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Anodic oxide films containing Ca and P of titanium biomaterial
Zhu, X., K. H. Kim, et al. (2001), Biomaterials 22(16): 2199-206.
Abstract: Anodic oxidation and oxide films of titanium in the new electrolyte of calcium glycerophosphate (Ca-GP) and calcium acetate (CA) were investigated by galvanostatic mode, SEM, XRD and EPMA. The anodic oxide film displayed porosity, intermediate roughness, and high crystallinity. Also, the oxide film is enriched with Ca and P and high in thickness without microcracks. According to the surface properties of the oxide film, the optimum condition was that the concentration of the electrolyte was 0.02 M Ca-GP and 0.15 M CA, and current density and final voltage were 70 A/m2 and ca. 350 V. The oxide film formed in the condition is 0.98 microm (Ra) rough, 5-7 microm thick, adhesive to the underlying substrate, and near 1.67 Ca/P ratio in the oxide film.

Anterior abdominal wall reconstruction with a Permacol implant
Liyanage, S. H., G. S. Purohit, et al. (2005), Br J Plast Surg
Abstract: Laparostomy wound management is a difficult problem especially with a stoma and the potential risk of infection. A case describing the use of a permanent porcine dermal collagen implant in the repair of a massive ventral hernia, in a patient with a large post-laparostomy defect and colostomy is outlined. The implant was not rejected, and after 12 months, there was no evidence of residual or recurrent hernia. The search for the ultimate biomaterial for reconstructing abdominal wall defects is ongoing. Collagen based implants appear to have many of the requirements that an ideal material should possess.

Anterior cervical discectomy and fusion involving a polyetheretherketone spacer and bone morphogenetic protein
Boakye, M., P. V. Mummaneni, et al. (2005), J Neurosurg Spine 2(5): 521-5.
Abstract: OBJECT: The authors reviewed clinical and radiographic outcomes in patients who had undergone anterior cervical discectomy and fusion (ACDF) involving the placement of polyetheretherketone (PEEK) spacers filled with recombinant human bone morphogenetic protein (rhBMP)-2. METHODS: Data obtained in 24 cases were retrospectively evaluated. The follow-up period ranged from 12 to 16 months (mean 13 months). Fifteen patients presented with radiculopathy, eight with myeloradiculopathy, and one with quadriparesis. Single-level ACDF was performed in 12 patients, two-level ACDF in nine, and three-level ACDF in three. Clinical outcomes were assessed using Odom criteria, and fusion was assessed by examining flexion-extension radiographs and computerized tomography scans in cases in which arthrodesis was questionable. Follow-up data were available for 23 patients. One patient died of medical complications unrelated to surgery 4 weeks after ACDF. Clinical outcomes were rated as good/excellent in 22 patients (95%) and fair in one (5%). Solid radiographically documented fusion, with evidence of solid bridging bone and no instability on flexion-extension x-ray films, was present in all cases. Complications included transient recurrent laryngeal nerve injury in one case, transient C-5 paresis in one, cerebrospinal fluid leakage in one, and transient dysphagia in two. CONCLUSIONS: Analysis of the results indicated that ACDF involving an rhBMP-2-filled PEEK spacer leads to good clinical outcomes (by Odum criteria) and solid fusion (even in multilevel cases) while avoiding the complications associated with harvesting iliac crest bone grafts.

Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies
Lu, H. H., J. A. Cooper, Jr., et al. (2005), Biomaterials 26(23): 4805-16.
Abstract: The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee, and limitations in existing reconstruction grafts have prompted an interest in tissue engineered solutions. Previously, we reported on a tissue-engineered ACL scaffold fabricated using a novel, three-dimensional braiding technology. A critical factor in determining cellular response to such a graft is material selection. The objective of this in vitro study was to optimize the braided scaffold, focusing on material composition and the identification of an appropriate polymer. The selection criteria are based on cellular response, construct degradation, and the associated mechanical properties. Three compositions of poly-alpha-hydroxyester fibers, namely polyglycolic acid (PGA), poly-L-lactic acid (PLLA), and polylactic-co-glycolic acid 82:18 (PLAGA) were examined. The effects of polymer composition on scaffold mechanical properties and degradation were evaluated in physiologically relevant solutions. Prior to culturing with primary rabbit ACL cells, scaffolds were pre-coated with fibronectin (Fn, PGA-Fn, PLAGA-Fn, PLLA-Fn), an important protein which is upregulated during ligament healing. Cell attachment and growth were examined as a function of time and polymer composition. While PGA scaffolds measured the highest tensile strength followed by PLLA and PLAGA, its rapid degradation in vitro resulted in matrix disruption and cell death over time. PLLA-based scaffolds maintained their structural integrity and exhibited superior mechanical properties over time. The response of ACL cells was found to be dependent on polymer composition, with the highest cell number measured on PLLA-Fn scaffolds. Surface modification of polymer scaffolds with Fn improved cell attachment efficiency and effected the long-term matrix production by ACL cells on PLLA and PLAGA scaffolds. Therefore based on the overall cellular response and its temporal mechanical and degradation properties in vitro, the PLLA braided scaffold pre-coated with Fn was found to be the most suitable substrate for ACL tissue engineering.

Antiangiogenic activity of 11,11'-dideoxyverticillin, a natural product isolated from the fungus Shiraia bambusicola
Chen, Y., Y. X. Zhang, et al. (2005), Biochem Biophys Res Commun 329(4): 1334-42.
Abstract: The fungus Shiraia bambusicola yields the phytochemical 11,11'-dideoxyverticillin, which has been shown to possess potent anticancer activity both in vitro and in vivo. In this study, we reveal that 11,11'-dideoxyverticillin has anti-angiogenic activities and explore the potential mechanisms for this effect. Treatment with 11,11'-dideoxyverticillin inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) with IC(50) values of 0.17+/-0.05muM for VEGF-stimulated cells and 0.39+/-0.08muM for serum-stimulated cells. 11,11'-Dideoxyverticillin also antagonized the antiapoptotic effects of VEGF on serum-deprived HUVECs, inhibited VEGF-induced HUVEC migration in vitro, and blocked serum-induced HUVEC tube formation. Moreover, 11,11'-dideoxyverticillin completely blocked VEGF-induced microvessel sprouting from Matrigel-embedded rat aortic rings and vessel growth in Matrigel plugs in mice. In addition, 11,11'-dideoxyverticillin decreased VEGF secretion by MDA-MB-468 breast cancer cells, and significantly suppressed VEGF-induced tyrosine phosphorylation of Flt-1 and KDR/Flk-1. This inhibition of receptor phosphorylation was correlated with a marked decrease in VEGF-triggered pERK activation and a dramatic increase in pP38 MAPK, but no apparent change in pAkt. Together, these findings strongly suggest that 11,11'-dideoxyverticillin is a structurally novel angiogenesis inhibitor.

Antiangiogenic activity of beta-eudesmol in vitro and in vivo
Tsuneki, H., E. L. Ma, et al. (2005), Eur J Pharmacol 512(2-3): 105-15.
Abstract: Abnormal angiogenesis is implicated in various diseases including cancer and diabetic retinopathy. In this study, we examined the effect of beta-eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea rhizome, on angiogenesis in vitro and in vivo. Proliferation of porcine brain microvascular endothelial cells and human umbilical vein endothelial cells (HUVEC) was inhibited by beta-eudesmol (50-100 microM). It also inhibited the HUVEC migration stimulated by basic fibroblast growth factor (bFGF) and the tube formation by HUVEC in Matrigel. beta-eudesmol (100 microM) blocked the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 induced by bFGF or vascular endothelial growth factor. Furthermore, beta-eudesmol significantly inhibited angiogenesis in subcutaneously implanted Matrigel plugs in mice and in adjuvant-induced granuloma in mice. These results indicate that beta-eudesmol inhibits angiogenesis, at least in part, through the blockade of the ERK signaling pathway. We considered that beta-eudesmol may aid the development of drugs to treat angiogenic diseases.

Antibacterial activity of restorative dental biomaterials in vitro
Boeckh, C., E. Schumacher, et al. (2002), Caries Res 36(2): 101-7.
Abstract: This study investigated the antibacterial effects against Streptococcus mutans of a fine-hybrid resin composite (FH-RC; Tetric ceram), an ion-releasing resin composite (Ariston pHc), a self-curing glass ionomer cement (SC-GIC; Ketac-Molar), a resin-modified GIC (RM-GIC; Photac-Fil), and a zinc oxide eugenol cement (ZOE; IRM). In a novel assay, bacterial suspensions were placed into narrow 20-microl conical cavities within the materials. After 0, 4, 8, 24, 48 h and 1 week of incubation, the suspensions were removed from the restoratives and the numbers of viable bacteria were determined. After incubation periods of 8 h or more, all restorative materials except the FH-RC showed significant growth inhibition when compared with controls. The strongest antibacterial activity was observed with ZOE. The inhibitory effect of Ariston pHc was similar to that of the SC-GIC and the RM-GIC. In the second assay, growth inhibition was evaluated in liquid cultures by incubating eluates of the materials with suspensions of S. mutans. Bacterial growth was determined up to 6 h by measuring absorption at 600 nm. The most marked inhibitory effect was again observed with ZOE. The SC-GIC caused a significant inhibition at all time intervals but the FH-RC, the RM-GIC and Ariston pHc exhibited no significant antibacterial effects. It is recommended to employ more than one method for assessing the antibacterial potential of restorative materials. Long-term clinical trials are necessary to determine whether the antimicrobial effects of dental materials are able to reduce the risk of secondary caries formation.

Antibiotic resistance of biomaterial-adherent coagulase-negative and coagulase-positive staphylococci
Naylor, P. T., Q. N. Myrvik, et al. (1990), Clin Orthop Relat Res(261): 126-33.
Abstract: Whether or not bacterial populations are massively enclosed in slime, it appears that antibiotic resistance, when compared to suspension organisms, is related to surface adhesion and to the specific material of the substratum. These findings are of significance in the understanding and treatment of biomaterial-localized infections.

Antifungal coating by biofunctionalized polyelectrolyte multilayered films
Etienne, O., C. Gasnier, et al. (2005), Biomaterials 26(33): 6704-12.
Abstract: The surface of medical devices is a common site of bacterial and fungal adhesion, first step to the constitution of a resistant biofilm leading frequently to chronic infections. In order to prevent such complications, several physical and chemical modifications of the device surface have been proposed. Here, we experiment a new type of topical antifungal coating using the layer-by-layer technique. The nanometric multilayer film obtained by this technique is functionalized by the insertion of a chromogranin A-derived antifungal peptide (CGA 47-66, chromofungin). We show that the embedded peptide keeps its antifungal activity by interacting with the fungal membrane and penetrating into the cell. In vitro studies demonstrate that such an antifungal coating is able to inhibit the growth of yeast Candida albicans by 65% and completely stop the proliferation of filamentous fungus Neurospora crassa. The cytotoxicity of such a coating was also assessed by growing human gingival fibroblasts at its surface. Finally, the antifungal coating of poly(methylmethacrylate), a widely used material for biomedical devices, is successfully tested in an in vivo oral candidiasis rat model. Taken together, these results assessed the functionalized multilayer films containing a new potent antifungal non-toxic peptide, as a novel and promising technique for local antifungal protection.

Anti-metastatic effects of curcusone B, a diterpene from Jatropha curcas
Muangman, S., M. Thippornwong, et al. (2005), In Vivo 19(1): 265-8.
Abstract: A new approach to cancer therapy in recent years has been to target the metastatic process. The anti-metastatic potential of curcusone B, a diterpene isolated from Jatropha curcas Linn. (Euphorbiaceae), a herbal plant that has been used in traditional folk medicine in many tropical countries, was investigated against 4 human cancer cell lines. Treatment with non-cytotoxic doses of curcusone B resulted in a strong reduction of in vitro invasion, motility and secretion of matrix-metalloproteinases (MMP) of the cancer cells, whereas the ability to adhere to a Matrigel-coated surface was variably sensitive to curcusone B treatment. Curcusone B, thus, effectively suppresses the metastatic processes at doses that are non-toxic to cells, which may be of therapeutic benefit for the treatment of metastatic cancers.

Antimicrobial behavior of polyelectrolyte multilayer films containing cetrimide and silver
Grunlan, J. C., J. K. Choi, et al. (2005), Biomacromolecules 6(2): 1149-53.

Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity
Nishida, Y., W. Knudson, et al. (2005), Exp Cell Res 307(1): 194-203.
Abstract: Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion.

Antitumor effect of antisense ODC adenovirus on human prostate cancer cells
Zhang, Y., X. X. Liu, et al. (2005), Prostate Cancer Prostatic Dis 8(3): 280-6.
Abstract: Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially prostate cancers. Some chemotherapeutic agents aimed to decrease ODC expression showed inhibitory effects on cancer cells. In this study, we examined the effect of adenoviral-transduced antisense ODC on prostate cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and LNCap. Expression of ODC and concentration of polyamines in cells were determined by Western blotting and HPLC. MTT (3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze the effect on cell growth. Cell cycle was evaluated by FCM and cellular invasion by Matrigel invasion assay. A nude mouse xenograft model was used to examine tumorigenicity. Expression of ODC in PC-3 and LNCap cells were reduced to 45 and 59%, and three polyamines were also decreased by the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and cell cycle arrested at G1 phase. Matrigel invasion assay showed relatively low invasion. Marked suppression of tumor formation was observed in the xenograft model. This study suggests that rAd-ODC/Ex3as has the antitumor effect on the human prostate cancer cells.

Aortic root reconstruction: from principles to numerical modeling
Cartier, R., A. Ranga, et al. (2005), Can J Cardiol 21(12): 1071-6.
Abstract: Reconstructing the aortic root represents a formidable task for modern cardiac surgery. By the time an individual reaches 75 years of age his or her aortic apparatus has been submitted to more than three billion cardiac cycles, leaving no place for engineering flaws or misconception. The rules that have been established through millions of years of evolution are strict and demanding. During the past two decades, the cardiovascular community has manifested a growing interest in this topic, especially in patients with medial degenerative disease. However, the ideal reconstruction is still to be devised. To achieve a physiological root reconstruction that preserves the diastolic and systolic function of the valve as well as prevents premature degeneration, a few principles have to be respected. Neglecting any one of them has consequences on the normal functioning of the aortic valve. Current surgical techniques have limitations due to the limited availability of biomaterial and the lack of useful tools to assess pathophysiological conditions and assist surgeons in designing better custom-made reconstructions of the aortic root. The authors present a review of the principles behind the physiology of the reconstruction of the aortic root, and review the literature on computerized models exploring the biomechanics and kinetics of the ascending aorta.

Apatite formation on poly(2-hydroxyethyl methacrylate)-silica hybrids prepared by sol-gel process
Costa, R. O., M. M. Pereira, et al. (2005), J Mater Sci Mater Med 16(10): 927-32.
Abstract: Hybrids of poly(2-hydroxyethyl methacrylate) (PHEMA), a polymer that has been employed in a wide variety of biomedical applications, and silica-gel, which exhibits a well-known bioactivity, were produced. The obtained hybrids were characterized and their in vitro ability to induce the formation of a calcium phosphate layer on the surface was evaluated. The surface area of hybrids decreased with increasing amounts of PHEMA so that hybrids with more than approximately 40% PHEMA are virtually non-porous. All hybrids induced the formation of a calcium phosphate layer on their surfaces when soaked into simulated body fluid. The induction time and the morphology of the apatite layer varied according to the polymer content.

Apatite/amelogenin coating on titanium promotes osteogenic gene expression
Du, C., G. B. Schneider, et al. (2005), J Dent Res 84(11): 1070-4.
Abstract: Osteoblast differentiation and extracellular matrix production are pivotal processes for implant osseointegration or bone tissue engineering. We hypothesized that a biomimetic coating on titanium surfaces, consisting of apatite and amelogenin, would promote such processes. Human Embryonic Palatal Mesenchymal pre-osteoblasts were used as a model for the evaluation of cell adhesion and spreading patterns, as well as mRNA expression of certain osteoblastic gene products. Real-time PCR showed significant (p < 0.05) increase in expression of type I collagen, alkaline phosphatase, and osteocalcin from cells grown on titanium with an apatite/amelogenin composite, as compared with that from cells grown on a pure titanium or apatite coating only. Osteocalcin expression was specifically stimulated by amelogenin added to the culture media. Enhanced attachment and cell spreading were also observed. The biomimetic coating promoting cell adhesion and osteoblast differentiation may have great potential for future dental and biomedical applications.

Apatitic calcium orthophosphates and related compounds for biomaterials preparation
Bonel, G., J. C. Heughebaert, et al. (1988), Ann N Y Acad Sci 523: 115-30.
Abstract: The authors show that to obtain well chemically defined apatitic bioceramics and to know the possible transformations of this material during sintering, it is necessary to prepare a good starting material. Moreover, they show that it is possible to prepare a new organic-inorganic phosphate compound. The precipitation of apatite in an aqueous medium at boiling temperature was studied using the methodology of experimental design. Independent variables were the volume of NH4OH in phosphate solution, the volume of NH4OH in calcium solution, and the time of precipitation; the response was the atomic Ca/P ratio of the obtained precipitate. A continuous variation of this ratio from 1.63 to 1.73 is observed. Implications of this result to the preparation of pure HA: Ca10(PO4)6(OH)2 is given. Moreover, when Ca/P greater than 1.67, HA reacts with Ca(OH)2 (after heating at 1000 degrees C in air for some days) to give rise to a single phase described as a modified HA (MHA), a Ca/P ratio of 1.75, an a value of 9.373 +/- 0.002 A, and a c value of 6.884 +/- 0.002 A. The reactivity (time versus temperature) of the MHA is described. If the precipitation of the calcium phosphate is realized at 37 degrees C in a water-ethanol medium in the presence of A2EP, a new apatite, chemically bonded to the organic molecule by pooling phosphate groups, is obtained.

Apoptotic markers on lymphocytes and monocytes are unchanged during single hemodialysis sessions using either regenerated cellulose or polysulfone membranes
Wu, C. C., T. N. Liao, et al. (2005), Clin Nephrol 64(3): 198-204.
Abstract: BACKGROUND: There is an increased rate of apoptosis of peripheral blood mononuclear cells (PBMCs) in patients undergoing hemodialysis (HD), but little is known about how different dialysis membranes may contribute to the process. We, therefore, studied the influence of two different dialysis membranes on apoptotic markers during HD. METHODS: 8 healthy controls and 8 patients on regular HD 3 times per week were enrolled in this cross-controlled study. Patients received HD using polysulfone and then regenerated cellulose dialysis membranes for one week each, sequentially. Serum was collected for C-reactive protein (CRP) detection; flow cytometry with dual antibody staining was used to measure the apoptotic markers Fas (CD95), FasL (CD 178) and TNF-R2 (CD120b) in T cells (CD3+), B cells (CD19+), and monocytes (CD14+) at 0, 15, 120 and 240 min after starting HD. We also measured total leukocyte numbers and differential white cell counts. RESULTS: Hemodialysis patients revealed lymphocytopenia, monocytopenia, higher CRP levels and higher Fas and TNF-R2 expression on lymphocytes and monocytes at baseline when compared with normal controls. Leukocyte numbers, including neutrophils, lymphocytes and monocytes, dropped significantly after 15 min of dialysis. There were no significant differences in Fas levels during hemodialysis on T and B lymphocytes or on monocytes. T lymphocyte FasL (CD 178) levels remained unchanged throughout the process. There was a significantly lower overall level of CD120b at 15 min of HD, whereas this marker was higher on monocytes after dialysis. There were no significant differences in the levels of apoptotic markers between the two membranes. CONCLUSION: Our results suggest that uremia itself contributes to PBMC apoptosis. The two different dialysis membranes used in this study did not influence apoptotic markers on PBMCs significantly, but increased TNF-R2 expression on monocytes during a single dialysis session.

Application of a combination of neutral red and amido black staining for rapid, reliable cytotoxicity testing of biomaterials
Ciapetti, G., D. Granchi, et al. (1996), Biomaterials 17(13): 1259-64.
Abstract: Cell viability and growth for cytotoxicity evaluation of materials for prosthetic devices has been tested using various methods. The aim of this study was to extend the choice of reliable methods to quantify cytotoxicity of materials in vitro. By measuring both viability and growth of cells exposed to biomaterials in vitro, two different parameters are analysed and quantified upon reading of the absorbance of coloured solutions in a spectrophotometer. Neutral red uptake and amido black staining of cells have been used for cell viability and cell number measurement, respectively: they have been found to be well correlated with the number of surviving cells. These methods have been adjusted to a 96-well microplate cell culture system and re-evaluated as simple and reliable methods for the quantitative assessment of biomaterial effect on cells.

Application of a kinetic gelation simulation to the characterization of in situ cross-linking biomaterials
Poshusta, A. K., C. N. Bowman, et al. (2002), J Biomater Sci Polym Ed 13(7): 797-815.
Abstract: Multifunctional monomers that are polymerized in situ to form highly cross-linked biomaterials have been an area of recent interest for medical applications. From a biomaterial application standpoint, the relationship between the reaction conditions, polymer structure, and final physical properties is important, particularly for in situ formed materials, as they must have optimum network properties immediately after Formation. However, multifunctional monomer reaction mechanisms are complicated by mobility restrictions on the reacting species, cyclization of pendant groups, unequal reactivity of functional groups, and structural heterogeneities. Also, experimental characterization of these complexities is difficult and limited by the insolubility of the resulting cross-linked structure. Thus, in this contribution, a kinetic gelation simulation was used to understand and characterize the evolution of in situ forming, three-dimensional polymer structures. Specifically, the reaction of tetrafunctional monomers (i.e. divinyl monomers) to form high strength networks with degradable cross-links was modeled. This work focuses on using a lattice-based model to characterize network properties important for biomaterial applications and compare them with an experimental system (i.e. cross-linked polyanhydrides) where appropriate. Simulated results for pendant group reactivity, kinetic chain lengths, and radical concentrations (trapped and free) are presented herein.

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Last Modified: 8 February 2006