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PubMed2000

Tissue-engineered bone regeneration.

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

Animals↗
PubMed1999

Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen.

In tissues, collagen forms the scaffold for cell attachment and migration, and it modulates cell differentiation and morphogenesis by mediating the flux of chemical and mechanical stimuli. We are constructing biomimetic environments by immobilizing a collagen-derived high-affinity cell-binding peptide P-15 in three-dimensional (3-D) templates. The cell-binding peptide can be expected to transduce mechanical forces. In their physiological environment, periodontal ligament fibroblasts (PDLF) are subject to significant mechanical forces. We have examined the behavior of human PDLF in culture on particulate bovine anorganic bone mineral (ABM) coated with P-15 (ABM-P-15). Greater numbers of cells associated with ABM-P-15 compared to ABM alone. Higher levels of incorporation of radiolabeled precursors in DNA and protein were consistent with the presence of larger numbers of cells on ABM-P-15 compared to ABM cultures. Scanning electron microscopic examination showed that cultures on ABM-P-15 generated highly oriented 3-D colonies of elongated cells and formed copious amounts of fibrous as well as membranous matrix reminiscent of ligamentous structures. PDLF cultured on ABM formed sparse monolayers with little order and a meager matrix. Alizarin Red stained the matrix of particle associated cells and inter-particle cellular bridges in P-15-associated cultures, indicating mineralization. 3-D colony formation and ordering of cells along with increased mineralization suggests that the coupling of cells to the ABM matrix through P-15 may provide a biomimetic environment permissive for cell differentiation and morphogenesis. Our studies suggest that ABM-P-15 templates may be effective as endosseous grafts, and, when seeded with PDLF, these matrices may serve as tissue engineered substitutes for autologous bone grafts.

Animals↗
PubMedDate not supplied

The future of clinical engineering in the 1990's.

The problems in hospitals which led to the development of the clinical engineering profession are described along with recent changes in the hospital environment. The authors discuss how the profession is adapting to these changes. Also discussed is the tendency for BMETs to move into clinical engineering roles.

Biomedical Engineering↗
PubMed2003

Preparation of polylactic acid/chitin composite material and its safety evaluation by animal experiments.

OBJECTIVE: To prepare a scaffold material with good biocompatibility and biodegradability by compounding polylactic acid (PLA) and chitin. METHODS: After preparation of PLA from lactic acid, the compounding of PLA and chitin was carried out by dissolving these 2 materials in one solution for reaction. The composite material was obtained and molded after the solvent was evaporized, and the safety tests of this resultant material were conducted in guinea pigs and New Zealand rabbits, respectively. RESULTS: In allergic test, the guinea pigs responded to the digestion solution of the composite material in almost the same manner as to normal saline (the latter serving as negative control), and no obvious allergic reaction was observed in the animals except those in positive control group. Pyrogenic test by injecting the digestion solution of the composite material in 6 rabbits found a raise in the body temperature less than 0.2 degrees Celsius, with the total increase (adding up the individual temperature raise) less than 1.0 degrees Celsius, to meet the accepted criteria for the pyrogenic test. In subsequent toxicity test, the rabbits showed no signs of agitation or inanimate behavior after injection. CONCLUSIONS: PLA/chitin composite material conforms to the ISO10993-1, and can be used as a basic scaffold material in tissue engineering.

Animals↗
PubMed1988

Marketing new medical devices.

The marketing concept says that a firm should focus all of its efforts on satisfying its customers, at a profit. This is really a a new philosophy of business, replacing a production-oriented philosophy which focused on organizing a firm's resources to make products and then selling them. The marketing concept calls for reorienting the firm's ways of doing things. Instead of trying to get customers to buy what the firm has produced, a marketing-oriented firm would try to sell what the customers want. The underlying principle of the marketing concept is that a firm should seek to meet the needs of customers, at a profit, rather than place its main emphasis on its own internal activities and utilization of its resources. These latter factors are also important, of course, but those who believe in the marketing concept feel that customers' needs should be the firm's primary focus and that resources should be organized to satisfy those needs. Give the customer what he needs--this may seem so obvious and logical that it is difficult to understand why the marketing concept is considered such a breakthrough. However, people haven't always done the logical and obvious. In a typical company, production men thought mainly about getting the product out. Accountants were only interested in balancing the books. Financial people were absorbed in the company's cash position. And salesmen were mainly concerned with getting orders. No one was particularly concerned with whether the whole system made sense. As long as the company made a profit, each department went merrily on its independent way, "doing its own thing." Unfortunately, they still do in the majority of companies today. Finding out customer's attitudes can avoid prejudices and stereotypes commonly found in the typical organization. The need for market research to avoid stereotypes can be dramatized by the following results from a large-scale survey of European adults: The average Frenchman uses almost twice as many cosmetics and beauty aids as his wife. The Germans and the French eat more spaghetti than the Italians. French and Italian housewives are not as interested in cooking as their counterparts in Luxembourg and Belgium. No firm can conduct its business successfully without trying to measure the actual size of markets, present and future. Quantitative measurements are essential for the analysis of market opportunity, the planning of marketing programs, and the control of marketing effort. The firm may make many measures of demand, varying in the level of product aggregation, the time dimension,a nd the space dimension.(ABSTRACT TRUNCATED AT 400 WORDS)

Accounting↗
PubMed2004

Surface engineering of prosthetic knee components.

Conventional total and uni-compartmental knee replacement designs usually incorporate metal femoral and tibial components with an ultra high molecular weight polyethylene (UHMWPE) bearing surface. The tibial components can be modular or monobloc and are of the fixed bearing type in the majority of cases. Mobile bearings are also in common use with a modular meniscal insert with either rotation only or a combination of rotation and translation. Wear of the UHMWPE components remains of primary concern in these prosthetic devices. Catastrophic wear and delamination has been largely addressed by improvements in UHMWPE quality and manufacturing methods, however, abrasive and adhesive wear of the UHMWPE components remains a concern for long-term survivorship of total knee replacement. This review very briefly covers published long-term survivorship of primary knee arthroplasties, primary wear mechanisms present in knee replacements and the potential for wear reduction by surface engineering of the metal wear counterfaces. There are several methods and materials available, which offer the potential for significantly reduced wear.

Biomedical Engineering↗
PubMed2002

Genomic and proteomic perspectives in cell culture engineering.

In the last few years, the number of biologics produced by mammalian cells have been steadily increasing. The advances in cell culture engineering science have contributed significantly to this increase. A common path of product and process development has emerged in the last decade and the host cell lines frequently used have converged to only a few. Selection of cell clones, their adaptation to a desired growth environment, and improving their productivity has been key to developing a new process. However, the fundamental understanding of changes during the selection and adaptation process is still lacking. Some cells may undergo irreversible alteration at the genome level, some may exhibit changes in their gene expression pattern, while others may incur neither genetic reconstruction nor gene expression changes, but only modulation of various fluxes by changing nutrient/metabolite concentrations and enzyme activities. It is likely that the selection of cell clones and their adaptation to various culture conditions may involve alterations not only in cellular machinery directly related to the selected marker or adapted behavior, but also those which may or may not be essential for selection or adaptation. The genomic and proteomic research tools enable one to globally survey the alterations at mRNA and protein levels and to unveil their regulation. Undoubtedly, a better understanding of these cellular processes at the molecular level will lead to a better strategy for 'designing' producing cells. Herein the genomic and proteomic tools are briefly reviewed and their impact on cell culture engineering is discussed.

Animals↗
PubMed2001

Evaluation of metallic and polymeric biomaterial surface energy and surface roughness characteristics for directed cell adhesion.

Directed cell adhesion remains an important goal of implant and tissue engineering technology. In this study, surface energy and surface roughness were investigated to ascertain which of these properties show more overall influence on biomaterial-cell adhesion and colonization. Jet impingement was used to quantify cellular adhesion strength. Cellular proliferation and extracellular matrix secretion were used to characterize colonization of 3T3MC fibroblasts on: HS25 (a cobalt based implant alloy, ASTM F75), 316L stainless steel, Ti-6Al4V (a titanium implant alloy), commercially pure tantalum (Ta), polytetrafluoroethylene (PTFE), silicone rubber (SR), and high-density polyethylene (HDPE). The metals exhibited a nearly five-fold greater adhesion strength than the polymeric materials tested. Generally, surface energy was proportional to cellular adhesion strength. Only polymeric materials demonstrated significant increased adhesion strength associated with increased surface roughness. Cellular adhesion on metals demonstrated a linear correlation with surface energy. Less than half as much cellular proliferation was detected on polymeric materials compared to the metals. However the polymers tested demonstrated greater than twice the amount of secreted extracellular matrix (ECM) proteins on a per cell basis than the metallic materials. Thus, surface energy may be a more important determinant of cell adhesion and proliferation, and may be more useful than surface roughness for directing cell adhesion and cell colonization onto engineered tissue scaffoldings.

3T3 Cells↗
PubMed2000

[An initial experiment study on allogenic tissue engineered cartilage].

OBJECTIVE: To investigate the formation of engineered cartilage in vivo with allogenic chondrocytes. METHODS AND MATERIALS: Joint cartilage from ewe embryos (Pregnancy: 100 days) was isolated and digested to obtain dissociated chondrocytes. Mixed chondrocytes with biomaterials (Pluronic 127) at the density 50 x 10(6)/ml, then implant the allograft complex subcutaneously. Collect the novel tissue every two weeks along for six months, weigh and stain (HE, Safranin O, Masson's trichrome) the sample tissues individually to evaluate the characteristics of novel tissue. RESULT: Novel cartilage can regenerate in allograft animals, with similar histological properties of chondrocytes, aminoglycin and collagen distribution to normal cartilage. The novel cartilage observed histologically showed apparent surrounding inflammatory cells in two and four week and the tissue of cartilage came to mature since the sixth week, with less inflammatory reaction, but not disappeared. CONCLUSION: Novel cartilage can generate in allograft animals with tissue engineering approach, with certain immunoreaction surrounding. Such reaction will be weakened gradually with time.

Animals↗
PubMed2006

Cartilage and bone tissue engineering using hydrogels.

Tissue engineering is an emerging field of regenerative medicine which holds promise for the restoration of tissues and organs affected by chronic diseases, age-linked degeneration, congenital deformity and trauma. During the past decade, tissue engineering has evolved from the use of naked biomaterials, which may just replace small area of damaged tissue, to the use of controlled three-dimensional scaffolds in which cells can be seeded before implantation. These cellularized constructs aims at being functionally equal to the unaffected tissue and could make possible the regeneration of large tissue defects. Among the recently developed scaffolds for tissue engineering, polymeric hydrogels have proven satisfactory in cartilage and bone repair. Major technological progress and advances in basic knowledge (physiology and developmental biology) are today necessary to bring this proof of concept to clinical reality. The present review focuses on the recent advances in hydrogel-based tissue engineered constructs potentially utilizable in bone and cartilage regenerative medicine.

Animals↗
PubMed1993

Technology evaluation in a US hospital: the role of clinical engineering.

Appropriate deployment of technological innovation contributes to improvement in the quality of healthcare delivered, containment of cost, and an increased access to the healthcare system. Hospitals have been allocating a significant portion of their resources to procuring and managing capital assets; they are continuously faced with demands for new medical equipment and are asked to manage existing inventory for which they are not well prepared. To objectively manage their investment, hospitals are developing medical technology management programmes that need pertinent information and methods for new equipment planning as well as for reduction in the ownership costs of existing equipment. Clinical engineers can identify new medical equipment, review their institution's technological position, develop equipment-selection criteria, supervise installations and monitor postprocurement performance to meet their hospital's programme's objectives. This programme, together with cost accounting analysis, will objectively guide the capital assets decisionmaking process. The result of systematic planning and execution, the programme will assure the lowest life-cycle costs at the best performance. The clinical engineer's skills and expertise are needed to facilitate the adoption of an objective methodology for implementing the programme, thus improving the match between the hospital's needs and budget projections, equipment performance and cost of ownership.

Biomedical Engineering↗
PubMed1999

Bioreaction network topology and metabolic flux ratio analysis by biosynthetic fractional 13C labeling and two-dimensional NMR spectroscopy.

Biosynthetically directed fractional 13C labeling of the proteinogenic amino acids is achieved by feeding a mixture of uniformly 13C-labeled and unlabeled carbon source compounds into a bioreaction network. Analysis of the resulting labeling pattern enables both a comprehensive characterization of the network topology and the determination of metabolic flux ratios. Attractive features with regard to routine applications are (i) an inherently small demand for 13C-labeled source compounds and (ii) the high sensitivity of two-dimensional [13C,1H]-correlation nuclear magnetic resonance spectroscopy for analysis of 13C-labeling patterns. A user-friendly program, FCAL, is available to allow rapid data analysis. This novel approach, which recently also has been employed in conjunction with metabolic flux balancing to obtain reliable estimates of in vivo fluxes, enables efficient support of metabolic engineering and biotechnology process design.

Amino Acids↗
PubMed2000

Engineering a living cell to desired metabolite concentrations and fluxes: pathways with multifunctional enzymes.

With molecular genetics enabling modulation of the concentrations of cellular enzymes, metabolic engineering becomes limited by the question of which modulations of the enzyme concentrations are required to bring about a desired pattern of cellular metabolism. In an earlier paper (Kholodenko et al. (1998). Biotechnol. Bioeng. 59, 239-247) we derived a method to determine the required modulations. This method, however, cannot be immediately applied to cellular pathways with enzymes catalyzing more than one step in metabolism (multifunctional enzymes). In the present paper we show to which extent the presence of multifunctional enzymes limits biotechological ambitions, which one might otherwise pursue in vain. In particular, it is impossible to change the concentration of a single intermediate and leave the rest of metabolism unperturbed if that intermediate interacts directly with a multifunctional enzyme. The analytical machinery of Metabolic Control Analysis is used to relate the desired and ensuing changes in the metabolic pattern. An explicit solution to this problem of engineering metabolism is then given in the form of a single matrix equation.

Animals↗
PubMed1994

A scientist's view of bioengineering.

So, to summarize: my themes in this lecture have been: 1. Bioengineering is a many-splendoured thing. 2. There are few differences in principle between scientists and engineers, and they need to work together and respect one another's special contribution. 3. The Department of Health has done much to enhance your career structure and prospects recently; now you have to help us to polish your image even further. 4. There is urgent need for collaboration amongst all parties if we are to counter some potentially deleterious effects of the recent NHS reforms on the work of clinical scientists and engineers. Finally, I wanted to thank you for admitting me, just a little way, into the magical world of biological engineering. Life has become infinitely more exciting since you did so, and I owe you all a considerable debt of gratitude.

Biomedical Engineering↗
PubMed2000

Combining chondrocytes and smooth muscle cells to engineer hybrid soft tissue constructs.

Engineering new tissues using cell transplantation may provide a valuable tool for reconstructive surgery applications. Chondrocyte transplantation in particular has been successfully used to engineer new tissue masses due to the low metabolic requirements of these cells. However, the engineered cartilaginous tissue is too rigid for many soft tissue applications. We propose that hybrid tissue engineered from chondrocytes and smooth muscle cells could reflect mechanical properties intermediate between these two cell types. In this study, rat aortic smooth muscle cells and pig auricular chondrocytes were co-cultured on polyglycolic acid fiber-based matrices to address this hypothesis. Mixed cell suspensions were seeded by agitating the polymer matrices and a cell suspension with an orbital shaker. After seeding, cell-polymer constructs were cultured in stirred bioreactors for 8 weeks. The cell density and extracellular matrix (collagen, elastin, and glycosaminoglycan) content of the engineered tissues were determined biochemically. After 8 weeks in culture, the hybrid tissue had a high cell density (5.8 x 108 cells/cm(3)), and elastin (519 microg/g wet tissue sample), collagen (272 microg/g wet tissue sample), and glycosaminoglycan (GAG; 10 microg/g wet tissue sample) content. Mechanical testing indicated the compressive modulus of the hybrid tissues after 8 weeks to be 40.8 +/- 4.1 kPa and the equilibrium compressive modulus to be 8.4 +/- 0.8 kPa. Thus, these hybrid tissues exhibited intermediate stiffness; they were less stiff than native cartilage but stiffer than native smooth muscle tissue. This tissue engineering approach may be useful to engineer tissues for a variety of reconstructive surgery applications.

Animals↗