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PubMed1999

Chondrocyte aggregation and reorganization into three-dimensional scaffolds.

Articular cartilage has a very limited self-repairing capacity; thus, chondral lesions normally result in chronic degeneration and, eventually, osteoarthritis development. Currently, tissue engineering offers a new tool for the clinical treatment of osteochondral defects. The present investigation aimed to develop an in vitro engineered cartilage using a new class of semisynthetic scaffolds. Two nonwoven meshes of hyaluronan esters (Hyaff(R) derivatives) were seeded with sternal chick embryo chondrocytes cultured for up to 21 days, after which time they were assessed for both the cellular growth profile and histological features. Avian chondrocytes easily adhered and proliferated onto hyaluronan-based scaffolds, demonstrating a significant preference for the fully esterified benzylic form. Histochemical staining revealed the presence of a neosynthesized glycosaminoglycan-rich extracellular matrix, and immunohistochemistry confirmed the deposition of collagen type II. Moreover, ultrastructural observations supported evidence that chondrocytes grown onto a hyaluronan-derived three-dimensional scaffold maintained their unique phenotype and organization in a cartilage-like extracellular matrix. These findings support the further pursuit of a transplantable engineered cartilage using human chondrocytes for the regeneration of chondral lesions.

Animals↗
PubMedDate not supplied

Cellular and metabolic engineering. An overview.

Metabolic engineering is defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques. Cellular engineering, a more inclusive term, is defined as the purposeful modification of cell properties using the same techniques. Examples of cellular and metabolic engineering are divided into five categories: 1. Improved production of chemicals already produced by the host organism; 2. Extended substrate range for growth and product formation; 3. Addition of new catabolic activities for degradation of toxic chemicals; 4. Production of chemicals new to the host organism; and 5. Modification of cell properties. Over 100 examples of cellular and metabolic engineering are summarized. Several molecular biological, analytical chemistry, and mathematical and computational tools of relevance to cellular and metabolic engineering are reviewed. The importance of host selection and gene selection is emphasized. Finally, some future directions and emerging areas are presented.

Bacteria↗
PubMed2005

Fibrin as a cell carrier in cardiovascular tissue engineering applications.

In cardiovascular tissue engineering approaches, efficient seeding methods are essential. To achieve this and to save time, cells can be encapsulated in gels. Combining the advantages of a gel as a cell carrier with the advantages of a fiber-based scaffold, providing structural integrity to the developing tissue, might offer several advantages. In this study, seeding by using fibrin as a cell carrier is compared to the conventional static seeding method with regard to tissue development. Seeding with fibrin resulted in less loss of soluble collagen into the medium and a more mature extracellular matrix in a shorter period of time. The use of fibrin degradation inhibitors was shown to inhibit extracellular matrix formation, although it did not hamper cell proliferation. The use of fibrin as a cell carrier to seed cells into a fiber-based scaffold may represent a promising, timesaving approach in cardiovascular tissue engineering applications.

Biocompatible Materials↗
PubMed2003

Nanotechnology: convergence with modern biology and medicine.

The worldwide emergence of nanoscale science and engineering was marked by the announcement of the National Nanotechnology Initiative (NNI) in January 2000. Recent research on biosystems at the nanoscale has created one of the most dynamic science and technology domains at the confluence of physical sciences, molecular engineering, biology, biotechnology and medicine. This domain includes better understanding of living and thinking systems, revolutionary biotechnology processes, the synthesis of new drugs and their targeted delivery, regenerative medicine, neuromorphic engineering and developing a sustainable environment. Nanobiosystems research is a priority in many countries and its relevance within nanotechnology is expected to increase in the future.

Biomedical Engineering↗
PubMed2004

Component engineering for an implantable system.

Component engineering is important for the development of implantable-type rotary blood pumps (RP). The authors are conducting elementary development of an implantable artificial heart. A sensor system detects information in the living body. An automatic control system performs the drive control. Energy is provided by a transcutaneous energy transmission system (TETS). Various artificial hearts are being created. Miniaturization resulting from an increase in operating frequency is planned. A vibrating flow pump (VFP) has a reduced size of pumping chamber because of the high-speed reciprocating movement. Undulation pump ventricular assist devices (UPVAD) are small, lightweight rotary pumps. VFPs are useful in the medical treatment of multiple organ failure (MOF). UPVADs are planned to be permanent-use RPs. The purposes of these two artificial hearts differ, although they have a common component. The authors are developing TETS by using amorphous fibers, making efficient power transmission possible. Control information input from a micro or nano sensor is realized. A control algorithm has been developed and baroreflex control has been successful. Artificial heart development, fully exploiting component engineering, continues.

Animals↗
PubMedDate not supplied

Skeletal muscle tissue engineering.

The reconstruction of skeletal muscle tissue either lost by traumatic injury or tumor ablation or functional damage due to myopathies is hampered by the lack of availability of functional substitution of this native tissue. Until now, only few alternatives exist to provide functional restoration of damaged muscle tissues. Loss of muscle mass and their function can surgically managed in part using a variety of muscle transplantation or transposition techniques. These techniques represent a limited degree of success in attempts to restore the normal functioning, however they are not perfect solutions. A new alternative approach to addressing difficult tissue reconstruction is to engineer new tissues. Although those tissue engineering techniques attempting regeneration of human tissues and organs have recently entered into clinical practice, the engineering of skeletal muscle tissue ist still a scientific challenge. This article reviews some of the recent findings resulting from tissue engineering science related to the attempt of creation and regeneration of functional skeletal muscle tissue.

Animals↗
PubMed1984

Paraplegic ambulation: a systems point of view.

Neurophysiological systems preserved distal to a complete spinal lesion, and relevant to walking, are reviewed in the manner of an engineering control systems analysis. On that basis, an outline is given of theoretical concepts, current developments and future possibilities for neuromuscular electrical stimulation to provide paraplegic ambulation.

Biomedical Engineering↗
PubMed1992

Conceptual design and cost estimate for a modified hemoglobin production plant.

Polymerized, pyridoxalated stroma-free hemoglobin (Poly PSFH), made from outdated human blood, has excellent attributes for use as a blood substitute. A hypothetical larger scale process for the production of Poly PSFH is detailed, and facility design and cost estimates are presented. This paper gives the opportunity to discuss the engineering activities of process scope definition, utilities selection, and aseptic processing techniques, etc. Compliance with cGMP and other FDA regulation will also be discussed.

Biomedical Engineering↗
PubMed1988

A survey of persons certified in clinical engineering and their thoughts on the profession.

A questionnaire was sent to 346 persons certified in clinical engineering (CCEs) worldwide. An impressive 72% return revealed the following: 57% of the CCEs are employed by hospitals, 15% by manufacturers, and 12% by academic institutions; 13% are consultants in private practice. Half of them have been with their current employer for over 9 years; their average age is 44.3 years. Thirty-six percent left hospitals for their present jobs. The median salary of the hospital-based CCEs was in the range of +40,000-45,000/year, whereas that of their non-hospital counterparts was in the range of +50,000-55,000/year. Of the nonhospital CCEs, 25% earned over +70,000/year, while only 3% of the hospital CCEs earned salaries in this category. The mean age of the hospitals CCEs is, however, 4.8 years less than that of the non-hospital CCEs. Although some comments on the profession were particularly critical, the respondents believed strongly that clinical engineering remains a viable career choice and has contributed significantly to health care. Underutilization of clinical engineering talents, particularly in the hospital setting, continues to be the predominate concern and greatest source of job-related frustration.

Adult↗
PubMed1999

Engineered smooth muscle tissues: regulating cell phenotype with the scaffold.

Culturing cells on three-dimensional, biodegradable scaffolds may create tissues suitable either for reconstructive surgery applications or as novel in vitro model systems. In this study, we have tested the hypothesis that the phenotype of smooth muscle cells (SMCs) in three-dimensional, engineered tissues is regulated by the chemistry of the scaffold material. Specifically, we have directly compared cell growth and patterns of extracellular matrix (ECM) (e.g. , elastin and collagen) gene expression on two types of synthetic polymer scaffolds and type I collagen scaffolds. The growth rates of SMCs on the synthetic polymer scaffolds were significantly higher than on type I collagen sponges. The rate of elastin production by SMCs on polyglycolic acid (PGA) scaffolds was 3.5 +/- 1.1-fold higher than that on type I collagen sponges on Day 11 of culture. In contrast, the collagen production rate on type I collagen sponges was 3.3 +/- 1.1-fold higher than that on PGA scaffolds. This scaffold-dependent switching between elastin and collagen gene expression was confirmed by Northern blot analysis. The finding that the scaffold chemistry regulates the phenotype of SMCs independent of the scaffold physical form was confirmed by culturing SMCs on two-dimensional films of the scaffold materials. It is likely that cells adhere to these scaffolds via different ligands, as the major protein adsorbed from the serum onto synthetic polymers was vitronectin, whereas fibronectin and vitronectin were present at high density on type I collagen sponges. In summary, this study demonstrates that three-dimensional smooth muscle-like tissues can be created by culturing SMCs on three-dimensional scaffolds, and that the phenotype of the SMCs is strongly regulated by the scaffold chemistry. These engineered tissues provide novel, three-dimensional models to study cellular interaction with ECM in vitro.

Animals↗
PubMed2002

Personal meaning and ethics in engineering.

The study of engineering ethics tends to emphasize professional codes of ethics and, to lesser degrees, business ethics and technology studies. These are all important vantage points, but they neglect personal moral commitments, as well as personal aesthetic, religious, and other values that are not mandatory for all members of engineering. This paper illustrates how personal moral commitments motivate, guide, and give meaning to the work of engineers, contributing to both self-fulfillment and public goods. It also explores some general frameworks for thinking about these commitments and calls for further exploration of them.

Attitude↗
PubMed1998

Prevention of focal intimal hyperplasia in rat vein grafts by using a tissue engineering approach.

The present study focused on the role of blood flow in the formation of focal intimal hyperplasia in vein grafts, as well as the development of an engineering approach that can be used to eliminate disturbed blood flow and prevent blood flow-related focal intimal hyperplasia. A rat vein graft model was constructed by interposing a jugular vein into the abdominal aorta with end-to-end anastomoses. Locally disturbed flow was identified by analyzing particle streak-lines in methyl salicylate-cleared and perfused vein grafts in vitro with a physiological Reynolds number. At day 10, 20, and 30 after surgery, focal intimal hyperplasia of the vein grafts was examined using a histological approach and the density of alpha-actin positive cells was determined using immunohistological and fluorescent approaches. Results showed that apparent eddy blood flow formed at the proximal, but not at the distal, end of the vein grafts due to graft-host diameter mismatch and local geometric distortions, and was associated with apparent focal intimal hyperplasia. The thickness of the alpha-actin positive layers of the proximal vein grafts was significantly higher than that of the distal grafts (192 +/- 27 vs. 94 +/- 18 microm, 278 +/- 55 vs. 124 +/- 20 microm, and 288 +/- 24 vs. 131 +/- 23 microm for day 10, 20. and 30, respectively). The density of the alpha-actin positive cells, however, was similar between the proximal and the distal regions (3569 +/- 361 vs. 3285 +/- 343 cells/mm2, 5540 +/- 650 vs. 5376 + 887 cells/mm2, and 5465 +/- 791 vs. 5278 +/- 524 cells/mm2 for day 10, 20, and 30, respectively). When eddy blood flow was eliminated by matching the graft-host diameters using a tissue engineering approach, the average thickness of the alpha-actin positive layers of the proximal (71 +/- 15, 86 +/- 16, and 85 +/- 14 microm for day 10, 20, and 30, respectively) and the distal vein grafts (68 +/- 13, 80 +/- 14, and 79 +/- 13 microm for day 10, 20, and 30, respectively) was reduced significantly. The density of the alpha-actin positive cells was also reduced significantly in the proximal (2946 +/- 359, 3261 +/- 295, 3472 +/- 599 cells/mm2 for day 10, 20, and 30, respectively) and in the distal regions (3151 +/- 511, 3466 +/- 687, 3593 +/- 688 cells/mm2 for day 10, 20, and 30, respectively). The thickness of the alpha-actin positive layers and the density of the alpha-actin positive cells were not significantly different between the proximal and distal regions of the engineered vein grafts at each observation time. These results suggest that eddy flow may develop in vein grafts and may facilitate the formation of focal intimal hyperplasia, and the vascular tissue engineering approach developed in this study may be used to prevent blood flow-related focal intimal hyperplasia in vein grafts.

Actins↗
PubMed2002

Why mechanobiology? A survey article.

The central paradigm of skeletal mechanobiology is that mechanical forces modulate morphological and structural fitness of the skeletal tissues-bone, cartilage, ligament and tendon. Traditionally, skeletal biomechanics has focussed on how these tissues perform the structural and locomotory functions of the vertebrate skeleton. In mechanobiology the central question is how these same load-bearing tissues are produced, maintained and adapted by cells as an active response to biophysical stimuli in their environment. The idea that 'form follows function' is not new, but we now believe that the scientific community has the knowledge and tools to prove, understand and use functional adaptation to benefit medicine and human health. In this Survey Article the philosophy and progress of skeletal mechanobiology are discussed. The revival of this science, with roots dating back to the 19th Century, is now driven by new developments in cellular, molecular and computational technologies. These developments are still in an early stage of application, but if modern mechanobiology fulfills the promises of its ambitions, the results will bring great benefits to tissue engineering and to the treatment and prevention of skeletal conditions such as congenital deformities, osteoporosis, osteoarthritis and bone fractures.

Animals↗
PubMed1996

Femoral shaft reconstruction using tissue-engineered growth of bone.

Tissue engineering is an interdisciplinary field that applies the principles and methods of engineering and the life sciences to the development of biologic substitutes. Bovine periosteum-derived cells were cultivated in vitro, put onto bioresorbable polymer fiber constructs, and allowed to grow until most of the fibers were coated with multiple layers of osteoblasts. Standardized 9-mm nonhealing defects were created in 24 male athymic rats femurs and bridged with titanium miniplates. In 12 animals, the defects were filled with polymer constructs containing periosteum-derived cells (experimental group); in another 12 animals, the defects were either left unfilled (control group I) or filled with polymer templates alone (control group II). After 12-week in vivo implantation, the new bone produced bridged the surgically created defects completely in seven of 10 cases. The animals of the control groups did not show significant bone formation in the gap. Histologic evaluation revealed bone formation in all experimental specimens with rests of cartilage islands showing hypertrophying chondrocytes indicative of enchondral bone formation. Tissue-engineered growth of bone resulted in healing of large segmental bone defects in an orthotopic site in an animal model. The findings of this study support potential applications of the technique of tissue-engineered growth of bone to clinical situations where local bone formation is needed.

Animals↗
PubMed1998

Tissue engineering of heart valves--human endothelial cell seeding of detergent acellularized porcine valves.

OBJECTIVE: Tissue engineering of heart valves represents a new experimental concept to improve current modes of therapy in valvular heart disease. Drawbacks of glutaraldehyde fixed tissue valves or mechanical valves include the short durability or the need for life-long anticoagulation, respectively. Both have in common the inability to grow, which makes valvular heart disease especially problematic in children. The aim of this study was to develop a new methodology for a tissue engineered heart valve combining human cells and a xenogenic acellularized matrix. METHODS: Porcine aortic valves were acellularized by deterging cell extraction using Triton without tanning. Endothelial cells were isolated in parallel from human saphenous veins and expanded in vitro. Specimens of the surface of the acellular matrix were seeded with endothelial cells. Analysis of acellularity was performed by light microscopy and scanning electron microscopy. Cell viability following seeding was assayed by fluorescence staining of viable cells. RESULTS: The acellularization procedure resulted in an almost complete removal of the original cells while the 3D matrix was loosened at interfibrillar zones. However the 3D arrangement of the matrix fibers was grossly maintained. The porcine matrix could be seeded with in vitro expanded human endothelial cells and was maintained in culture for up to 3 days to document the formation of confluent cultures. CONCLUSIONS: Porcine aortic valves can be almost completely acellularized by a non-tanning detergent extraction procedure. The xenogenic matrix was reseeded with human endothelial cells. This approach may eventually lead to the engineering of tissue heart valves repopulated with the patients own autologous cells.

Animals↗
PubMed1978

New sharing arrangements meet hospitals' technical support needs.

Just within thid decade, a variety of multihospital arrangements have been developed that make clinical engineering services available to hospitals on a shared basis. This article summarizes available data to describe the diverse approaches and organizational structures into which these programs are evolving.

Biomedical Engineering↗
PubMed1978

Clinical engineering from the administrator's perspective.

Based on the results of a survey, investigators infer that hospital administrators have a "diverse, and, at times, inaccurate understanding of clinical engineering.". For instance, most hospitals would integrate their perceived clinical engineering function into their general maintenance operation. Among other things, results indicate that administrators have not fully accepted the need to have a professional person to provide these services.

Attitude↗