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[Biomaterials and the living system].

Biomaterials, whatever their applications: cardiovascular surgery, orthopaedic surgery, ophthalmology, plastic surgery, urology, membranes for renal dialysis have some common approach. It is a very interdisciplinary field that needs intervening bioengineers, M.D, biologists and materials scientists. It is a domain with special emphasis on responsability because of the very severe consequence of these material failures. After an overview of these materials and their applications, we will briefly present here the evaluation systems of these biomaterials, including laboratory tests, mechanical tests as well as biological ones. Then we will project in the future to insist on three main orientations: tissue engineering, optimised materials for some precise function and also how new techniques of applied genetic could modify this field in deep in the future.

Biocompatible Materials↗

Biological therapies for breast carcinoma: concepts for improvement in survival.

Systemic treatments for breast carcinoma have improved substantially over the past quarter century. New insights into cancer biology, refinements in biotechnology, and bioengineering of macromolecules hold the promise of even greater reductions in breast and other cancer mortality as a result of biologicals. As exemplified by the clinical results with the monoclonal antibody to HER-2 for antigen-specific passive immunotherapy, biological therapies for breast carcinoma hold substantial promise. The objective of this report is to highlight aspects of preclinical and clinical research on other biologicals for breast carcinoma that also hold potential for improving patient survival. As examples of the potential of cytokines to modulate breast carcinoma cell proliferation and tumor growth, data on cytokines (interferons) with pleiotropic effects and a lymphokine (interleukin-10) acting on T cells and macrophages will be reviewed. HER-2 has promise as a vaccine for active specific immunotherapy; these data will be summarized. Progress on these and other biologicals promises that this will be another modality of therapy resulting in improved survival for patients with both early and metastatic breast carcinoma in the next millennium.

Animals↗

[Biological safety problems on the brink of the 21st century].

The review deals with the prospects of development of means of bioindication, one of the key elements in the country's biological safety system. The level of their development is determined by the state-of-the-art of methodology and techniques for detection of ultralow concentrations of biomolecular markers and by the advances in bioengineering and molecular diagnosis. In the authors' opinion, great progress should be soon obvious in the design of specific indication means (biosensor devices and systems for multicomponent analysis due to the use of laser sources of stimulation and new long-luminescent markers (chelates of lanthanoids and metallic porphyrins) for the homogeneous and non-dissociative schemes of solid-phase analysis. This review is followed by the collected subject-matter papers of the scientists of the State Research Institute of Biological Instrument-Making Industry who have been actively engaged in the design of bioindication technical facilities.

Aerosols↗

[Detection of high-risk group with irritant hand dermatitis].

Patients with atopy and especially these with atopic skin diseases, hand eczema and dishidrosis have been identified as a high-risk group developing irritant hand dermatitis. To improve prevention pre-occupational examinations (screening tests) in youth have been proposed. Dermatological examinations, questionnaires and some bioengineering techniques are usually suggested. The necessity of application of ASD score has been confirmed. Because of the high irritant hand eczema morbility and socio-economic consequences detection of high-risk group plays a special role. It is possible by means of: 1. Special questionnaires 2. Dermatological examinations, education, observation 3. Conception and realization of skin--safe working conditions.

Dermatitis, Contact↗

[New developments in the treatment of diabetic foot ulcers].

Diabetic foot ulcers are frequent: 12,000 Dutch diabetes patients have such an ulcer. The ulcers have a multifactorial aetiology: polyneuropathy, biomechanical stress, infection, deficient footwear and to a less extent ischaemia are the major factors. The principles of ulcer treatment are relief of pressure, restoration of skin perfusion, treatment of infection, intensive wound care, metabolic control, treatment of comorbidity, and instruction of the patient. Wound healing is slow. The impaired wound healing is probably caused by deficiencies in local growth factors, changes in the extracellular matrix, diminished fibroblast function, decreased antimicrobial activity of leukocytes and disturbances in the macro- and microcirculation. In recent years several new treatment strategies have been developed to stimulate wound healing in diabetic foot ulcers. These (partly experimental) treatments include: topical growth factors, extracellular matrix products, bioengineered human skin, granulocyte colony stimulating factor and hyperbaric oxygen therapy. In particular recombinant human platelet derived growth factor (becaplermin) has proved to be clinically effective in chronic neuropathic foot ulcer and has been approved in the Netherlands.

Becaplermin↗

[Mechanotransduction and tensegrity (I)].

The current review deals with mechanotransduction by means of an architectural model of cell function called tensegrity. This concept was introduced by D. E. Ingber in order to frame more focused mechanisms of mechano-transduction, i.e. different signaling pathways, which are less able to predict global cellular behaviour in response to stress, into a coherent mechano-chemical theory of cell function. Tensegrity structures are made and held up by interconnecting a continuous series of tension elements with a discontinuous series of compression resistant struts, in a simple "stick and string" model. These structures develops an intrinsic stabilizing tension called prestress and reacts by global rearrangements of their configuration to a local action of a mechanical stress. The only requirement of a tensegrity network is that tension is continuous and compression is local. At the cellular level the theory assumes that membrane, nucleus and all the organelles are hard-wired by the insoluble cytoskeletal (CSK) scaffold. More than that, the interconnection between CSK and the extracellular matrix (ECM) provides an efficient mechanical couple responsible for changes in cell shape and movement. Cell shape, in turn, regulates cellular function. Focal adhesion complexes, which mediate the CSK-ECM interaction are viewed as integrative devices for both mechanical signaling and soluble factor-dependent signaling. Furthermore, the tensegral molecular network is considered to be a solid-state regulatory system of all cell functions. The way tensegrity influences molecular mechanics, cellular response tuning and coordinated behaviour of large scale structures are also discussed. Besides its conceptual importance, the tensegrity model has multiple applications, being used in combined approach of cell biology, bioengineering, architecture, and biomechanics in order both to improve cell culture and its subsequent applications and the open the way to a more complex technology of tissular engineering.

Animals↗

Acute burns.

Burn injuries are complex cutaneous traumas cared for by many plastic surgeons. Care is stratified by burn size, depth, and associated injuries. Advances in surgical technique, wound care, and bioengineered skin have resulted in excellent outcomes for most burn survivors. Moderate burn injuries can be treated effectively by an interested and experienced plastic surgeon.

Acute Disease↗

Functional and morphological studies of photodamaged skin on the hands of middle-aged Japanese golfers.

The skin of golfers' hands provides a suitable model to study the effect of chronic sun exposure, because one of their hands is exposed to the outer environment, especially sunlight, while the other one is always protected by a glove during play. Our purpose was to find out the influence of photodamage on the properties of the skin surface of middle-aged Japanese by using non-invasive methods. We measured hydration state, and water barrier function of the stratum corneum (SC) and the color of the skin of the dorsum of the hands. In a separate study, we evaluated the skin surface contour by using replicas taken from the skin in a slightly stretched or relaxed position. We found a significant decrease in hydration of the skin surface of the exposed skin as compared to that of the protected skin, whereas no such difference was found with transepidermal water loss, a parameter for water barrier function of the SC. Luminance of skin color was also reduced in the sun-exposed skin. Replica analysis revealed that large wrinkles developing in a relaxed position were more prominent on the exposed than on the protected skin, while fine furrows noted in a slightly stretched position were shallower on the former than the latter. The data obtained indicate that the chronically exposed skin of golfers' hands shows morphological and functional changes resulting from long time exposure to the outer environment especially sunlight. Furthermore, bioengineering non-invasive methods are found to be useful to detect early photodamage of the skin in a more quantitative fashion which is rather difficult to demonstrate clinically.

Biophysics↗

Culture of vascular cells in tridimensional (3-D) collagen: a methodological review.

Experimental models based on the culture of cells within tridimensional (3-D) gels add a 3-D organization to the classical 2-D culture of vascular cells. They allow the study of cell structure in an environment which is more representative of the in vivo situation and the investigation of cellular functions which cannot be studied using the basic 2-D models. This review shows examples of the use of cultures of vascular cells (endothelial cells, smooth muscle cells as well as fibroblasts) in 3-D collagen matrices for the study of cellular functions as diverse as angiogenesis, extracellular matrix reorganization, migration through 3-D collagen gels or phenotype modulation. It also describes recent advances in the in vitro reconstruction of biological blood vessels by bioengineering. A method for the preparation of 3-D collagen gels is described.

Cells, Cultured↗

Health technology assessment.

The developing role and use of diagnostic imaging continue to emerge as disease management paradigms are refined and clinical guidelines are employed more often. Health technology assessment, HTA (also known as health care technology assessment), is fundamentally a form of policy research. By formulating effective HTA, the short- and long-term effects of health care technology are studied in a systematic and multidisciplinary way. The fundamental aim of all HTA is to assist those individuals and organizations who stand to benefit from a new health technology (patients), those who will apply the technology (providers), and those who will pay for it (payers) to make better decisions about the technology they utilize by supplying information that is of a high scientific standard and population-based. Effective HTA is especially useful to health care providers, payers, professional groups in health care, manufacturers, political decision-makers and the general public or consumers of health care technology because it represents a process through which effective technology can be identified and ineffective technology can be understood in the context of its limitations. HTA is a multidisciplinary undertaking requiring combined expertise in clinical medicine, epidemiology, biostatistics, bioengineering, health economics, administration, psychology, sociology, ethics and legal science. Additionally, the experiences and opinions of health technology users and consumers of health care (especially patient advocacy groups) are needed to form an overall accurate understanding of the technology under review.

Costs and Cost Analysis↗

Innovations in design and technology. The story of hip arthroplasty.

The current study reviews the early history of surgeon-initiated trial and error development in hip joint arthroplasty and the subsequent methodological evolution to proper criteria for hypothesis testing using bioengineers and other research scientists. The interplay and relationships to industry, universities, scientific organizations, and the Food and Drug Administration with respect to device development in hip arthroplasty are reviewed. The ethics of and responsibilities to involved parties are outlined, citing the history of many contemporary developments. Examples are provided from the evolution and introduction of unsuccessful innovations, and the problems inherent in the current methodology of the approval process from the Food and Drug Administration using the 5-10K, Investigative Device Exemption, and the Pre-Market Approval protocols. The pros and cons of randomized trials for devices are outlined with the conclusion that they are not appropriate for device introduction. The proper, rational methodology for introduction of new devices is a phased-in clinical trial process after pertinent bench testing. Finally, the ethical dilemmas created by managed care are addressed. Industry involvements of the surgeon-spokesmen are cited.

Device Approval↗

Effect of alpha-1 antitrypsin Portland variant (alpha 1-PDX) on HIV-1 replication.

The present work investigated the potential role of alpha-1 antitrypsin Portland variant (alpha 1-PDX), a bioengineered serine proteinase inhibitor (serpin), in the interference with the viral replication of HIV-1, induction of syncytia and maturation of envelope glycoprotein gp160 to gp120 and gp41. A Jurkat lymphoid cell line transfected with a plasmid containing the alpha 1-PDX cDNA (J-PDX) and expressing the protein in a stable manner was infected with HIV-1(Lai). Controls were Jurkat cells transfected with the same vector pcDNA3 without the cDNA insert (J-pcDNA3). The results showed that viral replication of HIV-1 was significantly inhibited with a delay in replication kinetics in J-PDX cells as compared with J-pcDNA3 cells. In addition, a comparison of the infectious capacity of viruses produced in the presence and absence of alpha 1-PDX revealed that this capacity differed. It was found that alpha 1-PDX exerts its effect by interfering with the formation of syncytia between J-PDX cells infected with gp160 recombinant vaccinia virus, or after infection by HIV-1 and co-culture with uninfected Molt-4 cells. In contrast, when the same experiments were performed with J-pcDNA3 cells, a large number of syncytia was obtained. Analysis of viral proteins by Western blotting and densitometry showed that the inhibition of the cytopathic effect of HIV-1 and viral replication was correlated with the capacity of alpha 1-PDX to interfere with the maturation of gp160 to gp120 and gp41.

Blotting, Western↗

Tissue engineering in wound repair.

Tissue-engineering products can cover wounds and provide a microenvironment that stimulates their repair. To date, Graftskin (APLIGRAF, Organogenesis Inc, Canton, MA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ) is the most advanced bioengineered skin product. Graftskin is a bilayered living skin construct consisting of a dermis and a well-differentiated epidermis. The epidermal cells (keratinocytes) and dermal cells (fibroblasts) are obtained from neonatal foreskin. The efficacy of Graftskin in healing venous ulcers was evaluated in a prospective, randomized study of 240 patients at 14 centers over a 6-month period. Patients received either compression therapy plus Graftskin or compression therapy alone (active control). Clinical efficacy was defined as complete wound closure. Treatment with Graftskin was more effective than compression alone as measured by time to complete wound closure and frequency of complete wound closure by 6 months. When applied to hard-to-heal wounds (> 1 year's duration), Graftskin was 3 times more effective than compression therapy alone in achieving complete wound closure at 8 weeks (32% vs 10%, P = .008) and 2 times more effective by 24 weeks (47% vs 19%, P = .002). Graftskin is highly effective in healing venous ulcers, particularly those of long duration, that have proved hard to heal with conventional modalities.

Bandages↗

Effective treatment strategies for diabetic foot wounds.

Nonhealing foot ulcers in patients with diabetes are the leading cause of complications such as infection and amputation. This is a review of the traditional methods of good wound care for the diabetic foot ulcer. We also introduce newer methods for the treatment of these ulcers including hyperbaric oxygen therapy, bioengineered tissue, and recombinant platelet-derived growth factor-BB. By using a multidisciplinary team approach to care and integrating traditional and new wound-healing technologies, the goal of the US Department of Health and Human Services to lower the diabetic amputation rate by 40% may be achieved.

Bandages↗

Acute Burns.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the pathophysiology of burn injury. 2. Calculate burn size and resuscitation requirements and predict survival. 3. Treat inhalation injury. 4. Describe preoperative selection, intraoperative procedures, and postoperative protocols for patients who require surgical care for their burn injuries. 5. Know the survival and functional outcomes of burn injury. Burn injuries are complex cutaneous traumas cared for by many plastic surgeons. Care is stratified by burn size, depth, and associated injuries. Advances in surgical technique, wound care, and bioengineered skin have resulted in excellent outcomes for most burn survivors. Moderate burn injuries can be treated effectively by an interested and experienced plastic surgeon. (Plast. Reconstr. Surg. 105: 2482, 2000.)

Journal Article↗

2nd European symposium on liquid ventilation.

After the successful meeting in Berlin, advances and research results in the understanding of liquid ventilation has been performed. About 80 applied and basic scientists met in the 1st European Symposium, from clinicians (pediatricians, neonatologists, intensivists, etc.) to other basic scientists (physiologists, biologists, bioengineerings, etc.). Furthermore, we also invited representatives of pharmaceutic industry interested in this hot topic. Our main goal is to provide an opportunity for all liquid researchers in this field to meet together and with the top scientists of Liquid Ventilation Research. We planned to provide both a scientific and a friendly atmosphere to enhance the exchange of experiences and to facilitate future plans. We hope this 2nd European Symposium will be a continuation point for collaboration of groups in Europe, to study all research aspects of the technique to carry on future trials. There are still a lot of unanswered questions to be solved. Among the unsolved issues and practical questions we would like to point out the following items: 1. Perfluorocarbon: which product to use and how to deliver it. 2. Perfluorocarbon interactions in the lung. 3. Perfluorocarbon. Toxicity and cytoprotection. 4. Partial Liquid Ventilation: ventilatory strategies from delivering to weaning. 5. Impact of Partial Liquid Ventilation Experimental and clinical aspects. 6. General discussion and plan for the future. We know that none of these questions can be completely answered now, but hope collaboration and communication will bring us closer to achieve these goals. Moreover, concerted actions should be started to search for research grant founding. For all those reasons we would like to thank all active and passive participants, who came to Bilbao to present, discuss and foster future work in Liquid Ventilation.

Acute Disease↗

Tissue engineering in periodontics using rhBMP-2.

The results of these studies show that rhBMP-2 clearly enhances regeneration in periodontal defects (Figures 2&3). The extent of regeneration appears to be significantly influenced by the nature of the carrier material used to deliver the rhBMP-2 to the periodontal wound. While the positive effects of rhBMP-2 on osteogenesis are well established, less is known about the way in which rhBMP-2 effects cementogenesis, or its role in the formation of a new periodontal ligament. From the studies reviewed, it would appear that rhBMP-2 facilitate in the formation of cellular cementum on previously denuded root surfaces. This newly formed cementum has also been shown to support an organised periodontal ligament attachment. Mechanisms related to the possible role of rhBMP-2 in ankylosis are presently unclear and will require further investigation as such sequelle may complicate the clinical utility of rhBMP-2 in periodontal regeneration. Root resorption has also been reported in the above mentioned studies and appears to be related to the concentration of rhBMP-2. Further research directed at understanding how different carriers influence the way in which the rhBMP-2 is released during wound healing should assist researchers with how to best apply these bioengineered proteins to ultimately achieve a more predictable regeneration of the periodontal attachment apparatus. Moreover, additional research into the differing biologic effects of other members of the BMP family of proteins may also hold further promise in the application of this technology to periodontal regeneration.

Animals↗

Articular cartilage transplantation. Current and future limitations and solutions.

The ultimate goal of replacing cartilage with a bioengineered graft, autologous graft, or allograft is to replace the damaged articulating surface with tissue containing the anatomical, biomechanical, and functional properties of native articular cartilage, which will have resultant satisfactory clinical outcome. For transplanted articular cartilage to obtain the original histologic arrangement of hyaline cartilage with secure incorporation into host tissue, progressive integrated multidisciplinary research must continue. Although autologous chondrocyte transplantation of the talus is not yet FDA approved, this technique may provide the surgeons with a cutting-edge method to treat patients with nondegenerative osteochondral lesions of the talus and possibly other articulating joints of the foot.

Ankle Joint↗