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Tissue engineering principles in orthopaedic surgery.

Advances in the fields of biotechnology and biomaterials offer the orthopaedic surgeon the exciting possibility of repair or regeneration of tissue lost to injury, disease, or aging. The promising area of tissue engineering represents a multidisciplinary approach aimed at solving some of the most perplexing biologic problems, namely, the creation of new tissues and organs similar to the original tissues and organs. In addition, strategies using new synthetic polymer formulations can facilitate tissue replacement and represent alternatives to tissue regeneration in certain conditions. Although biotechnology has broad application over many medical specialties, orthopaedics is receiving a large focus of the research effort devoted to techniques for developing bone, articular cartilage, ligaments, and tendons. Because bioengineered tissue and/or techniques to stimulate tissue regeneration soon may be used clinically, orthopaedic surgeons should have a working knowledge of the basic concepts involved. Terms, such as biomaterial, biotechnology, matrices of synthetic or biologic polymers or both, adhesion, cohesion, porosity, induction, conduction, stem cell, progenitor cell, mesenchymal cell, tissue growth factor, bone morphogenetic protein, mitogenic and chemotactic factors, and numerous other terms will become part of the working language of clinicians of the twenty-first century.

Animals↗

Gas flow and mixing in the airways.

OBJECTIVE: To survey the current state of scientific knowledge of gas flow and mixing in pulmonary airways, especially at high frequencies. DATA SOURCES: Results from the authors' own laboratory studies and Western bioengineering literature on respiratory fluid mechanics. STUDY SELECTION: This survey concentrates on understanding the principal physical mechanisms that underlie the enhancement of airway gas transport in high-frequency oscillation. The results of experimental, computational, and mathematical studies are described. DATA SYNTHESIS: The topic was covered by seven presenters at the Münster Meeting on High Frequency Ventilation, January 31 to February 2, 1993. Six of these presentations are summarized in the six sections of this paper under the following headings: Introductory Survey; Three-Dimensional Numerical Simulation of Inspiratory and Expiratory Flows in Small Airways; Computational and Experimental Models of High-Frequency Oscillation; Unsteady Gas Mixing in Airways; Gas Dispersion From the Lagrangian Viewpoint; and Soluble Gas Mass Transfer in Tubes and Airways. CONCLUSIONS: The dominant mechanism for the enhancement of gas transport along airways at high frequency is likely to lie in the coupling of the secondary motions caused by airway curvature with the oscillatory longitudinal flow. However, laboratory experiments and theoretical analyses have led only to an accurate simulation of the phenomena in idealized geometries, not in real lungs.

Animals↗

Education of clinical engineers in the 1990s.

This paper presents definitions of the terms bioengineering, biomedical engineering and clinical engineering. These definitions lead to the conclusion that clinical engineers must be individuals with at least a four-year bachelor's degree in an engineering specialty who are also well versed in the design, modification and testing of medical instrumentation. Educational programs for clinical engineers in the 1990s must be based upon clear definitions of these professionals' roles. Clinical engineering education should include direct professional experience obtained through internship programs similar to the program described here.

Biomedical Engineering↗

Biomedical engineering education in Canada, 1996.

This paper updates the information contained in a previously published paper, ¿Bioengineering Education in Canada, 1988,¿ which appeared in the Journal of Clinical Engineering (Volume 13, No. 5). It describes the current biomedical engineering and biomedical engineering technology programs available in Canada, but does not attempt to evaluate them. There are no undergraduate degree programs specifically in biomedical engineering, although three universities have created options in biomedical engineering in undergraduate programs. Also, the clinical engineering program at the University of British Columbia has been discontinued.

Biomedical Engineering↗

Establishment of a clinical engineering department in a Venezuelan national reference hospital.

Since 1976, Clinical Engineering (CE) has been studied at the Simón Bolívar University (USB) as part of the Bioengineering Studies program developed at that University. However, it was not until 1996 that Clinical Engineering activities were established in a Venezuelan hospital. This paper describes how the USB, using its own human resources, has achieved the establishment of a Clinical Engineering Department in a national reference hospital for the first time.

Biomedical Engineering↗

Technology assessment--a survey of the clinical engineer's role within the hospital.

Advancements in technology are vital to improve clinical outcomes within the medical community and, in particular, to healthcare systems. The need for a systematic approach to analyzing, assessing and selecting the best new technology for individual hospitals continues to increase in response to this technological growth. To determine the use of technology assessment, the effectiveness of different methods, and the role of clinical engineers and bioengineers in this process, a survey was conducted of clinical engineering departments throughout the United States. The results reveal that technology assessment programs are widely utilized as a team effort between hospital departments. Clinical engineers are playing a key role within these teams as technology managers.

Attitude of Health Personnel↗

Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease.

Severe pancreatic exocrine insufficiency leading to malabsorption of nutrients is one of the most important late features of chronic pancreatitis. In contrast to other key enzymes, pancreatic synthesis and secretion of lipase is impaired more rapidly, its intraluminal survival is shorter due to its higher susceptibility against acidic and proteolytic denaturation, and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is in general more severe and occurs several years before clinical malabsorption of protein or starch. Apart from the detrimental effects of nutrient deficiency, profound alterations of upper gastrointestinal secretory and motor functions may be an additional and hitherto underestimated consequence of increased nutrient delivery to distal intestinal sites. Effective reduction of nutrient malabsorption in pancreatic insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. Modern enteric-coated pancreatin microsphere preparations attempt to achieve this by optimizing the size of individual microspheres and chemical properties of the coating. However, lipid digestion cannot be completely normalized in most patients by current standard therapy. In the future, acid and protease stable bacterial and fungal lipases with additional pH optima in the acidic milieu or animal or bioengineered human gastric lipase preparations may offer superior therapeutic alternatives. This review first summarizes current knowledge about secretion and luminal fate of pancreatic enzymes and their effects on nutrient digestion in health and chronic pancreatitis. Second, rationale, current standards, options, and future aspects of enzyme replacement therapy are discussed.

Amylases↗

Pullout strengths of self-reinforced poly-L-lactide (SR-PLLA) rods versus Kirschner wires in bovine femur.

OBJECTIVE: To determine the relative amount of fixation of self-reinforced poly-L-lactide (SR-PLLA) rods and Kirschner wires in bovine cancellous bone by comparing their pullout strength DESIGN: An in vitro laboratory study was performed using bovine femurs. Ten two-millimeter-diameter pins of each type were inserted into cancellous bone and then pulled out, using a material testing machine. The maximum force (pullout strength) was selected over other measurements to compare the amount of fixation of the two types of pins. All of the pins were retrieved for microscopic analysis. A paired t test was performed to analyze the differences between the pullout strength of the two types of pins. SETTING: Orthopaedic Bioengineering Laboratory, University of Louisville School of Medicine, Louisville, Kentucky, U.S.A. SPECIMENS: Two young fresh bovine distal femurs, ten two-millimeter-diameter Kirschner wires, ten two-millimeter-diameter bioabsorbable SR-PLLA rods MAIN OUTCOME MEASUREMENTS: Pullout strength in Newtons, and microscopic pin surface aspect after insertion. RESULTS: Significant differences were noted between the maximum force required to remove the two types of pins (p < 0.01) The K-wire mean pullout force was 37.7 N (SD 13.6), and the SR-PLLA rod mean pullout force was 53.6 N (SD 19.3). Microscopic analysis indicated surface modification only on the SR PLLA rods. DISCUSSION: SR-PLLA composites have shown comparable clinical results to their metallic counterparts. In this study, the pullout strength of SR-PLLA rods was compared with that of conventional K-wires. A significant difference (p < 0.01) favoring bioabsorbable pullout strength was noted. The bioabsorbable pin surface modification during insertion is an interesting finding that warrants further investigation as a potential source of improved fixation. CONCLUSION: SR-PLLA rods retain their hold in bovine cancellous bone better than K-wires. This finding offers to the orthopaedic surgeon more information about new pin fixation methods.

Animals↗

Children and genetically engineered food: potentials and problems.

Changes in food production and dietary practices are occurring faster than our understanding of their potential impact on children's health. Traditionally, pediatric gastroenterologists have studied food with respect to its nutritive value and digestibility, its influence on metabolism, its growth-promoting characteristics, and its relationship to risk and severity of disease. Biotechnology is now expanding the science of food to include disease prevention and treatment, as well as the feeding of children on a global scale. Bioengineered ("genetically modified", or "transgenic") plants were initially developed to enhance the food supply by increasing crop yields. Such previously developed transgenic plants are now prevalent worldwide and appear in many processed food products. The implementation of the technology of genetic modulation of food plants has led to considerable fear, controversy, and confusion as the understanding of the technology is poor in the general population. This review presents an overview of genetically modified food crops and their potential unique benefits and risks to children's health. Political, economical, and ecological issues related to transgenic crops are not discussed.

Child↗

Descartes' law of reciprocal innervation.

Reciprocal innervation plays a crucial role in the fine motor control exhibited in body movements and this is especially true for the precise ocular rotations demanded of the extrinsic muscles of the eye. Although Galen, in 157 AD, was knowledgeable in human anatomy and muscle function, it was Descarted, who in 1626 first conceived of model for the nervous system controller, of a muscular mechanism for movement of the extra-ocular plant, and of reciprocal innervation as the linking principle to provide for control of agonist and antagonist muscles. Bell, in 1826, and Sherrington in 1893, clearly demonstrated reciprocal innervation in their experimental animals. Additional qualitative neurophysiological evidence supporting the concept of reciprocal innervation has been provided by clinical case reports, by electromyographic recording from the extraocular muscles, and by monitoring single unit activity in the extraocular motor nuclei. Recently the applicatio of bioengineering concepts, such as time optimal control and quantitative models to elucidate the nature of the neural signals sent by the brain to command eye movements have further emphasized the importance of Descartes' "Law of Reciprocal Innervation."

Animals↗

Tissue engineering of peripheral nerves: A comparison of venous and acellular muscle grafts with cultured Schwann cells.

Bioengineering is considered to be the laboratory-based alternative to human autografts and allografts. It ought to provide "custom-made organs" cultured from patient's material. Venous grafts and acellular muscle grafts support axonal regeneration only to a certain extent because of the lack of viable Schwann cells in the graft. We created a biologic nerve graft in the rat sciatic nerve model by implanting cultured Schwann cells into veins and acellular gracilis muscles, respectively. Autologous nerve grafts and veins and acellular muscle grafts without Schwann cells served as controls. After 6 and 12 weeks, regeneration was assessed clinically, histologically, and morphometrically. The polymerase chain reaction analvsis showed that the implanted Schwann cells remained within all the grafts. The best regeneration was seen in the control; after 12 weeks the number of axons was increased significantly compared with the other grafts. A good regeneration was noted in the muscle-Schwann cell group, whereas regeneration in both of the venous grafts and the muscle grafts without Schwann cells was impaired. The muscle-Schwann cell graft showed a systematic and organized regeneration including a proper orientation of regenerated fibers. The venous grafts with Schwann cells showed less fibrous tissue and disorganization than the veins without Schwann cells, but failed to show an excellent regeneration. This might be attributed to the lack of endoneural-tube-like components serving as scaffold for the sprouting axon. Although the conventional nerve graft remains the gold standard, the implantation of Schwann cells into an acellular muscle provides a biologic graft with basal lamina tubes as pathways for regenerating axons and the positive effects of Schwann cells producing neurotrophic and neurotropic factors, and thus, supporting axonal regeneration.

Animals↗

Lipase supplementation therapy: standards, alternatives, and perspectives.

Treatment of steatorrhea by lipase supplementation therapy has become more successful in the last decade due to better understanding of the physiology and pathophysiology of the digestive process. Porcine lipase has been the therapeutic standard for several decades and will continue to be the treatment of choice in pancreatic exocrine insufficiency. Modern therapeutic concepts recommend administration of 25,000-40,000 units of porcine lipase per meal using pH-sensitive pancreatin microspheres. In case of treatment failure, the dose should be increased, compliance should be checked, and other reasons for malabsorption should be excluded. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed for optimizing treatment. In this article, pathophysiologic characteristics of pancreatic exocrine insufficiency, prerequisites for use of alternative lipase sources as well as currently available lipases of nonporcine origin, and new developments are discussed. Current literature suggests that bovine lipase products present a theoretical alternative but play no major role in the western world. Fungal lipase has inferior properties compared with conventional products. Bacterial lipase products show promising potential and offer future therapeutic alternatives. Moreover, human pancreatic lipase gene transfer and application of bioengineered human gastric lipase appear on the horizon.

Animals↗

Passive stiffness of the lumbar torso in flexion, extension, lateral bending, and axial rotation. Effect of belt wearing and breath holding.

This work investigated the passive bending properties of the intact human torso about its three principal axes of flexion: extension, lateral bending, and axial rotation. Additionally, the effects of wearing an abdominal belt and holding the breath (full inhalation) on trunk stiffness was investigated. The torsos of 22 males and 15 females were subjected to bending moments while "floating" in a frictionless jig with isolated torso bending measured with a magnetic device. Belts and breath holding appear to stiffen the torso about the lateral bending and axial rotation axes but not in flexion or extension. Torsos are stiffer in lateral bending and capable of storing greater elastic energy. Regression equations were formulated to define stiffness and energy stored for input to biomechanical models that examine low back function and for bioengineers designing hardware for stabilization and bracing or investigation of traumatic events such as automobile collision.

Abdomen↗

Reversal of diabetes in mice by xenotransplantation of a bioartificial pancreas in a prevascularized subcutaneous site.

BACKGROUND: The subcutaneous site has been regarded as a potential site for a bioartificial pancreas. Transplantation of islets, encapsulated by the development of diverse biocompatible materials and structural designs, can reverse hyperglycemia in diabetic recipients. METHODS: Approximately 750 Sprague-Dawley rat islets macroencapsulated in an agarose/poly (styrene sulfonic acid) mixed gel were implanted into a prevascularized subcutaneous site. The site was constructed by subcutaneous injection of basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres in streptozotocin-induced C57BL/6 diabetic mice. Diabetic mice treated with bFGF-free gelatin microspheres and diabetic mice without any treatment undergoing the same subcutaneous transplantation were used as controls. After transplantation, non-fasting blood glucose, body weight, intraperitoneal glucose tolerance test, and histologic evaluations were processed. RESULTS: All the recipients undergoing the subcutaneous xenograft returned to normoglycemia within 1 week after transplantation. Eight of 10 recipients in the bFGF+ group maintained normoglycemia for a period of 38-101 days and gradually gained increase of body weight. Two of 10 recipients became hyperglycemic again when the grafts were respectively retrieved at days 31 and 63. Intraperitoneal glucose tolerance tests at month 1 and 2 revealed significant ameliorated glucose tolerance but a tendency to reduced glucose tolerance when compared respectively with those of the streptozotocin-induced diabetic mice and normal mice. Histologic examination revealed that islets within the retrieved grafts at days 31 and 63 were viable and intact; no fibrotic overgrowth was present around the surface of grafts. CONCLUSIONS: A successfully prevascularized subcutaneous site could be constructed by a tissue bioengineering approach. Xenotransplantation of the agarose/poly (styrene sulfonic acid) mixed gel-based bioartificial pancreas in the prevascularized subcutaneous site could reverse diabetes in mice.

Animals↗

Biomaterials in functional reconstruction.

Recent initiatives in the development of biomaterials for functional reconstruction involve the alloplasts, the biological and the bioengineered biomaterials. Anti-infective alloplastic biomaterials (Foley catheters coated with rifampicin/minocycline bonded to silicone or ciprofloxacin liposome-containing hydrogel) allow a reduction in the rate of bacterial contamination, but the risk of future bacterial resistance is a matter for concern. New generations of biologic collagen-based tissue-matrix grafts are derived from bladder (bladder acellular matrix graft and bladder submucosa collagen matrix), ureter or small intestine (subintestinal submucosa). There are high hopes that these materials may have applications in augmentation cystoplasty. Using tissue engineering (autologous cells expanded in vitro and grafted onto biodegradable matrix), biocompatible malleable penile prostheses have been obtained experimentally. Most of the results obtained with these new biomaterials are exclusively experimental, but they offer great hope for future functional reconstruction of the urinary tract.

Bacterial Infections↗

Endoscopic and surgical repair of the ureter.

Endoscopy has justified its leading position in ureteral surgery. Recent advances in this field have pushed forward the frontiers and enabled the treatment of difficult ureteral strictures and congenital abnormalities such as megaureter and ureteroceles. The use of the ileum is, however, still the reference for ureteral replacement. An ileal ureter may be performed laparoscopically, but it remains an invasive procedure. In the near future the development of ureteral prostheses could simplify the management of ureteral replacement. For that purpose, and in selected cases, alloplastic ureteral prostheses may already have clinical applications. Bioengineered ureteral prostheses are still at an experimental stage.

Humans↗

Reducing time to treatment in acute myocardial infarction.

The earliest possible initiation of reperfusion therapy is necessary to prevent extended necrosis, preserve ventricular function, and reduce morbidity and mortality from acute myocardial infarction. Therefore, improving the time to thrombolysis is a critical goal of patient management. Four complementary strategies have been employed in an attempt to shorten the time to thrombolytic therapy: (1) public education to shorten the delay in summoning help, (2) prehospital thrombolysis by trained emergency-response personnel, (3) implementation of emergency department thrombolysis protocols, (4) and the use of rapid diagnostic techniques to confirm acute myocardial infarction. Currently available fibrinolytic agents do not lend themselves to emergency use. Therefore, new thrombolytic agents have been bioengineered with characteristics that make them better suited for use in this setting. Two of these agents, TNK-t-PA and nPA, have extended half-life profiles that permit single-bolus dosing--an important consideration when fibrinolytic therapy is initiated outside the coronary care unit. The most effective system will integrate these complementary strategies to deliver continuous patient care from the time of the call for help, through emergency response, transportation, hospital admission, assessment, and initiation of thrombolytic therapy.

Clinical Protocols↗

Burns and amputations: a 24-year experience.

Although the management of the severely burnt extremity poses a significant therapeutic dilemma, burn injuries resulting in amputation are uncommon, In such cases, however, amputation can reduce the rate of mortality. In a total of 1858 patients from January 1980 to January 2004, there were 34 amputations in 27 patients. There were 23 men (age range, 14-64 years) and 4 women (age range, 34-85 years). The majority of amputations from burns caused by flame injury predominantly after motor vehicle accidents, with only eight cases resulting from high-voltage electrical injury. Nine patients required immediate amputations, with the rest being delayed. There were three deaths, with a survival rate of 89%. The majority of single lower-limb amputees and only one of seven bilateral amputees were independently mobile. The presence of pre-existing psychiatric disease significantly impaired rehabilitation. Free tissue transfer and the usage of bioengineered materials may help reduce the incidence of amputations.

Adolescent↗