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  • 1
    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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  • 2
    ISSN: 0021-9304
    Keywords: biomaterials ; polyurethanes ; infection ; infection resistance ; surface modification ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3½, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 142-153, 1998.
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  • 3
    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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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 321-331 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: As reported in Part I (“In vivo testing of crosslinked polyethers. I. Tissue reactions and biodegradation,” J. Biomed. Mater. Res., this issue, pp. 307-320), microscopical evaluation after implantation of crosslinked (co)polyethers in rats showed differences in the rate of biodegradation, depending on the presence of tertiary hydrogen atoms in the main chain and the hydrophilicity of the polyether system. In this article (Part II) the biostability will be discussed in terms of weight loss, the swelling behavior, and changes in the chemical structure of the crosslinked polyethers after implantation. The biostability increased in the order poly(POx) 〈 poly(THF-co-OX) 〈 poly(THF) for the relatively hydrophobic polyethers. This confirmed our hypothesis that the absence of tertiary hydrogen atoms would improve the biostability. On the other hand, signs of biodegradation were observed for all polyether system studied. Infrared surface analysis showed that biodegradation was triggered by oxidative attack on the polymeric chain, leading to the formation of carboxylic ester and acid groups. It also was found that in the THF-based (co)polyethers, α-methylene groups were more sensitive than β-methylene groups. For a hydrophilic poly(THF)/PEO blend, an increase in surface PEO content was found, which might be due to preferential degradation of the PEO domains. © 1996 John Wiley & Sons, Inc.
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  • 6
    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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  • 7
    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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  • 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
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effect of local gentamicin release through a vicinal collagen sponge or through preoperative solution-dipping of rat lead samples was investigated in an early-infection model. The efficacy of these methods and their effect on tissue response were determined. It was demonstrated that both methods of local gentamicin release suppress lead-related infectious complications as compared to the control lead, which showed a high presence of inflamed/infected tissues and bacterial growth at each explantation time point. The first day the vicinal collagen sponge was more effective in suppressing the infection than was the solution-dipped lead, probably because there is a faster and higher dose release of gentamicin from the sponge. However, continued implantation time revealed that gentamicin release from the solution-dipped lead was more effective than the sponge. This supports our hypothesis that the presence of lumina are decisive for bacterial growth and persistence of implant-related infections. © 1997 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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