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Bioactive and biocompatible pieces of HA/sol-gel glass mixtures obtained by the gel-casting method
Padilla, S., S. Sanchez-Salcedo, et al. (2005), J Biomed Mater Res A 75(1): 63-72.
Abstract: Hydroxyapatite (HA)/glass mixtures have shown a faster bioactive behaviour than HA itself. On the other hand, the gel-casting method is a simple and reproducible colloidal method to produce ceramic pieces with complex shapes. In this work, pieces of HA/glass mixtures were prepared by the gel-casting method. A study for obtaining concentrated slurries of these mixtures is reported; the bioactivity and biocompatibility of the obtained pieces have been studied also. The influence of pH, dispersant concentration, the content and milling of glass, and the way to prepare the suspensions were investigated. The lowest viscosity and better rheological properties were achieved with the lowest glass content, when the glass was added after the dispersion of the HA powder and when the glass was not milled after calcination. Fluid suspensions with a high solid content (50 vol.%) could be prepared and well-shaped pieces were obtained from these slurries. These pieces showed in vitro bioactive behavior in simulated body fluid; additionally, the proliferation and spreading assays with osteoblastic cells (HOS) showed that the pieces are biocompatible. The results obtained indicate that the gel-casting of HA/glass mixtures produces bioactive and biocompatible pieces with the required shapes. Therefore, these materials could be good candidates for clinical applications and scaffolds for tissue engineering.

Bioactive biomaterials
Hubbell, J. A. (1999), Curr Opin Biotechnol 10(2): 123-9.
Abstract: The most important advances in the field of biomaterials over the past few years have been in bioactive biomaterials. Materials have been developed to incorporate bioactivity through biological recognition, including incorporation of adhesion factors, polyanionic sites that mimic the electrostatics of biological regulatory polysaccharides, and cleavage sites for enzymes involved in cell migration. Materials have also been developed to be active in biological environments by undergoing phase changes in situ, including transformations from liquid precursors to solids and from soluble materials to materials that are immobilised on tissue surfaces.

Bioactive bone cements containing nano-sized titania particles for use as bone substitutes
Goto, K., J. Tamura, et al. (2005), Biomaterials 26(33): 6496-505.
Abstract: Three types of bioactive polymethylmethacrylate (PMMA)-based bone cement containing nano-sized titania (TiO2) particles were prepared, and their mechanical properties and osteoconductivity are evaluated. The three types of bioactive bone cement were T50c, ST50c, and ST60c, which contained 50 wt% TiO2, and 50 and 60 wt% silanized TiO2, respectively. Commercially available PMMA cement (PMMAc) was used as a control. The cements were inserted into rat tibiae and allowed to solidify in situ. After 6 and 12 weeks, tibiae were removed for evaluation of osteoconductivity using scanning electron microscopy (SEM), contact microradiography (CMR), and Giemsa surface staining. SEM revealed that ST60c and ST50c were directly apposed to bone while T50c and PMMAc were not. The osteoconduction of ST60c was significantly better than that of the other cements at each time interval, and the osteoconduction of T50c was no better than that of PMMAc. The compressive strength of ST60c was equivalent to that of PMMAc. These results show that ST60c is a promising material for use as a bone substitute.

Bioactive composite materials for tissue engineering scaffolds
Boccaccini, A. R. and J. J. Blaker (2005), Expert Rev Med Devices 2(3): 303-17.
Abstract: Synthetic bioactive and bioresorbable composite materials are becoming increasingly important as scaffolds for tissue engineering. Next-generation biomaterials should combine bioactive and bioresorbable properties to activate in vivo mechanisms of tissue regeneration, stimulating the body to heal itself and leading to replacement of the scaffold by the regenerating tissue. Certain bioactive ceramics such as tricalcium phosphate and hydroxyapatite as well as bioactive glasses, such as 45S5 Bioglass, react with physiologic fluids to form tenacious bonds with hard (and in some cases soft) tissue. However, these bioactive materials are relatively stiff, brittle and difficult to form into complex shapes. Conversely, synthetic bioresorbable polymers are easily fabricated into complex structures, yet they are too weak to meet the demands of surgery and the in vivo physiologic environment. Composites of tailored physical, biologic and mechanical properties as well as predictable degradation behavior can be produced combining bioresorbable polymers and bioactive inorganic phases. This review covers recent international research presenting the state-of-the-art development of these composite systems in terms of material constituents, fabrication technologies, structural and bioactive properties, as well as in vitro and in vivo characteristics for applications in tissue engineering and tissue regeneration. These materials may represent the effective optimal solution for tailored tissue engineering scaffolds, making tissue engineering a realistic clinical alternative in the near future.

Bioactive glass and bioabsorbable membrane in the treatment of a maxillary class II furcation defect: case report with 6-month re-entry
Giusto, T. J. (2005), Compend Contin Educ Dent 26(1): 41-2, 44, 46 passim; quiz 52-3.
Abstract: The combination of bone graft materials with guided tissue regenerative procedures has been shown to have predictable positive results in periodontal defects, especially furcations. The following case report will demonstrate a severe class II furcation defect in a maxillary molar that was treated with combination therapy using bioactive glass and a bioabsorbable membrane made of a copolymer of polylactic/polyglycolic acid. Six-month re-entry revealed substantial clinical fill of the furcation defect. Comparison radiographs also demonstrated fill in the region.

Bioactive glass efficacy in the periodontal healing of intrabony defects in monkeys
Villaca, J. H., A. B. Novaes, Jr., et al. (2005), Braz Dent J 16(1): 67-74.
Abstract: The purpose of this study was the histomorphologic analysis of the efficacy of bioactive glass particles with a narrow size range (Biogran) in the periodontal healing of 2-wall intrabony defects in monkeys. The 2-wall defects were made in the mesial area of the left and right second premolars of four monkeys, filled with gutta-percha and, after 15 days, they were debrided and either naturally filled with coagulum (control) or implanted with bioactive glass (test). In the control sites, the junctional epithelium migrated up to the base of the defect. The presence of newly formed cementum was more significant in the test defects. Both control and test sites showed newly formed bone at the base of the defect. The test defects presented foci of newly formed bone around and within the glass particles localized in the middle third, distant from the defect walls. Histologic analysis showed that the 300- to 355-microm bioactive glass particles aided new periodontal insertion. In conclusion, the tested bioactive glass had better healing potential than debridement only. The graft material showed a promising inhibition of apical migration of the junctional epithelium and greater cementum deposition on the radicular surface of the intrabony defects. The replacement of bioactive glass particles by new bone occurred due not only to an osteoconductive property, but also to an osteostimulatory capacity. Future investigations should evaluate this potential comparatively or together with other grafting materials, regenerative techniques and biological modifiers, as well as assess the longitudinal stability of the new attachment.

Bioactive hydroxyapatite coatings on polymer composites for orthopedic implants
Auclair-Daigle, C., M. N. Bureau, et al. (2005), J Biomed Mater Res A 73(4): 398-408.
Abstract: Hydroxyapatite [HA, Ca10(PO4)6(OH)2] coatings on polymer composite substrates were investigated for their bioactivity and their physicochemical and mechanical characteristics. HA holds key characteristics for use in orthopedic applications, such as for coating of the femoral stem in a hip replacement device. The plasma-spray technique was used to project HA onto a carbon fiber/polyamide 12 composite substrate. The resulting HA coatings exhibited mechanical adhesion as high as 23 MPa, depending on the surface treatment of the composite substrate. The purpose of this investigation was to evaluate the bioactivity of an HA-coated composite substrate. HA- coated samples have been immersed in simulated body fluid (SBF) and maintained within a shaker bath for periods of 1, 7, 14, 21, and 28 days at 37 degrees C. Scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction techniques were performed on the samples before and after immersion into SBF. SBF was analyzed using inductively coupled plasma atomic emission spectrometry for element concentration and evaluation of the solution's purity. SBF conditioning led to the deposition of crystalline HA onto the surface of the coatings. The calcium-to-phosphorous ratios of initial HA coating and of newly deposited HA were respectively 1.72 and 1.65, close to the HA theoretical calcium/phosphorous value of 1.67. Results demonstrated that bioactive HA coatings were produced by plasma spraying, because SBF conditioning induced newly formed HA with high crystallinity. Mechanical adhesion of the HA coatings was not significantly affected upon SBF conditioning.

Bioactive technologies for hemocompatibility
Tanzi, M. C. (2005), Expert Rev Med Devices 2(4): 473-92.
Abstract: The contact of any biomaterial with blood gives rise to multiple pathophysiologic defensive mechanisms such as activation of the coagulation cascade, platelet adhesion and activation of the complement system and leukocytes. The reduction of these events is of crucial importance for the successful clinical performance of a cardiovascular device. This can be achieved by improving the hemocompatibility of the device materials or by pharmacologic inhibition of the key enzymes responsible for the activation of the cascade reactions, or a combination of both. Different strategies have been developed during the last 20 years, and this article attempts to review the most significant, by dividing them into three main categories: bioinert or biopassive, biomimetic and bioactive strategies. With regard to bioactive strategies, particular attention is given to heparin immobilization and recent related technologies. References from both scientific literature and commercial sites are provided. Future development and studies are suggested.

Bioactivity of metallic biomaterials with anatase layers deposited in acidic titanium tetrafluoride solution
Wu, J. M., F. Xiao, et al. (2003), J Mater Sci Mater Med 14(12): 1027-32.
Abstract: A simple and versatile treatment was developed to provide various metallic biomaterials such as Ti, NiTi, Ta and SUS 316L stainless steel with in vitro bioactivity or ability to deposit carbonate-incorporated apatite in a simulated body fluid (Kokubo solution). A well-crystallized anatase layer deposited on the metallic biomaterials surfaces after soaking them at 60 degrees C for 24 h in an aqueous solution of titanium tetrafluoride (40 mM) whose pH was adjusted to 1.9 with HCl. The as-coated anatase layers did not deposit apatite. When heated at 300 degrees C they were so bioactive as to deposit apatite within 5 day(s) in the Kokubo solution. The trace amount of fluorine weakly bound in the as-coated anatase layers was suggested to be one of the factors that suppressed the bioactivity.

Bioactivity of titanium following sodium plasma immersion ion implantation and deposition
Maitz, M. F., R. W. Poon, et al. (2005), Biomaterials 26(27): 5465-73.
Abstract: Bio-activation of titanium surface by Na plasma immersion ion implantation and deposition (PIII and D) is illustrated by precipitation of calcium phosphate and cell culture. The bioactivity of the plasma-implanted titanium is compared to that of the untreated, Na beam-line implanted and NaOH-treated titanium samples. Our data show that the samples can be classified into two groups: non-bioactive (untreated titanium and beam-line Na implanted titanium) and bioactive (Na-PIII and D and NaOH-treated titanium). None of the four types of surfaces exhibited major cell toxicity as determined by lactate dehydrogenase (LDH) release. However, the LDH release was higher on the more bioactive PIII and NaOH-treated surfaces. From a morphological point of view, cell adherence on the NaOH-treated titanium is the best. On the other hand, the cell activity and protein production were higher on the non-bioactive surfaces. The high alkaline phosphatase activity per cell suggests that the active surfaces support an osteogenic differentiation of the bone marrow cells at the expense of lower proliferation. The use of Na-PIII and D provides an environmentally cleaner technology to improve the bioactivity of Ti compared to conventional wet chemical processes. The technique is also particularly useful for the uniform and conforming treatment of medical implants that typically possess an irregular shape and are difficult to treat by conventional ion beam techniques.

Bio-artificial periosteum for severe open fracture--an experimental study of osteogenic cell/collagen sponge composite as a bio-artificial periosteum
Hattori, K., T. Yoshikawa, et al. (2005), Biomed Mater Eng 15(3): 127-36.
Abstract: In an attempt to reduce complications in cases of severe open fracture, we developed a bio-artificial periosteum composed of osteogenic cells and collagen sponge. In the present study, we evaluated the osteogenic potential of the bio-artificial periosteum in vivo and in vitro. After 4-week incubation in vitro, the bio-artificial periosteum had high alkaline phosphatase activity and osteocalcin content. Moreover, energy dispersive X-ray analysis revealed numerous crystal structures consisting of P and Ca on the surface of the bio-artificial periosteum. Using a rat model for severe bone injury, we examined the bone formation process in defect sites covered with the bio-artificial periosteum. New bone formation occurred in the central part of the bone defect as well as at the bone edge. We conclude that by using the bio-artificial periosteum, the fracture site benefited from an improved osteogenic environment. These results indicate that a clinical trial to further evaluate this technique should be conducted.

Bioartificial tracheal grafts: can tissue engineering keep its promise?
Walles, T. (2004), Expert Rev Med Devices 1(2): 241-50.
Abstract: A huge variety of graft materials and transplantation approaches have been applied for decades in order to generate a clinically applicable tracheal substitute; so far, without success. Today, tissue engineering, the creation of man-made functional biological organs or tissue replacements from biodegradable carrier structures and autologous cells, may represent an alternative to the shortage of suitable grafts for reconstructive airway surgery. Partial success has been obtained by numerous groups following different concepts and strategies. In this article, tissue engineering approaches towards the bioartificial airway prosthesis are discussed, focusing primarily on recent developments in the field.

Bioaugmentation with a Bacillus sp. to reduce the phytoavailable Cd of an agricultural soil: comparison of free and immobilized microbial inocula
Jezequel, K., J. Perrin, et al. (2005), Chemosphere 59(9): 1323-31.
Abstract: In order to reduce the cadmium potentially available for plants, soil bioaugmentation was performed by using a Bacillus sp. In a pot experimentation, sterilized and non-sterilized soils were inoculated using free or immobilized cells entrapped in alginate beads. This test was carried out with different inoculum sizes (2 x 10(10) and 2 x 10(11)CFU kg(-1) dw of soil) and alginate bead compositions (10 and 15 g of both alginate and CaCl(2) l(-1)). Then, the soil pots were incubated at 20 degrees C and the soil humidity was kept at a level of 20%. After 3 weeks of a batch incubation, the potentially phytoavailable Cd was reduced up to a factor of 14. The bioaugmentation resulted in the soil colonization by Bacillus sp. thanks to an increase of the cell concentration up to 1.8 log units. However, in comparison to the cells being inoculated in a free mode, the immobilization of the cells did not significantly improve the survival of the cells in the soil. Although the resulting effect not being highly pronounced, the potentially phytoavailable Cd correlated with the cell concentration in a surprisingly positive way. What is more, the Bacillus concentrations in the soil were positively correlated with the inoculum, too.

Biobrane in bairns with burns and bugs?
Knight, R. J., D. P. Mather, et al. (2005), Burns 31(5): 655-6.

Biocatalytic synthesis of highly ordered degradable dextran-based hydrogels
Ferreira, L., M. H. Gil, et al. (2005), Biomaterials 26(23): 4707-16.
Abstract: We have prepared unique macroporous and ordered dextran-based hydrogels using a single-step biocatalytic transesterification reaction between dextran and divinyladipate in neat dimethylsulfoxide. These hydrogels show a unimodal distribution of interconnected pores with average diameters from 0.4 to 2.0 microm depending on the degree of substitution. In addition, the hydrogels show a higher elastic modulus for a given swelling ratio than chemically synthesized dextran-based hydrogels. In vivo studies in rats show that the hydrogel networks are degradable over a range of time scales from 5 to over 40 days, and possess good biocompatibility, as reflected in only a mild inflammatory reaction and minor fibrous capsule formation during the time-frame of subcutaneous implantation. These combined properties may offer competitive advantages in biomedical applications ranging from tissue engineering to controlled drug delivery.

Bioceramics composition modulate resorption of human osteoclasts
Ramaswamy, Y., D. R. Haynes, et al. (2005), J Mater Sci Mater Med 16(12): 1199-205.
Abstract: Biomaterials used in bone regeneration are designed to be gradually resorbed by the osteoclast and replaced by new bone formed through osteoblastic activity. The aim of the present study is to analyze the role of osteoclasts in the resorption process. The attachment of human osteoclasts and the appearance of their resorption lacunae, when cultured on either the resorbable crystalline, calcium orthophosphate materials or on the long-term stable bioceramic material was investigated. The resorbable materials contain Ca(10)[K,Na](PO(4))(7) (AW-Si) and Ca(2)KNa(PO(4))(2) (GB14, GB9 & D9/25) as their main crystal phases, however they differ in their total solubility. These differences result from small variations in the composition. The long-term stable material consist of about 30% fluorapatite beside calcium zirconium phosphate (Ca(5)(PO(4))3F + CaZr(4)(PO(4))(6)) and shows a very small solubility. AW-Si has an alkali containing crystalline phase, Ca(10)[K,Na](PO(4)). While GB14, GB9 and D9/25 contain the crystalline phase Ca(2)KNa(PO(4))(2) with small additions of crystalline and amorphous diphosphates and/or magnesium potassium phosphate (GB14). D9/25 and AW-Si is less soluble compared to GB14, and GB9 among the resorbable materials. Resorbable and long-term stable materials vary in their chemical compositions, solubility, and surface morphology. Osteoclasts modified the surface in their attempts to resorb the materials irrespective of the differences in their physical and chemical properties. The depth and morphology of the resorption imprints were different depending on the type of material. These changes in the surface structure created by osteoclasts are likely to affect the way osteoblasts interact with the materials and how bone is subsequently formed.

Biochemical and physico-chemical aspects of biomaterials calcification
Krasovskaya, S. M., L. D. Uzhinova, et al. (1991), Biomaterials 12(9): 817-20.
Abstract: Intrinsic tissue calcification mainly results from increased penetration of plasma proteins into the leaflets of bioprosthetic cardiac valves. The loss of activity of natural calcification inhibitors changes tissue properties and promotes pathological processes. N-vinylpyrrolidone, 3-amino-1,1-hydroxypropylendiphosphonic acid, O,O-diethylvinylphosphonates and antiaggregant (acryloilsalicylic acid) were used to decrease porosity and prevent calcification. gamma-radiation and glutaraldehyde were used to immobilize these agents. Tissue calcification was studied using subcutaneous implantation of the samples in young rats. The study indicates that the copolymerization of N-vinylpyrrolidone, O,O-diethylvinylphosphonates and acryloilsalicylic acid decreases calcium and phosphorous accumulation during in vivo experiments.

Biochemical markers evaluation of RAW transformed cells during treatment with various biomaterials
Johnston, W., S. Carr, et al. (1999), Biomed Sci Instrum 35: 217-22.
Abstract: Upon introduction into the human body, biomaterials initially trigger a foreign-body inflammatory response. Furthermore, the wear debris associated with such materials as those used for orthopedic implants, artificial heart valves, and dental implants can cause the body to mount an inflammatory response. This involves the production of phagocytic macrophages that ingest the foreign material while simultaneously producing cytokines that serve as chemotactic agents for an amplified immune response. Currently titanium (Ti), polyethylene (PE), tricalcium phosphate (TCP) and hydroxyapatite (HA) are widely used as biomaterials in medical implants, and particle size is an important factor in the development of orthopedic, dental, and medical implants. The objective of this study was to investigate the effect of various biomaterials (Ti, mixed particle size polyethylene (MPE), ultra high molecular weight polyethylene (UHMWPE), mixed particle size TCP (MTCP), < 0.38 micron TCP (S-TCP), and hydroxyapatite (HA)) on the inflammatory reactions expressed by transformed RAW macrophages. RAW transformed monocytes were obtained from the American Cell Culture Line, (Rockville, MD). The cells were allowed to incubate in contact with the materials for intervals of 24, 48, and 72 hours. Biochemical tests and morphological evaluations were performed after each time point, including screening for cell number, cell protein levels, supernatant protein levels, lactate dehydrogenase (LDH), Maliondialdehyde (MDA), catalase by following standard lab protocols.

Biochemical surface modification of Ti-6Al-4V for the delivery of protein to the cell-biomaterial interface
Wojcik, S. M. and D. A. Puleo (1997), Biomed Sci Instrum 33: 166-71.
Abstract: Biochemical surface modification involves delivery of biomolecules to the tissue-implant interface to induce desired cell and tissue responses. We have previously had success in immobilizing and retaining bioactive molecules on Co-Cr-Mo but not on Ti-6Al-4V. The purpose of this study was to modify the gamma-aminopropyltriethoxysilane (APS) scheme to enable successful attachment of protein to the surface of Ti-6Al-4V. Ti-6Al-4V samples were silanized with organic (acetone) solutions of APS and dried at increasing temperatures. Concentrations resulting in 2-4 NH2 per nm2 of nominal surface area were incubated in physiological saline for up to 96 hr to assess retention of amino groups. A model protein, trypsin, was coupled to silanized Ti-6Al-4V via glutaraldehyde. The samples were then incubated in saline, and the activity of residual immobilized enzyme was quantified. After drying at 45, 80, or 115 degrees C, the NH2 groups were lost from the surface by 24 hr of incubation in saline. On samples dried at 150 degrees C, with 4% APS, the number of NH2 groups increased after 8 hr and remained relatively constant through 96 hr. Likewise, at 150 degrees C with 2% APS the surface density of NH2 groups reached a maximum at 24 hr and remained relatively constant up to 96 hr. When incubated for 96 hr, Ti-6Al-4V with 4% APS and dried at 150 degrees C retained approximately 31% of the activity initially immobilized, whereas protein on 45 degrees C or adsorbed samples was lost by 24-48 hr.

Biocompatibility analysis of different biomaterials in human bone marrow cell cultures
Wilke, A., J. Orth, et al. (1998), J Biomed Mater Res 40(2): 301-6.
Abstract: A cell culture system for biocompatibility testing of hip implant materials is described. Human bone marrow cells have been chosen because these cells are in direct contact with the biomaterial after implantation in situ. The sensitivity of this method is evaluated for materials which are already being used as implants in humans and animal, e.g., hydroxyapatite (HA) ceramic, pure titanium, and ultra-high-molecular-weight polyethylene (UHMWPE). As indicative parameters of biocompatibility primary cell adherence, cell number, cell proliferation, production of extracellular matrix, cell vitality, and cell differentiation are described. After 2 weeks in culture, obvious differences between the biomaterials with respect to the indicative parameters could be observed. Cell numbers were greatest on the HA specimens. In the case of titanium alloys, we observed a decreased number of cells. The production of extracellular matrix was high for the HA ceramics but reduced for titanium specimens. The polymers allowed only a few adherent cells and showed no signs of extracellular matrix production. The results can be correlated astonishingly well to animal experiments and clinical experiences. Therefore, we suggest that this cell culture system seems to be a useful tool for biocompatibility testing of bone implantation materials. It also helps reduce animal experiments. With the help of flow cytophotometry, we analyzed the influence of biomaterials on large numbers of cells with respect to differentiation. There were similar populations of T cells and monocytes on all specimens tested. Extended B-cell and granulocyte populations, however, were observed with titanium and UHMWPE. Most osteocalcin-containing cells adhered to the HA ceramics.

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