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PubMed1984

Impact of bioengineering on noninvasive diagnostics.

Out of a number of important methods used in laboratory angiology, only a limited group was selected to be discussed in this symposium. Phonoangiography is reviewed from the qualitative and quantitative viewpoint for its practical value and accessibility. Various aspects of pressure and volume detection of the eye pulse are discussed from the viewpoint of carotid artery disease and its noninvasive diagnosis, with special reference to oculoplethysmography as well as the Gee-pneumooculoplethysmography. Impedance plethysmography (IPG) is one of the controversial techniques used in laboratory angiology, with its main application currently in the area of diagnosis of venous obstructive disease. The dilemma of application of IPG in the diagnosis of arterial disease is discussed mainly from an engineering point of view. Spectral analysis will be covered in view of the fast emergence of Doppler Duplex scanning as the major diagnostic mode in extracranial carotid artery disease.

Auscultation↗
PubMed2005

Ovine panel reactive antibody assay of HLA responsivity to allograft bioengineered vascular scaffolds.

BACKGROUND: Increasing evidence implicates immune response as a contributing factor in the failure of allograft valve transplants. Increases in panel reactive antibodies have been identified in human subjects. To correlate these responses with novel preimplantation processing methods to reduce cellularity, both a relevant panel reactive antibody assay and a chronic implantation animal model are necessary. We modified a human flow cytometric panel reactive antibody assay for ovine model use to detect antibody responses to residual antigen-loading decellularized scaffolds engineered from pulmonary artery tissue. METHODS: A clinical panel reactive antibody assay was modified with anti-sheep antibodies. Dimethyl sulfoxide cryopreserved (n = 4) and decellularized scaffolds (n = 8) fashioned as patches from pulmonary arteries were implanted for study. Fresh (nonprocessed) tissue implants were used as positive controls (n = 2), and sham-treated animals were used as negative controls (n = 2). Baseline, 10-week, and 20-week blood samples were assayed for panel reactive antibody levels. Immunohistochemistry with anti-major histocompatibility complex antibodies were performed on preimplantation scaffolds. RESULTS: Chronic implants of fresh tissue stimulated strong panel reactive antibody responses. Classically cryopreserved tissues provoked modest panel reactive antibody responses to major histocompatibility complex I antigen and no response to major histocompatibility complex II antigen. Decellularized tissue scaffolds provoked minimal to no panel reactive antibody responses to either major histocompatibility complex I or II antigen. Immunohistochemistry correlated with the panel reactive antibody results by identifying significant amounts of major histocompatibility complex I and II in fresh tissue, reduced antigen staining in cryopreserved control tissues, and minimal amounts in decellularized tissues. CONCLUSIONS: These studies with an ovine modified panel reactive antibody assay confirmed minimal immune allosensitization to transplanted decellularized tissue patches. Qualifying criteria for putative tissue-engineered scaffolds should include minimal recipient panel reactive antibody response.

Analysis of Variance↗
PubMed2002

Modulating diseased skin with tissue engineering: actinic purpura treated with Apligraf.

BACKGROUND: Actinic purpura (AP) is an important medical issue and quality of life issue in the elderly. Current treatment of AP is limited to prevention of cutaneous aging. OBJECTIVE: To assess the utility of tissue engineered skin (Apligraf, Organogenesis, Canton, MA) as a tissue modulator in diseased skin and as treatment for AP. METHODS: A thin partial-thickness section of AP was removed from the forearm of an elderly gentleman and replaced with fenestrated Apligraf. Healing, durability and cosmetic outcome were assessed. RESULTS: Apligraf-treated skin healed rapidly with good clinical "take." Lack of new skin tears and resultant erosions or ulcer formation suggests improved durability of the Apligraf-treated area occurred. CONCLUSION: These results suggest that tissue engineered skin modulates aged dermal tissue to behave in a more sturdy fashion. Furthermore, in selected cases Apligraf may represent a treatment option for AP.

Aged↗
PubMed1992

Graft engineering: the evolution of hematopoietic transplantation.

In vivo therapeutic manipulation as well as ex vivo grafting are important strategies for bone marrow manipulation and transplantation. This review article discusses the early techniques for marrow processing and manipulation as a background for discussing later graft engineering protocols, as well as preclinical and experimental protocols designed to modify transplantation biology at the multidisciplinary level. The direction of future trials in graft transplantation is also discussed.

Biomedical Engineering↗
PubMed2004

[Biomedical information on the internet using search engines. A one-year trial].

The internet is a communication medium and content distributor that provide information in the general sense but it could be of great utility regarding as the search and retrieval of biomedical information. Search engines represent a great deal to rapidly find information on the net. However, we do not know whether general search engines and meta-search ones are reliable in order to find useful and validated biomedical information. The aim of our study was to verify the reproducibility of a search by key-words (pediatric or evidence) using 9 international search engines and 1 meta-search engine at the baseline and after a one year period. We analysed the first 20 citations as output of each searching. We evaluated the formal quality of Web-sites and their domain extensions. Moreover, we compared the output of each search at the start of this study and after a one year period and we considered as a criterion of reliability the number of Web-sites cited again. We found some interesting results that are reported throughout the text. Our findings point out an extreme dynamicity of the information on the Web and, for this reason, we advice a great caution when someone want to use search and meta-search engines as a tool for searching and retrieve reliable biomedical information. On the other hand, some search and meta-search engines could be very useful as a first step searching for defining better a search and, moreover, for finding institutional Web-sites too. This paper allows to know a more conscious approach to the internet biomedical information universe.

Information Storage and Retrieval↗
PubMed2001

Anhydrobiotic engineering of bacterial and mammalian cells: is intracellular trehalose sufficient?

Anhydrobiotic engineering aims to confer a high degree of desiccation tolerance on otherwise sensitive living organisms and cells by adopting the strategies of anhydrobiosis. Nonreducing disaccharides such as trehalose and sucrose are thought to play a pivotal role in resistance to desiccation stress in many microorganisms, invertebrates, and plants, and in vitro trehalose is known to confer stability on dried biomolecules and biomembranes. We have therefore tested the hypothesis that intracellular trehalose (or a similar molecule) may be not only necessary for anhydrobiosis but also sufficient. High concentrations of trehalose were produced in bacteria by osmotic preconditioning, and in mammalian cells by genetic engineering, but in neither system was desiccation tolerance similar to that seen in anhydrobiotic organisms, suggesting that trehalose alone is not sufficient for anhydrobiosis. In Escherichia coli such desiccation tolerance was achievable, but only when bacteria were dried in the presence of both extracellular trehalose and intracellular trehalose. In mouse L cells, improved osmotolerance was observed with up to 100 mM intracellular trehalose, but desiccation was invariably lethal even with extracellular trehalose present. We conclude that anhydrobiotic engineering of at least some microorganisms is achievable with present technology, but that further advances are needed for similar desiccation tolerance of mammalian cells.

Animals↗
PubMed1994

Design of nasoseptal cartilage replacements synthesized from biodegradable polymers and chondrocytes.

Reconstructive and aesthetic surgery of the nose is a challenging problem in facial plastic surgery. In this study, biodegradable polymers composed of polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) and their co-polymers were used to produce templates to transplant cells and promote regeneration of structural cartilage. A highly porous anatomically shaped three-dimensional non-woven PGA fibre network was sprayed with a coating polymer solution. Reinforcement of the outer circumference of the 12 nasoseptal constructs using high molecular weight PLLA further stabilized the constructs during the process of neomorphogenesis of cartilage, both during in vitro incubation and in vivo implantation. These cell transplantation devices also proved to be adhesive substrates for dissociated bovine chondrocytes. When implanted subcutaneously into nude mice, the polymer templates guided the reorganization after 8 wk of the bovine chondrocytes into neocartilage in the precisely designed size and shape of the original size and shape of the polymer delivery device. All implants loaded with chondrocytes showed evidence of formation of histologically organized hyaline cartilage. The implantation of nasal scaffolds without cells did not show cartilage formation. The technique of tissue engineered growth of cartilage has potential applications in orthopaedic, plastic and reconstructive, and craniomaxillofacial surgery.

Animals↗
PubMed2001

Tissue-engineered cartilage composite with expanded polytetrafluoroethylene membrane.

The authors report a new approach using expanded polytetrafluoroethylene (ePTFE) membrane as pseudoperichondrium to support engineered cartilage. Swine auricular chondrocytes were isolated and mixed with fibrin glue to achieve a final concentration of 40 x 10(6) cells per milliliter. The fibrin glue-cell suspension was assembled with ePTFE and the constructs were implanted into the dorsal subcutaneous pockets of nude mice for 12 weeks. Two experimental groups were prepared in this study: (1) ePTFE placed in the central part of the specimen in group 1 and (2) ePTFE placed on the outside surfaces in group 2. All specimens were subjected to histological and gross mechanical evaluation. Histological results showed neocartilage formation in both groups. The integration between neocartilage and ePTFE forms a tight bond. Gross mechanical testing revealed that the flexibility of specimens in group 2 were similar to that of native cartilage with intact perichondrium, whereas the flexibility of specimens in group 1 were poor. From these results the authors conclude that it is possible to produce a tissue-engineered cartilage framework using ePTFE as a support material to simulate the perichondrium.

Animals↗
PubMedDate not supplied

Bioengineering education, 1986--Part V.

As Part V of the Journal's series on Bioengineering Education in the U.S., this paper describes college-level programs in the states of Connecticut, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Vermont. Each program is concerned with the broad areas of science and engineering that work together to solve medical problems. The purpose of this series is not to evaluate each program, but to illustrate the breadth of Bioengineering and related programs available today.

Biomedical Engineering↗
PubMed2003

Biological alchemy: engineering bone and fat from fat-derived stem cells.

Adipose tissue contains a population of pluripotent stem cells capable of differentiating along multiple mesenchymal cell lineages. In this study the authors isolated these fat-derived stem cells successfully from Lewis rats and induced differentiation along adipogenic and osteogenic lineages in vitro and in vivo. Induction was stimulated by exposing stem cells to lineage-specific induction factors. Adipocyte-inducing media contained dexamethasone, insulin, and isobutyl-methylxanthine. Osteoblast inducing media contained dexamethasone, beta-glycerophosphate, and ascorbic acid. Undifferentiated stem cells were maintained in minimal essential media alpha and fetal bovine serum. At 10 days, cells cultured in adipogenic media differentiated into adipocytes in vitro, as evidenced by positive Oil red O staining of lipid vacuoles. At 21 days, cells cultured in osteogenic media differentiated into osteoblasts in vitro as demonstrated by Alizarin red staining of a calcified extracellular matrix and immunohistochemical staining for osteocalcin. Differentiated cells were seeded at a density of 5 x 106 cells onto 15 x 15-mm polyglycolic acid grafts and implanted subcutaneously into three groups of Lewis rats: Group I contained undifferentiated stem cell grafts, group II contained adipocyte grafts, and group III contained osteoblast grafts. At weeks 4 and 8, in vivo fat formation was demonstrated in group II rats, as confirmed by Oil red O staining. At 8 weeks, group III rats demonstrated in vivo bone formation, as confirmed by the presence of osteocalcin on immunohistochemistry and the characteristic morphology of bone on hematoxylin-eosin staining. Group I rats demonstrated no in vivo bone or fat formation at either time interval. These results demonstrate the ability to isolate pluripotent stem cells from adipose tissue, to induce their differentiation into osteoblasts and adipocytes in vitro, and to form bone and fat subsequently in vivo. This is the first published report of in vivo bone formation from fat-derived stem cells. These cells may eventually serve as a readily available source of autologous stem cells for the engineering of bone and fat.

Adipocytes↗
PubMed2001

Visual prostheses.

The development of man-made systems to restore functional vision in the profoundly blind has recently undergone a renaissance that has been fueled by a combination of celebrity and government interest, advances in the field of bioengineering, and successes with existing neuroprosthetic systems. This chapter presents the underlying physiologic principles of artificial vision, discusses three contemporary approaches to restoring functional vision in the blind, and concludes by presenting several relevant questions to vision prostheses. While there has been significant progress in the individual components constituting an artificial vision system, the remaining challenge of integrating these components with each other and the nervous system does not lie strictly in the realm of neuroscience, medicine, or engineering but at the interface of all three. In spite of the apparent complexity of an artificial vision system, it is not unreasonable to be optimistic about its eventual success.

Biomedical Engineering↗
PubMed2005

Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells.

Human bone marrow (BM) mesenchymal stem/progenitor cells are potentially attractive targets for ex vivo gene therapy. The potential of lentiviral vectors for transducing BM mesenchymal cells was examined using a self-inactivating vector that expressed the green fluorescent protein (GFP) from an internal cytomegalovirus (CMV) promoter. This vector was compared with oncoretroviral vectors expressing GFP from the CMV promoter or a modified long-terminal repeat that had been optimized for long-term expression in stem cells. The percentage of GFP-positive cells was consistently higher following lentiviral versus oncoretroviral transduction, consistent with increased GFP mRNA levels and increased gene transfer efficiency measured by polymerase chain reaction and Southern blot analysis. In vitro GFP and FVIII expression lasted for several months post-transduction, although expression slowly declined. The transduced cells retained their stem/progenitor cell properties since they were still capable of differentiating along adipogenic and osteogenic lineages in vitro while maintaining high GFP and FVIII expression levels. Implantation of lentivirally transduced human BM mesenchymal cells using collagen scaffolds into immunodeficient mice resulted in efficient engraftment of gene-engineered cells and long-term transgene expression in vivo. These biocompatible BM mesenchymal implants represent a reversible, safe, and versatile protein delivery approach because they can be retrieved in the event of an unexpected adverse reaction or when expression of the protein of interest is no longer required. In conclusion, efficient gene delivery with lentiviral vectors in conjunction with the use of bioengineered reversible scaffolds improves the therapeutic prospects of this novel approach for gene therapy, protein delivery, or tissue engineering.

Adipogenesis↗
PubMed1998

Isolation of human osteoblast-like cells and in vitro amplification for tissue engineering.

As the field of dental implants continues to grow at a rapid rate so does our quest to find new techniques to enhance bone grafting. Tissue engineering is an exciting new technique in bone grafting. Therefore, the purposes of this study were to develop a simple, reproducible method to isolate human osteoblast-like cells (HOBs) and to evaluate in vitro cell proliferation within 2 different 3-dimensional (3-D) constructs targeted for tissue engineering applications. Ultimately, HOBs that have been amplified within 3-D constructs may be employed for bone regeneration techniques, such as onlay and sinus grafting prior to implant placement. Our cell isolation protocol employed human fetal calvaria tissue sequentially digested with trypsin and collagenase. The HOB cells from only the third and fourth digests were obtained, cultured and evaluated within the constructs. An osteoblast-like phenotype was in part verified for these HOB cells by demonstrating a significantly higher alkaline phosphatase activity than for human gingival fibroblasts, and a comparable level to the osteoblast cell line MG-63. The HOB cells were cultured within either poly (D,L-lactide) (PLA) or a fused fiber ceramic and evaluated for the ability to support in vitro HOB amplification. HOB proliferation was validated by scanning electron microscopy, identifying cells throughout the 3-D constructs. Continuous cell viability was demonstrated for the duration of the 33-day evaluation period and the extent of cell amplification reached approximately 20 times the seeding density. The in vitro amplification results further indicate that tissue engineering strategies with either the PLA or fused fiber construct may be suitable for bone regeneration therapy for dental implants.

Biomedical Engineering↗
PubMed1990

NDSU undergraduate design projects for the disabled.

Disabled persons of average means cannot afford custom made devices or adaptations to manufactured devices to meet their individual needs. Consequently, many disabled individuals have not been able to live as independently as society demands. At North Dakota State University, the need to give undergraduate electrical engineering students practical design experience has been fulfilled by requiring the students to design and build adaptive devices for the disabled. Consequently, the successful results of this effort have fulfilled the needs of two diverse human groups--student engineers and the disabled community. Presented is an effective approach used at North Dakota State University to manage senior design students.

Biomedical Engineering↗
PubMedDate not supplied

[Development of medical technology in a scientific and technical revolution].

Necessity of developing preventive medicine and increasing the efficacy of treatment-and-diagnostic process, as well as economic factors predetermine the expansion of use of modern technique in medicine and introduction of new technological principles. Fundamental scientific researches, development of new medical technique, progress in biotechnology, foundation of biotechnological centers, improvement of medical education and training of clinical engineers play a significant role in the solution of this problem. The experience of some countries in organization of training and use of biotechnologists in health service system is discussed.

Biomedical Engineering↗
PubMedDate not supplied

Applicability of personnel management concepts to clinical engineering practice.

Personnel management concepts are reviewed for inclusion in clinical engineering basic and continuing education curricula. The management function is evaluated from the aspect of formal and informal leadership, two-way communication, voluntary cooperation, and the direction and discipline of the clinical engineering staff. Prerequisites examined in support of these activities include an effective organizational structure, man-to-job matching, personal needs, and job satisfaction. Steps propounded for stimulating communications between the clinical engineer and his multidisciplinary clients include adjustments to his own role model and to his educational technique so as to accord more with the specific role models of his audience.

Biomedical Engineering↗
PubMed2006

Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential.

Previously, we have demonstrated the long-term survival of myocardial cell sheet constructs in vivo, with microvascular network formation throughout the engineered tissues. The understanding and control of these vascularization processes are a key factor for creating thicker functional tissues. Here, we show that cardiac cell sheets express angiogenesis-related genes and form endothelial cell networks in culture. After non-invasive harvest and stacking of cell sheets using temperature-responsive culture dishes, these endothelial cell networks are maintained and result in neovascularization upon in vivo transplantation. Interestingly, we also discovered that all of the graft vessels are derived from the grafts themselves and these vessels migrate to connect with the host vasculature. Finally, blood vessel formation within the grafts can be controlled by changing the ratio of endothelial cells. In conclusion, myocardial tissue grafts engineered with cell sheet technology have their own inherent potential for the in vivo neovascularization that can be regulated in vitro.

Animals↗