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A bioengineering analysis of human muscle and joint forces in the lower limbs during running.

A two-dimensional, dynamic bioengineering model of the lower limbs was developed in order to estimate muscle and joint forces present during running at 4.5 m s-1. Data were collected from four subjects using a force platform and cine film. Individual X-rays and anthropometric data from the lower limbs were utilized to produce accurate bone models of the subjects' legs. Electromyographic verification of the model was undertaken while a runner was undergoing treadmill running at 4.5 m s-1. Results indicate that peak muscle forces of 22 times subject body weight (22 BW) could be present in the quadriceps muscle group and 7 BW in the gastrocnemius. The anterior shin muscles were found to be active for the first 9% of stance phase only, and compressive loads of 33 BW were found in the knee joint. The relationship between these high forces in the lower limbs and running related injuries is discussed.

Adult↗

Therapeutic neovascularization: contributions from bioengineering.

A number of pathological entities and surgical interventions could benefit from therapeutic stimulation of new blood vessel formation. Although strategies designed for promoting neovascularization have shown promise in preclinical models, translation to human application has met with limited success when angiogenesis is used as the single therapeutic mechanism. While clinical protocols continue to be optimized, a number of exciting new approaches are being developed. Bioengineering has played an important role in the progress of many of these innovative new strategies. In this review, we present a general outline of therapeutic neovascularization, with an emphasis on investigations using engineering principles to address this vexing clinical problem. In addition, we identify some limitations and suggest areas for future research.

Angiogenesis Inducing Agents↗

Bioengineering education, 1986--Part III.

This paper presents an overview of the Bioengineering programs available today in the northern midwest states of Illinois, Iowa, South Dakota, Minnesota, and Wisconsin. Two-year and four-year undergraduate programs and graduate programs are described, including contact information and course requirements. As Part III of the Journal's continuing series on college-level education for the fields of Biomedical and Clinical Engineering, the purpose of the paper is not to evaluate each program, but to illustrate the breadth of programs offered.

Biomedical Engineering↗

Bioengineering education, 1986--Part VI.

This paper constitutes the sixth part of the Journal's series on college-level Bioengineering programs. Contact information and descriptions of programs at 16 colleges or universities in the states of Kentucky, Maryland, Pennsylvania, Virginia, and West Virginia, and the District of Columbia, are presented herein. It is not the intent of this paper to evaluate each program, but to illustrate the breadth of biomedical and related engineering educational opportunities in this area of the United States.

Biomedical Engineering↗

Bioengineering education, 1986--Part VII.

This paper concludes the Journal's series on Bioengineering Education in the United States. In this issue, college-level programs in the states of Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, South Carolina, and Tennessee are described. These programs range from two-year bachelor degree, master's degree, doctoral degree, and M.D./Ph.D. combined programs. The intent of this paper is not to evaluate the various programs, but to illustrate the breadth of biomedical and related engineering educational opportunities in this region.

Biomedical Engineering↗

Regeneration of intraoral defects after tumor resection with a bioengineered human dermal replacement (Dermagraft).

The experiences of seven patients with squamous cell carcinomas of the oral cavity who underwent reconstruction with a bioengineered human dermal replacement (Dermagraft) are examined. The human dermal replacement consists of fibroblasts seeded onto a three-dimensional polymer scaffold to create a living dermal structure. In this setting, the fibroblasts secrete a mixture of growth factors and matrix proteins in physiological concentration that is essential for wound healing and epithelization. The fibroblast tissue remains metabolically active after cryopreservation and can be used as an off-the-shelf tissue to cover medium-sized defects and avoid donor-site morbidity. In the first series of patients treated with this tissue, defect closure was achieved without functional problems, allowing optimal postoperative monitoring for tumor recurrence.

Aged↗

Bioengineered implantation of megalin-expressing cells: a potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure.

Patients who have renal failure and are on dialysis therapy experience serious complications caused by low-molecular-weight uremic toxin proteins normally filtered by glomeruli and metabolized by proximal tubule cells (PTC). Dialysis-related amyloidosis is one such complication induced by systemic deposition of amyloid proteins derived from 12-kD beta(2)-microglobulin (beta(2)-m). Despite the use of high-flux membrane hemodialysis devices and direct absorbent columns, the removal of beta(2)-m is suboptimal, because the effects are transient and insufficient. Megalin is expressed in the apical membranes of PTC and recognized as a multiligand endocytic receptor that binds numerous low-molecular-weight proteins, including beta(2)-m. This study tested the feasibility of an intracorporeal therapeutic model of continuous beta(2)-m removal using megalin-expressing cell implantation. By cell association and degradation assays, rat yolk sac-derived L2 cells were identified to internalize and degrade beta(2)-m via megalin. The cells were effectively implanted within the subcutaneous tissues of nude mice using a type I collagen scaffold and a method inducing local angiogenesis. After nephrectomy and intraperitoneal injection with (125)I-beta(2)-m, it was found that the implanted cells took up the labeled ligand, efficiently removing it from the blood. Bioengineered implantation of megalin-expressing cells may represent a new supportive therapy for dialysis patients to compensate for the loss of renal protein metabolism and remove uremic toxin proteins.

Animals↗

A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part II. Bioengineering implants to optimize bone replacement in reconstruction of cranial defects.

The present study investigated hydroxyapatite biomaterials implanted in critical-size defects in the calvaria of adult sheep to determine the optimal bioengineering of hydroxyapatite composites to facilitate bone ingrowth into these materials. Five calvarial defects measuring 16.8 mm in diameter were made in each of 10 adult sheep. Three defects were filled with cement paste composites of hydroxyapatite and beta-tricalcium phosphate as follows: (1) 100 percent hydroxyapatite-cement paste, (2) 60 percent hydroxyapatite-cement paste, and (3) 20 percent hydroxyapatite-cement paste. One defect was filled with a ceramic composite containing 60 percent hydroxyapatite-ceramic, and the fifth defect remained unfilled. One year after implantation, the volume of all biomaterials was determined by computed tomography, and porosity and bone replacement were determined using backscatter electron microscopy. Computed tomography-based volumetric assessment 1 year after implantation demonstrated that none of the unfilled cranial defects closed over the 1-year period, confirming that these were critical-size defects. There was a significant increase in volume in both the cement paste and ceramic implants containing 60 percent hydroxyapatite (p < 0.01). There was no significant change in volume of the remaining cement paste biomaterials. Analysis of specimens by backscatter electron microscopy demonstrated mean bone replacement of 4.8 +/- 1.4 percent (mean +/- SEM) in 100 percent hydroxyapatite-cement paste, 11.2 +/- 2.3 percent in 60 percent hydroxyapatite-cement paste, and 28.5 +/- 4.5 percent in 20 percent hydroxyapatite-cement paste. There was an inverse correlation between the concentration of hydroxyapatite and the amount of bone replacement in the cement paste for each composite tested (p < 0.01). Bone replacement in 60 percent hydroxyapatite-ceramic composite (13.6 +/- 2.0 percent) was not significantly different from that in 60 percent hydroxyapatite-cement paste. Of note is that the ceramic composite contained macropores (200 to 300 microm) that did not change in size over the 1-year period. All cement paste composites initially contained micropores (3 to 5 nm), which remained unchanged in 100 percent hydroxyapatite-cement paste. Cement paste implants containing increased tricalcium phosphate demonstrated a corresponding increase in macropores following resorption of the tricalcium phosphate component. Bone replacement occurred within the macropores of these implants. In conclusion, there was no significant bone ingrowth into pure hydroxyapatite-cement paste (Bone Source, Stryker-Leibinger Inc., Dallas, Texas) in the present study. The introduction of macropores in a biomaterial can optimize bone ingrowth for reconstruction of critical-size defects in calvaria. This was demonstrated in both the ceramic composite of hydroxyapatite tested and the cement paste composites of hydroxyapatite by increasing the composition of a rapidly resorbing component such as beta-tricalcium phosphate.

Animals↗

Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface.

BACKGROUND: Limbal stem-cell deficiency by ocular trauma or diseases causes corneal opacification and visual loss. Recent attempts have been made to fabricate corneal epithelial graft constructs, but the technology is still evolving. We have developed a novel cell-sheet manipulation technology using temperature-responsive culture surfaces to generate functional, cultivated corneal epithelial cell sheet grafts. METHODS: Human or rabbit limbal stem cells were cocultured with mitomycin C-treated 3T3 feeder layers on temperature-responsive culture dishes at 37 degrees C. Cell sheets were harvested from the dishes after 2 weeks by reducing temperature to 20 degrees C. Histologic analyses, immunoblotting, and colony-forming assay were performed to characterize the cell sheets. Autologous transplantation was undertaken to reconstruct the corneal surfaces of rabbits with experimentally induced limbal stem cell deficiencies. RESULTS: Multilayered corneal epithelial sheets were harvested intact simply by reducing the temperature, without the use of proteases. Cell-cell junctions and extracellular matrix on the basal side of the sheet, critical to sheet integrity and function, remained intact. A viable population of corneal progenitor cells, close in number to that originally seeded, was found in the sheets. Harvested sheets were easily manipulated, transplantable without any carriers, and readily adhesive to corneal stroma so that suturing was not required. Corneal surface reconstruction in rabbits was highly successful. CONCLUSIONS: Cell sheet engineering technology allows us to create intact, transplantable corneal epithelial cell sheets that retain stem cells from limbal stem cells expanded ex vivo. Our research indicates highly promising clinical capabilities for our bioengineered corneal epithelial sheet.

3T3 Cells↗

Restoration of cardio-circulatory regulation by rate-adaptive pacemaker systems: the bioengineering view of a clinical problem.

In the past, the development of rate-adaptive (sensor-controlled) pacemaker systems seems to have been determined primarily by the availability, compatibility and other properties of the technical sensor. This paper, however, focuses on the system-physiological aspect in an attempt to answer the question to what extent physiological cardiovascular control is restored by the pacemaker system. This is a question which should be asked before attempting to design a sensor-controlled system and especially before designing multisensor systems with infinite combinations. Four categories are defined: direct bridging ("shunting"), open loop systems, closed systems using cardiorespiratory or metabolic coupling and those using cardiac signals. Further subdivisions are shown. From the bioengineering as well as from the physiological viewpoint a system should preferably not combine sensors from one and the same of these categories. At present direct bridging is available only for the atrioventricular (AV)-block, so that for sick-sinus-syndrome (SSS) patients feedback control via cardiac signals ("inotropic" pacemaker) comes nearest the goal without, however, ideally bridging the gap. Open-loop systems should no longer be developed as single-sensor systems. A well developed activity sensor, however, which quickly pinpoints the most prominent stressor of cardiovascular control is best suited to complement another sensory system achieving closed-loop control. New and promising concepts orientated toward direct bridging are the analysis of monophasic action potentials and the "dromotropic" concept, both of which seek direct correlation with the "chronotropic" information not available in SSS patients.

Adaptation, Physiological↗

Perspectives on MEMS in bioengineering: a novel capacitive position microsensor.

We describe a novel capacitive position sensor using micromachining to achieve high sensitivity and large range of motion. These sensors require a new theoretical framework to describe and optimize their performance. Employing a complete description of the electrical fields, the sensor should deviate from the standard geometries used for capacitive sensors. By this optimization, the sensor gains a twofold increase in sensitivity. Results on a PC board 10x model imply that the micromachined sensor should achieve a sensitivity of less than 10 nm over 500-micron range of travel. Some bioengineering applications are addressed, including positioning of micromirrors for laser surgery and dose control for implantable drug delivery systems.

Drug Delivery Systems↗

Electrical impedance compared with other non-invasive bioengineering techniques and visual scoring for detection of irritation in human skin.

A new, non-invasive device, which enables local measurements of electrical impedance to a controlled depth, has been used to evaluate the degree of irritation in human skin. The results have been compared with those obtained using other non-invasive techniques, i.e. with transepidermal water loss (TEWL), electrical capacitance moist measurement (ECM), laser-Doppler flowmetry (LDF), and visual scoring. Sodium lauryl sulphate solutions (0.1-5.0%), and a blank, were applied in Finn Chambers for 24 h on the volar forearm of 10 healthy volunteers. Values were recorded before application of the test chambers, and at 1 h, 24 h, 1 week and 2 weeks after removal. Thus, both the degree of initial damage and the healing process were monitored. There was close agreement among values obtained using electrical impedance, TEWL and visual readings. Results obtained using ECM and LDF were not consistent with the other three methods. In evaluating irritation of the skin, the practical situation may influence the choice of bioengineering tools. In most circumstances, a combination of methods would be preferable.

Adult↗

Biocompatibility: bioengineering aspects.

Bioengineers have contributed to biocompatibility research. Many materials have been designed, synthesized, and characterized by use of various analytical instruments. The blood compatibility of materials has been studied by focusing on the blood-material interfacial reactions. Although much information has been accumulated regarding such local reactions, understanding of biocompatibility is still limited. A more global approach to study is needed. A new approach to understanding biocompatibility is proposed and discussed. Three points are stressed: interaction within body's defense system and its effect on blood-material reactions; induction of a systemic reaction by a local reaction, which then affects the blood-material interaction; the time sequence of such interactions between local and systemic reactions. To establish a logical approach to study biocompatibility is most important at this moment for the future progress in biocompatibility research.

Biocompatible Materials↗

Molecular bioengineering of biomaterials in the 1990s and beyond: a growing liaison of polymers with molecular biology.

An important trend in biomaterials research and development is the synthesis of polymers that combine capabilities of biologic recognition (biomimetic) with special physicochemical properties of the synthetic polymer system. Another important trend in such "molecular bioengineering" is to develop, perhaps via computer-aided molecular design, new artificial biomimetic systems by exact placement of functional groups on rigid polymer backbones, cross-linked structures, or macromolecular assemblies. In this way, biocatalytic functioning or biorecognition similar to enzymes and antibodies can be achieved without the inherent instability often encountered with the native biomolecules or assemblies. Perhaps the most exciting trend in biomaterials research and development is the availability of new biomolecules, e.g., via protein engineering and of hardy cells with specific biofunctions and bioresponses that can be tailored to specific medical or biotechnological needs. The wide variety of ways that such biomolecules and cells can be combined with polymeric biomaterials provides tremendously exciting opportunities for the biomaterials scientists and engineers. In addition to these synthetic approaches, new and exciting analytical tools, such as the scanning tunneling microscope and the atomic force microscope, are permitting study on a molecular scale of individual and small clusters of proteins and other biomolecular assemblies on surfaces. Cell attachments and spreading may also be visualized at various depths within the cell using the confocal laser microscope. Such analytical techniques can lead to important new knowledge about biologic interactions with biomaterials and, therefore, to development of even more biocompatible implants and devices. This paper overviews the present state of polymeric biomaterials and highlights the important and exciting opportunities generated by the liaison of these materials with molecular biology.

Biocompatible Materials↗

Cardiac valve prostheses: pathological and bioengineering considerations.

Cardiac valve replacement with mechanical prosthetic or bioprosthetic devices enhances patient survival and quality of life. Nevertheless, prosthesis-associated complications are frequent and contribute significantly to outcome. Thromboembolic complications are the most important problems in patients with mechanical valves, necessitating chronic anticoagulation in all patients receiving them. In contrast, patients with bioprosthetic valves, composed of chemically treated animal tissues, generally do not require anticoagulants. However, bioprostheses fail frequently by degeneration, especially that involving cuspal calcification. This paper reviews the pathological and bioengineering considerations in the selection of cardiac prosthetic valves and the management of patients who have received these devices. The significance, morphology, and pathogenesis of the observed major complications and other alterations during function are described in detail. Contemporary investigative trends are summarized, including studies of inhibition of mineralization and other degenerative changes in bioprostheses, improved design rigid mechanical valves with pyrolytic carbon occluders and the development of central-flow, flexible polymeric leaflet valves.

Biomedical Engineering↗

Bioengineering and the patch test.

Several non-invasive techniques based on different physical principles have been developed to investigate skin function and have been used for patch test assessment. In the present paper, the advantages and the defects of these methods are described in the light of the more recent data available in literature. Meanwhile, the eye and the fingers still remain the simplest method to assess skin irritancy. Bioengineering techniques could provide efficient recording systems for monitoring skin color, skin blood flow and barrier function damage, useful to the investigator rather than to the clinician.

Colorimetry↗

Intra-and inter-individual variations in transepidermal water loss on the face: facial locations for bioengineering studies.

The volar forearm is the favored location for bioengineering studies. However, transepidermal water loss (TEWL), which is an important indicator of the function of the epidermal barrier, shows regional variations, and for the evaluation of cosmetic formulations, facial skin would be more suitable. In this study, we have compared 10 facial locations with 1 test site on the volar forearm for absolute TEWL values, reproducibility, and correlation. Measurements were performed over 3 consecutive days. The TEWL values of the facial test sites were higher compared to forearm values and did not correlate with the forearm. On the face, there was a good correlation between the values of the right compared to the left side of the face. The sites superior to the nervus supraorbitalis, the medial borders of the musculus masseter, and the center of the chin proved to be locations with relatively stable TEWL values. There was a greater variability at the center of the forehead and at the center of the cheeks. It is recommended that TEWL measurements on facial locations with stable TEWL values are used for the evaluation of cosmetic formulations.

Adult↗

Bioengineered tissues: the science, the technology, and the industry.

OBJECTIVE: The bioengineering of tissues and organs, sometimes called tissue engineering and at other times regenerative medicine, is emerging as a science, as a technology, and as an industry. The goal is the repair, replacement, and/or the regeneration of tissues and organs. The objective of this paper is to identify and discuss the major issues that have become apparent. RESULTS: One of the critical issues is that of cell source, i.e. what will be the source of the cells to be employed? Another critical issue is the development of approaches for the fabrication of substitute tissues/organs and/or vehicles for the delivery of biological active molecules for use in the repair/regeneration of tissues. A third critical issue, one very much related to cell source, is that of immune acceptance. In addition, there are technological hurdles; there are additional issues such as the scale-up of manufacturing processes and the preservation of living-cell products for off-the-shelf availability. Although the initial products have been superficially applied skin substitutes, as this fledgling industry continues to evolve, it is beginning to focus on a wider range of more invasive and complicated products. From a public health perspective, the real opportunity may be in addressing chronic diseases, as well as the transplantation crisis (i.e. the tremendous disparity between patient need for vital organs and donor availability) and, equally important is the challenge of neural repair. CONCLUSION: These are the grand challenges, and the scientific community, business/private sector, and federal government must mobilize itself together in this emerging area to translate the benchtop science to the patient bedside.

Biocompatible Materials↗