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This article outlines some of the factors influencing the choice of a suitable reactor for using immobilized biocatalysts. We have concentrated on biochemical engineering parameters of immobilized biocatalysts, which are important with respect to their application in industrial processes.
Biomaterials play a critical role in the engineering of new functional genitourinary tissues for the replacement of lost or malfunctioning tissues. They provide a temporary scaffolding to guide new tissue growth and organization and may provide bioactive signals (e.g., cell-adhesion peptides and growth factors) required for the retention of tissue-specific gene expression. A variety of biomaterials, which can be classified into three types--naturally derived materials (e.g., collagen and alginate), acellular tissue matrices (e.g., bladder submucosa and small-intestinal submucosa), and synthetic polymers [e.g., polyglycolic acid, polylactic acid, and poly(lactic-co-glycolic acid)]--have proved to be useful in the reconstruction of a number of genitourinary tissues in animal models. Some of these materials are currently being used clinically for genitourinary applications. Ultimately, the development or selection of appropriate biomaterials may allow the engineering of multiple types of functional genitourinary tissues.
Metabolic Engineering offers an opportunity to forge a link between metabolic physiologists, working with mammalian systems and metabolic engineers. Many parallels may be drawn between the specific modification of metabolic networks to improve cellular properties and the analysis of metabolic networks in search of causes of disease. At the core of both fields is the measurement of fluxes. This issue of Metabolic Engineering highlights important topics: mammalian metabolic physiology where estimating fluxes is challenging. The challenges come from compartmentation of metabolites, from dilution of tracer by endogenous pools, and from the difficulty of sampling relevant pools. The common theme across these investigations is the use of isotopic tracers. The wide variety of tracers and tracer analysis techniques in use in mammalian metabolic physiology reflects the complexity of the systems under study. In presenting these examples from the field of mammalian metabolic physiology, our goal is to strengthen the linkages between physiologists and engineers as we develop our knowledge and appreciation of the complexity of metabolic networks.
Cartilage cells are normally studied under atmospheric pressure conditions and without loading. However, since cartilage exists in a condition of reduced oxygen and intermittent hydrostatic pressure we hypothesized lower partial oxygen pressures (PO2) and different intermittent hydrostatic pressures (IHP) would increase articular chondrocyte proliferation and matrix production and to stabilize chondrocyte phenotype in vitro. Monolayers of adult bovine articular chondrocytes were cultured under 5% or 21% PO2 in combination with IHP (0.2 MPa amplitude, frequencies 5/5s = 0.1 Hz, 30/2 or 2/30 min on/off loading). We measured proliferation (3H-thymidine incorporation) and collagen secretion (protein-binding assay, collagen type II-ELISA and immunocytochemical staining of pericellular collagen types I, II and IX). Reduced PO2 stimulated proliferation and collagen type II and IX secretion of chondrocytes in comparison to 21% PO2. Additionally, collagen type I expression was delayed by low PO2, indicating a stabilization of the cell phenotype. IHP 5/5s and 30/2 min inhibited proliferation but increased collagen secretion (pericellular collagen type IX was decreased). IHP 30/2 min delayed first expression of collagen type I. In contrast, IHP 2/30 min increased proliferation, but lowered collagen expression. All stimulating or inhibiting effects of PO2 and IHP were additive and vice versa. Reduced PO2 and different settings of IHP increased proliferation, collagen secretion, and phenotype stability of chondrocytes. The oxygen- and IHP-induced effects were additive, suggesting that a combination of these parameters might be a useful tool in cartilage tissue engineering.
Collagen-based biomaterials in the form of sponges (bovine type I collagen, both native and cross-linked by treatment with diphenylphosphorylazide, noted control and DPPA sponges respectively) were tested as three-dimensional scaffolds to support chondrocyte proliferation with maintenance of the phenotype in order to form neocartilage. Control and DPPA sponges were initially seeded with 10(6) or 10(7) foetal bovine epiphyseal chondrocytes and maintained for 4 weeks in culture under static conditions in RPMI/NCTC medium with 10% FCS and without addition of fresh ascorbic acid. Both supports were always present during the study and a partial decrease in size and weight was detected only with control sponges, both seeded and unseeded. Cell proliferation was only noted in the 10(6) cells-seeded sponges (4-fold increase after 4 weeks of culture). Specific cartilage collagens (types II and XI) were deposited in the matrix throughout the culture and traces of type I collagen were noticed only in the culture medium after 2-3 weeks and 4 weeks in the case of 10(6) and 10(7) cells-seeded sponges, respectively. Glycosaminoglycans accumulated in the matrix, up to 1.8 and 9.8% of total dry weight after one month with both seeding conditions, which was much lower than in the natural tissue. In the 10(7) cells-seeded sponges, mineral deposition, observed with unseeded sponges, was significantly decreased (2- to 3-fold). These in vitro results indicate that both collagen matrices can support the development of tissue engineered cartilage.
Intensity-modulated radiotherapy (IMRT) has been considered as a means of providing dose distributions that conform to concave target volumes. For computer-controlled multileaf collimators (MLCs) to be used to modulate x-ray beams, some procedure must be used to determine the sequence of leaf positions used to produce the desired modulation. This article derives and compares four leaf-sequencing algorithms. MLC leaf sequencing can be accomplished by representing the areal intensity modulation of a beam with a series of beam profiles. A velocity-modulation equation for computing the modulation required for a one-dimensional profile, described originally using more extensive algebra, is derived using a graphic approach. The velocity-modulation approach is compared with an equal incremental step-and-shoot approach derived by Bortfeld and Boyer. An areal step-and-shoot technique derived by Xia and Verhey is introduced and compared with the profile-by-profile methods. Finally, an approach is considered using multiple repeated arcs developed by Yu. This wide variety of methods can yield an approach to IMRT that conforms to the engineering constraints imposed by the design of a particular linear accelerator.
The success of cell seeded constructs for the repair of collagenous tissues may be improved by the use of mechanical stimulation in vitro. A mechanical loading apparatus, termed the cell straining system, was developed according to a set of design criteria, to enable cell seeded constructs to be cyclically loaded in tension. A suitable cell seeded collagen gel model system was used to characterise the apparatus. These gels were subjected to a cyclic strain of 10% superimposed on two separate tare loads of 2 and 10 mN, while being maintained in cell culture conditions. The computer controlled apparatus was shown to be capable of monitoring the individual loads on six specimens simultaneously, to an accuracy of 0.02 mN. Results indicated a wide variability between individual specimens. Following cyclic loading, the cell seeded collagen gels exhibited an increase in structural stiffness compared with the unloaded controls. This novel and versatile apparatus will provide a means of enhancing structural and mechanical integrity of tissue engineered repair systems.
Cell seeding of three-dimensional polymer scaffolds is the first step of the cultivation of engineered tissues in bioreactors. Seeding requirements of large scaffolds to make implants for potential clinical use include: (a) high yield, to maximize the utilization of donor cells, (b) high kinetic rate, to minimize the time in suspension for anchorage-dependent and shear-sensitive cells, and (c) high and spatially uniform distribution of attached cells, for rapid and uniform tissue regeneration. Highly porous, fibrous polyglycolic acid scaffolds, 5-10 mm in diameter and 2-5 mm thick, were seeded with bovine articular chondrocytes in well-mixed spinner flasks. Essentially, all cells attached throughout the scaffold volume within 1 day. Mixing promoted the formation of 20-32-micron diameter cell aggregates that enhanced the kinetics of cell attachment without compromising the uniformity of cell distribution. The kinetics and possible mechanisms of cell seeding were related to the formation of cell aggregates by a simple mathematical model that can be used to optimize seeding conditions for cartilage tissue engineering.
Morphogenesis is the developmental cascade of pattern formation and body plan establishment, culminating in the adult form. It has formed the basis for the emerging discipline of tissue engineering, which uses principles of molecular developmental biology and morphogenesis gleaned through studies on inductive signals, responding stem cells, and the extracellular matrix to design and construct spare parts that restore function to the human body. Among the many organs in the body, bone has considerable powers for regeneration and is a prototype model for tissue engineering. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and has permitted the isolation of bone morphogens, such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are also involved in the morphogenesis of organs other than bone. The symbiosis of the mechanisms underlying bone induction and differentiation is critical for tissue engineering and is governed by both biomechanics (physical forces) and context (microenvironment/extracellular matrix), which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue architecture elucidated in bone morphogenesis may provide insights into tissue engineering and be universally applicable for all organs/tissues, including bones and joints.
Biomaterials play a pivotal role in field of tissue engineering. Biomimetic synthetic polymers have been created to elicit specific cellular functions and to direct cell-cell interactions both in implants that are initially cell-free, which may serve as matrices to conduct tissue regeneration, and in implants to support cell transplantation. Biomimetic approaches have been based on polymers endowed with bioadhesive receptor-binding peptides and mono- and oligosaccharides. These materials have been patterned in two- and three-dimensions to generate model multicellular tissue architectures, and this approach may be useful in future efforts to generate complex organizations of multiple cell types. Natural polymers have also played an important role in these efforts, and recombinant polymers that combine the beneficial aspects of natural polymers with many of the desirable features of synthetic polymers have been designed and produced. Biomaterials have been employed to conduct and accelerate otherwise naturally occurring phenomena, such as tissue regeneration in wound healing in the otherwise healthy subject; to induce cellular responses that might not be normally present, such as healing in a diseased subject or the generation of a new vascular bed to receive a subsequent cell transplant; and to block natural phenomena, such as the immune rejection of cell transplants from other species or the transmission of growth factor signals that stimulate scar formation. This review introduces the biomaterials and describes their application in the engineering of new tissues and the manipulation of tissue responses.
When engineers function in a biomechanics clinic team, collecting information for the definition and solution of problems, and developing solutions in a logical pattern, then establishment of criteria by which to judge actions and results at various stages are essential. In our procedures, we make the most general statement we can which will indicate the goal we have for the patient or the type of patient being considered. Based on this, we proceed with a breakdown of the goal into increasingly explicit statements keeping the objective in focus. Eventually, with the criteria we need in order to decide "yes or no" to any aspect of the solution developing, we consider the constraints. These we see as imposed by the life-requirements of the patient, the effects of the physical environment, the limitations imposed by the social environment, and the limits of available technology including the skills of the designers, the manufacturing capabilities and the distribution system with which the designers must cope. When a "checklist" of requirements and limits has been established, the "critical eye" watches over the rehabilitation engineer as he in effect watches over himself!
This paper discusses the contribution of engineering to medicine, and the relationships that exist between the two disciplines. Engineers have followed a rational approach to analyse the physician's needs and have begun to bridge the gap between engineering and medicine. As a result, there has been a proliferation of life-saving products made by the industrial sector of society. The author offers suggestions for engineers and doctors to help them improve communications and better understand each other's problems.
The New England Medical Center can be traced back to 1796 when the Boston Dispensary opened the first HMO. Now, the center complex covers four city blocks, offers 47 medical residency programs, has over $20 million in funded research, and includes a medical school, dental school, and the Human Nutrition Research Center. The Medical Engineering Department began in 1971 as a joint venture between the center and Tufts University. Operated on a "fee-for-service" basis, the department consists of nine people in medical engineering and an additional four in radiology engineering. The department performs quality assurance and preventive maintenance work, along with as-needed repairs, throughout the center on an equipment roster that includes over 1,200 computer terminals and printers, 58 intensive care beds, and 200+ I.V. pumps. Specialized equipment allows the department to perform audiology repairs. Future goals include integrating the radiology repair staff into the medical engineering group, improving the group's productivity, and eliminating some of the existing service contracts.
Chronic foreign body reactions have limited the successful application of alloplastic implants for treatment of temporomandibular joint (TMJ) disorders. There is a great clinical need for new materials with enhanced properties for application in the diarthrodial joint. Photopolymerizations may provide many advantages for fabricating new biomaterials for the TMJ and may address some of the notable differences between the TMJ and other articulations. Specifically, the feasibility of trans-tissue (i.e. through the skin) photopolymerizations may yield less-invasive surgical procedures. Also, novel 3-dimensional photoprocessing techniques may be used to fabricate patient-specific alloplastic devices for improved compliance and efficacy. Finally, the mild conditions necessary for photopolymerizations make the reaction ideal for encapsulating cells with the potential to create constructs for tissue engineering, which may be beneficial for disk replacement therapies.
Advances in endovascular treatment of vascular disease have focused on basic and translational research of vascular disease and endovascular devices. Clinical trials serve to establish the safety and efficacy of engineering advances that incorporate this research. Recent position statements by the Food and Drug Administration (FDA) emphasize that research into conducting these trials in a timely and cost-effective manner (critical path research) is as important to patient care as the engineering advances themselves. This article reviews the recent FDA documents discussing critical path research, highlighting those topics that the FDA emphasizes. Several directions of translational research in which engineering advances may contribute to enhanced device design and improved patient care are reviewed.
This paper reviews the way in which teeth damaged by caries may be repaired clinically. The mechanical effects of caries are described, as are the materials available to repair the damage caused by this disease. Studies are reported which have shown that caries reduces the compressive strength of the tooth to less than 50 per cent of its original value and that, by use of appropriate materials and placement techniques, this can be restored to some 80 per cent of this value. However, very few studies have been carried out which view tooth repair from an engineering perspective. Instead, emphasis is placed on determining clinical durability of repairs. This is related to repair strength but brings in other factors, such as the oral hygiene of the patient. Despite this complication, durability studies show that modern restorative materials perform well under clinical conditions, from which it may be concluded that the repair process allows a structure to be fabricated that is essentially sound from an engineering viewpoint, even if inferior to the original tooth structure provided by nature.
During the past three decades, significant advances have been made in the field of transplantation. However, clinical obstacles such as donor scarcity, cost, infection and life-long immunosuppression(especially within the pediatric age group) have become the major limitations for organ transplantation. This article discusses the recent progresses as well as the remaining challenges in tissue engineering that may enable such technology to replace organ transplantation. Additionally, we describe a practical method for tissue engineering in the field of cardiovascular surgery.
OBJECTIVE: To explore the possibility of detergent acellularized porcine heart valve serving as a scaffold for tissue engineering valve. METHODS: The porcine aortic valves were acellularized by use of trypsin-EDTA. Triton X-100, RNase and DNase treatment. Biomechanical characteristics of fresh valves and acellularized valve were tested; also fresh valves, acellularized valve and valves treated with method of bioprothetic treatment were implanted subcutaneously in rats; frequently seeded with bovine aortic endothelial cells(BAECs), and then cultured for 7 days. RESULTS: The acellularization procedure resulted in complete removal of the cellular components while the construction of matrix was maintained. The matrix could be successfully seeded with in vitro expanded BAECs, which formed a continuous monolayer on the surface. There is no significant difference of PGI2 secretion of BAECs between cells seeded onto the acellular leaflets and that onto the wells of 24-wells plate (P > 0.05). CONCLUSION: Acellularied porcine aortic valve can be applied as a scaffold to develop tissue engineering heart valve.