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Compatibility of lyotropic liquid crystals with viruses and mammalian cells that support the replication of viruses
Cheng, L. L., Y. Y. Luk, et al. (2005), Biomaterials 26(34): 7173-82.
Abstract: We report a study that investigates the biocompatibility of materials that form lyotropic liquid crystals (LCs) with viruses and mammalian cells that support the replication of viruses. This study is focused on aqueous solutions of tetradecyldimethyl-amineoxide (C(14)AO) and decanol (D), or disodium cromoglycate (DSCG; C(23)H(14)O(11)Na(2)), which can form optically birefringent, liquid crystalline phases. The influence of these materials on the ability of vesicular stomatitis virus (VSV) to infect human epitheloid cervical carcinoma (HeLa) cells was examined by two approaches. First, VSV was dispersed in aqueous C(14)AO+ D or DSCG, and then HeLa cells were inoculated by contacting the cells with the aqueous C(14)AO + D or DSCG containing VSV. The infectivity of VSV to the HeLa cells was subsequently determined. Second, VSV was incubated in LC phases of either C(14)AO + D or DSCG for 4 h, and the concentration (titer) of infectious virus in the LC was determined by dilution into cell culture medium and subsequent inoculation of HeLa cells. Using these approaches, we found that the LC containing C(14)AO + D caused inactivation of virus as well as cell death. In contrast, we determined that VSV retained its infectivity in the presence of aqueous DSCG, and that greater than 74-82% of the HeLa cells survived contact with aqueous DSCG (depending on concentration of DSCG). Because VSV maintained its function (and we infer structure) in LCs formed from DSCG, we further explored the influence of the virus on the ordering of the LC. Whereas the LC formed from DSCG was uniformly aligned on surfaces prepared from self-assembled monolayers (SAMs) of HS(CH(2))(11)(OCH(2)CH(2))(4)OH on obliquely deposited films of gold in the absence of VSV, the introduction of 10(7)-10(8) infectious virus particles per milliliter caused the LC to assume a non-uniform orientation and a colorful appearance that was readily distinguished from the uniformly aligned LCs. Control experiments using cell lysates with equivalent protein concentrations but no virus did not perturb the uniform alignment of the LC.

Compatibility of tissue conditioners and dental stones: effect on surface roughness
Murata, H., G. Hong, et al. (2005), J Prosthet Dent 93(3): 274-81.
Abstract: STATEMENT OF PROBLEM: Although the primary use of tissue conditioners is to treat abused mucosa, these materials are also frequently used as functional impression materials. No information was identified on the effect that these materials may have on the surface of the resultant dental stone cast. PURPOSE: This study evaluated the compatibility of 3 tissue conditioners with dental stones and changes in surface conditions over time. MATERIAL AND METHODS: Three tissue conditioners (COE-comfort, Soft-conditioner, and Visco-gel) and 4 dental stones (Capstone DF, New Plastone, Die Stone, and New Fujirock) were evaluated. One impression material (Examixfine) was used as a control. Tissue conditioner disks were made by pouring freshly mixed material into a polypropylene container, pressing the material down with a glass plate, and then removing the plate 2 hours later. The disks were then stored in distilled water for 0 or 24 hours, or 3, 7, or 14 days. Subsequently, each dental stone was mixed and poured over the top of each disk and allowed to remain for 60 minutes. Twenty-five disk-shaped specimens, 18 x 2 mm, for each tissue conditioner/stone cast combination were prepared. Mean surface roughness (Ra) values of the dental stone casts made from the tissue conditioners were determined using a profilometer. Five measurements for each specimen were made. Data were analyzed with 1- and 3-way analysis of variance and the Student-Newman-Keuls test (alpha=.05). Detail reproduction was also determined using a ruled test block, as specified in ISO specification 4823. RESULTS: Contribution ratios determined by 3-way analysis of variance indicated that the surface roughness values were significantly more influenced by the time of immersion in water (P <.0005, contribution ratio rho=37%), than the type of tissue conditioner (P <.0005, rho=19%) or dental stone used (P <.0005, rho=1%). The best surface quality was obtained with a New Fujirock cast (0.81 +/- 0.06 microm), followed by New Plastone (0.83 +/- 0.12 microm) and Die Stone (0.85 +/- 0.05 microm) casts, in combination with Visco-gel without immersion in water, and those were nearly equivalent in surface roughness to a Die stone cast from Examixfine. The surface roughness values of all specimens, especially the COE-comfort/stone cast combinations, significantly increased with tissue conditioner immersion time (P <.0005). Visco-gel tended to produce a better surface quality during the test periods than the other materials. All stone casts made from the tissue conditioners not immersed in water reproduced 20-microm or 50-microm lines, while the detail diminished over time with immersion. CONCLUSION: The type of tissue conditioner, and especially immersion time, had a significant effect on the surface quality of dental stone casts. The type of dental stone used is less important.

Competitive adsorption of vitronectin with albumin, fibrinogen, and fibronectin on polymeric biomaterials
Fabrizius-Homan, D. J. and S. L. Cooper (1991), J Biomed Mater Res 25(8): 953-71.
Abstract: Vitronectin (VN) was competitively adsorbed with human serum albumin (HSA), fibrinogen (FGN), and fibronectin (FN) from binary component mixtures in order to compare the relative affinities of these proteins for various polymer materials. Competitive adsorption was monitored by incubating radiolabeled protein solutions inside 0.125-in. i.d. tubing of the polymers, flushing with buffer, and measuring the adherent radioactivity. Adsorption experiments at equal mass concentrations of the competing proteins revealed that VN comprises at least 75% by weight of the adsorbed protein when competitively adsorbed with HSA and approximately 50% by weight when competitively adsorbed with FGN and FN on all surfaces except a poly(ethylene oxide)-based polyurethane where it comprised closer to 80 wt%. When VN was competitively adsorbed in the presence of increasing amounts of HSA, FGN, and FN, the amount of VN adsorbed on a weight basis was diminished the most by FGN. HSA had the least inhibitory effect at low bulk concentrations and FN had the weakest effect at higher bulk concentration levels. When HSA, FGN, and FN were competitively adsorbed in the presence of increasing amounts of VN, VN diminished their adsorption on a weight basis in the order: HSA greater than FN greater than FGN.

Complement activation and bioincompatibility. The terminal complement complex for evaluation and surface modification with heparin for improvement of biomaterials
Mollnes, T. E., V. Videm, et al. (1991), Clin Exp Immunol 86 Suppl 1: 21-6.
Abstract: The degree of biocompatibility of biomaterials can be evaluated using various assay systems detecting activation of the blood cascade systems, leukocytes or platelets. Activation of complement is one mechanism associated with adverse effects observed when bioincompatible materials are used. We present data showing that the terminal complement complex, an indicator of terminal pathway activation, is suitable for evaluation of biocompatibility of biomaterials such as cardiopulmonary bypass devices. Furthermore, our results suggest that bioincompatibility is improved when artificial surfaces are modified with end point attached functionally active heparin.

Complement activation and inflammation triggered by model biomaterial surfaces
Tang, L., L. Liu, et al. (1998), J Biomed Mater Res 41(2): 333-40.
Abstract: Biomaterial-mediated complement activation repeatedly has been invoked as a trigger of phagocyte reactions and inflammation. However, a direct correlation between complement activation and inflammatory responses to biomaterial surfaces has yet to be established. Using an animal implantation model and gold surfaces bearing various thiol-linked functionalities, we investigated the potency of different surface groups in prompting complement activation in vitro and surface-mediated accumulation of inflammatory cells in vivo. Among the surfaces tested, mercaptoglycerol- and mercaptoethanol-bearing surfaces engendered the strongest inflammatory responses, as reflected by the accumulation of large numbers of adherent neutrophils and monocytes/macrophages. In contrast, L-cysteine-coated surfaces caused only minor inflammatory responses, and both glutathione-modified and untreated gold implants attracted minimal numbers of inflammatory cells. The accumulation of inflammatory cells on mercaptoglycerol surfaces appears to arise from surface-mediated complement activation because complement-depleted animals failed to exhibit inflammatory responses to mercaptoglycerol-modified implants. Furthermore, there is a close relationship between surface-mediated complement activation (as measured by in vitro iC3b/C5b-9 generation and C3 deposition) and in vivo inflammatory responses. At least in this animal model and with these model surfaces, our results indicate that surface-mediated complement activation can be responsible for the subsequent accumulation of inflammatory cells on implant surfaces.

Complement activation by biomaterials
Johnson, R. J. (1990), Prog Clin Biol Res 337: 507-12.

Complement activation mediates cellular adhesion to synthetic biomaterials
Ward, C. A. and P. G. Kalman (1989), Med Prog Technol 15(1-2): 63-75.
Abstract: The possibility has arisen that it is the complement proteins of blood plasma that mediates cellular adhesion following the exposure of a synthetic material to blood. There are two means of investigating this possibility. One is by pharmacologically rendering the complement system of an animal incapable of being activated before its blood is exposed to a material and determining the effect on the degree of cellular adhesion that results. The second is to leave the hemostasis system fully in tact but to modify the material so that the material activates less complement when it is exposed to blood and to determine if this also reduces the degree of cellular adhesion. We review the results of a series of studies that involve both of these approaches. The evidence from both indicate that the complement system mediates cellular adhesion to synthetic materials.

Complement activation produced by biomaterials
Chenoweth, D. E. (1986), ASAIO Trans 32(1): 226-32.

Complement activation produced by biomaterials
Chenoweth, D. E. (1988), Artif Organs 12(6): 508-10.
Abstract: The complement-activating potential of biomaterials may be defined by appropriate application of C3a and C5a anaphylatoxin radioimmunoassays. Studies performed with hemodialysis membranes demonstrate that blood contact with these model biomaterials results in complement activation that may be ascribed to specific properties of the material surface. Further delineation of these chemical and physical properties may permit design of biocompatible materials.

Complement inhibition reduces material-induced leukocyte activation with PEG modified polystyrene beads (Tentagel) but not polystyrene beads
Gorbet, M. B. and M. V. Sefton (2005), J Biomed Mater Res A 74(4): 511-22.
Abstract: With isolated leukocytes, inhibiting complement reduced material-induced leukocyte activation (CD11b) with polyethylene glycol modified polystyrene beads (PS-PEG), but not with polystyrene beads (PS). The PS-PEG beads (TentaGel) were complement activating as measured by SC5b-9 levels consistent with the sensitivity of these beads to leukocyte inhibition with complement inhibitors. Following contact with PS and PS-PEG beads, isolated leukocytes in plasma and in the absence in platelets were found to significantly upregulate CD11b, while TF expression and exposure of phosphatidylserine remained at background levels. Complement inhibition by means of sCR1 partially reduced CD11b upregulation on PS-PEG beads, but had no effect with PS beads. Pyridoxal-5-phosphate (P5P) was able to significantly reduce both CD11b upregulation and exposure of phosphatidylserine with PS-PEG beads, although it did not appear to inhibit SC5b-9 production. Pentamidine and NAAGA inhibited complement and were effective in reducing CD11b upregulation with both PS and PS-PEG. However, they also had an inhibitory effect on leukocyte signaling mechanisms, precluding their utility for further study in this context. Leukocyte adhesion occurred to similar extents on both PS and PS-PEG beads. While sCR1 and P5P blocked adhesion and activation (for adherent leukocytes) on PS-PEG beads, they had no effect on leukocytes adherent to PS beads. The role of complement in leukocyte activation and adhesion was found to be material-dependent. Thus, leukocyte-material compatibility may be resolved by complement inhibition in some but not all cases. For these other materials (example here was PS), other mechanisms, such as fibrinogen adsorption and direct leukocyte release, may need exploitation to minimize leukocyte activation and adhesion.

Complete root coverage at multiple sites using an acellular dermal matrix allograft
Mehlbauer, M. J. and H. Greenwell (2005), Compend Contin Educ Dent 26(10): 727-8, 730-3; quiz 734-5.
Abstract: This study reports results of root coverage treatment with a coronally positioned flap and an acellular dermal matrix allograft. The same protocol was followed as in a previous university study to determine if the results could be duplicated in a private practice setting. Complete root coverage was obtained on most defects. Use of an acellular dermal matrix allograft avoided the postoperative morbidity associated with harvesting palatal connective tissue. The unlimited supply of the allograft allowed extended flaps to achieve multiple site root coverage, which proved to be a practical and predictable procedure in these cases.

Complications and toxicities of implantable biomaterials for facial aesthetic and reconstructive surgery
Homsy, C. A. (1998), Plast Reconstr Surg 102(5): 1766-8.

Complications and toxicities of implantable biomaterials used in facial reconstructive and aesthetic surgery: a comprehensive review of the literature
Rubin, J. P. and M. J. Yaremchuk (1997), Plast Reconstr Surg 100(5): 1336-53.
Abstract: The use of implantable biomaterials has become an integral part of aesthetic and reconstructive surgery of the face. Metals are used for fracture fixation devices, whereas polymers are used primarily for bone or soft-tissue substitution. This review of the scientific literature examines the risks and complications of these materials. First, we present an overview of commonly used materials. Second, we address general considerations of toxicity relevant to all biomaterials. Third, we present data from a large number of clinical series on the incidence of complications for individual materials used in specific applications.

Composite biomaterials based on ceramic polymers. I. Reinforced systems based on Al2O3/PMMA/PLLA
Rodriguez-Lorenzo, L. M., A. J. Salinas, et al. (1996), J Biomed Mater Res 30(4): 515-22.
Abstract: Composite biomaterials with good mechanical response and a partially biodegradable character were prepared by the free radical polymerization of mixtures of alpha-Al2O3, low-molecular-weight but crystalline poly(L-lactic acid) (PLLA), and methyl methacrylate (MMA). Cylindrical specimens prepared with different composition were characterized by thermogravimetry, calorimetry, 1H-NMR spectroscopy, and x-ray diffraction (XRD). The in vitro biodegradative process was studied in different media, following variations of the pH, gravimetric weight loss of the specimens, and crystalline domain change by XRD after immersion in pure water and buffered solutions at pH 4.0 and pH 8.0 for 90 days. Formation of a relatively porous structure with good cohesion after the biodegradative treatment (confirmed by SEM) was observed. These systems can be considered for applications in orthopedic surgery as filling biomaterials and even as control drug-delivery systems.

Composite biomaterials with chemical bonding between hydroxyapatite filler particles and PEG/PBT copolymer matrix
Liu, Q., J. R. de Wijn, et al. (1998), J Biomed Mater Res 40(3): 490-7.
Abstract: In an effort to make composites from hydroxyapatite and a PEG/PBT copolymer (Polyactive 70/30), chemical linkages were introduced between the filler particles and polymer matrix using hexamethylene diisocyanate as a coupling agent. Infrared spectra (IR) and thermal gravimetric analysis (TGA) confirmed the presence of Polyactive 70/30 on the surface of HA filler particles. The amount of chemically bound polymer was 4.7 wt.%, as determined by TGA. The mechanical properties of the composites, that is, tensile strength and Young's modulus, were improved significantly by the introduction of a chemical linkage between the filler particles and polymer matrix compared to control composites. This method provides an effective way to introduce chemical linkage between HA filler particles and a polymer matrix. By optimizing the grafting process, a further improvement of the mechanical properties in the composites can be expected.

Composite formation from hydroxyapatite with sodium and potassium salts of polyphosphazene
Greish, Y. E., J. D. Bender, et al. (2005), J Mater Sci Mater Med 16(7): 613-20.
Abstract: The low temperature synthesis of composites potentially suitable as bone substitutes which form in vivo, was investigated. The composites were comprised of stoichiometric hydroxyapatite (SHAp) and water-soluble poly phosphazenes. These constituents were selected because of their biocompatibility, and were mixed as powders with a phosphate buffer solution (PBS) to form the composites. The effects of poly[bis(sodium carboxylatophenoxy)phosphazene] (Na-PCPP) or poly[bis(potassium carboxylatophenoxy) phosphazene] (K-PCPP) on stoichiometric hydroxyapatite (SHAp) formation from tetracalcium phosphate and anhydrous dicalcium phosphate were assessed. The kinetics and reaction chemistries of composite formation were followed by isothermal calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. In the presence of 1% by weight of polyphosphazenes, composites comprised of SHAp and calcium cross-linked polymer salts were formed. Thus a mechanism for binding between polymer chains was established. Elevated proportions (5 and 10% by weight) of polyphosphazene, however, resulted in the inhibition of SHAp formation. This is attributed to the formation of viscous polymer solution coatings on the calcium phosphate precursors, retarding their reaction, and consequently inhibiting SHAp formation.

Composite PHB-GGF conduit for long nerve gap repair: a long-term evaluation
Mohanna, P. N., G. Terenghi, et al. (2005), Scand J Plast Reconstr Surg Hand Surg 39(3): 129-37.
Abstract: Two to four cm nerve gaps in the rabbit common peroneal nerve were bridged with poly-3-hydroxybutyrate (PHB) conduits containing either glial growth factor (GGF) (PHB-GGF) or alginate matrix (PHB-ALG), and with empty PHB conduit (E-PHB). PHB-GGF significantly increased nerve regeneration up to 63 days following repair of long nerve gaps and the regeneration was sustained long term leading to motor organ reinnervation. At 120 days postoperatively, GGF addition significantly increased the quantity of Schwann cell and axonal regeneration compared to those in control conduits. In PHB-GGF conduits there were more minifascicles of myelinated fibres compared to the controls. The distal nerve of PHB-GGF and E-PHB conduits showed greater regeneration than that of PHB-ALG grafts, although all distal nerves contained fewer myelinated fibres than grafted conduits. Consistently, PHB-GGF conduits significantly reduced the muscle mass percentage loss compared to controls. In conclusion, GGF-containing conduits promoted sustained axonal regeneration and improved target muscle reinnervation.

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component
Bellon, J. M., N. Garcia-Honduvilla, et al. (2005), Hernia 9(4): 338-43.
Abstract: The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP+h) or Vicryl (PP+v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08+/-5.09, PP+h: 18.55+/-4.96, P+v: 69.69+/-16.81%), neoperitoneal thickness (PP: 256.17+/-21.68, PP+h: 83.11+/-19.63, PP+v:213.72+/-35.90 mum) and macrophage counts (PP: 8.73+/-1.16, PP+h: 27.33+/-4.13, PP+v: 31.24+/-3.08%) showed significant differences (P<0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP+h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.

Composite prostheses used to repair abdominal wall defects: physical or chemical adhesion barriers?
Bellon, J. M., N. Serrano, et al. (2005), J Biomed Mater Res B Appl Biomater 74(2): 718-24.
Abstract: In a composite prosthesis, the component placed at the peritoneal interface takes the form of a physical or chemical barrier. In this experimental study performed on the white New Zealand rabbit, several composites were examined to establish the effectiveness of these barriers at impeding adhesion formation. The biomaterials tested were two polypropylene prostheses (PP) with the physical barriers of expanded polytetrafluoroethylene or polyurethane (PP + ePTFE and PP + PU) and two prostheses (one polyester and the other PP) with the absorbable chemical barriers of polyethylene glycol/glycerol and hyaluronate, respectively (PO + gl and PP + hy). The composites were used to repair 7 x 5 cm defects created in the abdominal wall of the animals by placing the implant in contact with the visceral peritoneum and the subcutaneous tissue and fixing it to recipient tissue by 4/0 polypropylene running suture. Fourteen days after surgery the animals were sacrificed and specimens were taken for light microscopy and scanning electron microscopy. Adhesions developing at the prosthesis/visceral peritoneal interface were quantified. All the prostheses induced optimal mesothelialization. Composites with physical barriers behaved similarly in terms of provoking adhesions. However, the prostheses with chemical barriers differed in their effectiveness at preventing adhesions. Overall, the best results were obtained with the PP + PU composite.

Composition of bone and apatitic biomaterials as revealed by intravital Raman microspectroscopy
Penel, G., C. Delfosse, et al. (2005), Bone 36(5): 893-901.
Abstract: Microcharacterization of biominerals allows a better understanding of the pathophysiological events that occur in calcified tissues and synthetic biomaterials. Different methods have been extensively used to conduct such investigations. A new model for the intravital study of the composition and structure of membranous bone by Raman microspectroscopy is described. Titanium bone chambers equipped with a fused-silica optical window were implanted transcutaneously in the calvaria of New Zealand rabbits. The implanted optical windows were well tolerated, and spectral acquisitions were performed without any additional invasive procedure. Bone and implanted apatitic biomaterials were analyzed at different times after surgery. All Raman bands were unambiguously identified in the bone and biomaterial spectra. The main PO4 and CO3 Raman bands in bone spectra were consistent with those found in the carbonated apatite spectrum. The major collagen bands were always observed around 1200-1300 (amide III) and 1600-1700 (amide I) delta cm(-1) and, 1400-1470 and 2800-3100 delta cm(-1) (bending and stretching modes of CH groups, respectively). The phenylalanine (Phe) band was identified in all spectra at 1003 delta cm(-1) and overlapped that of the weak HPO4(2-) ion. The CH bands frequently overlapped the lipid bands. However a distinct protein and lipid bands were detected at 2950 and 2852 delta cm(-1), respectively. In bone areas close to blood vessels, the Raman signature of hemoglobin was detected with a characteristic band at 754 delta cm(-1). The changes observed in bone varied as a function of time and location. The composition and structure of all of the biomaterials studied--including those that were resorbable--seemed to remain stable over time and location. We report for the first time the complete intravital study of Raman spectra of bone and calcium phosphate biomaterials over a period of 8 months. This new approach does not require specimen preparation and allows simultaneous observation of mineral and organic bone constituents over time, which therefore should provide insightful information about their relationship.


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