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  • 1
    Electronic Resource
    Electronic Resource
    TISSUE ENGINEERING: Current State and Prospects (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 52 (2001), S. 443-451 
    Details
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Abstract Organ shortage and suboptimal prosthetic or biological materials for repair or replacement of diseased or destroyed human organs and tissues are the main motivation for increasing research in the emerging field of tissue engineering. No organ or tissue is excluded from this multidisciplinary research field, which aims to provide vital tissues with the abilities to function, grow, repair, and remodel. There are several approaches to tissue engineering, including the use of cells, scaffolds, and the combination of the two. The most common approach is biodegradable or resorbable scaffolds configured to the shape of the new tissue (e.g. a heart valve). This scaffold is seeded with cells, potentially derived from either biopsies or stem cells. The seeded cells proliferate, organize, and produce cellular and extracellular matrix. During this matrix formation, the starter matrix is degraded, resorbed, or metabolized. First clinical trials using skin or cartilage substitutes are currently under way. Both the current state of the field and future prospects are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.med.52.1.443
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  • 2
    Electronic Resource
    Electronic Resource
    The cardiopulmonary consequences of high-risk congenital diaphragmatic hernia (1988)
    Springer
    Pediatric surgery international 3 (1988), S. 1-5 
    Details
    ISSN: 1437-9813
    Keywords: Diaphragmatic hernia ; Respiratory distress ; ECMO
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cardiopulmonary effects of high-risk congenital diaphragmatic hernia have been studied in 50 neonates at The Children's Hospital Boston, from October 1982 through February 1987. Extracorporeal membrane oxygenation (ECMO) was added in February 1984 as therapy for infants who failed to respond to conventional therapy and had 100% predicted mortality. Twenty-three patients received ECMO support; 19 underwent cardiac catheterization immediately after surgery and had hemodynamic parameters measured and pulmonary angiograms performed. The infants fell into two physiologic groups based on their ability to achieve a postductal P O2 ≥ 100: “responders” and “nonresponders” to conventional therapy. “Responders” most often began with left-to-right shunting, and therefore had a pulmonary vascular bed large enough to accept a full cardiac output, even though it was hypoplastic. Their episodes of right-to-left shunting were mostly caused by severe pulmonary aterial vasospasm, which could be reversed in many instances. “Nonresponders” never showed an ability to accept a cardiac output, and therefore had severe hypoplasia as a limiting condition. Survival was 68% in the “responders” and 8% in the “nonresponders”. Overall survival was 49%. Of the patients placed on ECMO, 82.6% were weaned successfully but 65.2% died eventually, most often due to complications of chronic ventilator support. Preliminary analysis of the lungs demonstrated significant iatrogenic damage, but showed some evidence of pulmonary growth. These data suggest that if support can be provided with less iatrogenic injury after ECMO, pulmonary vascular remodeling and growth may be sufficient for improved survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177071
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  • 3
    Electronic Resource
    Electronic Resource
    Prevascularization of porous biodegradable polymers (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 42 (1993), S. 716-723 
    Details
    ISSN: 0006-3592
    Keywords: prevascularization ; cell transplantation ; biodegradable polymers ; organ regeneration ; tissue engineering ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Highly porous biocompatible and biodegradable polymers in the form of cylindrical disks of 13.5 mm diameter were implanted in the mesentery of male syngeneic Fischer rats for a period of 35 days to study the dynamics of tissue ingrowth and the extent of tissue vascularity, and to explore their potential use as substrates for cell transplantation. The advancing fibrovascular tissue was characterized from histological sections of harvested devices by image analysis techniques. The rate of tissue ingrowth increased as the porosity and/or the pore size of the implanted devices increased. The time required for the tissue to fill the device depended on the polymer crystallinity and was smaller for amorphous polymers. The vascularity of the advancing tissue was consistent with time and independent of the biomaterial composition and morphology. Poly(L-lactic acid) (PLLA) devices of 5 mm thickness, 24.5% crystallinity, 83% porosity, and 166 μm median pore diameter were filled by tissue after 25 days. However, the void volume of prevascularized devices (4%) was minimal and not practical for cell transplantation. In contrast, for amporphous PLLA devices of the same dimensions, and the similar porosity of 87% and median pore diameter of 179 μm, the tissue did not fill completely prevascularized devices, and an appreciable percentage (21%) of device volume was still available for cell engraftment after 25 days of implantation. These studies demonstrate the feasibility of creating vascularized templates of amorphous biodegradable polymers for the transplantation of isolated or encapsulated cell populations to regenerate metabolic organs and tissues. © 1993 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260420606
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  • 4
    Electronic Resource
    Electronic Resource
    Localized delivery of epidermal growth factor improves the survival of transplanted hepatocytes (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 422-429 
    Details
    ISSN: 0006-3592
    Keywords: hepatocytes ; transplantation ; polylactic acid ; drug delivery ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Hepatocyte transplantation may provide a new approach for treating a variety of liver diseases if a sufficient number of the transplanted cells survive over an extended time period. In this report, we describe a technique to deliver growth factors to transplanted hepatocytes to improve their engraftment. Epidermal growth factor (EGF) was incorporated (0.11%) into microspheres (19 ± 12 μm) fabricated from a copolymer of lactic and glycolic acid using a double emulsion technique. The incorporated EGF was steadily released over 1 month in vitro, and it remained biologically active, as determined by its ability to stimulate DNA synthesis, cell division, and long-term survival of cultured hepatocytes. EGF-containing microspheres were mixed with a suspension of hepatocytes, seeded onto porous sponges, and implanted into the mesentery of two groups of Lewis rats. The first group of animals had their portal vein shunted to the inferior vena cava prior to cell transplantation (portal-caval shunt = PCS), and the second group of animals did not (non-PCS). This surgical procedure improves the survival of transplanted hepatocytes. The engraftment of transplanted hepatocytes in PCS animals was increased two-fold by adding EGF microspheres, as compared to adding control microspheres that contained no growth factors. Devices implanted into non-PCS animals had fewer engrafted hepatocytes than devices implanted into PCS animals, regardless of whether blank or EGF-containing microspheres were added. These results first indicate that it is possible to design systems which can alter the microenvironment of transplanted hepatocytes to improve their engraftment. They also suggest that hepatocyte engraftment is not improved by providing single growth factors unless the correct environment (PCS) is provided for the transplanted cells. © 1996 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation (1993)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 27 (1993), S. 183-189 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A novel method was developed to prepare threedimensional structures with desired shapes used as templates for cell transplantation. The produced biomaterials are highly porous with large surface/volume and provide the necessary space for attachment and proliferation of the transplanted cells. The processing technique calls for the formation of a composite material with nonbonded fibers embedded in a matrix followed by thermal treatment and the selective dissolution of the matrix. To evaluate the technique, poly(glycolic acid) (PGA) fiber meshes were bonded using poly(L-lactic acid) (PLLA) as a matrix. The bonded structures were highly porous with values of porosity up to 0.81 and area/volume ratios as high as 0.05 μm-1. © 1993 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.820270207
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  • 6
    Electronic Resource
    Electronic Resource
    Long-term engraftment of hepatocytes transplanted on biodegradable polymer sponges (1997)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 37 (1997), S. 413-420 
    Details
    ISSN: 0021-9304
    Keywords: tissue engineering ; polylactic acid ; hepatocytes ; transplantation ; portal vein ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hepatocyte transplantation may provide an alternative to orthotopic liver transplantation to treat liver failure. However, suitable systems to transplant hepatocytes and promote long-term engraftment must be developed. In this study, highly porous, biodegradable sponges were fabricated from poly (L-lactic acid) (PLA), and poly (DL-lactic-co-glycolic acid) (PLGA), and utilized to transplant hepatocytes into the mesentery of three groups of Lewis rats. The portal vein was shunted to the inferior vena cava in one group of rats (PCS). The second group of animals received a PCS and a 70% hepatectomy on the day of sponge-hepatocyte implantation (PCS + HEP), and the control group (CON) received no surgical stimulation. The sponges were vascularized by ingrowth of fibrovascular tissue over the first 7 days in vivo. Approximately 95-99% of the implanted hepatocytes (determined utilizing computer-assisted image analysis) died in all three experimental groups during this time. The number of engrafted hepatocytes in the CON group further decreased over the next 7 days to 1.3 ± 1.1% of the original cell number. However, the number of engrafted hepatocytes in the PCS and PCS + HEP increased over this time to 6 ± 1% and 5 ± 2%, respectively. The number of engrafted hepatocytes in the PCS group continued to increase over the next 2.5 months to a value of 26 ± 12% of the initial cell number, and a large number of engrafted hepatocytes was still present at 6 months. These results indicate that stable new tissues can be engineered by transplanting hepatocytes on biodegradable sponges into heterotopic locations if appropriate stimulation is provided. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 37, 413-420, 1997.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Hepatocyte culture on biodegradable polymeric substrates (1991)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 38 (1991), S. 145-158 
    Details
    ISSN: 0006-3592
    Keywords: biodegradable polymeric substrates ; cell adhesion ; liver cell culture ; albumin secretion ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The interactions of primary rat liver cells with biodegradable polymeric substrates were investigated in vitro to assess the suitability of the polymer materials for use in cell transplantation devices. The kinetics of cell adhesion to, and the growth and biochemical function of cells maintained on, films formed from poly (D,L-lactic-co-glycolic acid, 88: 12) (PLGA) or from a 50/50 (w/w) blend of PLGA and poly (L-lactic acid) (PLLA) were evaluated in comparison to two control substrates, matrigel coated or collagen-coated polystyrene petri dishes. The rate of cell adhesion to both types of polymeric substrates was similar to the rate of adhesion to the collagen control substrate, but of the two polymers, only the blend was suitable for extended culture. Hepatocytes maintained on the polymer blend films showed retention of differentiated cell function as measured by the rate of albumin secretion-the rate of albumin secretion by cells on the films was the same as the rate for cells on matrigel and reached a level in the range of reported in vivo levels (140-160 μg/106 cells/24 h). In contrast, albumin secretion by hepatocytes maintained on collagen-coated polystyrene culture dishes declined over five days to a level one third that of the initial level and one fifth that of cells maintained on the polymer blend films on day five. Such retention of differentiated cell function by hepatocytes in culture has previously been observed only when hepatocytes were cultured in the presence of exogenous extracellular matrix proteins or were cocultured with another cell type. In addition to retention of differentiated function, the cells maintained on the polymer blend films also displayed rates of DNA synthesis similar to controls maintained on collagen-coated polystyrene, a substrate optimal for DNA synthesis.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260380207
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