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PubMed1997

Tissue engineering, morphogenesis, and regeneration of the periodontal tissues by bone morphogenetic proteins.

Tissue engineering is the emerging field of science developing techniques for fabrication of new tissues for replacement based on principles of cell and developmental biology and biomaterials. Morphogenesis is the cascade of pattern formation and the attainment of form of the various organs and the organism as a whole. The periodontium consist of the periodontal ligament, cementum, and alveolar bone. Bone has considerable potential for regeneration and therefore is a prototypic model for tissue engineering. The three main ingredients for tissue engineering are regulatory signals, responding stem cells, and extracellular matrix. Recent advances in molecular biology of the bone morphogenetic proteins (BMPs) have set the stage for tissue engineering of bone and related tissues, including the periodontium. Bone-derived BMPs, with a collagenous matrix as carrier, induced cementum and alveolar bone regeneration in surgically created furcation defects in the primate. It is noteworthy that there was morphogenesis of periodontal ligament and a faithful insertion of Sharpey's fibers into cementum. In the same furcation model, recombinant human osteogenic protein-1 (rhOP-1, also known as BMP-7), in conjunction with the collagenous carrier, induced extensive cementogenesis with insertion of Sharpey's fibers into the newly formed cementum. The observation that BMPs induce cementogenesis and periodontal ligament formation indicates that these proteins may have multiple functions in vivo not limited to cartilage and bone induction. The rapid advances in the molecular biology of BMPs and their receptors bode well for novel strategies to engineer the regeneration of the periodontal tissues.

Alveolar Process↗
PubMed2005

Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection.

Because CD4+ T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4+ T cells could enhance an antitumor response mediated by similarly gene-engineered CD8+ T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T-cell populations composed of various proportions of CD4+ and CD8+ cells and then determined the antitumor reactivity of these mixtures. Gene-modified CD4+ and CD8+ T cells were shown to specifically secrete Tc1 (T cytotoxic-1) or Tc2 cytokines, proliferate, and lyse erbB2+ tumor targets following antigen ligation in vitro. In adoptive transfer experiments using severe combined immunodeficient (scid) mice, we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8+ and CD4+ T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8+) engineered T cells. Transferred CD4+ T cells had to be antigen-specific (not just activated) and secrete interferon gamma (IFN-gamma) to potentiate the antitumor effect. Importantly, antitumor responses in these mice correlated with localization and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent rechallenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy.

Adoptive Transfer↗
PubMed2005

Extracellular stimulation in tissue engineering.

The field of tissue engineering has created a need for biomaterials that are capable of providing biofunctional and structural support for living cells outside of the body. Most of the commonly used biomaterials in tissue engineering are designed based on their physicochemical properties, thus achieving precise control over mechanical strength, compliance, porosity, and degradation kinetics. Biofunctional signals are added to the scaffold by tethering, immobilizing, or supplementing biofunctional macromolecules, such as growth factors, directly to the scaffold material. The challenge in tissue engineering remains to find the correct balance between the biofunctional and the physical properties of the scaffold material for each application. Moreover, the ability to modulate communication between cells and the extracellular environment using the engineered scaffold as the actuator can provide a significant advantage in tissue engineering. In this study, a unique scaffold material is presented. The material interchangeably combines biofunctional and structural molecules by fusing the two into a single backbone macromolecule. This integration provides the basis for practical, effective, and high-resolution control of both the biofunctional and the physical properties of the scaffold material. This new scaffold material has proven effective with smooth muscle, cardiac, cartilage, and human embryonic stem cell cultures. The advantages of this approach as well as the potential applications of this unique scaffold material are discussed.

Animals↗
PubMed2000

Tissue engineering: confronting the transplantation crisis.

Tissue engineering is the development of biological substitutes and/or the fostering of tissue regeneration/remodelling. It is emerging as a technology which has the potential to confront the crisis in transplantation caused by the shortage of donor tissues and organs. With the development of this technology, ther is emerging a new industry which is at the interface of biotechnology and the traditional medical implant field. For this technology and the associated industry to realize their full potential, there are core, enabling technologies that need to be developed. This is the focus of the Georgia Tech/Emory Center for the Engineering of Living Tissues, newly established in the United States, with an Engineering Research Center Award from the National Science Foundation. With the development of these core technologies, tissue engineering will evolve from an art form to a technology based on science and engineering.

Biomedical Engineering↗
PubMed2005

Bioreactor design for tissue engineering.

Bioreactor systems play an important role in tissue engineering, as they enable reproducible and controlled changes in specific environmental factors. They can provide technical means to perform controlled studies aimed at understanding specific biological, chemical or physical effects. Furthermore, bioreactors allow for a safe and reproducible production of tissue constructs. For later clinical applications, the bioreactor system should be an advantageous method in terms of low contamination risk, ease of handling and scalability. To date the goals and expectations of bioreactor development have been fulfilled only to some extent, as bioreactor design in tissue engineering is very complex and still at an early stage of development. In this review we summarize important aspects for bioreactor design and provide an overview on existing concepts. The generation of three dimensional cartilage-carrier constructs is described to demonstrate how the properties of engineered tissues can be improved significantly by combining biological and engineering knowledge. In the future, a very intimate collaboration between engineers and biologists will lead to an increased fundamental understanding of complex issues that can have an impact on tissue formation in bioreactors.

Animals↗
PubMedDate not supplied

Glucose transporter content and glucose uptake in skeletal muscle constructs engineered in vitro.

Engineered muscle may eventually be used as a treatment option for patients suffering from loss of muscle function. The metabolic and contractile function of engineered muscle has not been well described; therefore, the purpose of this experiment was to study glucose transporter content and glucose uptake in engineered skeletal muscle constructs called myooids. Glucose uptake by way of 2-deoxyglucose and GLUT-1 and GLUT-4 transporter protein content was measured in basal and insulin-stimulated myooids that were engineered from soleus muscles of female Sprague-Dawley rats. There was a significant increase in the basal 2-deoxyglucose uptake of myooids compared with adult control (fivefold), contraction-stimulated (3.4-fold), and insulin-stimulated (threefold) soleus muscles (P = 0.0001, 0.0001, and 0.0001, respectively). In addition, there was a significant increase in the insulin-stimulated 2-deoxyglucose uptake of myooids compared with adult control soleus muscles in basal conditions (6.5-fold) and adult contraction-stimulated (4.5-fold) and insulin- stimulated (3.9-fold) soleus muscles (P = 0.0001, 0.0001, and 0.0001, respectively). There was a significant 30% increase in insulin-stimulated compared with basal 2-deoxyglucose uptake in the myooids. The myooid GLUT-1 protein content was 820% of the adult control soleus muscle, whereas the GLUT-4 protein content was 130% of the control soleus muscle. Myooid GLUT-1 protein content was 6.3-fold greater than GLUT-4 protein content, suggesting that the glucose transport of the engineered myooids is similar in several respects to that observed in both fetal and denervated skeletal muscle tissue.

Animals↗
PubMed2002

Matrices for tissue-engineered skin.

Academic, clinical and industrial efforts are increasingly being directed toward the use of molecular- and cell-based therapies for diagnosis and treatment of a great number and broad variety of pathologies and injuries. Hence, tissue engineering is, next to genetic engineering, widely heralded as the healthcare technology heir of the revolutionary advances in life sciences. In a cost-controlled healthcare environment, only those technologies capable of providing a major enhancement to quality of life and a reduction in expenditure will be driven forward. Skin tissue engineering concepts based on the application of a scaffold/cell construct represent a treatment concept with the clear potential to meet this criterion. Several important issues concerning the research and product strategy (e.g., choice of matrix of natural or synthetic polymer origin and the use of autogenic versus allogenic cells) remain to be fully resolved. However, there is little doubt that wound regeneration via modern tissue engineering strategies will present significant therapeutic benefits when compared with existing treatments. This paper reviews the biography and future research directions of matrices used in skin tissue engineering.

Adipose Tissue↗
PubMed2006

Education and research in biomedical engineering of the Budapest University of Technology and Economics.

Biomedical Engineering is a relatively new interdisciplinary science. This review paper presents the biomedical engineering activity, which is carried out at the Budapest University of Technology and Economics (BUTE) and its partner institutions. In the first parts the main goals and the curriculum of the Biomedical Engineering Education Program is presented. The second part of the paper summarizes the most important biomedical engineering researches most of them carried out in the Biomedical Engineering Laboratory of BUTE.

Biomedical Engineering↗
PubMed2004

Numerical method to determine mechanical parameters of engineering design in rock masses.

This paper proposes a new continuity model for engineering in rock masses and a new schematic method for reporting the engineering of rock continuity. This method can be used to evaluate the mechanics of every kind of medium; and is a new way to determine the mechanical parameters used in engineering design in rock masses. In the numerical simulation, the experimental parameters of intact rock were combined with the structural properties of field rock. The experimental results for orthogonally-jointed rock are given. The results included the curves of the stress-strain relationship of some rock masses, the curve of the relationship between the dimension Delta and the uniaxial pressure-resistant strength sc of these rock masses, and pictures of the destructive procedure of some rock masses in uniaxial or triaxial tests, etc. Application of the method to engineering design in rock masses showed the potential of its application to engineering practice.

Algorithms↗
PubMed2005

Cartilage engineering from ovine umbilical cord blood mesenchymal progenitor cells.

We aimed to determine whether three-dimensional (3D) cartilage could be engineered from umbilical cord blood (CB) cells and compare it with both engineered fetal cartilage and native tissue. Ovine mesenchymal progenitor cells were isolated from CB samples (n=4) harvested at 80-120 days of gestation by low-density fractionation, expanded, and seeded onto polyglycolic acid scaffolds. Constructs (n=28) were maintained in a rotating bioreactor with serum-free medium supplemented with transforming growth factor-beta1 for 4-12 weeks. Similar constructs seeded with fetal chondrocytes (n=13) were cultured in parallel for 8 weeks. All specimens were analyzed and compared with native fetal cartilage samples (n=10). Statistical analysis was by analysis of variance and Student's t-test (p<.01). At 12 weeks, CB constructs exhibited chondrogenic differentiation by both standard and matrix-specific staining. In the CB constructs, there was a significant time-dependent increase in extracellular matrix levels of glycosaminoglycans (GAGs) and type-II collagen (C-II) but not of elastin (EL). Fetal chondrocyte and CB constructs had similar GAG and C-II contents, but CB constructs had less EL. Compared with both hyaline and elastic native fetal cartilage, C-II and EL levels were, respectively, similar and lower in the CB constructs, which had correspondingly lower and similar GAG levels than native hyaline and elastic fetal cartilage. We conclude that CB mesenchymal progenitor cells can be successfully used for the engineering of 3D cartilaginous tissue in vitro, displaying select histological and functional properties of both native and engineered fetal cartilage. Cartilage engineered from CB may prove useful for the treatment of select congenital anomalies.

Animals↗
PubMed2004

The application of recombinant human collagen in tissue engineering.

Collagen is the main structural protein in vertebrates. It plays an essential role in providing a scaffold for cellular support and thereby affecting cell attachment, migration, proliferation, differentiation, and survival. As such, it also plays an important role in numerous approaches to the engineering of human tissues for medical applications related to tissue, bone, and skin repair and reconstruction. Currently, the collagen used in tissue engineering applications is derived from animal tissues, creating concerns related to the quality, purity, and predictability of its performance. It also carries the risk of transmission of infectious agents and precipitating immunological reactions. The recent development of recombinant sources of human collagen provides a reliable, predictable and chemically defined source of purified human collagens that is free of animal components. The triple-helical collagens made by recombinant technology have the same amino acid sequence as human tissue-derived collagen. Furthermore, by achieving the equivalent extent of proline hydroxylation via coexpression of genes encoding prolyl hydroxylase with the collagen genes, one can produce collagens with a similar degree of stability as naturally occurring material. The recombinant production process of collagen involves the generation of single triple-helical molecules that are then used to construct more complex three-dimensional structures. If one loosely defines tissue engineering as the use of a biocompatible scaffold combined with a biologically active agent (be it a gene or gene construct, growth factor or other biologically active agent) to induce tissue regeneration, then the production of recombinant human collagen enables the engineering of human tissue based on a human matrix or scaffold. Recombinant human collagens are an efficient scaffold for bone repair when combined with a recombinant bone morphogenetic protein in a porous, sponge-like format, and when presented as a membrane, sponge or gel can serve as a basis for the engineering of skin, cartilage and periodontal ligament, depending on the specific requirements of the chosen application.

Animals↗
PubMed2005

Insulin-transferrin-selenium prevent human chondrocyte dedifferentiation and promote the formation of high quality tissue engineered human hyaline cartilage.

This study was to investigate the effects of insulin-transferrin-selenium (ITS) on the proliferation and quantitative gene expression of adult human nasal septum chondrocytes in monolayer culture expansion and the formation of tissue engineered hyaline cartilage. Effects of ITS on human nasal septum chondrocytes monolayer culture expansion and gene expression were evaluated in various culture media either added with 2% fetal bovine serum (FBS) or 1 ng/mL basic fibroblast growth factor plus 1 ng/mL transforming growth factor or both serum and growth factors supplementation in comparison with medium added with 10%FBS. Chondrocytes cultured in medium added with 2% fetal bovine serum and growth factors either supplemented with or without ITS were then mixed with pluronic F-127 hydrogel for in vivo tissue engineered cartilage formation in nude mice model. Engineered tissues were removed after 8 weeks of implantation and evaluated with histological staining, immunohistochemistry, transmission electron microscopy and quantitative gene expression analysis. ITS promoted human chondrocytes proliferation and reduced chondrocytes dedifferentiation in media supplemented with serum and growth factors. ITS with 2% FBS and growth factors provided 15-fold increased in chondrocytes number by the end of the culture period compared to the standard culture medium used in chondrocytes culture (medium added with 10% FBS). Engineered tissue resulted from ITS supplementation demonstrated higher quality of cartilage formation. In conclusion, our study has demonstrated the benefits of ITS supplementation in human chondrocytes monolayer culture and tissue engineering cartilage formation.

Adult↗
PubMed1996

Bad ethics, good ethics and the genetic engineering of animals in agriculture.

Genetic engineers have been remiss in addressing ethical and social issues emerging from this powerful new technology, a technology whose, implications for agriculture are profound. As a consequence of this failure, society has been uneasy about genetic engineering of animals and has had difficulty distinguishing between genuine and spurious ethical issues the technology occasions. Many of the most prominent concerns do not require a serious response. On the other hand, concerns about a variety of possible risks arising from genetic engineering of animals require careful consideration and dialogue with the public. Such concerns are an admixture of ethics and prudence. A purely ethical challenge, however, hitherto not addressed, is represented by problems of animal welfare that arise out of genetically engineering agricultural animals. A principle of "conservation of welfare" is suggested as a plausible moral rule to guide such genetic engineering.

Animal Experimentation↗
PubMed1981

Engineering design and appropriate technology.

A new type of engineering degree course, entitled Engineering Design and Appropriate Technology (EDAT), at the University of Warwick, is described. After explaining the term 'appropriate technology' and its relationship to 'alternative and intermediate technology', the need for a new approach to teaching engineering design is developed. The reasons why present engineering undergraduates receive an education ill-suited to work in appropriate technology are examined. Implicit assumptions underlying all the teaching are claimed to produce graduates unfitted for work in many important fields, such as small firms, job creation, and overseas development. A new set of assumptions to underlie the teaching of appropriate technology are put forward and the resulting implications for the engineering design curriculum are examined. The development of the EDAT course is then described, and finally the course structure and teaching methods are outlined.

Education↗
PubMed2001

Insulin in tissue engineering of cartilage: a potential model system for growth factor application.

Investigation of novel experimental application systems for growth factors or other bioactive substances in tissue engineering is often limited by high costs of substances and would benefit from a defined and easily controllable model tissue system. Herein, we demonstrate a potential three-dimensional in vitro system using engineered cartilage as a model tissue and readily available insulin as a model drug. Previously it has been shown that insulin-like growth factor-I (IGF-I) has profound effects on tissue-engineered cartilage in vitro. Insulin is known to bind to the IGF-I receptor and to elicit significant responses in cartilage. In this study, bovine articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured for up to 7 weeks. Exogenous insulin (0.05-50 microg/ml) increased the growth rate and the glycosaminoglycan fraction of tissue-engineered cartilage, decreased the cell number in the tissue constructs, and improved the morphological appearance, with 2.5 microg/ml being the most favorable concentration. The observed effects of insulin were similar to effects of IGF-I (0.05 microg/ml) and were in agreement with the reported binding constants of IGF-I and insulin at the IGF-I receptor. Besides the possibility to employ insulin as a potent substance to improve tissue-engineered cartilage, the presented easily controllable in vitro system may be used in the future to evaluate experimental growth factor application devices using economically favorable insulin as a model protein.

Animals↗
PubMed2005

Stability and repeat regeneration potential of the engineered liver tissues under the kidney capsule in mice.

Liver tissue engineering using hepatocyte transplantation has been proposed as a therapeutic alternative to liver transplantation toward several liver diseases. We have previously reported that stable liver tissue with the potential for liver regeneration can be engineered at extrahepatic sites by transplanting mature hepatocytes into an extracellular matrix. The present study was aimed at assessing the liver tissue persistence after induced regeneration by hepatectomy and repeat regeneration potential induced by repeat hepatectomy. Mouse isolated hepatocytes mixed in EHS extracellular matrix gel were transplanted under both kidney capsules of isogenic mice. The hepatocyte survival persisted for over 25 weeks. In some of the mice, we confirmed that the grafted hepatocytes developed a thin layer of liver tissues under the kidney capsule, determined by specific characteristics of differentiated hepatocytes in cord structures between the capillaries. We then assessed the regenerative potential and persistence of the exogenous liver tissue. To induce liver regeneration, we performed a two-thirds hepatectomy at 70 days after hepatocyte transplantation. Three weeks after this procedure, the engineered liver tissues showed active regeneration, reaching serum marker protein levels of 261 +/- 42% of the prehepatectomy level. We found that the regenerated liver tissue was stably maintained for 100 days (length of the experiment). Repeat regeneration potential was established by performing a repeat hepatectomy (that had been two-thirds hepatectomized at day 70) 60 days after the initial hepatectomy. Again, the regenerated engineered liver tissues showed active regeneration as there was an approximately twofold increase in the serum marker protein levels. The present studies demonstrate that liver tissue, which was recognized as a part of the host naive liver in terms of the regeneration profile, could be engineered at a heterologous site that does not have access to the portal circulation.

Animals↗
PubMed1976

[Considerations on graduate education of sanitary engineering in Latin America].

The author reviews the profound process of change in Latin America which presents serious problems for environmental engineering and, consequently, for education in the various disciplines that comprise this specialization. The explosive growth of knowledge and the increase responsibilities of professionals place extreme pressure on engineering schools. These schools are forced to consider curricular changes as well as changes in admission policies and in the image and the service which they should present to society. At the present time, 25 engineering schools offer an "option" of sanitary engineering and 12 schools offer graduate courses for an M.A. in environmental engineering. In the schools themselves, a combination of fulltime and part-time professors prevails. Graduate teaching programs are expected to provide: a) increasingly complex, new scientific and technologic knowledge, b) duly selected disciplines; and c) balanced management techniques. Certain plans of action may be considered. Among these are increasing the number of schools that offer graduate courses, revising curricula, encouraging higher enrollment, including research as a standard element in teaching and, in general, seeking higher standards of excellent. Prospects for the future seem to indicate that the following actions should be taken: 1) increasing interdisciplinary programs; 2) making use of the potential offered by continuing education; and 3) encouraging the development of doctoral studies.

Curriculum↗
PubMedDate not supplied

Role of the biomedical engineer in nuclear medicine.

Throughout the short history of the development of radioactivity applied in the biomedical field, there have been many contributions made by engineers. With the advent of Nuclear Medicine as a well systematized specialty and its mushrooming in hospitals, the opportunities for biomedical engineers have increased. This article is written from the viewpoint of historic perspective in order to display the different aspects and situations where engineers, and particularly biomedical and clinical engineers, can participate in Nuclear Medicine. Finally, a more detailed survey is made of the activities of biomedical engineers in the nuclear medicine department.

Biomedical Engineering↗