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Developing macroporous bicontinuous materials as scaffolds for tissue engineering
Martina, M., G. Subramanyam, et al. (2005), Biomaterials 26(28): 5609-16.
Abstract: Calcareous skeletal elements (ossicles) isolated from the seastar, Pisaster giganteus, were characterized and tested as potential biocompatible substrates for cellular attachment. These ossicles have a remarkably robust open-framework architecture with an interconnected network of ca. 10 microm diameter pores. Scanning electron and confocal microscopy was used to characterize the cell-substrate interaction. Cell culturing experiments revealed that the cells firmly attach to the ossicle surface, forming cell aggregates of several layers thick. The anchored cells extended to form 'bridges' between the openings in the bicontinuous framework and the degree of coverage increased as culture time progressed. Osteoblasts grown on the ossicles were found to be viable up to 32 days after initial seeding, as proven by assaying with AlamarBlue and FDA/PI staining indicating the ossicle's potential as an alternative highly effective tissue scaffold. Given the limitation in availability of this natural material, the results presented here should be seen as offering guidelines for future development of synthetic materials with physical and chemical properties strongly conducive to bone repair and restoration.

Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone
Teixeira, M., M. J. Alonso, et al. (2005), Eur J Pharm Biopharm 59(3): 491-500.
Abstract: The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter <170 nm, a narrow size distribution (polydispersity index <0.1), and a negative surface charge (zeta potential <-36 mV). Their incorporation efficiencies were 33% for XAN and 42% for 3-MeOXAN. The presence of the xanthones did not affect the nanospheres size and zeta potential. DSC studies indicated that XAN and 3-MeOXAN were dispersed at a molecular level within the polymeric nanomatrix. Nanocapsules were also nanometric (mean size <300 nm) and exhibited a negative charge (zeta potential <-36 mV). Their incorporation efficiency values (>77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN.

Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem
Halder, A., S. Mukherjee, et al. (2005), J Microencapsul 22(1): 67-80.
Abstract: The objective of this investigation is to develop a multi-unit sustained release dosage form of a water soluble drug from a completely aqueous environment avoiding the use of any organic solvent. The drug was complexed with resin and calcium alginate or polyethyleneimine-treated calcium alginate beads loaded with the resinate were prepared by a ionic/polyelectrolyte complexation method. The effect of different formulation variables on the characteristics of the beads was investigated. Although the drug release from spherical and smooth-surfaced calcium alginate beads in both acidic and alkaline dissolution media were slower than those obtained from plain resinate, none of the variables were found to prolong the drug release considerably due to rapid swelling and disintegration of calcium alginate beads in alkaline medium. On the other hand, drug release from polyethyleneimine-treated calcium alginate beads in acidic medium did not increase appreciably following a burst release. However, in alkaline medium, the drug release was found to increase gradually and extend over a different period of time depending on the intensity of polyethyleneimine treatment. Scanning electron micrographs revealed the formation of a dense membrane around the resinate-loaded calcium alginate matrix. The membrane appeared to be responsible for reduced swelling and protracted disintegration of the beads resulting in slow release of the drug. The results indicate that sustained release of a water soluble drug from polyethyleneimine-treated calcium alginate beads could be achieved by adjusting the formulation variables.

Development and potential of a biomimetic chitosan/type II collagen scaffold for cartilage tissue engineering
Shi, D. H., D. Z. Cai, et al. (2005), Chin Med J (Engl) 118(17): 1436-43.
Abstract: BACKGROUND: Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering. METHODS: Chitosan of 88% deacetylation was prepared via a modified base reaction procedure. A freeze-drying process was employed to fabricate a three-dimensional composite scaffold consisting of chitosan and type II collagen. The scaffold was treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. Ultrastructure and tensile strength of the matrix were carried out to assess its physico-chemical properties. After subcutaneous implantation in rabbits, its in vivo biocompatibility and degradability of the scaffold were determined. Its capacity to sustain chondrocyte growth and biosynthesis was evaluated through cell-scaffold co-culture in vitro. RESULTS: The fabricated composite matrix was porous and sponge-like with interconnected pores measuring from 100-250 microm in diameter. After cross-linking, the scaffold displayed enhanced tensile strength. Subcutaneous implantation results indicated the composite matrix was biocompatible and biodegradable. In intro cell-scaffold culture showed the scaffold sustained chondrocyte proliferation and differentiation, and maintained the spheric chondrocytic phenotype. As indicated by immunohistochemical staining, the chondrocytes synthesized type II collagen. CONCLUSIONS: Chitosan and type II collagen can be well blended and developed into a porous 3-D biomimetic matrix. Results of physico-chemical and biological tests suggest the composite matrix satisfies the constraints specified for a tissue-engineered construct and may be used as a chondrocyte carrier for cartilage tissue engineering.

Development and properties of polycaprolactone/hydroxyapatite composite biomaterials
Azevedo, M. C., R. L. Reis, et al. (2003), J Mater Sci Mater Med 14(2): 103-7.
Abstract: Polycaprolactone/hydroxyapatite (PCL/HA) composites were prepared by two different procedures. The first one consists of a conventional blending of the polymer and the reinforcement material in an extruder. The second method consists of grafting of PCL on the surface of HA particles. This was achieved by a ring opening polymerization of caprolactone in the presence of HA, where its OH groups act as initiators. By this method, it was possible to obtain, in one step, a composite of PCL and surface modified HA. In both methods different percentages of filler were used to obtain several composites. These composites were characterized with respect to their mechanical properties, in the dry and wet state, by means of tensile tests on compression molded samples. The polymer/filler interface was analyzed by scanning electron microscopy. Water uptake and weight loss degradation experiments were also performed. An increase in the modulus for higher amounts of filler was, as expected, observed in the composites obtained by both processes. Furthermore, the mechanical properties of the materials in the wet state are considerably lower than those in the dry state. However, this difference is more significant for the composites obtained by conventional blending than for composites obtained by the grafting procedure, indicating that the later procedure can be an adequate route to reduce water susceptibility of PCL/HA composites.

Development of a biologic prosthetic composite for cartilage repair
Mardones, R. M., G. G. Reinholz, et al. (2005), Tissue Eng 11(9-10): 1368-78.
Abstract: At present there is no satisfactory treatment for deep osteochondral defects. Here we report the development of a biologic prosthetic composite containing periosteum from 2-month-old rabbits and a porous tantalum scaffold. When cultured under chondrogenic conditions, the composites form a robust hyaline-like cartilage outgrowth that is attached to the porous scaffold by fibrous tissue ingrowth. The mechanical properties of these composites are similar to those of normal osteochondral plugs after only 6 weeks in culture. Thus, porous tantalum scaffolds are compatible with the chondrogenic capacity of periosteum. We hypothesize that these periosteum-porous tantalum composites will be useful for the repair of major osteochondral defects. However, in vivo experiments using biological resurfacing of large osteochondral defects with a porous tantalum scaffold and autologous periosteal graft in animal models are necessary to further explore this possibility. The implications of a successful method for cartilage regeneration would be great in terms of the number of patients affected and the quality of life for each of those patients.

Development of a large titanium bone chamber to study in vivo bone ingrowth
Hannink, G., P. Aspenberg, et al. (2006), Biomaterials 27(9): 1810-6.
Abstract: In the bone conduction chamber (BCC) various materials and factors have been tested for their effect on bone graft incorporation and bone healing. However, biomaterials often have to be crushed to fit in this small chamber. Since cellular responses to biomaterials are influenced by the size and shape of particles, research concerning the evaluation of biomaterials is limited by the dimensions of this bone chamber. We enlarged and modified the BCC in order to be able to investigate the in vivo influences of biomaterials, growth factors and bone graft processing on tissue and bone ingrowth. Seven goats received four bone chambers each, three modified models and a BCC. The first model (BCC+) had two ingrowth openings, similar to that of the BCC. The second model had two round ingrowth openings (ROU). The third model had a open bottom for bone ingrowth (BOT). After 12 weeks, bone ingrowth distances were measured on histological sections and using muCT. Bone ingrowth was significantly higher (p=0.009 and 0.008) in the ROU compared to the BCC+ and the BOT, respectively. Similar results were found using muCT. The ROU model performed most similar to the BCC (gold standard) and is considered to be a promising new tool in biomaterials research.

Development of a model for assessment of biomaterial encrustation in the upper urinary tract
Tunney, M. M., M. C. Bonner, et al. (1996), Biomaterials 17(10): 1025-9.
Abstract: A need exists for ureteral stent materials capable of preventing or reducing encrustation. The aim of this study, therefore, was to develop an in vitro model producing biomaterial encrustation similar to that on stents in vivo. Three models were designed and evaluated. Polyurethane stent sections were immersed in human urine (37 degrees C, 5% CO2): (1) with and (2) without crushed human kidney stone and (3) in an artificial urine (37 degrees C, 5% CO2). Encrustation of similar composition, as determined by infrared spectroscopy, X-ray diffraction and energy dispersive X-ray analysis, formed on stent materials in vivo, in artificial urine and in human urine with crushed kidney stone. Magnesium ammonium phosphate (struvite) and calcium phosphate (hydroxyapatite) predominated in all encrustations. The reproducibility and ease of use of the artificial urine model provided optimum encrustation assessment of materials presently used in ureteral stents and evaluation of novel biomaterials.

Development of a new ultrasonic technique for bone and biomaterials in vitro characterization
Lefebvre, F., Y. Deblock, et al. (2002), J Biomed Mater Res 63(4): 441-6.
Abstract: Classical techniques based on bone imaging allow visual examination or provide quantitative parameters like bone mineral density, which is a mass per unit of surface. Unfortunately, these techniques are generally expensive. A new method of bone characterization that uses ultrasound techniques is presented in this article. This method is able to evaluate mechanical properties like Young's modulus E and cortical bone thickness with low-frequency transducers and does not require the use of a coupling medium. Some results of Young's modulus measurements are presented and compared to the literature values and the pulse echo method.

Development of a novel biomaterial, hydroxyapatite/collagen (HAp/Col) composite for medical use
Itoh, S., M. Kikuchi, et al. (2005), Biomed Mater Eng 15(1-2): 29-41.
Abstract: A hydroxyapatite/type I collagen (HAp/Col) composite, aligning hydroxyapatite nano-crystals along collagen molecules, has been synthesized. The biocompatibility, osteoconductivity and efficacy as an rhBMP-2 carrier of this novel biomaterial implanted in the weight-bearing site have been examined. The HAp/Col implants adsorbing 0 or 400 microg/ml of rhBMP-2 were implanted into bone defects of tibiae in 3 beagle dogs and fixed according to the Ilizarov method. As a control, bone defects of 20 mm remaining in 2 beagle dogs and the dogs were allowed to walk using a Ilizarov external skeletal fixator. The radiological and histological findings suggest that the implants induce bone remodeling units and are a superior carrier of rhBMP-2 due to the stimulation of early callus and new bone formation. As a next step, anterior fusion was carried out on 6 beagle dogs with the implants adsorbing 400 microg/ml of rhBMP-2, and 9 dogs with the implants without rhBMP-2. In 3 dogs of the rhBMP-treated group, as well as 6 dogs of the non-rhBMP-treated group, the implant was fixed with a poly-L-lactide plate. Histological and radiographical analysis suggest that enhancement of callus formation and bone bridging by rhBMP-treatment is effective to prevent collapse of the implant.

Development of a novel UV indicator and dosimeter film
Mills, A., S. K. Lee, et al. (2005), Analyst 130(7): 1046-51.
Abstract: A novel UV indicator is described, comprising nanocrystalline particles of titania dispersed in a film of a polymer, hydroxyl ethyl cellulose (HEC), containing: a mild reducing agent, triethanolamine (TEOA) and a redox indicator, methylene blue (MB). The UV indicator film is blue-coloured in the absence of UV light and loses colour upon exposure to UV light, attaining within a few min a steady-state degree of bleaching that can provide a measure of the irradiance of the incident light. The original blue colour of the film returns once the source of UV light is removed. The spectral characteristics of a typical UV indicator film, and its components, are discussed and the UV-absorbing action of the titania particles highlighted. From the measured %bleaching undergone by a typical UV indicator as a function of light irradiance the indicator appears fully bleached, within 7 min, by a UV irradiance of 3 mW cm(-2) or greater. The mechanism by which the UV indicator works is described. The reversible nature of the UV indicator is removed by covering a typical UV indicator with a thin, largely oxygen impermeable, polymer film, such as the regenerated cellulose found in Sellotape. The product is a UV dosimeter, the response of which is related to the intensity and duration of the incident UV light, as well as the amount of titania in the film. A typical UV dosimeter film is fully bleached by 250 mJ cm(-2) of UV light. The possible use of these novel indicators to measure UV exposure levels, irradiance and dose, is discussed.

Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction
Courtman, D. W., C. A. Pereira, et al. (1994), J Biomed Mater Res 28(6): 655-66.
Abstract: There is evidence to suggest that the cellular components of homografts and bioprosthetic xenografts may contribute to calcification or immunogenic reactions. A four-step detergent and enzymatic extraction process has been developed to remove cellular components from bovine pericardial tissue. The process results in an acellular matrix material consisting primarily of elastin, insoluble collagen, and tightly bound glycosaminoglycans. Light and electron microscopy confirmed that nearly all cellular constituents are removed without ultrastructural evidence of damage to fibrous components. Collagen denaturation temperatures remained unaltered. Biochemical analysis confirmed the retention of collagen and elastin and some differential extraction of glycosaminoglycans. Low strain rate fracture testing and high strain rate viscoelastic characterization showed that, with the exception of slightly increased stress relaxation, the mechanical properties of the fresh tissue were preserved in the pericardial acellular matrix. Crosslinking of the material in glutaraldehyde or poly(glycidyl ether) produced mechanical changes consistent with the same treatments of fresh tissue. The pericardial acellular matrix is a promising approach to the production of biomaterials for heart valve or cardiovascular patching applications.

Development of a resorbable macroporous cellulosic material used as hemostatic in an osseous environment
Laurence, S., R. Bareille, et al. (2005), J Biomed Mater Res A 73(4): 422-9.
Abstract: The control of bleeding is a frequently encountered therapeutic problem, particularly during dental surgery. The most efficient substances used to resolve this problem are not risk-free because of their animal or human origins, so cellulosic materials are potentially of interest. The aim of this study was to develop a resorbable macroporous cellulosic material for use as a resorbable hemostatic agent in bone sites. The degradation and the cytocompatibility of the cellulosic material versus controls were evaluated and its behaviour in vivo was studied. An original process using calcium carbonate powder as inverse matrix was used to develop a macroporous material. In order to predegrade the cellulosic material for hemostatic use, oxidation was performed with periodate. A dialdehyde component unstable at physiological pH was thus obtained. The material was found to have cytotoxicity, biocompatibility, and resorption properties similar to control but its hemostatic power was higher.

Development of a single dose tetanus toxoid formulation based on polymeric microspheres: a comparative study of poly(D,L-lactic-co-glycolic acid) versus chitosan microspheres
Jaganathan, K. S., Y. U. Rao, et al. (2005), Int J Pharm 294(1-2): 23-32.
Abstract: Stable polymeric microspheres capable of controlled release of tetanus toxoid (TT) for periods ranging from days to over months were developed. TT was stabilized, encapsulated in microspheres prepared from poly(D,L)-lactide-co-glycolide (PLGA) and chitosan by using protein stabilizer (trehalose) and its immune response was compared. The influence of co-encapsulated protein stabilizer on tetanus toxoid's stability and release from the microspheres was studied. The protein stabilizer (trehalose) prevented structural losses and aggregation of microencapsulated TT. To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polymer, we also co-incorporated into the polymer an antacid, (Mg(OH)2), which neutralized the acidity during degradation of the polymer and also prevented TT structural losses and aggregation. The in vitro release experiments with PLGA and chitosan microspheres were performed and the release of TT was increased up to 80-90%. The antigen integrity was investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by coomassie brilliant blue staining. The SDS-PAGE analysis confirmed that antigen integrity was not affected by the encapsulation procedure. In addition, the immunogenicity of PLGA and chitosan microspheres based single dose vaccine was evaluated in guinea pigs and compared with multiple doses of alum adsorbed TT. Results indicated that a single injection of PLGA and chitosan microspheres containing TT could maintain the antibody response at a level comparable to the booster injections of conventional alum adsorbed vaccines. The both PLGA and chitosan based stable vaccine formulations produced an equal immune response. Hence chitosan can be used to replace the expensive polymer PLGA. This approach should have potential application in the field of vaccine delivery.

Development of a system to adsorb drugs onto calcium phosphate materials
Queiroz, A. C., J. D. Santos, et al. (2005), J Mater Sci Mater Med 16(7): 641-6.
Abstract: Several studies were carried out in order to reduce the systemic use of antibiotics due to the high concentration required to provide the minimum inhibitory concentration (MIC) at infected sites. The aim of this study was to develop a system of drug adsorption onto commercial hydroxyapatite (HA, Ca10(PO4)6(OH)2) and glass reinforced hydroxyapatite (GR-HA) granules. The drug will then be released for the local treatment of periodontitis. The antibiotics used in this study were metronidazole, a specific antibiotic indicated for the systemic treatment of periodontitis, and ampicillin, a wide spectrum antibiotic. UV spectroscopy was used to measure the amount of drug adsorbed onto HA and GR-HA granules. Results showed that metronidazole was unable to adsorb on the material's surface, as opposed to ampicillin which adsorbed both onto HA and GR-HA. Preliminary release kinetics studies were carried out using a flow through dissolution system. Results are discussed in terms of the influence of the different surface characteristics of the materials on the adsorption processes.

Development of amine-containing polymeric particles
Tauro, J. R. and R. A. Gemeinhart (2005), J Biomater Sci Polym Ed 16(10): 1233-44.
Abstract: The objective of this study was to synthesize and characterize particles as a drug-delivery platform for gliomas, a highly advanced and invasive stage of brain tumor with poor prognosis. Poly(aminoethyl methacrylate-co-methyl methacrylate) particles were prepared by suspension polymerization and poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles were prepared by emulsion (w/o) polymerization. Amine groups of the particles were complexed with tetrachloroplatinate to form a cisplatin-like molecule. Particles were characterized with respect to size, zeta-potential, amine content, loading efficiency and drug release. Poly(aminoethyl methacrylate-co-methyl methacrylate) particles had diameters of below 10 microm, whereas the poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles had diameters of approx. 1 microm. Poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles had a more positive zeta-potential as compared to poly(aminoethyl methacrylate-co-methyl methacrylate) particles, although the amino-group content of both particles was almost equivalent. The net positive charge on the particles decreased after complexation with tetrachloroplatinate for both types of particles. Both particles had very high platinum-loading efficiency (>85%) and showed slow release of platinum over time. Particles had relatively low cytotoxicity (LC50 > 100 microg/ml) and demonstrated a high degree of association with cells. Complexation with poly(aminoethyl methacrylate-co-methyl methacrylate) particles significantly reduced the toxicity of platinum. The poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles have potential for being an effective drug-delivery platform and continued investigation is warranted.

Development of an artificial vertebral body using a novel biomaterial, hydroxyapatite/collagen composite
Itoh, S., M. Kikuchi, et al. (2002), Biomaterials 23(19): 3919-26.
Abstract: Hydroxyapatite/collagen (HAp/Col) composites having a bone-like nanostructure were synthesized and shaped into implants. This study was designed to develop an artificial vertebra system using this novel implant for anterior fusion of the cervical spine. Anterior fusion was carried out on 6 beagle dogs with the implants adsorbing rhBMP-2 (400 microg/ml). and 9 dogs with the implants without rhBMP-2. In 3 dogs of the rhBMP-treated group, as well as 6 dogs of the non-rhBMP-treated group, the implant was fixed with a poly-L-lactide plate and 2 titanium screws. Implants were taken out after 13 weeks from each 3 dogs in the rhBMP(-):plate(-). rhBMP(-):plate(+) and rhBMP(+):plate(+) groups. Also, the implants were removed from each 3 dogs in the rhBMP(-):plate(+) and rhBMP(+):plate(+) groups after 24 weeks. Histological and radiographical analysis suggested that since the larger part of the composite material was absorbed within 13 weeks, reduction of the intervertebral distance was caused, and that enhancement of callus formation and bone bridging by rhBMP-treatment was effective to prevent collapse of the implant, even though an effect of anterior plate-fixation was not obvious. The HAp/Col implant adsorbing rhBMP-2 may be a suitable replacement for the existing ceramics in anterior interbody fusion of the cervical spine.

Development of an ectopic site for islet transplantation, using biodegradable scaffolds
Dufour, J. M., R. V. Rajotte, et al. (2005), Tissue Eng 11(9-10): 1323-31.
Abstract: Clinical islet transplantation in liver has achieved normoglycemia. However, this site may not be ideal for islet survival. To create a more optimal site for islet transplantation, we have developed a construct with biodegradable scaffolds. Islets were seeded in scaffolds and transplanted into the epididymal fat pad of diabetic BALB/c mice. Controls included islets transplanted underneath the kidney capsule or into the fat pad without scaffolds. All animals with islets in scaffolds or the kidney became normoglycemic and maintained this metabolic state. When islets were transplanted without scaffolds the time to achieve normoglycemia was significantly increased and less than 45% of mice survived. An oral glucose tolerance test was performed on the scaffold and kidney groups with similar blood glucose levels and area under the curve values between the groups. Grafts were removed at more than 100 days posttransplantation and all animals became hyperglycemic. There was no significant difference in insulin content between the grafts and all grafts were well vascularized with insulin-positive beta cells. Therefore, islets in scaffolds function and restore diabetic animals to normoglycemic levels, similar to islets transplanted underneath the kidney capsule, suggesting scaffolds can be used to create a site for islet transplantation.

Development of an infection-resistant bifunctionalized Dacron biomaterial
Aggarwal, P., M. D. Phaneuf, et al. (2005), J Biomed Mater Res A 75(1): 224-31.
Abstract: A novel infection-resistant biomaterial was created by applying the antibiotic Ciprofloxacin (Cipro) to a recently developed bifunctionalized polyethylene terephthalate ("polyester," Dacron) material using textile-dyeing technology. Dacron was modified via exposure to ethylenediamine (EDA) to create amine and carboxylic acid sites within the polymer backbone. Cipro was applied to the bifunctionalized Dacron construct under varied experimental conditions, with resulting antimicrobial activity determined via zone of inhibition. Dacron segments treated at a liquor ratio of 20:1, with 5% Cipro on weight of fabric (owf), at pH 8 for 4 h at 70 degrees C followed by autoclaving showed antimicrobial activity for 78 days (length of study). Segments treated similarly but without autoclaving lost activity within 1 day. Dyeing time and temperature did not significantly affect antibiotic release/activity, but segments dyed at pHs higher or lower than 8 had less antimicrobial activity. The long-term infection resistance provided by this technique may answer major problems of infection from which implantable Dacron biomedical devices suffer.

Development of an infection-resistant, bioactive wound dressing surface
Phaneuf, M. D., M. J. Bide, et al. (2005), J Biomed Mater Res A 74(4): 666-76.
Abstract: Trauma, whether caused by an accident or in an intentional manner, results in significant morbidity and mortality. The goal of this study was to develop a novel biomaterial surface in vitro and ex vivo that provides both localized infection resistance nd hemostatic properties. Our hypothesis is that a combination of specific surface characteristics can be successfully incorporated into a single biomaterial. Functional groups were created with woven Dacron (Cntrl) material via exposure to ethylenediamine (C-EDA). The antibiotic ciprofloxacin (Cipro) was then applied to the C-EDA material using pad/autoclave technique (C-EDA-AB) followed by surface immobilization of the coagulation cascade enzyme thrombin (C-EDA-AB-Thrombin). Antimicrobial activity by the C-EDA-AB surface persisted for 5 days compared with Cntrl and dipped controls, which lasted <1 h. C-EDA-AB-Thrombin surfaces had 2.6- and 105-fold greater surface thrombin activity compared with nonspecifically bound thrombin and Cipro-dyed surfaces, respectively. Surface thrombus formation ex vivo was evident after 1 min of exposure, with thrombus organization evident by 2.5 min. In contrast, C-EDA-AB and Cntrl segments showed only blood protein adsorption on the fibers. Thus, this study demonstrated that Cipro and thrombin can be simultaneously incorporated onto a biomaterial surface while maintaining their respective biological activities.

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Last Modified: 8 February 2006