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  • Polymer and Materials Science  (15)
  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 26 (1992), S. 1091-1110 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Collagen-based biomaterials have found various applications in the biomedical field. However, collagen-based biomaterials may induce cytotoxic effects. This study evaluated possible cytotoxic effects of (crosslinked) dermal sheep collagen (DSC) using a 7-d-methylcellulose cell culture with human skin fibroblasts. Non-crosslinked DSC (NDSC), hexamethylene-diisocyanate-crosslinked DSC (HDSC), and glutaraldehyde-crosslinked DSC (GDSC), their extracts (1 × 10 d to 4 × 10 d extracts), or the corresponding extracted DSC samples were tested. Cell growth was evaluated by cell counting, while cell morphology was assessed by light microscopy and transmission-electron microscopy. Both GDSC and, to a lesser extent, HDSC, induced cytotoxicity, observed as inhibited cell growth and deviant cell morphology. The deviant morphology consisted of extensive accumulations of lipid, reduction in the amount and dilatation of rough endoplasmatic reticulum, increased inclusions of cell remnants, and relatively rounded cell membranes. With HDSC, both primary cytotoxicity, due to extractable products from the material, and secondary cytotoxicity, possibly due to a release of cytotoxic products resulting from enzymatic cell-biomaterial interactions, could be discriminated. With GDSC, however, no clear distinction between primary and secondary cytotoxicity could be made. With NDSC, only primary cytotoxicity, measured as low inhibition of cell proliferation, but without deviant morphoIogy, was observed. These remarkable differences in cytotoxicity are discussed in relation to residual agents and specific crosslinks present i n DSCs as a consequence of processing and the crosslinking agents used. The residual agents and the specific crosslinks give rise to differ- ences in direct release of products and in sensitivity to hydrolysis and enzymatic breakdown.
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  • 2
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 29 (1995), S. 149-155 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The influence of ethylene oxide gas treatment on the in vitro degradation behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase is described. The results obtained were compared with the degradation behavior of either nonsterilized or γ-sterilized DSC. Upon ethylene oxide sterilization, reaction of ethylene oxide with the free amine groups of DSC occurred, which resulted in a decreased helix stability, as indicated by a lowering of the shrinkage temperature of all three types of DSC. Except for the low strain modulus the mechanical properties of the ethylene oxide sterilized materials were not significantly altered. γ-Sterilization induced chain scission in all three types of DSC, resulting in a decrease of both the tensile strength and the high strain modulus of noncrosslinked and crosslinked DSC. When exposed to a solution of bacterial collagenase, ethylene oxide sterilized materials had a lower rate of degradation compared with nonsterilized DSC. This has been explained by a reduced adsorption of the collagenase onto the collagen matrix as a result of the introduction of pendant N-2-hydroxy ethyl groups. © 1995 John Wiley & Sons, Inc.
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  • 3
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 29 (1995), S. 1425-1436 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Collagen-based skin substitutes are among the most promising materials to improve regeneration of full-thickness wounds. However, additional meshed grafts or cultured epidermal grafts are still required to create epidermal regeneration. To avoid this, we substituted collagen-based split grafts, i.e., grafts with a separated top and bottom layer, in a rat full-thickness wound model and compared regeneration with nontreated, open control wounds. We hypothesized that epidermal regeneration would occur in the split in between the two layers, with the top layer functioning as a clot/scab and the bottom layer as a dermal substitute. Two types of dermal sheep collagen (DSC) split grafts were tested: one with a top layer of noncrosslinked DSC (NDSC) and bottom layer of hexamethylenediisocyanate crosslinked DSC (HDSC), further called N/HDSC; and the second with both a top and bottom layer of HDSC (H/HDSC). With the N/HDSC split graft NDSC did not function as a sponge for formed exudate and as a consequence the split was no longer available to facilitate epidermal regeneration. In contrast, with the H/HDSC graft the split facilitated proliferation and differentiation of the epidermal cells in the proper way. With this graft, clot formation was restricted to the top layer, which was rejected after 8 weeks, while the bottom layer functioned during gradual degradation as a temporary matrix for the formation of autologous dermal tissue. H/HDSC strongly inhibited infiltration of myofibroblasts, resulting in a 30% wound contraction, while a 100% contraction was found with the open control wound. The results show that H/HDSC split-grafts function conforms to the hypothesis in regeneration of large, full-thickness wounds without further addition of seeded cells or use of meshed autografts. © 1995 John Wiley & Sons, Inc.
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  • 4
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A surface modification technique was developed to achieve controlled release of gentamicin from implanted polyurethane (PU) rat lead samples. PU tubing first was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. This surface modification technique resulted in release of gentamicin base (GB) and was applied either to the inner luminal surface only (PU-GB-1x) or to both the inner and outer surfaces (PU-GB-2x). First we investigated whether the early tissue response was harmfully compromised when surface-modified rat lead samples were implanted without any infectious challenge. Additionally, the efficacy of this type of local gentamicin therapy was investigated by establishing its effect on tissue response and its ability to prevent lead-related infections after inoculation with Staphylococcus aureus. It was demonstrated that the applied surface modification(s) did not induce adverse effects although an increase in the infiltration of granulocytes and macrophages and an increase in the formation of wound fluid and fibrin were observed. This effect was stronger with PU-GB-2x than with PU-GB-1x. With bacterial inoculation the applied surface modification successfully suppressed the infectious challenge, PU-GB-2x more effectively than PU-GB-1x. PU-GB-2x also was more effective when compared to the gentamicin-delivery methods discussed in the first part of this two-part study, i.e., release through a vicinal gentamicin-containing collagen sponge and preoperative gentamicin solution-dipping of rat lead samples. © 1997 John Wiley & Sons, Inc.
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  • 5
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 41 (1998), S. 202-210 
    ISSN: 0021-9304
    Keywords: IFN-γ ; macrophages ; giant cells ; inflammatory reactions ; biomaterials ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Biomaterials are increasingly used for clinical applications. However, loss of function may occur owing to tissue reactions, which are mainly caused by a variety of inflammatory reactions. Recently, we demonstrated that macrophages (MØ) and T cells play key roles in these reactions. Since immunological studies showed that the T cell-derived cytokine interferon-γ (IFN-γ) activates MØ, the aim of this study was to investigate the possibility of modulating tissue reactions to biodegradable biomaterials by inactivating IFN-γ. Dermal sheep collagen (DSC) was used as a test biomaterial. DSC impregnated with anti-IFN-γ or phosphate-buffered saline (control) was implanted in rats. The results showed that cellular ingrowth and formation and function of giant cells were strongly delayed by anti-IFN-γ. Also, MHC class II expression was strongly inhibited. In the treated DSC, some huge giant cells were formed at the interface but association with the DSC bundles did not occur. Finally, in both the control and treated DSC, T cells and NK cells were rarely detected. This study demonstrates that IFN-γ plays an important role in the inflammatory reaction to biomaterials. This reaction can be modulated by anti-IFN-γ, which warrants further studies of anti-IFN-γ for clinical application to prevent unwanted tissue reactions to biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 202-210, 1998.
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  • 6
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 21 (1987), S. 701-718 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A systematic study of the effects of polymer surface properties on the interaction with human endothelial cells (HEC) may lead to the development of small-diameter vascular grafts. HEC, suspended in culture medium containing 20% serum adhered and spread onto moderately wettable polymers such as TCPS (tissue culture polystyrene). Reduced or no adhesion of HEC was observed upon the hydrophobic polymers PETP (polyethyleneterephthalate, Dacron) and FEP (fluoroethylenepropylene copolymer, Teflon). Polymers precoated with the proteins albumin (Alb), high density lipoprotein (HDL), and immunoglobulin G (IgG) inhibited the adhesion of HEC, whereas fibronectin (Fn) coátings promoted cell adhesion. Endothelialization of PETP and FEP only occurred after precoating of these materials with Fn. The adsorption of Fn, Alb, HDL, and IgG from solutions of different serum concentrations onto TCPS, PETP, and FEP was related to the adhesion of HEC. Serum Fn only adsorbed onto TCPS, with the maximum at 0.1% serum concentration. Maximal cell adhesion onto TCPS was also observed after pretreatment with a solution containing 0.1% serum. The cell adhesion inhibiting proteins Alb and HDL preferentially adsorbed at higher serum concentrations. Desorption of these proteins and exchange for, e. g., cellular Fn may result in cell spreading and proliferation of HEC upon TCPS.
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  • 7
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 28 (1994), S. 353-363 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanatecrcrosslinked DSC (HDSC) seldom induced an increased infiltration of neutrophils or macrophages, as compared with normal wound healing; whereas new formation of collagen was observed. DSC crosslinked with glutaraldehyde (GDSC) followed by reaction with NaBH4 shortly after implantation showed an increased infiltration of neutrophils with a deviant morphology. Furthermore, a high incidence of calcification was observed, which may explain the minor ingrowth of giant cells and fibroblasts, and the poor formation of new rat collagen. Acyl azide-crosslinked DSC (AaDSC) first induced an increased infiltration of macrophages, and then of giant cells, both with high lipid formation. AaDSC degraded at least twice as slowly as HDSC and GDSC, finally leaving a matrix of newly formed rat collagen. Samples crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (ENDSC) induced the same mild cellular reaction as HDSC; whereas, similar to AaDSC, the degradation rate was slow and an optimal rat collagen matrix was formed. Of the crosslinked DSC samples, ENDSC seems most promising for tissue regeneration. © 1994 John Wiley & Sons, Inc.
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  • 8
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 353-360 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Collagens may be used as biomaterials for soft tissue reconstruction, e.g., the abdominal wall. We previously developed a biocompatible dermal sheep collagen (DSC), which in an abdominal wall reconstruction model showed controlled biodegradation and functioned as a matrix for ingrowth of fibroblasts but not of muscle. It was hypothesized that regeneration of muscle via DSC may be possible by seeding of muscle cells. Using a syringe, mouse C2C12 myoblasts were seeded in DSC disks and incubated in methylcellulose-based growth medium, changed at 24 h into differentiation medium. An estimated 85% of the cells were well distributed, especially in the top half of the DSC disks. Some 15% of the cells ended up on top. At 4 h, all cells showed a spherical morphology, sometimes with clear adhesion plaques. At 24 h, cells on the top started to form a “capsule” with well-spread cells. Underneath the capsule, of the remaining 85% of the cells, approximately 30% showed adhesion and spreading on/in between collagen bundles. At day 3 after the addition of differentiation medium, the spread cells showed first indications of myotube formation. At day 7, myotube formation had proceeded, while extracellular matrix, i.e., collagen and elastin, had been deposited. This study shows that myoblast seeding into DSC is feasible, resulting in a reasonable cell distribution and survival of 45% of the cells. The surviving cells are able to differentiate into myotubes and form an extracellular matrix. © 1996 John Wiley & Sons, Inc.
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  • 9
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 307-320 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The in vivo biocompatibility and biodegradation of crosslinked (co)polyethers with and without tertiary hydrogen atoms in the main chain and differing in hydrophilicity were studied by means of subcutaneous implantation in rats. After 4 days, 1 month, and 3 months postimplantation, the tissue reactions and interactions were evaluated by light microscopy (LM) and transmission electron microscopy (TEM). Poly(tetrahydrofuran) (poly(THF)), poly(propylene oxide) (poly(POx)), and poly(tetrahydrofuran-co-oxetane) (poly-(THF-co-OX)) were tested as relatively hydrophobic polyethers, and poly(ethylene oxide) (PEO) and a poly(THF)/PEO blend were used as more hydrophilic materials. In general, all polyethers showed good biocompatibility with respect to tissue reactions and interactions, with low neutrophil and macrophage infiltration, a quiet giant cell reaction, and formation of a thin fibrous capsule. For the relatively hydrophobic polyethers studied, the biostability increased in the order poly(POx) 〈 poly(THF-co-OX) 〈 poly(THF), probably indicating that the absence of tertiary hydrogen atoms has a positive effect on the biostability. Concerning the more hydrophilic materials, crosslinked PEO showed the highest rate of degradation, probably due to the mechanical weakness of the hydrogel in combination with the highest presence of giant cells as a result of the high porosity. A frayed surface morphology was observed after implantation of the crosslinked poly(THF)/PEO blend, which might be due to preferential degradation of PEO domains. © 1996 John Wiley & Sons, Inc.
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  • 10
    ISSN: 0021-9304
    Keywords: T cells ; phagocytosis ; collagens ; biocompatibility ; biomaterials ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Unwanted tissue reactions are often observed resulting in events such as early resorption of the biomaterial, loosening of the implant, or a chronic (immunologic) response. From immunologic studies it is known that inflammatory reactions can be modulated by use of (anti)-growth factors or anti-inflammatory drugs. Before this can be employed with respect to biomaterials, the role of individual factors (humoral and cellular) has to be studied. In this part of the investigation, the role of T cells was studied by use of T-cell-deficient (nude) rats and control (AO) rats. Hexamethylenediisocyanate-crosslinked dermal sheep collagen (HDSC) was selected as the test material. The results showed that T cells or T cell-related factors played a prominent role in the attraction of macrophages and the formation of giant cells, their antigen presentation, and their phagocytotic capacity. As a consequence, degradation of HDSC was strongly delayed. This study also showed that infiltration of fibroblasts and creation of stromal areas in HDSC was restricted to areas subjected to degradation. However, in time, absence of T cells resulted in increased formation and maturation of autologous rat collagen. Results obtained suggest that the inflammatory reaction to biomaterials might be modulated by controlling T-cell activation. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 398-406, 1998.
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