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  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 29 (1995), S. 1053-1060 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hydroxyapatite (HA), heat-treated hydroxyapatite (HAH), and fluorapatite (FA) coatings on titanium were loaded with human growth hormone (GH), and the subsequent release was monitored in vitro. The amount of GH released was significantly increased from the HA coating that had received a post-plasma-spraying heat treatment prior to incorporation of the growth hormone. Scanning electron microscopy was used to assess the surfaces of the ceramic coatings prior and postincubation with GH. Surface changes were observed on the HA and HAH coatings but not on the FA coatings after incubation with GH. Osteoblast-like cells were grown on the coatings and maintained in culture. Scanning electron microscopy was used to study the morphology of the cells and the interaction of the cells with the ceramic coatings. We used thymidine uptake and DNA content to determine the relative rates of cell division on the different coatings; the optimum rate of cell proliferation was observed on the HAH coating loaded with 0.1 IU/mL GH. © 1995 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 635-643 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The release of human growth hormone (hGH) from hormone loaded bone cement was previously shown to enhance osteoid formation. hGH is a complex protein and its incorporation into such cements may compromise its bioactivity. We therefore characterized the release of hGH from a series of methacrylate systems based upon poly(ethylmethacrylate) (PEMA). Different mixtures of two monomers, hydroxyethyl-methacrylate (HEMA) and n-butylmethacrylate (n-BM) were used to provide polymers with graded water uptakes. Exclusive use of only one of the monomers resulted in enhanced cytotoxicity and also reduced release of the bioactive hormone. Combinations of the monomers improved the recovery of bioactivity from the polymers and reduced their cytotoxicity. hGH released from the polymer with the lowest water uptake (100% n-BM, 0% HEMA) had an exceptionally low bioactivity: immunoactivity ratio, suggesting that the bioactive site of the hormone is particularly susceptible to disruption when it is incorporated into this matrix. © 1996 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 34 (1997), S. 47-55 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Previous studies showed that recombinant human growth hormone (hGH) released from hormone-loaded poly(methylmethacrylate) (PMMA) cement stimulated osteoid formation in a rabbit model. Local delivery of hGH from cemented hip arthroplasties may thereby provide a means of reducing the problem of aseptic loosening. We have investigated two different formulations of PMMA as delivery systems for bioactive hGH. The bioactivity of the hormone release in vitro was monitored with an eluted stain assay (ESTA). The hGH was also measured by an immunoassay, which provides an alternative assessment of structural integrity of the hormone released. In addition, we adapted the ESTA bioassay to assess the in vitro cytotoxicity of the cements. Using unloaded cements, the undiluted eluates from both types of PMMA proved cytotoxic. This cytotoxicity could be diluted out, and the procedure allowed us to measure the bioactivity of hGH in the eluates from hormone-loaded cements independent of their cytotoxicity. The major fraction of the bioactivity was released from both of the PMMA cements during the first 24 h, but the hormone remained detectable in eluates collected after 36 days of elution. Comparison of the bio- and immunoactivity of the hGH released showed that the ratio of these two activities (i.e., the B:I ratio) was constant over this time period. However, in parallel studies in which hormone-loaded discs were stored under dry conditions prior to elution, we found that the B:I ratio then declined markedly. This suggests that fully hydrated conditions, such as when the discs are bathed in assay medium, are necessary to maintain the bioactivity of the hGH. Both cements released only ∼1% of the hormone originally incorporated, but the hGH concentration which accumulated in the eluates were high in physiologic terms (∼1000 mU/L). © 1997 John Wiley & Sons, Inc.
    Additional Material: 4 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 40 (1998), S. 204-213 
    ISSN: 0021-9304
    Keywords: growth hormone delivery ; bioactivity ; poly(∊-caprolactone); solvent casting; particulate leaching ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We have characterized the biodegradable material poly(∊-caprolactone) (PCL) as a delivery system for recombinant human growth hormone (hGH). Two contrasting methods for the manufacture of the biomaterial were investigated: namely, solvent casting and solvent casting particulate leaching; the latter yielded porous PCL discs. The degree of porosity, which was assessed by scanning electron microscopy, could be controlled by incorporating selected concentrations of particulate sodium chloride during the manufacturing process. Bioactive hGH released from the PCL preparations was quantified with a highly sensitive and precise bioassay which was based upon hGH activation of rat lymphoma Nb2 cells. Eluates obtained from control discs of PCL which had not been loaded with hGH proved to be nontoxic when tested on these cells. The release of bioactive hGH from hormone-loaded nonporous discs of PCL was found to be a direct function of the initial hormone loading dose. Increased porosity of the discs manufactured by solvent casting particulate leaching increased the delivery of hGH from discs which had been immersion loaded. However, hGH release after surface loading was independent of porosity. Hormone concentrations were also assessed by immunoassay so that the ratios of bio- to immunoactivity (B:I ratio) of the hormone release could be determined. We found that the B:I ratio of the hormone after release from unstored discs was identical to that of the hormone prior to its incorporation into the PCL, demonstrating that the mild incorporation procedures utilized had not adversely affected the structural integrity of the hormone. However, if the hormone-loaded discs were stored at 37°C prior to elution, the B:I ratios of the hGH released decreased indicating that this compromised the bioactive site. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 204-213, 1998
    Additional Material: 3 Ill.
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