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Press-formable CaO-MgO-SiO(2)-TiO(2)-Ag(2)O glass as a biomaterial
Nonami, T. and S. Tsutsumi (2000), J Biomed Mater Res 50(1): 8-15.
Abstract: Glass-ceramics were investigated to obtain a glass with a composition of CaO. MgO. 2SiO(2). 0.375TiO(2). 0.007Ag(2)O. The glass melted at 1500 degrees C and could be cast. Crystallization of diopside of this glass is controlled by volume nucleation and growth processes. In a crystallization treatment at 850 degrees -870 degrees C, this glass presented a milky white, semitransparent color. The crystals formed were diopside, their crystal grain diameter was 1-2 micrometer, and crystallization was 15-25%. The bending strength of the glass produced by a crystallization treatment of 25 min at 850 degrees C was 400 MPa, which is suitable for artificial bones. This crystallized glass also was extremely stable, with no weight loss after stability testing in artificial saliva. The softening point, as determined from the viscosity curve, was 830 degrees C, and the crystallization temperature was 895 degrees C. Thus this glass can be press-formed at a temperature of 830 degrees -880 degrees C. Actual press-forming at a pressure of 0.64 MPa was carried out for 40 min at 850 degrees C and resulted in the formation of desired shapes. Given its ready formation into desired shapes and its great strength after crystallization, such glass is applicable for use as artificial bones and as dental roots and crowns.

Pressing on: the legacy of Percy W. Bridgman
McMillan, P. F. (2005), Nat Mater 4(10): 715-8.
Abstract: A hundred years ago, Percy Bridgman invented mechanical devices that dramatically expanded the high-pressure range available for carrying out physics and chemistry experiments into an unprecedented regime of high densities. His pioneering work revolutionized condensed matter research. His spirit remains alive today as researchers continue to push back the boundaries of high-pressure science.

Prevascularization of a biomaterial using a chorioallontoic membrane
Sanders, J. E., S. G. Malcolm, et al. (2002), Microvasc Res 64(1): 174-8.

Prevention and treatment of amputation neuroma by an atelocollagen tube in rat sciatic nerves
Sakai, Y., M. Ochi, et al. (2005), J Biomed Mater Res B Appl Biomater 73(2): 355-60.
Abstract: To evaluate the potential of the atelocollagen tube as a cap for amputation neuromas, the histological and histochemical characteristics of the neuroma and spinal cord were compared with those following silicone capping. Four weeks after the transection of 18 rat sciatic nerves, the amputated neuroma was resected, and the nerve stump inserted into an atelocollagen or silicone tube. The histological changes in the nerve ends and c-fos expression in the dorsal horn of the fourth lumbar spinal cord were evaluated at 4 weeks postoperatively. The regenerated nerve structure in the atelocollagen or silicone tube was very thin. In contrast, a typical bulbous neuroma was observed in the control group (the nerve stump was left in place). The atelocollagen and silicone tube groups demonstrated fewer c-fos-expressed cells in the spinal cord than the controls. These results suggest that capping by an atelocollagen tube, like that by a silicone tube, might successfully prevent an amputated neuroma from forming, and suppress induced pain. The atelocollagen tube may be a promising biomaterial for the prevention or treatment of a painful amputation neuroma.

Prevention of calcification of glutaraldehyde-crosslinked porcine aortic cusps by ethanol preincubation: mechanistic studies of protein structure and water-biomaterial relationships
Vyavahare, N. R., D. Hirsch, et al. (1998), J Biomed Mater Res 40(4): 577-85.
Abstract: Clinical usage of bioprosthetic heart valves (BPHVs) fabricated from glutaraldehyde-pretreated porcine aortic valves is restricted due to calcification-related failure. We previously reported a highly efficacious ethanol pretreatment of BPHVs for the prevention of cuspal calcification. The aim of the present study is to extend our understanding of the material changes brought about by ethanol and the relationship of these material effects to the ethanol pretreatment anticalcification mechanism. Glutaraldehyde-crosslinked porcine aortic valve cusps (control and ethanol-pretreated) were studied for the effects of ethanol on tissue water content and for spin-lattice relaxation times (T1) using solid state proton NMR. Cusp samples were studied for protein conformational changes due to ethanol by ATR-FTIR spectroscopy. The changes in cuspal tissue-cholesterol (in vitro) interactions also were studied. Cusp material stability was assessed in terms of residual glutaraldehyde content and collagenase degradation. Water content of the cusp samples was decreased significantly due to ethanol pretreatment. The cuspal collagen conformational changes (per infrared spectroscopy) brought about by ethanol pretreatment were persistent even after rat subdermal implantation of cusp samples for 7 days. In vitro cholesterol uptake by cusps was greatly reduced as a result of ethanol pretreatment. Ethanol pretreatment of cusps also resulted in increased resistance to collagenase digestion. Cuspal glutaraldehyde content was not changed by ethanol pretreatment. We conclude that ethanol pretreatment of bioprosthetic heart valve cusps causes multi-component effects on the tissue/material and macromolecular characteristics, which partly may explain the ethanol-pretreatment anticalcification mechanism.

Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose-based bioresorbable membrane: a prospective, randomized, evaluator-blinded multicenter study
Cohen, Z., A. J. Senagore, et al. (2005), Dis Colon Rectum 48(6): 1130-9.
Abstract: INTRODUCTION: Postoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients. METHODS: Twelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no anti-adhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision. RESULTS: Data were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose. CONCLUSIONS: Glycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.

Prevention of thrombus formation on biomaterials exposed to blood using different antiplatelet drugs: experimental study in dogs
Escudero, M. C., L. Alvarez, et al. (1994), J Biomed Mater Res 28(1): 1-6.
Abstract: An ex vivo shunt, established in dogs between both femoral arteries and right atrium, has been used to quantify the platelet deposition on six prosthetic materials used in the construction of cardiovascular prostheses: highly porous knitted Dacron (intervascular HP 800, 1400 mL/cm2/min/120 mm Hg), low-porosity woven Dacron (intervascular LP 200, 200 mL/cm2/min/120 mm Hg), double velour knitted Dacron, Avcothane 51 elastomere, and the mesothelial and epipericardial surfaces of bovine pericardium. In the search for a method to prevent platelet thrombi formation on these materials, we studied four groups of dogs: group 1 (control), group 2 (5 mg/kg body weight (BW)/day acetylsalicylic acid), group 3 (20 mg/kg BW/day acetylsalicylic acid), and group 4 (5 mg/kg BW/day acetylsalicylic acid plus 5 mg/kg BW/day dipyridamole). Platelets were labeled with 111In-oxine. The least thrombogenic material was Avcothane 51 elastomere. The only effective treatment for reduction of platelet deposition on the six materials was 5 mg/kg BW/day of acetylsalicylic acid. The dose used in group 3 only decreased the deposition of platelets on three of the six materials studied. The treatment employed in group 4 did not significantly reduce the deposition of platelets on any of the materials when compared with the control group.

Primary adhesion of Pseudomonas aeruginosa to inanimate surfaces including biomaterials
Ahearn, D. G., R. N. Borazjani, et al. (1999), Methods Enzymol 310: 551-7.

Primary antitumor immune response mediated by CD4+ T cells
Corthay, A., D. K. Skovseth, et al. (2005), Immunity 22(3): 371-83.
Abstract: Gene-targeted mice have recently revealed a role for lymphocytes and interferon-gamma (IFNgamma) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNgamma activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages.

Proapoptotic, antimigratory, antiproliferative, and antiangiogenic effects of commercial C-reactive protein on various human endothelial cell types in vitro: implications of contaminating presence of sodium azide in commercial preparation
Liu, C., S. Wang, et al. (2005), Circ Res 97(2): 135-43.
Abstract: Recent experimental studies suggest C-reactive protein (CRP) may be a potential mediator of atherosclerosis and its complications. However, there is growing criticism of in vitro CRP studies that use commercial CRP preparations containing biologically active contaminants. The effects of commercial CRP, dialyzed commercial CRP (dCRP) to remove azide, and sodium azide (NaN3) alone at equivalent concentrations to the undialyzed preparation were tested at varying concentrations on human umbilical vein endothelial cells (HUVEC), circulating endothelial outgrowth cells (EOC), and endothelial progenitor cells (EPC) in vitro. CRP and NaN3 alone exhibited equivalent concentration-dependent, proapoptotic effects on HUVEC, EOC, and EPC (P<0.01 versus control), whereas dCRP had no such effect. Similarly, CRP and NaN3 alone caused equivalent concentration-dependent decreases in migration, proliferation, and matrigel tube formation (P<0.01 versus control) in EOC and HUVEC, whereas dCRP had absolutely no effect on these biological functions at any of the concentrations used. We conclude that proapoptotic, antiproliferative, antimigratory, and antiangiogenic effects of this commercial CRP preparation on a number of endothelial cell phenotypes in culture may be explained by the presence of sodium azide in this preparation. This study has implications for interpretation of in vitro studies using CRP preparations containing azide at equivalent or higher concentrations.

Probabilistic fasteners with parabolic elements: biological system, artificial model and theoretical considerations
Gorb, S. N. and V. L. Popov (2002), Philos Transact A Math Phys Eng Sci 360(1791): 211-25.
Abstract: Probabilistic fasteners are attachment devices composed of two surfaces covered with cuticular micro-outgrowths. Friction-based fasteners demonstrate high frictional forces when the surfaces come into contact. Attachment in this case is based on the use of the surface profile and mechanical properties of materials, and is fast, precise and reversible. The best-studied examples composed of parabolic elements are the wing-locking mechanism in beetles and the head arrester in dragonflies. This study combines experimental data of force measurements, obtained in an artificial model system, and theoretical considerations based on the simple model of behaviour of probabilistic fasteners with parabolic elements. Elements of the geometry in both cases correspond to the biological prototypes. Force measurements on the artificial system show that the attachment force is strongly dependent on the load force. At small loads, the increase of attachment is very slow, whereas rapid increase of attachment was detected at higher loads. At very high loads, a saturation of the attachment force was revealed. A simple explanation of the attachment principle is that with an increasing load elements of both surfaces slide into gaps of the corresponding part. This results in an increase of lateral loading forces acting on elements. High lateral forces lead to an increase of friction between single sliding elements. An analytical model which describes behaviour of the probabilistic fasteners with parabolic elements is proposed.

Probing surface adhesion forces of Enterococcus faecalis to medical-grade polymers using atomic force microscopy
Senechal, A., S. D. Carrigan, et al. (2004), Langmuir 20(10): 4172-7.
Abstract: The aim of this study was to compare the initial adhesion forces of the uropathogen Enterococcus faecalis with the medical-grade polymers polyurethane (PU), polyamide (PA), and poly(tetrafluoroethylene) (PTFE). To quantify the cell-substrate adhesion forces, a method was developed using atomic force microscopy (AFM) in liquid that allows for the detachment of individual live cells from a polymeric surface through the application of increasing force using unmodified cantilever tips. Results show that the lateral force required to detach E. faecalis cells from a substrate differed depending on the nature of the polymeric surface: a force of 19 +/- 4 nN was required to detach cells from PU, 6 +/- 4 nN from PA, and 0.7 +/- 0.3 nN from PTFE. Among the unfluorinated polymers (PU and PA), surface wettability was inversely proportional to the strength of adhesion. AFM images also demonstrated qualitative differences in bacterial adhesion; PU was covered by clusters of cells with few cell singlets present, whereas PA was predominantly covered by individual cells. Moreover, extracellular material could be observed on some clusters of PU-adhered cells as well as in the adjacent region surrounding cells adhered on PA. E. faecalis adhesion to the fluorinated polymer (PTFE) showed different characteristics; only a few individual cells were found, and bacteria were easily damaged, and thus detached, by the tip. This work demonstrates the utility of AFM for measurement of cell-substrate lateral adhesion forces and the contribution these forces make toward understanding the initial stages of bacterial adhesion. Further, it suggests that initial adhesion can be controlled, through appropriate biomaterial design, to prevent subsequent formation of aggregates and biofilms.

Problems and challenges of biomaterials in cardiovascular applications: a status report
Bruck, S. D. (1983), Biomater Med Devices Artif Organs 11(4): 271-80.
Abstract: Biomaterials used as implants and in various devices must exhibit long-term (years) compatibility with the physiological environment, including blood, and additionally must also remain stable to perform mechanical functions, excepting applications where biodegradation is required. This paper focuses on problems and challenges of polymeric materials in contact with blood in the following categories: (1) artificial heart valves, (2) cardiovascular assist devices and artificial hearts, (3) vascular prostheses, and (4) the biological evaluation of materials prior to their human use, especially with respect to species related hematological differences of experimental animals. Besides thrombosis (which is the most obvious consequence of incompatibility), the calcification of chemically treated tissue prostheses as well as synthetic elastomers used in many cardiovascular devices is discussed in terms of biochemical and physico-chemical parameters together with its significance in long-term (years) implant applications. Complement activation brought about by contact of blood with foreign surfaces has received less than deserved attention in the evaluation of biomaterials and devices, despite the potentially serious problems. Relative ignorance in selecting appropriate animals for the biological evaluation of biomaterials whose hematological profiles and behavior of platelets, red and white cells to trauma and response to foreign surfaces differ decisively from those of humans, often leads to less than meaningful predictions for eventual clinical uses. The state-of-art realities are examined in conjunction with medical, societal, ethical, and economic boundaries.

Problems people involved in the field of biomaterials can face
Andreopoulos, A. G. (1994), J Biomater Appl 8(3): 185-7.

Procedure for quantification of platelet adhesion to biomaterials by radioscintigraphy
Resmi, K. R., N. Varghese, et al. (2004), Thromb Res 114(2): 121-8.
Abstract: Detection of adhered platelets on biomaterial surface that has blood-contacting application is an important test to assess its thrombogenicity. Usually, for measurement of platelet adhesion, after exposure to platelet-rich plasma (PRP) under standardized conditions the test surface is rinsed to remove non-adherent cells and is analyzed under scanning electron microscopy (SEM) to detect morphology of adhered cell and degree of aggregate formation. However, being a qualitative test it is unlikely to give an accurate estimate of platelets adhered to the surface. On the other hand, use of radiolabels enables quantification of platelets deposited on a material or device. Because of high gamma emission of (111)In, it can be used for radioscintigraphy, however, its short half life (2.5 days) is a major hurdle in using it for quantification of platelet adhesion. (125)I is a relatively strong radiolabel that is easily tagged to most of the proteins and has a relatively long half-life (60 days). The major objectives of this study are to standardize the labeling conditions to get good (125)I activity on platelets, while maintaining normal cell function after they are labeled. Considering all possible uncertainties, quantity of isotope and platelets to be used and the conditions of iodination reaction are established to get repeatable and reproducible labeling of platelets. Further, it is demonstrated that (125)I-platelets can be used to determine total number of cells adhered to titanium surface, which is known to be used as a blood-contacting biomaterial.

Process design of chondrocyte cultures with monolayer growth for cell expansion and subsequent three-dimensional growth for production of cultured cartilage
Kino-oka, M., Y. Maeda, et al. (2005), J Biosci Bioeng 100(1): 67-76.
Abstract: The subculture of rabbit chondrocytes with serial passaging was carried out for cell expansion on a collagen-coated surface, and the morphological transition of round-shaped cells to spindle-shaped ones was examined. The observation of cytoskeletal formation by staining F-actin and vinculin supported the view that the round-shaped cells were in the process of differentiation with immature stress fibers relating to less cellular polarity. The cellular morphology was estimated in terms of the distribution of roundness, R(C), during the subculturing on the collagen substrate. The frequency of the number of round-shaped cells, which was defined as the ratio of the number of cells with R(C) >0.9 against the total cell number, was correlated in a logarithmic formula with the number of population doublings during the subcultures. Kinetic models were adopted for the process design of the combined culture of chondrocytes with monolayer growth on the collagen substrate and subsequent three-dimensional growth in Atelocollagen gel, employing the boundary conditions based on the population balance between differentiated and dedifferentiated cells. The combined culture was performed successfully according to the process design scheduled as monolayer growth for 240 h and three-dimensional growth for 264 h, the number of seed cells being 68% of that in the conventional culture for 504 h where monolayer growth for cell expansion was not included.

Processing of an apatite-mullite glass-ceramic and an hydroxyapatite/phosphate glass composite by selective laser sintering
Lorrison, J. C., K. W. Dalgarno, et al. (2005), J Mater Sci Mater Med 16(8): 775-81.
Abstract: The work presented details the results of an investigation into the feasibility of using Selective Laser Sintering (SLS) to directly produce customised bioceramic implants. The materials used were bioactive in nature and included a glass-ceramic and a combination of hydroxyapatite and phosphate glass. The glass-ceramic was selected from the range of apatite-mullite materials in the SiO2.Al2O3.CaO.CaF2.P2O5 series, due to their potentially suitable biological and mechanical properties. The hydroxyapatite and phosphate glass combination was chosen to allow an alternative production approach to be investigated. The viability of using both these materials with the SLS process was assessed and the process route and resulting material properties characterised using a variety of techniques including Differential Thermal Analysis (DTA), X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM).The results obtained indicate that it was possible to produce multiple layer components from both materials using the SLS process. The glass-ceramic materials could only be processed at very low scan speeds and powers, yielding relatively brittle components. It was though possible to produce parts from the hydroxyapatite and phosphate glass combination across a much wider range of parameters, producing parts which had a greater potential for possible implant production.

Procoagulant phenotype of endothelial cells after coculture with biomaterial-treated blood cells
Rose, S. L. and J. E. Babensee (2005), J Biomed Mater Res A 72(3): 269-78.
Abstract: Understanding endothelial cell (EC)/blood/biomaterial interactions is crucial for the advancement of cardiovascular devices that often fail because of the lack of nonthrombogenic biomaterials. To begin to assess these interactions, a static EC/blood cell/biomaterial model was used. Isolated blood cells were pretreated with model biomaterial beads with different surface chemistries: polystyrene (PS), and PS beads grafted with 3-kDa polyethylene glycol (PEG) with either a hydroxyl (PS-PEG-OH) or amine (PS-PEG-NH(2)) terminal group at 5.4 or 54 x 10(4) beads/mL. Biomaterial-treated monocytes, neutrophils, or platelets were applied to human umbilical vein ECs (HUVECs) for 5 or 24 h of static coculture, and the resultant procoagulant HUVEC phenotype was characterized using several methods. Flow cytometry was used to assess surface expression of tissue factor (TF), adenosine triphosphate diphosphohydrolase, phosphatidylserine, and thrombomodulin, a functional TF assay was used to assess TF activity, and a plasma recalcification assay examined clotting times on HUVECs. Static coculture of HUVEC with biomaterial-treated neutrophils induced a procoagulant phenotype as exemplified by upregulation of TF expression and total functional activity, and downregulation of adenosine triphosphate diphosphohydrolase and thrombomodulin expression. The plasma recalcification assay demonstrated that HUVECs cocultured with biomaterial-treated monocytes significantly shortened clotting times, with some effect of similarly treated neutrophils.

Product liability implications of biomaterials in the United States
Price, J. M. (1994), Clin Mater 16(4): 223-7.

Production of glucosinolate hydrolysis products in Farsetia aegyptia suspension cultures following elicitation
Al-Gendy, A. A. and G. B. Lockwood (2005), Fitoterapia 76(3-4): 288-95.
Abstract: Levels of glucosinolates in Farsetia aegyptia var. ovalis suspension cultures were monitored after treatment with yeast extract, chitosan, methyl jasmonate, ampicillin, and Phytophthora infestans autoclaved mycelia as elicitors. Glucosinolates were identified, and an estimation of their levels obtained from their hydrolysis products. Yeast extract improved glucotropaeolin (benzyl-glucosinolate) and glucocheirolin [3-(methylsulfonyl)propyl-glucosinolate] accumulation, and production of sec-butyl, isobutylglucosinolate and gluconasturtiin (2-phenylethyl-glucosinolate) was only detected in yeast elicited cultures. Increases were shown in glucotropaeolin levels in cultures elicited using methyljasmonate, and chitosan and methyljasmonate in combination.


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