than regeneration. In addition, preservation of structures, such as Hertwig's epithelial root sheath, may have an important bearing on the success of this approach and should be further investigated.

Regenerative Endodontics: Barriers and Strategies for Clinical Translation

PubMed Central

Kim, Sahng G.; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y.; Yang, Rujing; Zhou, Xuedong; Mao, Jeremy J.

2014-01-01

SYNOPSIS Despite a great deal of enthusiasm and effort, regenerative endodontics has encountered substantial challenges towards clinical translation. Recent adoption by the American Dental Association (ADA) of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for the majority of endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Dental pulp stem cells may appear to be a priori choice for dental pulp regeneration. However, dental pulp stem cells may not be available in a patient who is in need of pulp regeneration. Even if dental pulp stem cells are available autologously or perhaps allogeneically, one must address a multitude of scientific, regulatory and commercialization barriers, and unless these issues are resolved, transplantation of dental pulp stem cells will remain a scientific exercise, rather than a clinical reality. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation. Given the functions and scale of dental pulp and dentin, regenerative endodontics is poised to become one of the early biological solutions in regenerative dental medicine. PMID:22835543

Erich Regener and the ionisation maximum of the atmosphere

NASA Astrophysics Data System (ADS)

Carlson, P.; Watson, A. A.

2014-12-01

In the 1930s the German physicist Erich Regener (1881-1955) did important work on the measurement of the rate of production of ionisation deep under water and in the atmosphere. Along with one of his students, Georg Pfotzer, he discovered the altitude at which the production of ionisation in the atmosphere reaches a maximum, often, but misleadingly, called the Pfotzer maximum. Regener was one of the first to estimate the energy density of cosmic rays, an estimate that was used by Baade and Zwicky to bolster their postulate that supernovae might be their source. Yet Regener's name is less recognised by present-day cosmic ray physicists than it should be, largely because in 1937 he was forced to take early retirement by the National Socialists as his wife had Jewish ancestors. In this paper we briefly review his work on cosmic rays and recommend an alternative naming of the ionisation maximum. The influence that Regener had on the field through his son, his son-in-law, his grandsons and his students, and through his links with Rutherford's group in Cambridge, is discussed in an appendix. Regener was nominated for the Nobel Prize in Physics by Schrödinger in 1938. He died in 1955 at the age of 73.

Traditional or regenerative periodontal surgery?-a comparison of the publications between two periodontal journals over time.

PubMed

Staubli, Noémie; Schmidt, Julia C; Buset, Sabrina L; Gutekunst, Claudia J; Rodriguez, Fabiola R; Schmidlin, Patrick R; Walter, Clemens

2018-01-01

The objective is to compare the amount and content of publications regarding traditional or regenerative periodontal surgery in the years 1982/1983 and 2012/2013 in two leading periodontal journals of North America and Europe. The search was carried out in the Journal of Periodontology and Journal of Clinical Periodontology. Four reviewers screened the articles and allocated the topics with respect to periodontal surgery. The distribution of articles with respect to traditional or regenerative periodontal surgery was then compared between the journals and the respective time periods. Out of 1084 screened articles, 145 articles were included. Articles with periodontal surgery content amounted to 18% for the first time period and to 11% for the second time period. In the years 1982/1983, 7% of articles in the Journal of Periodontology and 8% in the Journal of Clinical Periodontology referred to traditional periodontal surgery, while 8% (Journal of Periodontology) and 5% (Journal of Clinical Periodontology) examined regenerative periodontal surgery. The distribution changed 30 years later, with 1% (Journal of Periodontology) and 3% (Journal of Clinical Periodontology) traditional periodontal surgery and 7% and 6% regenerative periodontal surgery content. While the clinical need for traditional periodontal surgery remained, research in this important field decreased. Publications rather tended to focus on adjunctive regenerative measures. Periodontal surgery with adjunctive regenerative measures is an established and well-documented clinical procedure. However, with respect to the dominance of horizontal bone loss in periodontally diseased patients, there is a need for ongoing research with focus on traditional periodontal surgery.

Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis.

PubMed

Andriolo, Luca; Merli, Giulia; Tobar, Carlos; Altamura, Sante Alessandro; Kon, Elizaveta; Filardo, Giuseppe

2018-02-06

The aim of this study was to document the available evidence on the use of regenerative techniques for the treatment of femoral head osteonecrosis (or avascular necrosis of femoral head, AVN) and to understand their benefit compared to core decompression (CD) alone in avoiding failure and the need for total hip replacement (THR). The search was conducted on three medical electronic databases according to PRISMA guidelines. The studies reporting number and timing of failures were included in a meta-analysis calculating cumulative survivorship with a Kaplan-Mayer curve. Moreover, the results on failures in treatment groups reported in RCT were compared with those documented in control groups, in order to understand the benefit of biological therapies compared to CD for the treatment of AVN. Forty-eight studies were included in this systematic review, reporting results of different types of regenerative techniques: mesenchymal stem cell implantation in the osteonecrotic area, intra-arterial infiltration with mesenchymal stem cells, implantation of bioactive molecules, or platelet-rich plasma. Overall, reported results were good, with a cumulative survivorship of 80% after ten year follow-up, and better results when regenerative treatments were combined to CD compared to CD alone (89.9% vs 70.6%, p < 0.0001). Regenerative therapies offer good clinical results for the treatment of AVN. The combination of CD with regenerative techniques provides a significant improvement in terms of survivorship over time compared with CD alone. Further studies are needed to identify the best procedure and the most suitable patients to benefit from regenerative treatments for AVN.

Waterless Clothes-Cleaning Machine

NASA Technical Reports Server (NTRS)

Johnson, Glenn; Ganske, Shane

2013-01-01

A waterless clothes-cleaning machine has been developed that removes loose particulates and deodorizes dirty laundry with regenerative chemical processes to make the clothes more comfortable to wear and have a fresher smell. This system was initially developed for use in zero-g, but could be altered for 1-g environments where water or other re sources are scarce. Some of these processes include, but are not limited to, airflow, filtration, ozone generation, heat, ultraviolet light, and photocatalytic titanium oxide.

Perspective: Neuroregenerative Nutrition.

PubMed

Steindler, Dennis A; Reynolds, Brent A

2017-07-01

Good health while aging depends upon optimal cellular and organ functioning that contribute to the regenerative ability of the body during the lifespan, especially when injuries and diseases occur. Although diet may help in the maintenance of cellular fitness during periods of stability or modest decline in the regenerative function of an organ, this approach is inadequate in an aged system, in which the ability to maintain homeostasis is further challenged by aging and the ensuing suboptimal functioning of the regenerative unit, tissue-specific stem cells. Focused nutritional approaches can be used as an intervention to reduce decline in the body's regenerative capacity. This article brings together nutrition-associated therapeutic approaches with the fields of aging, immunology, neurodegenerative disease, and cancer to propose ways in which diet and nutrition can work with standard-of-care and integrated medicine to help improve the brain's function as it ages. The field of regenerative medicine has exploded during the past 2 decades as a result of the discovery of stem cells in nearly every organ system of the body, including the brain, where neural stem cells persist in discrete areas throughout life. This fact, and the uncovering of the genetic basis of plasticity in somatic cells and cancer stem cells, open a door to a world where maintenance and regeneration of organ systems maintain health and extend life expectancy beyond its present limits. An area that has received little attention in regenerative medicine is the influence on regulatory mechanisms and therapeutic potential of nutrition. We propose that a strong relation exists between brain regenerative medicine and nutrition and that nutritional intervention at key times of life could be used to not only maintain optimal functioning of regenerative units as humans age but also play a primary role in therapeutic treatments to combat injury and diseases (in particular, those that occur in the latter one-third of the lifespan). © 2017 American Society for Nutrition.

Plastic Surgery Challenges in War Wounded II: Regenerative Medicine

PubMed Central

Valerio, Ian L.; Sabino, Jennifer M.; Dearth, Christopher L.

2016-01-01

Background: A large volume of service members have sustained complex injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). These injuries are complicated by contamination with particulate and foreign materials, have high rates of bacterial and/or fungal infections, are often composite-type defects with massive soft tissue wounds, and usually have multisystem involvement. While traditional treatment modalities remain a mainstay for optimal wound care, traditional reconstruction approaches alone may be inadequate to fully address the scope and magnitude of such massive complex wounds. As a result of these difficult clinical problems, the use of regenerative medicine therapies, such as autologous adipose tissue grafting, stem cell therapies, nerve allografts, and dermal regenerate templates/extracellular matrix scaffolds, is increased as adjuncts to traditional reconstructive measures. Basic and Clinical Science Advances: The beneficial applications of regenerative medicine therapies have been well characterized in both in vitro studies and in vivo animal studies. The use of these regenerative medicine techniques in the treatment of combat casualty injuries has been increasing throughout the recent war conflicts. Clinical Care Relevance: Military medicine has shown positive results when utilizing certain regenerative medicine modalities in treating complex war wounds. As a result, multi-institution clinical trials are underway to further evaluate these observations and reconstruction measures. Conclusion: Successful combat casualty wound care often requires a combination of traditional aspects of the reconstructive ladder/elevator with adoption of various regenerative medicine therapies. Due to the recent OIF/OEF conflicts, a high volume of combat casualties have benefited from adoption of regenerative medicine therapies and increased access to innovative clinical trials. Furthermore, many of these patients have had long-term follow-up to report on clinical outcomes that substantiate current treatment paradigms and concepts within regenerative medicine, reconstructive, and rehabilitation care. These results are applicable to not only combat casualty care but also to nonmilitary patients. PMID:27679752