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Bone and cartilage tissue engineering.

Tissue engineering of musculoskeletal tissues, particularly bone and cartilage, is a rapidly advancing field. In bone, technology has centered on bone graft substitute materials and the development of biodegradable scaffolds. Recently, tissue engineering strategies have included cell and gene therapy. The availability of growth factors and the expanding knowledge base concerning the genetics and regulation of bone formation have generated new materials for tissue-engineering applications. This information base also has benefited cartilage tissue engineering. The problems are more complex, however, and the solutions appear more elusive. Advances in scaffold design and cell culture have improved the prognosis for success.

Animals↗

Reflections on tissue engineering and trauma therapy.

Although all of Trauma Care has remarkably improved during the latter half of the last century the treatment of burn injury has substantially out paced other areas and serves as an excellent example illustrating the improvements taking place in the treatment of injured patients. Although Trauma treatment lagged behind the rest of medicine in mid-century today it rests solidly on the cutting edge of advancing therapeutic knowledge and practice in areas of metabolism, immunology, infection control, critical care, tissue engineering and the delivery of clinical care. It is important to understand what has happened to allow the treatment of injury to be so effective. The bench mark therapeutic moves that have had major effects allowing the present highly effective treatment are: immediate tailored fluid resuscitation, preventive (prophylactic) and topical antibiotics, metabolically designed nutritional therapy and most important early definitive repair of the injury. All must be delivered early after trauma if they are to be optimally effective in preventing the complications of injury that are devastating if encountered. Unfortunately, all problems are not solved by todays treatment of injury, improved as it is. These problems are largely related to an inexact understanding: of the physiologic changes of aging, of the exact pathophysiologic events in inhalation injury and multisystem organ failure and of the technology required to replace those body parts damaged by the injury itself that lead to death or to healing with loss of function. There will be major improvements in the understanding and ability to effectively deal with the problems of aging and inhalation injury through basic and clinical research but perhaps the major improvement in injury treatment will come through the ability to replace worn out, defective or damaged body parts through technologies that resemble regeneration. Here the concepts of Tissue Engineering have much to contribute and it is worth exploring the donation of Tissue Engineering to dermal replacement following burn injury to serve as an example of what types of additions to treatment Tissue Engineering can make.

Burns↗

Tissue engineering of the vascular system: from capillaries to larger blood vessels.

Tissue engineering is a novel approach to the repair of wounded tissues. Application of this technology to the vascular system is important because of the fundamental nutritional role of the vasculature. This perspective is currently being applied to the first tissue-engineered organ: the skin. Knowledge of capillary constitution and factors inducing their formation has led to attempts to induce their formation in reconstructed skin. Such vascular conduits grown in vitro could also benefit the nutrition of tissues and organs in vivo. The paper reviews recent progress in the in-vitro development of vascularised skin and tissue-engineered blood vessels. It points out the necessity of obtaining pure and well-characterised cultures of the different cell populations that are the basic building blocks of the reconstructions. The importance of an adequate cell-culture environment (nutrients and bi- or tri-dimensional scaffolds for cells) for success in elaborating a reconstructed living tissue able to replace the original is emphasised. Engineered tissues can serve not only as tissue replacements but also as in-vitro models for research in organ physiology and physiopathology. These tissues are also attractive vehicles for gene therapy, one of the more promising new methods of disease treatment.

Blood Vessels↗

Engineering of human vascular aortic tissue based on a xenogeneic starter matrix.

BACKGROUND: The goal for tissue engineering of vascular grafts is the replacement of a diseased vessel with a functional and stable graft. We now introduce a new concept for the tissue engineering of vessels. The idea was to humanize a previously acellularized, but structurally intact, xenogeneic vessel by repopulation with human autologous cells. To this purpose, a gentle nondenaturing and nondeterging acellularization procedure for xenogeneic aortas was developed. This structure was reseeded with pre-expanded peripheral vascular endothelial cells (EC) and myofibroblasts using specifically designed bioreactors. METHODS: Aortas from 15-30 kg female landrace pigs were acelullarized with a 0.1% trypsin solution for between 24 and 96 hr. Human vascular cells were harvested from saphenous vein biopsy specimens. Acellularized vessels were reseeded with EC and myofibroblasts. Cell viability after reseeding was assayed by fluorescence staining. Morphologic features of the acellularized matrix and tissue engineered vessel was assayed by transmission and scanning electron microscopy and histologic analysis. Nitric oxide-synthetase activity was investigated by mass spectrometric analysis of bioreactor supernatants. The in vivo immune response was tested by subcutaneous implantation of acellularized porcine aortic tissue in a rat model. RESULTS: The acellularization procedure resulted in an almost complete removal of the original resident cells, and the 3-D matrix was loosened at interfibrillar zones. However, the 3-D arrangement of the matrix fibers was grossly maintained. The 3-D matrix was covered with a fully confluent human endothelial cell layer obtained by continuous stress challenge in the bioreactor. Myofibroblasts migrated into positions formerly occupied by the xenogeneic cells. Nitric oxide synthetase activity was maintained in the bioartificial graft. T-lymphocyte and CD18 positive leukocyte infiltrate were greatly reduced after acellularization of porcine aortic specimens after implantation in the rat. CONCLUSIONS: Porcine vessels were acellularized and consecutively fully repopulated with human EC and myofibroblasts. This approach may eventually lead to the engineering of vessels immunologically acceptable to the host using a relatively short preparation period of 2-3 weeks. We expect matrix turnover in vivo leading to a gradual assimilation of the matrix structure by the host mediated by the hosts autologous cells.

Animals↗

[Tissue engineering: possibilities and perspectives].

Successful tissue engineering requires intensive co-oporation between clinicians, biologists (cell culture, gene therapy), chemical engineers (biomaterials) and industrial partners. In case of wound healing tissue engineered constructs have already been applied successfully in burns and chronic wounds. In order to improve carrier and matrix function biomaterials still have to be optimized. The potential of such constructs might even be enhanced by gene therapeutical methods. The complex mammalian organism has to be considered as the gold standard and the model for perfect tissue engineering. The problem of vascularization of complex organs yet has to be solved. In general it seems to be more promising to substitute deficient components in vivo and to rely on modulating influences within the host organism rather than to create complex organs ex vivo.

Animals↗

The role of tissue engineering.

Tissue engineering is expected to have a great impact on wound repair. Tissue-engineering techniques bring a new element of rational design and development into therapeutic medicine. Increasing the understanding of the biology of wound repair will accelerate the improvement of patient care, and the knowledge of basic biologic processes will be applied to the development of new products. Tissue-engineered skin will be reviewed and directions for new products will be illustrated. In the future, tissue engineering is likely to continue to yield products that are rationally designed, robotically manufactured, and increasingly customized to fit patient needs.

Culture Techniques↗

[Cell transplantation in surgery--reality and prospects for tissue engineering].

Traditionally surgical repair of tissue defects and loss or failure of function has relied on mechanical means, medical (drug) treatment, autologous and allogenic transplantation, and alloplastic/synthetic devices. Tissue engineering represents a new interdisciplinary field of applied research combining engineering and biosciences together with clinical application (mainly in surgical specialities) to develop living substitutes for tissues and organs. The understanding of cell-cell interactions and chemical signalling (growth factors) and the selection of appropriate matrices (cell-matrix interaction) is the key for success. Gene therapy represents the logical combination with tissue engineering on the molecular biology level. Application of cultivated skin and cartilage has already become reality, engineering of vascularized, more complex organs remains a challenge for this century.

Cells, Cultured↗

Tissue engineering of the small intestine by acellular collagen sponge scaffold grafting.

Tissue engineering of the small intestine will prove a great benefit to patients suffering from short bowel disease. However cell seeding in tissue engineering, such as fetal cell use, is accompanied by problems of ethical issues, rejection, and short supply. To overcome these problems, we carried out an experimental study on tissue engineering of the small intestine by acellular collagen sponge scaffold grafting. We resected the 5 cm long jejunum from beagle dogs and reconstructed it by acellular collagen sponge grafting with a silicon tube stent. The graft was covered with the omentum. At 1 month after operation, the silicon stent was removed endoscopically. Animals were sacrificed 1 and 4 months after operation, and were examined microscopically. Neo-intestinal regeneration was observed and the intestinal mucosa covered the luminal side of the regenerated intestine across the anastomosis. Thus, the small intestine was regenerated by tissue engineering technology using an acellular collagen sponge scaffold.

Animals↗

[Induction of Th1 immune response against tumor by genetically engineered fusion of tumor cells and dendritic cells].

OBJECTIVE: To study the antitumor activity of engineered fusion of tumor cell and dendritic cells (DC). METHODS: J558 tumor cells were transfected with mouse IL-12 (mIL-12) gene and then fused with DCs to develop a hybrid-engineered tumor vaccine. BALB/c mice were challenged with wild-type J558 tumor cells 14 days after vaccinated with hybrid-engineered J558. RESULTS: mIL-12 was detected at (870 +/- 60) pg.(10(5) cells)(-1).ml(-1) in the culture supernatants and the cell-fusion rate was about 30% by co-focal microscopy. In addition, the lymphocytes from popliteal nodes and groin nodes of these mice vaccinated with hybrid-engineered J558 secreted higher levels of IFN-gamma than that of other control mice, and vaccination of mice with the fusion vaccine induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo. CONCLUSION: It suggested that vaccination of mice with the fusion vaccine induced stronger Th1-dominant responses and this approach could perhaps be applied to clinical settings of DCs-based cancer vaccines.

Animals↗

Usability evaluation of an experimental text summarization system and three search engines: implications for the reengineering of health care interfaces.

This paper describes the comparative evaluation of an experimental automated text summarization system, Centrifuser and three conventional search engines - Google, Yahoo and About.com. Centrifuser provides information to patients and families relevant to their questions about specific health conditions. It then produces a multidocument summary of articles retrieved by a standard search engine, tailored to the user's question. Subjects, consisting of friends or family of hospitalized patients, were asked to "think aloud" as they interacted with the four systems. The evaluation involved audio- and video recording of subject interactions with the interfaces in situ at a hospital. Results of the evaluation show that subjects found Centrifuser's summarization capability useful and easy to understand. In comparing Centrifuser to the three search engines, subjects' ratings varied; however, specific interface features were deemed useful across interfaces. We conclude with a discussion of the implications for engineering Web-based retrieval systems.

Angina Pectoris↗

[Preparation of ethanol-diesel fuel blends and exhausts emission characteristics in diesel engine].

The technology that diesel oil is partly substituted by ethanol can reduce diesel engine exhausts emission, especially fuel soot. This research is concentrated on preparation of ethanol-diesel blend fuel and exhausts emission characteristics using diesel engine bench. Absolute ethanol can dissolve into diesel fuel at an arbitrary ratio. However, a trace of water (0.2%) addition can lead to the phase separation of blends. Organic additive synthesized during this research can develop the ability of resistance to water and maintain the stability of ethanol-diesel-trace amounts of water system. The effects of 10%, 20%, and 30% ethanol-diesel fuel blends on exhausts emission, were compared with that of diesel fuel in direct injection (DI) diesel engine. The optimum ethanol percentage for ethanol-diesel fuel blends was 20%. Using 20% ethanol-diesel fuel blend with 2% additive of the total volume, bench diesel engine showed a large amount decrease of exhaust gas, e.g. 55% of Bosch smoke number, 70% of HC emission, and 45% of CO emission at 13 kW and 1540 r/min. Without the addition of additive, the blend of ethanol produced new organic compounds such as ethanol and acetaldehyde in tail gas. However, the addition of additive obviously reduced the emission of ethanol and acetaldehyde.

Aldehydes↗

[Search engine of genetics journals from Medline (PubMed)].

To help geneticists look up genetics journals more quickly and exactly,this paper developed this search engine of genetics journals. The paper exploited the search engine with genetics journals sources of Medline database in NCBI, indexed and listed 173 names of genetics journals from Medline. Then obtained one search engine concerning genetics journals after making every journal's super linkage. The search engine can search out not only all articles' titles of 173 genetics journals but also some articles' titles of the journals each year quickly, exactly and dynamically. We can further obtain all articles' abstracts and some full texts in PubMed.

Genetics↗

Food safety evaluation of crops produced through genetic engineering--how to reduce unintended effects?

Scientists started applying genetic engineering techniques to improve crops two decades ago; about 70 varieties obtained via genetic engineering have been approved to date. Although genetic engineering offers the most precise and controllable genetic modification of crops in entire history of plant improvement, the site of insertion of a desirable gene cannot be predicted during the application of this technology. As a consequence, unintended effects might occur due to activation or silencing of genes, giving rise to allergic reactions or toxicity. Therefore, extensive chemical, biochemical and nutritional analyses are performed on each new genetically engineered variety. Since the unintended effects may be predictable on the basis of what is known about the insertion place of the transgenic DNA, an important aim of plant biotechnology is to define techniques for the insertion of transgene into the predetermined chromosomal position (gene targeting). Although gene targeting cannot be applied routinely in crop plants, given the recent advances, that goal may be reached in the near future.

Consumer Product Safety↗

[Preparation of biodiesel from waste edible oils and performance and exhaust emissions of engines fueled with blends of the biodiesel].

The purpose of this study is to evaluate the effect of biodiesel on environment and to investigate the effect of the biodiesel made of waste edible oils on the performance and emissions of engines. Life cycle assessment (LCA) of biodiesel and diesel was introduced and the results of the LCA of both the fuels were given. The technological process of biodiesel production from waste edible oils, which is called transesterification of waste oils and methanol catalyzed with NaOH, was presented. Two turbocharged DI engines fueled with different proportions of biodiesel and diesel, namely, B50 (50% biodiesel + 50% diesel) and B20 (20% biodiesel + 80% diesel), were chosen to conduct performance and emission tests on a dynamometer. The results of the study indicate that there was a slight increase in fuel consumption by 8% and a drop in power by 3% with the blends of biodiesel, compared with diesel, and that the best improvements in emissions of smoke, HC, CO and PM were 65%, 11%, 33% and 13% respectively, but NOx emission was increased. The study also shows that it is satisfied to fuel engines with the low proportion blends of the biodiesel, without modifying engines, in performance and emissions.

Air Pollutants↗

[Prevalence of hypertension among railroad engine operators at a metallurgical plant].

The article comments on a study of the labour conditions peculiarities of industrial rail-way engine operators and the epidemiology of hypertension disease in this professional group. 962 persons (both mechanics and their subordinates) were examined, all of them males, 20-59 years of age, with the duration of work: less than 10 years--366 cases, 11-20 years--483 cases, over 20 years--113 cases. The analysis of hypertension prevalence revealed that the morbidity rate was markedly higher among the engine teams' personnel as compared with the depot workers. The morbidity rate difference between the industrial rail-way engine mechanics and main-line engine mechanics was insignificant. The high morbidity rate necessitates improvements of the labour conditions, e.g. working shift cuts, establishment of physical rehabilitation and psycho-emotional relaxation units, as well as rational diet.

Adult↗

[Comparative study of the behavior of particulate emissions from diesel and gasoline engines in animal lungs: elimination rate and induction of benzo(a)pyrene hydroxylase and ethoxycoumarin de-ethylase].

The emitted particulates of five diesel-engined and two gasoline-engined passenger cars were investigated for the elimination rate from hamster lungs after intratracheal instillation. In addition extracts of these particulates were studied for their influence on the mixed function oxidase activity (MFO; Benzo(a)pyrene Hydroxylase, Ethoxycoumarine Deethylase). Differences in the elimination rates of diesel soot and particulates from gasoline engines were not found. Compared with the blanc the extracts of diesel soot from two vehicles proved to give a moderate increase of the MFO activity, but a significant difference to the blanc was observed with the extracts of the gasoline engines. It should be mentioned that the effects were studied without taking into account the quantitative relations of the emissions in the ambient air. However, the amounts of particulates were extremely high in relation to the natural conditions. In the limits of our test model there is no indication of a higher toxicity of diesel-emissions.

7-Alkoxycoumarin O-Dealkylase↗

Cancer immunotherapy of established tumors with IL-12. Effective delivery by genetically engineered fibroblasts.

IL-12 is a heterodimeric cytokine produced by macrophages, mitogen stimulated- or EBV infected-B lymphocytes, keratinocytes, and probably dendritic cells, with important immunoregulatory functions in vitro and in vivo. It directly stimulates activated NK and T cells to produce high levels of IFN-gamma, enhances their cytolytic activity, and promotes maturation of Th1 cells as well as IL-2-activated B cells. We have tested paracrine delivery of IL-12 using autologous or allogeneic fibroblasts engineered to secrete high levels of IL-12 to treat established tumors. Injection of IL-12-engineered fibroblasts at the site of an established (day 8) MCA207 sarcoma could efficiently eliminate or suppress tumor growth in a dose-dependent manner, requiring delivery of > 150 ng/kg/dose of bioactive IL-12. Weekly inoculations for 3 wk could also be used to effectively treat a day 4 sarcoma located intradermally in the opposite flank (80% protection using autologous fibroblasts), resulting in long-term protective antitumor immunity. In less immunogenic tumors (MCA102, MC38), 7-day established lung metastases could be significantly reduced (p = 0.001) following IL-12 delivery by fibroblasts and systemic administration of low doses of IL-2. Histologic findings included a mixed infiltrate of CD4+ and CD8+ T effectors and macrophages in the regressing sarcoma on day 21. In a day 41 MCA207 sarcoma locally injected in situ, similar findings were observed. No lymphoid hyperplasia or tissue necrosis were noted in liver, spleen, or lungs in mice receiving repeated inocula of IL-12-engineered fibroblasts. Tests of liver and renal function monitored during the repetitive weekly treatments were within the normal range. IL-12-engineered fibroblasts thus seem to serve as a safe and efficient means to deliver IL-12 in these three tumor models.

Animals↗

The Engineer's Thumb or Sherlock Holmes on the trail of 'the uncanny'.

Freud identified 'primal phantasies' (life in the womb, 'primal scene', seduction, castration). It is argued that 'The Engineer's Thumb', a short story from 'The Adventures of Sherlock Holmes', draws its uncanniness from the fact that it is underpinned by all the primal phantasies described by Freud. 'The Engineer's Thumb' therefore illustrates what analytical interpretation can contribute to the understanding of certain literary works. 'The Engineer's Thumb' may also serve as an introduction to a broader study of the Freudian concept of 'the uncanny'. This study seems to confirm what Freud said when he pointed out that 'an uncanny experience occurs either when infantile complexes which have been repressed are once more revived by some impression, or when primitive beliefs which have been surmounted seem once more to be confirmed' (1919, p. 249). 'The Engineer's Thumb' has another interesting feature: in this short story. Conan Doyle, by setting up a 'talking cure', anticipates the creation of psychoanalysis and highlights in a striking way certain aspects of what was to become psychoanalytical treatment.

Fantasy↗