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Interfacial phenomena and biomaterials
Andrade, J. D. (1973), Med Instrum 7(2): 110-9.

Interferon-gamma protects against biomaterial-associated Staphylococcus epidermidis infection in mice
Boelens, J. J., T. van der Poll, et al. (2000), J Infect Dis 181(3): 1167-71.
Abstract: Survival of Staphylococcus epidermidis inside macrophages has been recognized as a pivotal process in the pathogenesis of biomaterial-associated infection (BAI). Interferon (IFN)-gamma is a potent activator of macrophages. This study examined whether subcutaneous injections of IFN-gamma can reverse macrophage deactivation induced by implanted biomaterials. Mice received subcutaneous implants combined with an injection of 106 S. epidermidis to induce an experimental BAI. Subsequently, 3 groups of mice received subcutaneous injections of 25,000 IU IFN-gamma 3 times weekly, 10,000 IU IFN-gamma 3 times in 2 weeks, or saline 3 times weekly (saline control), respectively. A fourth group received no injections (control). Segments and tissues of the IFN-gamma-treated mice were significantly less (P<.05) culture positive than those of the control groups. Histologically, the high numbers of intracellularly persisting gram-positive cocci observed in the control mice were absent in the IFN-gamma-treated mice. These data indicate that IFN-gamma protects against experimental BAI.

Interlaboratory standards for physicochemical and biological testing of biomaterials
Ward, R. S., B. J. Tsuchiyama, et al. (1981), Trans Am Soc Artif Intern Organs 27: 410-5.

Interleukin-1 receptor type I gene-deficient mice are less susceptible to Staphylococcus epidermidis biomaterial-associated infection than are wild-type mice
Boelens, J. J., T. van der Poll, et al. (2000), Infect Immun 68(12): 6924-31.
Abstract: Elevated concentrations of interleukin-1 (IL-1) were found in tissue surrounding biomaterials infected with Staphylococcus epidermidis. To determine the role of IL-1 in biomaterial-associated infection (BAI), IL-1 receptor type I-deficient (IL-1R(-/-)) and wild-type mice received subcutaneous implants of silicon elastomer (SE) or polyvinylpyrrolidone-grafted SE (SEpvp), combined with an injection of 10(6) CFU of S. epidermidis or sterile saline. Neither mouse strain was susceptible to BAI around SE. IL-1R(-/-) mice with SEpvp implants had a no abscess formation and a reduced susceptibility to persistent S. epidermidis infection. The normal foreign body response, characterized by giant-cell formation and encapsulation, was delayed around SEpvp in wild-type mice but not in IL-1R(-/-) mice. This coincided with enhanced local IL-4 production in IL-1R(-/-) mice. These data suggest that inhibition of local IL-1 activity may be beneficial for the outcome of BAI.

Interleukin-25 and interleukin-13 production by alveolar macrophages in response to particles
Kang, C. M., A. S. Jang, et al. (2005), Am J Respir Cell Mol Biol 33(3): 290-6.
Abstract: Particle inhalation-induced lung inflammation acts as an adjuvant to allergens or respiratory viral infection in a process that is mediated by macrophages and epitheliums. The production of interleukin (IL)-4 and IL-13 by activated T cells is involved in the augmentation of Th2-type immune responses to particles, and IL-25 induces the synthesis of IL-4 and IL-13. However, whether IL-13 and IL-25 are directly regulated by particle instillation in the lung has not been studied. The aim of this study was to reveal particle induction of IL-13 and IL-25 in the lung. TiO(2) instillation potently induced the mRNA expression for IL-25 and IL-13 in lung tissue extracts 24 h after treatment, as compared with the sham group. Immunostaining for IL-25 and IL-13 showed strong positivity for macrophages in the inflammatory lung lesions of TiO(2)-treated rats. The alveolar macrophages expressed IL-25 and IL-13 24 h after in vitro stimulation with TiO(2) particles in dose- and time-dependent manners, with maximal induction at 24 and 48 h after stimulation, respectively. The sequence of the rat IL-25 gene is 95% homologous with the mouse IL-25 gene. These findings indicate that alveolar macrophages play an important role in particle-induced lung inflammation via direct induction of IL-13 and IL-25 production.

Interleukin-4 inhibits tumor necrosis factor-alpha-induced and spontaneous apoptosis of biomaterial-adherent macrophages
Brodbeck, W. G., M. S. Shive, et al. (2002), J Lab Clin Med 139(2): 90-100.
Abstract: Biocompatibility of implanted materials is determined by the host foreign-body response, which is comprised of cellular (adherent monocytes and macrophages) and soluble (secreted cytokines) components. Modulating the presence, activity or both of adherent macrophages may increase or decrease the biocompatibility of implants because these cells remain adherent to the implant surface and fuse to form foreign-body giant cells (FBGCs), leading to failure of the implant. An attractive mechanism of eliminating these cells is through the induction of apoptosis; therefore ways of inducing or inhibiting apoptosis of biomaterial-adherent inflammatory cells are being investigated. We hypothesized that interleukin-4 (IL-4) promotes macrophage survival by inhibiting tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. We found that TNF-alpha induces apoptosis in a time- and dose-dependent manner, whereas IL-4 inhibits TNF-alpha-induced and spontaneous apoptosis of biomaterial-adherent macrophages. Blocking experiments and evaluation of shedding of soluble TNF receptor type I (TNF-RI) demonstrated that endogenous TNF-alpha production is responsible for spontaneous apoptosis of biomaterial-adherent cells and that IL-4 inhibits this apoptosis by increasing levels of shedding of soluble TNF-RI. These findings suggest that TNF-alpha and IL-4 play key roles in determining the fate of biomaterial-adherent cells and that fusion of macrophages into FBGCs is a mechanism for promoting inflammatory-cell survival on implanted materials.

Internal anal sphincter augmentation for fecal incontinence using injectable silicone biomaterial
Malouf, A. J., C. J. Vaizey, et al. (2001), Dis Colon Rectum 44(4): 595-600.
Abstract: PURPOSE: A disrupted or weak internal anal sphincter can lead to passive fecal incontinence. This muscle is not amenable to direct surgical repair. Previous preliminary attempts to restore functional continuity have included a cutaneous flap to fill an anal canal defect, and injection therapy using polytetrafluoroethylene, collagen, or autologous fat. Urologists have also used injections of collagen or silicone to enhance bladder neck function. This pilot study aimed to assess the efficacy of single or multiple injections of the silicone-based product Bioplastique for the symptoms of passive fecal incontinence caused by an anatomically disrupted or intact but weak internal anal sphincter. PATIENTS AND METHODS: Ten patients (6 females; median age, 64, range, 41-80 years) with passive incontinence secondary to a weak (n = 6) or disrupted (n = 4) internal anal sphincter were injected either circumferentially or at a single site, respectively. Patients were assessed before and six weeks after treatment by clinical assessment, two-week bowel diary card, anorectal physiologic testing, and endoanal ultrasound. Patients failing to show improvement after the first injection were offered a second injection six weeks after the first injection. Clinical assessment was further repeated at six months, and five patients had a further ultrasound examination. RESULTS: At six weeks, six of ten patients showed either marked improvement (n = 3) or complete cessation of leakage (n = 3). A further patient was greatly improved after a second injection. Three patients were not improved. At six months, two of the seven patients had maintained marked improvement, and one patient had maintained minor improvement; all of these three patients had circumferential multiple injections. Maximum resting and squeeze anal pressures did not differ significantly between before vs. six weeks after vs. six months after injection. At six weeks endoanal ultrasound (n = 9) confirmed the presence and correct position of the silicone in all but one patient who had experienced obvious external leakage of the product. At six months the silicone remained in the correct position in the five endosonographically assessed patients. Five of the initial patients experienced pain or minor ulceration at the injection site. CONCLUSIONS: Although clinically effective immediately after injection, the benefit of an injectable biomaterial was maintained in only a minority of patients. This occurred despite the continued presence of material in the correct anatomical site. Patients with diffuse weakness treated by circumferential injection seemed to be the most responsive, but further studies are required to clarify this.

International Symposium on Biomaterials in Dentistry and Medicine. UCLA Los Angeles USA December 27-29 1978
Hastings, G. W. (1979), J Biomed Eng 1(3): 215-6.

Interpretation of protein adsorption: surface-induced conformational changes
Roach, P., D. Farrar, et al. (2005), J Am Chem Soc 127(22): 8168-73.
Abstract: Protein adhesion plays a major role in determining the biocompatibility of materials. The first stage of implant integration is the adhesion of protein followed by cell attachment. Surface modification of implants (surface chemistry and topography) to induce and control protein and cell adhesion is currently of great interest. This communication presents data on protein adsorption (bovine serum albumin and fibrinogen) onto model hydrophobic (CH(3)) and hydrophilic (OH) surfaces, investigated using a quartz crystal microbalance (QCM) and grazing angle infrared spectroscopy. Our data suggest that albumin undergoes adsorption via a single step whereas fibrinogen adsorption is a more complex, multistage process. Albumin has a stronger affinity toward the CH(3) compared to OH terminated surface. In contrast, fibrinogen adheres more rapidly to both surfaces, having a slightly higher affinity toward the hydrophobic surface. Conformational assessment of the adsorbed proteins by grazing angle infrared spectroscopy (GA-FTIR) shows that after an initial 1 h incubation few further time-dependent changes are observed. Both proteins exhibited a less organized secondary structure upon adsorption onto a hydrophobic surface than onto a hydrophilic surface, with the effect observed greatest for albumin. This study demonstrates the ability of simple tailor-made monochemical surfaces to influence binding rates and conformation of bound proteins through protein-surface interactions. Current interest in biocompatible materials has focused on surface modifications to induce rapid healing, both of implants and for wound care products. This effect may also be of significance at the next stage of implant integration, as cell adhesion occurs through the surface protein layer.

Intraabdominal adhesion formation of polypropylene mesh Influence of coverage of omentum and polyglactin
Conze, J., K. Junge, et al. (2005), Surg Endosc 19(6): 798-803.
Abstract: BACKGROUND: Adhesions after intraabdominal surgical procedures are related to high morbidity and mortality. Biomaterials, particularly those made of polypropylene, in the intraabdominal position have to be considered as pathophysiological cofactor in a multifactorial process of adhesion formation. To investigate the adhesive potential induced by the biomaterial, an animal model was performed. In addition, the influence of coverage by omentum or a polyglactin barrier was investigated. METHODS: In, 18 Chinchilla rabbits the biomaterial was placed laparoscopically using the intraperitoneal onlay mesh technique. Using this model, a polypropylene-polyglactin mesh compound (PPMC) was used with three different implantation techniques: group 1, PPMC implantation without coverage (PPMC): group 2, PPMC implantation with additional omentum coverage (PPMC-O): and group 3, PPMC implantation with coverage of an absorbable polyglactin mesh (PPMC-V). The degree of adhesion formation was measured 90 days after implantation by computer-assisted planimetry. Morphometric examination followed the explantation analyzing the amount of foreign body response. RESULTS: We found a significant reduction of adhesion formation for the PPMC and PPMC-O groups compared to the PPMC-V group, in which dense adhesions were found. Morphometric investigations of the perifilamental granulomas of the pure (PPMC) group revealed a typical foreign body reaction with a mild to moderate fibrosis around all mesh fibers. However, tissue specimens of the PPMC-O and PPMC-V groups indicated a similar inflammatory reaction but significantly increased connective tissue formation around the polymer fibers compared to the pure PPMC group. CONCLUSION: The intraabdominal placement of a pure PPMC shows a neoperitonealization and perifilamental collagenous ingrowth with almost no adhesions. Coverage with omentum (PPMC-O) or polyglactin mesh (PPMC-V) resulted in a significant increase in inflammation and perifilamentary connective tissue formation.

Intracellular freezing in biomaterials
Diller, K. R., E. G. Cravalho, et al. (1972), Cryobiology 9(5): 429-40.

Intraocular lenses for pediatric implantation: biomaterials, designs, and sizing
Wilson, M. E., D. J. Apple, et al. (1994), J Cataract Refract Surg 20(6): 584-91.
Abstract: Posterior chamber intraocular lenses (IOLs) are being implanted in children with increasing frequency. However, with rare exceptions, only IOLs designed for adults are currently available. These lenses may be difficult to insert into small eyes. Since the pediatric crystalline lens is smaller than that of adults and because the capsular bag does not continue to grow after lensectomy, it is worthwhile to determine the biomaterials, designs, and sizes that may be appropriate for pediatric implantation. In a study of 50 pediatric eyes obtained postmortem, we have documented an estimated growth curve for the developing crystalline lens between birth and 16 years of age. Ninety percent of crystalline lens growth occurs during the first two years of life. Based on these data and this study using the Miyake posterior view analysis of implanted standard and prototype IOLs, we recommend the following: Clinical trials of capsular IOLs, downsized to approximately 10.0 mm diameter, are appropriate for children under two years of age. Capsular IOLs are defined as flexible open-loop, one-piece, all poly(methyl methacrylate), modified C-loop designs made specifically for in-the-bag placement. Because the rapid growth phase of the lens is complete by the age of two, we believe that downsizing the IOL is not necessary after this age unless axial length measurements indicate an unusually small eye. Standard flexible 12.0 mm to 12.5 mm diameter capsular IOLs can be safely implanted. Such lenses could be tolerated throughout life, obviating the need for later IOL exchange.

Intraoperative handling and wound healing: controlled clinical trial comparing coated VICRYL plus antibacterial suture (coated polyglactin 910 suture with triclosan) with coated VICRYL suture (coated polyglactin 910 suture)
Ford, H. R., P. Jones, et al. (2005), Surg Infect (Larchmt) 6(3): 313-21.
Abstract: BACKGROUND: Coated polyglactin 910 suture with triclosan was developed recently in order to imbue the parent suture, coated polyglactin 910, with antibacterial activity against the most common organisms that cause surgical site infections (SSI). Because such alterations could alter the physical properties of the suture, this study sought to compare the intraoperative handling and wound healing characteristics of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture in pediatric patients undergoing various general surgical procedures. METHODS: This was a prospective, randomized, controlled, open-label, comparative, single-center study. Pediatric patients (age 1-18 years) undergoing various surgical procedures were randomized in a 2:1 ratio to treatment with either coated polyglactin 910 suture with triclosan or coated polyglactin 910 suture. The primary endpoint was the surgeon's assessment of the overall intraoperative handling of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture without triclosan. The secondary endpoints included specific intraoperative suture handling measures and wound healing assessments. The suture handling measures were (1) ease of passage through tissue; (2) first-throw knot holding; (3) knot tie-down smoothness; (4) knot security; (5) surgical handling; (6) surgical hand; (7) memory; and (8) suture fraying. Assessment of wound healing included the following: Healing progress, infection, edema, erythema, skin temperature, seroma, suture sinus, and pain. Adverse events were recorded. RESULTS: Scores for intraoperative handling were favorable and not significantly different for both sutures, although coated polyglactin 910 suture with triclosan received more "excellent" scores (71% vs. 59%). Wound healing characteristics were comparable for both sutures except for pain on postoperative day 1. Significantly fewer patients treated with polyglactin 910 suture with triclosan reported pain on day 1 than patients who received the other suture (68% vs. 89%, p = 0.01). The overall incidence of adverse events was 18%; none was devicerelated. CONCLUSIONS: Coated polyglactin 910 suture with triclosan performed as well or better than traditional coated polyglactin 910 suture in pediatric patients undergoing general surgical procedures. The incidence of postoperative pain was significantly less in patients treated with coated polyglactin 910 suture with triclosan than the traditional suture. We speculate that polyglactin 910 suture with triclosan, by inhibiting bacterial colonization of the suture, reduced pain that can be an indicator of "subclinical" infection. Coated polyglactin 910 suture with triclosan may be a useful alternative in patients at increased risk of developing SSI.

Intraspinal metalloma resulting in late paraparesis
Tezer, M., U. Kuzgun, et al. (2005), Arch Orthop Trauma Surg 125(6): 417-21.
Abstract: The metal-related complications caused by orthopedic implants have long been a concern, but these problems have been considered mostly in the field of arthroplasty or internal fixation of fractures. The recent prevalence of spinal instrumentation has evoked a similar concern among spine surgeons. Here, we present a case of intraspinal metallosis adjacent to the pedicular hook occurring after treatment of vertebral fracture by posterior spinal instrumentation and fusion, and causing paraparesis at the 3rd postoperative year. Metallic granulomas can appear around the pedicular hooks as in the reported case. Crevice and fretting corrosion are results at the junctions of rod-screw, rod-hook, transverse connector rod and other connector rods in modular spinal implants. Adequate usage of transpedicular screws may inhibit the occurrence of such a complication. For this reason, further studies are necessary to increase metallic corrosive resistance to inhibit crevice and fretting corrosion.

Intrinsically radiopaque hydrogels for nucleus pulposus replacement
Boelen, E. J., C. S. van Hooy-Corstjens, et al. (2005), Biomaterials 26(33): 6674-83.
Abstract: Degeneration of the intervertebral disc is the most common cause of back pain. In case of early stage degenerative disc disease or traumatic herniations, a suitable treatment may be to replace the nucleus pulposus, preserving the annulus fibrosus. Eight new hydrogel biomaterials were prepared and studied for their potential as a nucleus replacement. The hydrogels were designed according to the following criteria: (i), they should exhibit adequate radiopacity; (ii), they should be non-cytotoxic; (iii), implantation in the dry state and subsequent swelling in situ to fill the entire nucleus cavity; (iv), after swelling they should match the physical-mechanical properties of the native nucleus. The approach was to use copolymers consisting of 2-(4'-iodobenzoyl)-oxo-ethyl methacrylate (4IEMA) and a hydrophilic building block (either N-vinyl-2-pyrrolidinone (NVP) or 2-hydroxyethyl methacrylate (HEMA)); 4 copolymers of NVP/4IEMA and 4 copolymers of HEMA/4IEMA in different compositions (5, 10, 15 and 20 mol% 4IEMA). The study comprised 1H-NMR analysis of the copolymerization reaction NVP+4IEMA. Furthermore, the copolymers were studied with respect to their swelling behavior, mechanical properties, cytotoxicity in vitro and X-ray contrast. Hydrogels with 5 mol% 4IEMA appear to meet all criteria: they are non-cytotoxic, have adequate physical-mechanical properties and feature sufficient radiopacity in a realistic model. The potential implications of these new results with respect to treatment of degenerative disc disease are discussed briefly.

Introduction of surface functional groups onto biomaterials by glow discharges
Sharma, C. P., G. Jayasree, et al. (1987), J Biomater Appl 2(2): 205-18.
Abstract: An attempt was made to graft the monomer HEMA to the polymer surface by "Glow discharge" technique. Experiments were carried out for different surfaces varying the exposure times of samples to HEMA and also as a function of glow discharge time. It was found that as the percentage of grafting increases the hydrophilicity also increases. Contact angle measurements were performed on these substrates, which confirmed the hydrophilic nature of the grafted samples compared to the controls. The role of protein adsorption and their effects to modulate the blood polymer interaction is briefly discussed. When a foreign material comes in contact with blood, the initial event is the adsorption of plasma proteins in parallel with the adhesion of platelets to the material. Albuminated surfaces discourage platelet adhesion while fibrinogen enhances the platelet attachment and thrombosis. Hence a decreased ratio of fibrinogen to albumin on a substrate can be correlated as an indication to its improved blood compatibility. Fibrinogen to albumin ratios of the grafted samples showed a reduction, indicating that albumin adsorption is high; which may make the modified surfaces non-thrombogenic.

Introduction to bioengineering: melding of engineering and biological sciences
Shoureshi, R. A. (2005), Otolaryngol Clin North Am 38(2): 185-97, v.
Abstract: Engineering has traditionally focused on the external extensions of organisms, such as transportation systems, high-rise buildings, and entertainment systems. In contrast, bioengineering is concerned with inward processes of biologic organisms. Utilization of engineering principles and techniques in the analysis and solution of problems in medicine and biology is the basis for bioengineering.This article discusses subspecialties in bioengineering and presents examples of projects in this discipline.

Introduction: surface and coating variability on implanted biomaterials
Steflik, D. E. and M. Meenaghan (1998), Implant Dent 7(4): 301-2.

Introductory remarks to the biotechnology applications in biomaterials workshop
Burlington, D. B. (1994), J Cell Biochem 56(2): 145-6.

Invasive properties of multidrug resistant human melanoma cells
Molinari, A., A. Stringaro, et al. (2005), Ital J Anat Embryol 110(2 Suppl 1): 135-41.
Abstract: Melanoma cells exhibit a high level of intrinsic or acquired resistance to the cytotoxic agents often associated with the over-expression of drug transporters such as P-glycoprotein (P-gp). In this in vitro study, we investigated the possible relationship between P-gp and CD44, the cell adhesion molecule involved in metastasis and tumor progression of melanoma cells. CD44 expression appeared to be similar in the parental sensitive M14 WT cells and in their resistant counterparts M14 ADR cells. Double-labeling of cryosectioned cells showed that P-gp and CD44 were transported from the synthesis loci to the cell periphery by different vesicles and began to coalesce in proximity of the plasma membrane; thus, P-gp and CD44 seemed to reach together the cell surface. Moreover, P-gp and CD44 appeared to be associated with ERM proteins. The invasive activities of both M14 WT and M14 ADR cells were analyzed by the "transwell chamber invasion" assay. M14 WT cells revealed low capacity to traverse the filters, both in the absence (motility) and in the presence (invasion) of a Matrigel coating. In comparison, M14 ADR cells displayed significantly higher motility and invasion. SEM observations showed that sensitive cells employed lamellar cytoplasmic extrusions to pass through the filter pores whereas resistant cells elongated along the hole through globular processes. In conclusion, the results herein reported suggest that drug resistance in melanoma cells appears associated with a more aggressive behaviour. P-gp and CD44 might cooperate to confer this more invasive phenotype.

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Last Modified: 8 February 2006