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Water and turf: fluoridation and the 20th-century fate of waterworks engineers.

Once central figures in American public health, waterworks engineers are no longer involved in many decisions made about the public water supplies. This paper argues that the profession's response to the early fluoridation movement of the 1940s and 1950s marked a change in the relationship between waterworks engineers and the other constitutive groups in public health and contributed to the disenfranchisement of the waterworks profession. Sensing a potentially divisive issue, two leaders of the profession, Abel Wolman and Linn Enslow, took steps they hoped would prevent a rift within the profession and allow waterworks engineering to continue its association with the wider public health community. Although the leaders saw the fluoridation issue differently, neither encouraged the profession to consider it openly or to take up the broader question of what limits, if any, should be placed on treating water supplies to meet human needs. Instead, they opted to locate authority for fluoridation outside the waterworks profession with dentists, doctors, and public health administrators. As a result, waterworks engineers conceded a great deal of the status and prestige associated with decision-making roles in community health issues and have largely faded from view.

Canada↗

Tissue-engineered osteochondral constructs in the shape of an articular condyle.

BACKGROUND: An entire articular condyle engineered from stem cells may provide an alternative therapeutic approach to total joint replacement. This study describes our continuing effort to optimize the chondrogenic and osteogenic differentiation from mesenchymal stem cells toward engineering articular condyles in vivo. METHODS: Primary rat bone-marrow mesenchymal stem cells were induced to differentiate into chondrogenic and osteogenic lineages in vitro and were suspended in polyethylene glycol-based hydrogel. The hydrogel cell suspensions, each at a density of 20 x 10(6) cells/mL, were stratified into two separate layers that were molded into the shape and dimensions of an adult human cadaveric mandibular condyle by sequential photopolymerization. The osteochondral constructs fabricated in vitro were implanted in the dorsum of immunodeficient mice for twelve weeks. RESULTS: De novo formation of articular condyles in the shape and dimensions of the adult human mandibular condyle occurred after a twelve-week period of in vivo implantation. Histological evaluation demonstrated two stratified layers of cartilaginous and osseous tissues, and yet there was mutual infiltration of cartilage-like and bone-like tissues into each other's territories. The cartilaginous portion was stained intensively to safranin O and expressed immunolocalized type-II collagen. Chondrocytes adjacent to the tissue-engineered osteochondral junction were enlarged and expressed type-X collagen, typical of hypertrophic chondrocytes. The osseous portion contained bone trabeculae-like structures and expressed immunolocalized type-I collagen, osteopontin, and osteonectin. CONCLUSIONS: A cell encapsulation density of 20 million cells/mL with in vivo incubation for twelve weeks yields further tissue maturation and phenotypic growth of both cartilage-like and bone-like tissues in the tissue-engineered articular condyle.

Animals↗

Application of biomedical engineering to neurosurgery.

Biomedical engineering is increasingly becoming very important also in neurosurgery. This article describes some examples of neurosurgical applications of biomaterials which play a central role in biomedical engineering. Since a large number of biomaterials are currently used in neurosurgery, only the biomaterials that have been developed in our laboratories in collaboration with neurosurgeons are briefly presented here. The biomaterials developed include devices used for interventional neurosurgery and bioabsorbable scaffolds for regeneration of dura mater and skull bone. We developed an immediately electrically detachable coil using a poly(vinyl alcohol) junction between the coil and the delivery wire. This is the first detachable coil developed in Japan and is currently under clinical trial. In addition to the coil used for interventional neurosurgery, the development of an embolic liquid is presented. As an alternative to allografts such as Lyodura, we developed a dural substitute from synthetic bioabsorbable polymers which are completely free from potential risk of latent virus infection. Finally, our experience in tissue engineering for skull bone regeneration using growth factors coupled with polymeric carriers is presented to demonstrate the promise of tissue engineering in the future.

Aneurysm↗

Biodegradable synthetic polymers for tissue engineering.

This paper reviews biodegradable synthetic polymers focusing on their potential in tissue engineering applications. The major classes of polymers are briefly discussed with regard to synthesis, properties and biodegradability, and known degradation modes and products are indicated based on studies reported in the literature. A vast majority of biodegradable polymers studied belongs to the polyester family, which includes polyglycolides and polylactides. Some disadvantages of these polymers in tissue engineering applications are their poor biocompatibility, release of acidic degradation products, poor processability and loss of mechanical properties very early during degradation. Other degradable polymers such as polyorthoesters, polyanhydrides, polyphosphazenes, and polyurethanes are also discussed and their advantages and disadvantages summarised. With advancements in tissue engineering it has become necessary to develop polymers that meet more demanding requirements. Recent work has focused on developing injectable polymer compositions based on poly (propylene fumarate) and poly (anhydrides) to meet these requirements in orthopaedic tissue engineering. Polyurethanes have received recent attention for development of degradable polymers because of their great potential in tailoring polymer structure to achieve mechanical properties and biodegradability to suit a variety of applications.

Biocompatible Materials↗

The future of clinical engineering: technology that enables improved patient care.

Speakers at this year's ACCE Symposium will describe in detail the scope and depth of technological and other factors that are at work changing the healthcare delivery paradigm. Other presenters will explore the impact the changes will likely have on the clinical engineering profession. Still others will outline the steps necessary for clinical engineers to take to effectively prepare for the challenges facing them. The experts agree: clinical engineering is at a critical crossroads. No one who intends to pursue clinical engineering or healthcare technology management over the next 10 years can afford to miss this year's meeting.

Biomedical Engineering↗

The potency of culture-expanded nasal septum chondrocytes for tissue engineering of cartilage.

Tissue engineering techniques to create extra autologous cartilage for reconstructive surgery receive more and more scientific and industrial attention. The objective of this experimental study was to assess the use of in vitro multiplied chondrocytes of the nasal septum for generation of cartilage grafts using tissue engineering techniques. Cells isolated from a biopsy of septal cartilage of rabbits and humans were expanded in culture to get a sufficient number of cells to engineer a cartilage graft. The drawback of the expansion procedure is that the cells lose their cartilaginous phenotype (dedifferentiation). We studied a method to reverse the dedifferentiation of expanded cells to stimulate them to produce cartilage matrix of good quality. Rabbit chondrocytes showed reversion of dedifferentiation (redifferentiation) when fetal calf serum was replaced by the growth factors IGF1 and TGFbeta2. This was expressed by increased glycosaminoglycan synthesis and increased numbers of collagen type II-producing cells. The redifferentiation capacity of septal cartilage cells of young rabbits was higher than that of adult rabbits. In human chondrocytes from the nasal septum redifferentiation could also be induced by replacement of serum with IGF1 and TGFbeta2. This method, however, was less efficient than in rabbits. Chondrocytes of older patients (>40 years old) were no longer sensitive to the growth factor treatment. In conclusion, our study demonstrates a method to regain cartilage phenotype in multiplied cells of nasal septum cartilage needed for tissue engineering of new cartilage. These results are promising for this technique to generate cartilage grafts for facial plastic surgery of the nasal septum.

Adult↗

Electrospinning collagen and elastin: preliminary vascular tissue engineering.

Significant challenges must be overcome before the true benefit and economic impact of vascular tissue engineering can be fully realized. Toward that end, we have pioneered the electrospinning of micro- and nano-fibrous scaffoldings from the natural polymers collagen and elastin and applied these to development of biomimicking vascular tissue engineered constructs. The vascular wall composition and structure is highly intricate and imparts unique biomechanical properties that challenge the development of a living tissue engineered vascular replacement that can withstand the high pressure and pulsatile environment of the bloodstream. The potential of the novel scaffold presented here for the development of a viable vascular prosthetic meets these stringent requirements in that it can replicate the complex architecture of the blood vessel wall. This replication potential creates an "ideal" environment for subsequent in vitro development of a vascular replacement. The research presented herein provides preliminary data toward the development of electrospun collagen and elastin tissue engineering scaffolds for the development of a three layer vascular construct.

Blood Vessel Prosthesis↗

Medical engineering education in Sweden with reference to other Nordic countries.

The education of biomedical engineers in Sweden is examined against the background [corrected] of the organisation of Swedish health care. The history of the introduction of engineers into medicine is briefly recounted, leading on to a description of the academic courses open to both undergraduate and graduate students and to a discussion of the status of biomedical engineering and of biomedical engineers within the health service. Future trends are suggested. The situation in other Nordic countries is also briefly discussed.

Biomedical Engineering↗

Cytokine delivery and tissue engineering.

Tissue engineering has been applied to various tissues, and particularly significant progress has been made in the areas of skin, cartilage, and bone regeneration. Inclusion of bioactive factors into the synthetic scaffolds has been suggested as one of the possible tissue engineering strategies. The growth factors are polypeptides that transmit signals to modulate cellular activities. They have short half-lives, for example, platelet-derived growth factor (PDGF), isolated from platelets, has a half life of less than 2 minutes when injected intravenously. Extended biological activity and the controlled release of growth factor are achieved by incorporating growth factor into the polymeric device. This review will focus on growth factor delivery for tissue engineering. Particular examples will be given whereby growth factors are delivered from a tissue-engineered device to facilitate wound healing and tissue repair.

Animals↗

Metabolic Engineering of Probiotic Saccharomyces boulardii Enables Intestinal 3-Hydroxybutyrate Delivery and Alters Short-Chain Fatty Acid Profiles in Mice.

3-Hydroxybutyric acid (3-HB) is a bioactive ketone body involved in the regulation of intestinal inflammation and metabolic homeostasis. Although engineered bacterial probiotics have been developed for localized 3-HB delivery, their susceptibility to antibacterial antibiotics may limit their use during concurrent antibiotic treatment. The probiotic yeast Saccharomyces boulardii offers an alternative host for intestinal 3-HB delivery because of its compatibility with antibacterial antibiotics and the availability of well-established genetic engineering tools. Here, we engineered S. boulardii for 3-HB production using Cas9-mediated genome editing. A heterologous 3-HB biosynthetic pathway was introduced into S. boulardii MYA-797, and endogenous acetyl-CoA and ethanol metabolism was subsequently rewired by overexpressing ACS1, deleting ADH1, and overexpressing ADH7. The optimized strain, SbDY02, produced 1.7 g/L 3-HB under microaerobic conditions. Oral administration of SbDY02 to C57BL/6J mice increased fecal 3-HB and short-chain fatty acid (SCFA) concentrations by 1.89-fold and 1.68-fold, respectively, compared with mice receiving the parental strain. Repeated administration also increased fecal acetate and circulating total SCFAs, butyrate, and propionate. In human colonic epithelial cells, purified 3-HB attenuated lipopolysaccharide-induced p38 MAPK phosphorylation, supporting its direct activity toward inflammation-associated epithelial signaling. To our knowledge, this study provides the first demonstration of a 3-HB-producing probiotic yeast and links central metabolic engineering of S. boulardii with increased 3-HB availability, altered SCFA profiles, and a host-relevant epithelial response.

3-hydroxybutyrate↗

A Reduced-Acidification Phenotype Simplifies Strain Engineering in Komagataeibacter and Enables One-Step Production of Melanated Bacterial Cellulose.

Komagataeibacter species are among the highest-yielding bacterial cellulose producers and offer a promising platform for the genetic engineering of functionalized bacterial cellulose. However, routine strain engineering remains limited by inefficient screening of genomic integrants and acidic culture conditions that inhibit acid-sensitive cellulose modifications. Here, we exploited the reduced-acidification phenotype of a Komagataeibacter sucrofermentans glucose dehydrogenase deletion mutant (Δgdh) to overcome both limitations. We developed a simple phenotypic screen based on reduced acidification to identify candidate colonies for subsequent molecular confirmation. We further exploited this phenotype by constructing a Δgdh::tyr1 strain that, after optimizing culture conditions, produced melanated bacterial cellulose in a single step, without the manual pH neutralization required by previous methods. Together, these results establish reduced acidification as a practical engineering phenotype that simplifies strain engineering and enables acid-sensitive modification of bacterial cellulose, thereby expanding the range of bacterial cellulose modifications achievable in Komagataeibacter.

Komagataeibacter sucrofermentans↗

Translational research for injectable tissue-engineered bone regeneration using mesenchymal stem cells and platelet-rich plasma: from basic research to clinical case study.

Translational research involves application of basic scientific discoveries into clinically germane findings and, simultaneously, the generation of scientific questions based on clinical observations. At first, as basic research we investigated tissue-engineered bone regeneration using mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in a dog mandible model. We also confirmed the correlation between osseointegration in dental implants and the injectable bone. Bone defects made with a trephine bar were implanted with graft materials as follows: PRP, dog MSCs (dMSCs) and PRP, autogenous particulate cancellous bone and marrow (PCBM), and control (defect only). Two months later, dental implants were installed. According to the histological and histomorphometric observations at 2 months after implants, the amount of bone-implant contact at the bone-implant interface was significantly different between the PRP, PCBM, dMSCs/ PRP, native bone, and control groups. Significant differences were also found between the dMSCs/PRP, native bone, and control groups in bone density. These findings indicate that the use of a mixture of dMSCs/ PRP will provide good results in implant treatment compared with that achieved by autogenous PCBM. We then applied this injectable tissue-engineered bone to onlay plasty in the posterior maxilla or mandible in three human patients. Injectable tissue-engineered bone was grafted and, simultaneously, 2-3 threaded titanium implants were inserted into the defect area. The results of this investigation indicated that injectable tissue-engineered bone used for the plasty area with simultaneous implant placement provided stable and predictable results in terms of implant success. We regenerated bone with minimal invasiveness and good plasticity, which could provide a clinical alternative to autogenous bone grafts. This might be a good case of translational research from basic research to clinical application.

Aged↗

Selection of cell source for ligament tissue engineering.

Use of appropriate types of cells could potentially improve the functionality and structure of tissue engineered constructs, but little is known about the optimal cell source for ligament tissue engineering. The object of this study was to determine the optimal cell source for anterior cruciate ligament (ACL) tissue engineering. Fibroblasts isolated from anterior cruciate ligament, medial collateral ligament (MCL), as well as bone marrow mesenchymal stem cells (MSC) were compared using the following parameters: proliferation rate, collagen excretion, expression of collagen type I, II, and III, as well as alpha-smooth muscle actin. Green fluorescent protein (GFP) transfected MSCs were used to trace their fate in the knee joints. MSC, ACL, and MCL fibroblasts were all highly stained with antibodies for collagen types I and III and alpha-smooth muscle actin while negatively stained with collagen type II. Proliferation rate and collagen excretion of MSCs were higher than ACL and MCL fibroblasts (p < 0.05), and MSCs could survive for at least 6 weeks in knee joints. In summary, MSC is potentially a better cell source than ACL and MCL fibroblasts for anterior cruciate ligament tissue engineering.

Animals↗

Age effects on vascular smooth muscle: an engineered tissue approach.

Tissue engineering of blood vessels offers a potential new therapy for patients with vascular occlusive disease. In addition, tissue engineering technologies offer the opportunity to study the biology of vascular cells in a biomimetic, three-dimensional environment. A model for vascular tissue engineering was used to study the effects of vascular cell age on extracellular matrix (ECM) deposition, cellular mitosis, and protein synthesis under controlled conditions in vitro. Blood vessels were grown using a three-dimensional polyglycolic acid (PGA) mesh that was seeded with either infant or adult porcine vascular smooth muscle cells. Mechanical forces in the form of pulsatile radial distension were applied for the duration of the 7-week growth period. Overall, infant cells exhibited higher levels of cellular proliferation, ECM deposition, and remodeling activity than cells derived from adult animals. In addition, vessels cultured from infant cells had enhanced physical properties compared to vessels cultured from adult cells. The differentiation state of the smooth muscle cells in the infant and adult constructs was unchanged from the native state. However, the levels of immature pro-collagen, although undetectable in the vessels grown from adult cells, were similar in native vessels and in vessels grown with infant cells. These studies have important implications for the study of aging and vascular disease and remodeling, as well as for the field of tissue engineering.

Age Factors↗

Engineering aspects of beta-lactam biosynthesis.

The adaptation of an existing industrial production line to boost production capacity (a hardware analogue of strain improvement) or to enable the production of a derivative of the original product is used as an example to explore the similarities between process design and engineering and metabolic pathway engineering. In the two fields the same principles appear to apply: for most process engineering solutions metabolic pathway engineering analogues can be found. Analogues are illustrated by reference to literature (e.g. overproduction of amino acid precursors at the 'bottom' of the pathway, relocalisation of proteins and overexpression of genes from the secondary metabolism). Some possible future applications are defined (e.g. supervisory manipulations as regulation by gene transcription factors).

Anti-Bacterial Agents↗

In vitro engineering of cartilage.

Because adult human cartilage shows poor capacity for repair and regeneration, innovative solutions are required for congenital and acquired degenerative cartilage lesions. Acquired lesions occur in young and old alike, the former being more at risk for sports-related injuries and the latter for age-related degenerative changes. Because cartilage is a relatively simple tissue with respect to its cellular homogeneity and avascularity, it has been a model for research of in vitro engineered tissues. Progress has been slow and obstructed on several levels. The adult chondrocyte has limited capacity for proliferation and has both catabolic and anabolic functions. These metabolic features must be controlled in order for engineered tissue to endure. Use of three-dimensional scaffolds can be combined with regulatory factors (cytokine, extracellular matrix [ECM], and mechanical) to optimize conditions for in vitro engineered cartilage. Cross-disciplinary interactions are likely to accelerate progress and to mediate application of advances made in other fields for consistently successful in vitro engineering of cartilage for all clinical needs.

Adult↗

Requirements engineering: the key to designing complex medical systems.

A variety of business systems, clinical work systems, instrumentation systems, information systems, infrastructure systems, and management systems interact to make the modern healthcare facility work. The key to designing for such a system is systems engineering, a skill often little appreciated among clinical engineers. At the heart of systems engineering is requirements engineering and management (REAM), which is defined as "the process of discovering, documenting and managing systems requirements." The principal activities of REAM include eliciting, understanding, negotiating, describing, validating, and managing system requirements. When REAM is done improperly, the resulting system will be satisfactory only if chance intervenes. Well-done REAM is likely to bring the project in on time, under budget, and at full performance.

Biomedical Engineering↗

Tissue engineering and skeletal diseases.

Tissue engineering, a cross between the science of the living organism and that of engineering, aims to replace, maintain or improve human tissue functions, by means of tissue substitutes containing living elements. Thus, it is about production of artificial tissue, using (alone or in combination) cells, matrix or bioactive factors. Their association gives rise to a hybrid biomaterial combining biological components (cells, growth factors or adhesion proteins) and materials (polymers, ceramics). The applications are wide-ranging, from the skin, to the liver, or to the cornea as well as to the locomotor system. Bone tissue engineering has advanced the most in this field, partly because of the progress made by research into bone substitutes, although cartilage and tendons are also concerned. This technology requires cell culture (committed cells or more often bone marrow stem cells), biomaterials (porous materials with controlled architecture and cements), growth factors (such as 'Bone Morphogenetic Proteins'), the proteins implicated in cell adhesion (such as fibronectin or the aminoacid sequences specifically recognised by integrin subunits) or gene therapy (notably using transfected stem cells). Tissue engineering and regenerative stimulation of tissue are now booming on experimental and industrial levels and clinical applications are increasingly numerous. Considering the potential of these technologies, they should continue to develop widely.

Biomedical Engineering↗