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Bioengineering in the Millennium, National Institute of Health Symposium, Bioengineering: Building the Future of Biology and Medicine.

This symposium identified the major challenges in biomedical research that will benefit from bioengineering applications. Attention was focused on the important role that bioengineers will play in future advances in biomedical research. There was considerable discussion about how to integrate bioengineering with biological research in meeting the challenges of the twenty-first century. Symposium presenters showcased the accomplishments of NIH-funded bioengineering researches and increased the visibility of bioengineering to NIH leaders, staff and members of the intramural and extramural research community. Recommendations were also made for future NIH-funded research projects. Attention was also placed on how basic bioengineering research can lead to commercialization of new health care technology and therefore maintain the Nation's leadership in this important area. New products, from biotechnology and novel devices for diagnosis and treatment, are marketed through interactions between universities, medical centers, small start-up firms, and larger, more established companies. In the United States the gross revenue of the bioengineering private sector industry involved in the manufacture of health care products already exceeds $40 billion. More than 750 persons attended this bioengineering symposium. Over 110 scientific posters and exhibits relating to biology and medicine were presented. They provided a forum for showcasing NIH-funded bioengineering projects and fostered future collaboration among academic investigators, industry and members of the small business community. The role of bioengineering in the 21st century has already been highlighted by the author as far as research, education and space age technologies are concerned. The contributions of Pugwash bioengineer, Maciej Natecz, a member of the Polish Academy of Sciences, was recognized by the Conference Planning Committee. He was honoured for his work in nuclear disarmament.

Biocompatible Materials↗

Bioengineering in the millennium.

This symposium identified the major challenges in biomedical research that will benefit from bioengineering applications. Attention was focused on the important role that bioengineers will play in future advances in biomedical research. There was considerable discussion about how to integrate bioengineering with biological research in meeting the challenges of the twenty-first century. Symposium presenters showcased the accomplishments of NIH-funded bioengineering researches and increased the visibility of bioengineering to NIH leaders, staff, and members of the intramural and extramural research community. Recommendations were also made for future NIH-funded research projects. Attention was also placed on how basic bioengineering research can lead to commercialization of new health care technology and therefore maintain the nation's leadership in this important area. New products, from biotechnology and novel devices for diagnosis and treatment, are marketed through interactions between universities, medical centers, small start-up firms, and larger, more established companies. In the United States the gross revenue of the bioengineering private sector industry involved in the manufacture of health care products already exceeds $40 billion. More then 750 persons attended this bioengineering symposium. Over 110 scientific posters and exhibits relating to biology and medicine were presented. They provided a forum for showcasing NIH-funded bioengineering projects and fostered future collaboration among academic investigators, industry, and members of the small business community. The contributions of Pugwash bioengineer, Maciej Natecz, a member of the Polish Academy of Sciences, was recognized by the Conference Planning Committee. He was honored for his work in nuclear disarmament. Indian medical scientists should note that this symposium provided a framework for the development of technology in biomedical sciences during the Twenty-First Century. Major concentrations in interdisciplinary research should occur at all of the premier research institutions in India.

Animals↗

Position of bioengineering education in Hungary.

Medical electronic equipment has been produced in Hungary since the early forties. Industrial production of bioengineering started only in 1957. At the same time the bioengineering section of the Scientific Society of Measurement and Automation was founded. This Section was instrumental in recognizing the necessity for and establishing a structured education programme in bioengineering which started in the Postgraduate Institute for Engineers within Budapest Technical University. Later this was incorporated in the programme of the Technical University as an optional subject. Today there is also a specialised engineering course at the Technical University. There are significant developments in the bioengineering education of physicians and medical students. This paper deals with the possibility of classification bioengineering devices which has proved useful in education in Hungary.

Biomedical Engineering↗

Relevance of multiparametric skin bioengineering in a prospectively-followed cohort of junior hairdressers.

There is conflicting evidence concerning predictors of individual susceptibility to develop irritant contact dermatitis in wet work. A cohort of initially 92 hairdresser apprentices was prospectively followed for 3 years. The association between anamnestic and clinical findings, and multiparametric skin bioengineering data (transepidermal water loss [TEWL], microcirculation, capacitance, pH, sebum, temperature) was investigated. The observation intervals were 3 months in the 1st year of training and 12 months thereafter. Of the 92 apprentices, 6 had already developed hand dermatitis on 1st examination, 20 dropped out or had occupational exposure longer than 7 weeks prior to investigation. Of the remaining 66 participants considered here, 19 (29%) developed moderate or severe dermatitis ("cases"), 32 minimal skin changes, 15 none within the observation period. Average incidence rate of hand dermatitis was 21.1 cases per 100 person years. Atopy score was not associated with the development of dermatitis, nor were the investigated basal bioengineering parameters, including TEWL, in a multivariable model. However, there was a significant increase in TEWL within the 1st year of training in presumptive "cases". The aim to develop an objective and predictive instrumentary for pre-employment counselling in wet work, by a combination of (a) clinical and (b) relevant non-invasive bioengineering parameters, has not yet been accomplished. Skin-provocation tests employing bioengineering seem to be required. Notwithstanding, work-related monitoring of basal biophysical skin-functions may become useful in the secondary prevention of occupational dermatitis.

Adolescent↗

Future opportunities for bioengineering research at the National Institutes of Health.

Bioengineering integrates physical, chemical, and mathematical sciences with engineering principles for the study of biology, medicine, dentistry, behavior, or health. It advances fundamental concepts, translates knowledge from molecular to organ system levels of understanding, and designs and fabricates innovative biologics, biomaterials, processes, medical and dental implants, devices, and bioinformatics for health promotion, disease prevention, diagnosis, treatment, and therapeutics to improve the health of all people. The National Institutes of Health in recent years has made numerous decisions to coordinate bioengineering activities across the various institutes and centers comprising the National Institutes of Health to increase efforts to support research and research training in bioengineering. This paper will focus on innovations from 1995 to the present that have catalyzed increased activities and opportunities in bioengineering across the National Institutes of Health and will highlight current activities related to tissue engineering at the National Institute of Dental and Craniofacial Research and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Biotechnology↗

Instrumentation for bioengineering.

A tremendous range of physical science problems and techniques, from all branches of engineering, are involved in bioengineering instrumentation. The examples I have cited typify the problems that arise, but the techniques we have used represent only an infinitesimal fraction of the resources that we must exploit. The main challenge to the bioengineer is that of defining the problem in terms of what is useful and economically justified. One must understand the possibilities of engineering development and the probability that an effort will reach any assignable goal within a given time. Only then is it possible to work out a practical solution to the instrumentation problem. It is very easy to become so absorbed in the engineering development that we lose sight of the final goal and the purpose of the development. It is also easy, in working out an experiment, to become obsessed with the need for a particular bit of data, or of too great a degree of precision, without considering that the cost of obtaining these data might not be justified by their value to the full development. Thus, the only principles that can be generally applied to a bioengineering problem are those which would apply to making any decision that leans heavily on judgment.

Bioengineering↗

Modelling medical devices: the application of bioengineering in surgery.

Medical device technology has an increasingly important role in surgical procedures. In this article, five case studies of bioengineering in surgery are described as follows: computer-aided design of vascular grafts; middle-ear prostheses; hip prosthesis stems for optimal cement pressurisation; prototype development of a device for measurement of abdominal sounds for monitoring digestive tract activity and a hand-access device for laparoscopic surgery. In each case, new bioengineering design methodologies are demonstrated. The general principles underlying the application of bioengineering in surgery are discussed.

Arthroplasty, Replacement, Hip↗

Prospects for the bioengineering of isoprenoid biosynthesis.

Over the last decade, our understanding of isoprenoid biosynthesis has progressed to the stage where specific strategies for the bioengineering of essential oil production can be considered. This review provides a current overview of the enzymology and regulation of essential oil isoprenoid biosynthesis. The reaction mechanisms of the synthases which produce many of the basic isoprenoid skeletons are described in detail. Coverage is also provided of the regulation of isoprenoid biosynthesis, including the roles played by tissue and subcellular compartmentation, and by partitioning of intermediates between different branches of isoprenoid metabolism. This provides necessary context for rationally targeting specific enzymes of metabolic pathways for bioengineering essential oil production. Wherever possible, emphasis is placed on research specific to essential oil isoprenoid biosynthesis, although relevant work related to other isoprenoids is also considered when it can provide useful insights. Finally, building upon this understanding of essential oil isoprenoid biosynthesis, several approaches to the bioengineering of isoprenoid metabolism are considered.

Dimethylallyltranstransferase↗

Product liability aspects of bioengineering.

The introduction of the Consumer Protection Act 1987 brought the problems of product liability directly into hospital bioengineering and medical physics departments. This law makes great demands upon manufacturers, but also on suppliers and maintainers of medical equipment. Departments which manage medical equipment carry a responsibility for ensuring the requirements of product liability are known by all those whose actions may affect the potential of a piece of equipment to injure or damage a patient. This paper addresses these problems from a bioengineering, rather than a legal, viewpoint. The problems of design, manufacture, modification, maintenance and use are discussed and examples of potential problems are identified. The paper concludes that as long as good standards of quality control and professionalism are applied in bioengineering and medical physics departments then there is little to be feared from this piece of legislation.

Biomedical Engineering↗

Enhancing the immunogenicity of bioengineered Listeria monocytogenes by passaging through live animal hosts.

Bioengineered Listeria monocytogenes can be used as a recombinant bacterial vaccine vector for the induction of strong cell-mediated immunity to passenger antigens. Listeria loses virulence after undergoing bioengineering techniques, thus decreasing its efficacy as a vaccine vector. We addressed this problem by examining the virulence, and the ability to induce CD8(+) T-cells, of Listeria monocytogenes vaccine strains before and after passaging through mice. We found that two in vivo passages are required to restore the induction of cell-mediated immunity to passenger antigens and maximum virulence to these strains. In addition, we found that after each passage, harvested bacteria must be cloned and checked for expression of the bioengineered gene to counter selection in favor of antigen loss mutants.

AIDS Vaccines↗

Surfactant irritation: in vitro corneosurfametry and in vivo bioengineering.

BACKGROUND/AIMS: Irritant reactions to surfactants, cleansing products, soaps and detergents are common in clinical and occupational dermatology. Mildness has become a major benefit claimed, and testing for mildness now ranks among the first concerns of the manufacturing industry. A wealth of publications deals with this problem, trying to improve the methodology, reduce the costs of testing and facilitate decision-making. Differences in vivo can be measured clinically and/or instrumentally. This is difficult, as commercially available products are generally safe to use and none are harsh in the absolute sense. METHODS: Nineteen different products (syndets, shampoos, personal cleansers), all claiming to be mild, were tested in vitro by a newly introduced method, corneosurfametry. For evaluating the aggressiveness of the products, the calculation of an index of irritation (IOI) was proposed. A concentration-effect curve of sodium lauryl sulfate (SLS) as standard and model surfactant was obtained. Some of the products were further tested in vivo with a flex wash test and with a soap chamber test and compared to SLS. Bioengineering methods (transepidermal water loss TEWL, skin color) were used to evaluate the results. RESULTS AND CONCLUSIONS: The results of the corneosurfametry allowed us to classify the products in three categories, with increasing aggressiveness towards the stratum corneum, according to their IOIs. The in vivo tests were not able to discriminate between the products, but ranks from the results of the bioengineering measurements showed a good correlation between TEWL changes, but not between colour changes, and IOIs from corneosurfametry. Corneosurfametry emerged as a simple, low-cost and fast method for ranking commercial products according to their mildness. However, the skin bioengineering techniques showed that some products could lead to skin reactions, such as erythema, that could not be detected by the in vitro technique.

Colorimetry↗

Bioengineering methods employed in the study of wound healing of sulphur mustard burns.

BACKGROUND/PURPOSE: Sulphur mustard (SM) is a potent incapacitating chemical warfare agent that remains a threat to war fighters and civilians worldwide. SM lesions may require weeks or months to heal, depending upon their severity. This study was undertaken to find a treatment regimen that promotes speedier healing of deep cutaneous SM burns in a weanling pig model. The principal objective of the study was to compare four treatment regimens and establish which achieved the shortest healing time. METHODS: Twelve Yorkshire Cross weanling pigs were exposed to SM liquid for 2h, generating six large deep dermal/full thickness burns on the ventrum of each animal. Three additional animals served as sham-exposed controls. Surgical intervention occurred at 48 h postexposure. Treatments included: (i) full-thickness debridement of the burns with a computer controlled, raster scanned continuous wave CO2 laser followed by autologous split-thickness skin grafting; (ii) full-thickness sharp surgical tangential excision followed by skin grafting, the 'Gold Standard' used in human deep dermal/full-thickness thermal burns management; (iii) partial-thickness laser ablation with no grafting; and (iv) partial-thickness sharp surgical excision with no grafting. Several non-invasive bioengineering methods were used to monitor the progress of wound healing throughout a 36-day healing period: reflectance colourimetry, evaporimetry, laser Doppler perfusion imaging and ballistometry. RESULTS: Bioengineering methods indicated that laser debridement followed by autologous split-thickness skin grafting was as efficacious in improving the wound healing of deep SM burns in weanling swine as the 'Gold Standard.' Regardless of the method of debridement, barrier function, skin colour and mechanical properties returned to near-normal levels within 15 days of treatment in the grafted sites. Regardless of surgical approach, blood flux levels remained approximately 50-60% of normal tissue throughout the 36-day postsurgical observation period. Mid-dermal debridement by sharp surgical tangential excision or laser ablation without the use of skin grafts did not produce as good a result as those attained through the use of grafts, but was better than no surgical treatment of the wounds. CONCLUSION: Bioengineering methods were useful in evaluating multiple characteristics during wound healing: (i) reflectance colourimetry for skin colour, (ii) evaporimetry to measure transepidermal water loss as an indicator of barrier function, (iii) laser Doppler perfusion imaging to assess cutaneous blood flow, and (iv) ballistometry to measure the mechanical properties of skin hardness and elasticity. Perhaps the most useful method was evaporimetry, as a restored barrier function was the best indicator of healed wounds. The use of reflectance colourimetry and ballistometry will continue in future wound healing studies for their contributions in judging cosmetic and functional outcomes. While useful, laser Doppler perfusion imaging was found to be rather time consuming. This methodology will be limited in the future to burn depth estimation prior to treatment, and for evaluation of pharmaceuticals specifically designed to improve or sustain blood flow into damaged areas.

Animals↗

Bioengineering and characterization of physeal transplant with physeal reconstruction potential.

Damage to physes is of serious consequences in children. Currently available treatments are limited and results are unpredictable. In this study, we attempted to treat proximal tibial physeal damage in rabbits with transplanted bioengineered physeal tissue. Resting chondrocytes from the reserve zone of costal cartilages of 6-week-old rabbits were pellet cultured in centrifuge tubes. The pellets were characterized histologically and biochemically with reference to the normal physis. The bioengineered tissue was then transplanted into partially damaged proximal tibial physis. Histological changes and proteoglycan metabolism of the transplants were monitored until 7 weeks posttransplantation. Our results showed that chondrocytes cultured by three-dimensional pellet exhibited cell division and the derived cells arranged in short columns similar to normal physis. They synthesized and deposited cartilaginous matrix and differentiated into hypertrophic chondrocytes marked by increases in cell size and alkaline phosphatase activity. The transplant incorporated well in host tissue with no sign of rejection for up to 7 weeks posttransplantation. A further 3-fold increase in thickness of the transplant within the host was observed. Endochondral ossification was demonstrated at 7 weeks posttransplantation. These results show that the bioengineered physeal tissue may have great potential in clinical management of physeal damage in children.

Animals↗

Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease.

PURPOSE: To bioengineer a corneal surface replacement using ex vivo expanded, cultured corneal epithelial stem cells seeded on a matrix derived from amniotic membrane and use this bioengineered graft to manage difficult ocular surface disease. METHODS: Fourteen patients with ocular surface disease unresponsive to standard medical and surgical treatments, including seven patients with presumed limbal stem cell deficiency were chosen for transplantation of a bioengineered composite corneal surface in eye each. Presumed corneal stem cells were harvested from either the patient's or related donor's limbus, expanded ex vivo, and cultivated on a carrier of modified human amniotic membrane. The resulting composite cultured tissue was transplanted to the ocular surface of the diseased eye, from which the abnormal tissue had been surgically removed. Ten patients received autologous grafts, and four received allogeneic grafts. RESULTS: A successful outcome, defined as restoration or improvement of vision, along with maintenance of corneal re-epithelialization and absence or recurrence of surface disease was obtained in 6 of the 10 patients with autologous procedures and in all 4 allogeneic transplants. Follow-up ranged 6-19 months with a mean of 13 months. CONCLUSIONS: This novel technique documents that presumed corneal epithelial stem cells can be harvested safely from the limbus, expanded successfully in vitro, and grown on denuded amniotic membrane. The resultant composite cultured tissue can be transplanted and appears to successfully manage eyes with difficult ocular surface disease, including those with stem cell deficiency. This technique minimizes the threat of damage or depletion to the contralateral or donor limbus.

Adult↗

A fibrin-based bioengineered ocular surface with human corneal epithelial stem cells.

PURPOSE: The purpose of the investigation was to prepare a bioengineered ocular surface tissue replacement consisting of (presumed) human corneal epithelial stem cells in a cross-linked fibrin gel for potential transplant. METHODS: Presumed human epithelial stem cells were harvested, isolated, and cultivated as previously described from adult donor corneas obtained from a tissue and organ bank. The cultured corneal epithelial stem cells were suspended in a fibronectin/fibrin gel cross-linked by factor XIII. Plasma components were derived from a fibrinogen-rich cryoprecipitate of human plasma. Suspended cells proliferated in the fibrin gel, giving rise to colonies that eventually coalesced to near confluence over the 15 days of cultivation. The gels were sectioned and immunostained for keratin 3 (AE5) and keratin 19. RESULTS: The fibrin gel product with corneal stem cells was easily manageable and maneuverable. Addition of the protease inhibitor aprotinin to the incubation medium prevented gel degradation; once it was removed, gels disintegrated within 24 hours. All of the cells cultivated in the fibrin gel stained positively for keratin 3 (AE5), indicating differentiation along the corneal epithelium lineage. Cells located in the center of the colonies were keratin 19-positive, suggesting a more primitive cell type. Growth kinetics were documented. CONCLUSIONS: A bioengineered ocular surface with a combination of presumed corneal epithelial stem cells in a cross-linked fibrin gel represents a potential improvement in current attempts to create a transportable, pliable, and stable tissue replacement. Since both the cells and the plasma components of the fibrin gel are of human origin, this technique provides the potential for a totally autologous bioengineered replacement tissue.

Adult↗

Bioengineering: the advent of metabiology (part I).

The ability to modify or replace organs or functions and to intervene in the transmission of hereditary characteristics is a fundamental turning point in the development of living organisms and of bioengineering. The history of bioengineering leading to this stage is briefly reviewed and reinterpreted. The view is proposed that bioengineering is the instrument by which metabiology - the continuance of biology with other means - is brought about. Metabiology deals with the study of living organisms as they can be modified by outside interventions on their functions, organs or sub-organs. Some of the fundamental questions raised by interventions from the outside on the organism - such as the loss of validity of the concept of homeostasis and the destruction of any vestige of orthogenesis - are briefly explored. Part II of this paper will appear in the next issue of this Journal.

Artificial Organs↗

Bioengineered corneas: how close are we?

Bioengineered corneas are substitutes for human donor tissue that are designed to replace part or the full thickness of damaged or diseased corneas. They range from prosthetic devices that solely address replacement of the cornea's function to tissue-engineered hydrogels that allow some regeneration of the host tissue. In addition, there are also bioengineered lenticules that may be implanted into the cornea to improve vision by altering the refractive properties of the eye, an alternative procedure to refractive surgery. In recent years, there have been significant developments in many areas of bioengineered corneas, such as the clinical trials of an artificial cornea designed as a prosthesis, the development of completely natural corneal replacements, and the development of biosynthetic matrices that permit host tissue regeneration. For correction of refractive errors, a synthetic corneal onlay that allows stable overgrowth of epithelium appears to be promising.

Biomedical Engineering↗