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Porcine-derived xenogeneic bone/poly(glycolide-co-lactide-co-caprolactone) composite and its affinity with rat OCT-1 osteoblast-like cells
Qu, X., Y. Wan, et al. (2006), Biomaterials 27(2): 216-25.
Abstract: Porcine-derived xenogeneic bone (PDXB) was derived from cancellous bone of adult porcine. Its morphology and structure were characterized by SEM, FTIR and XRD. A series of composite films consisting of PDXB and poly(glycolide-co-lactide-co-caprolactone) (PGLC) polymer were prepared. Because of the introduction of PGLC polymer, the PDXB/PGLC composites especially PDXB/PGLC(30/70) and PDXB/PGLC(50/50) showed good processability and mechanical properties. In addition, the hydrophilicity of the composites was enhanced as well since the PDXB component was hydrophilic. Osteoblast-like cells (OCT-1) were used as an in-vitro model to assess the affinity of the PDXB/PGLC composites. It was found that compared with the pure PGLC film, PDXB/PGLC(30/70) and PDXB/PGLC(50/50) composite films promoted cell attachment, proliferation and ALP (alkaline phosphatase) activity obviously. In addition, the cells preferred growing on the areas of exposed PDXB. It was considered that the hydrophilicity, osteoconductivity and appropriate surface roughness (Sa=3.30, 4.00 microm) induced by PDXB facilitate cell growth. However, the introduction of too much PDXB, such as PDXB/PGLC(70/30) film, would obtain an adverse effect on the cell growth since the value of Sa was up to 7.33 microm. It indicated that only the composites with appropriate surface topography could favor cell growth. Surface topography probably has a more important effect on cell growth process than surface chemistry.

Porosity of 3D biomaterial scaffolds and osteogenesis
Karageorgiou, V. and D. Kaplan (2005), Biomaterials 26(27): 5474-91.
Abstract: Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be approximately 100 microm due to cell size, migration requirements and transport. However, pore sizes >300 microm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vascularization, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.

Porous and electrically conductive polypyrrole-poly(vinyl alcohol) composite and its applications as a biomaterial
Li, Y., K. G. Neoh, et al. (2005), Langmuir 21(23): 10702-9.
Abstract: Bulk modification of polypyrrole (PPY) with poly(vinyl alcohol) (PVA) was carried out by the electropolymerization of pyrrole in the presence of PVA in the reaction solution, with tetraethylammonium perchlorate (TEAP) as the electrolyte. The surface morphology of the as-synthesized PPY-TEAP-PVA film was investigated using scanning electron microscopy, and the film was further characterized using X-ray photoelectron spectroscopy, electrical conductivity, the water contact angle, and BET surface area measurements. The PPY-TEAP-PVA composite is electrically conductive, hydrophilic, and microporous with a high surface area. Its potential as a biomaterial was investigated with respect to its blood compatibility and function as a substrate for biosensor fabrication and cell culture. The presence of PVA in the film attenuates blood protein adsorption, and the porous nature of the PPY-TEAP-PVA film results in a 10-fold increase in the amount of glucose oxidase covalently immobilized on the film over that on a nonporous PPY film. PC12 cell attachment and growth on the PPY-TEAP-PVA film was also shown to be enhanced compared with that on tissue culture polystyrene. The attached cells proliferated and formed a monolayer on the film surface after 48 h of seeding.

Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-beta1 for chondrocytes proliferation
Guo, T., J. Zhao, et al. (2006), Biomaterials 27(7): 1095-103.
Abstract: Cartilage defects as a result of disease or injury have a very limited ability to heal spontaneously. Recently, tissue engineering and local therapeutic gene delivery systems have been paid much attention in the cartilage natural healing process. Gene-activated matrix (GAM) blends these two strategies, serving as local bioreactor with therapeutic agents expression and also providing a structural template to fill the lesion defects for cell adhesion, proliferation and synthesis of extracellular matrix (ECM). In the current study, we used chitosan-gelatin complex as biomaterials to fabricate three-dimensional scaffolds and plasmid DNA were entrapped in the scaffolds encoding transforming growth factor-beta1 (TGF-beta1), which has been proposed as a promoter of cartilage regeneration for its effect on the synthesis of matrix molecules and cell proliferation. The plasmid DNA incorporated in the scaffolds showed a burst release in the first week and a sustained release for the other 2 weeks. The gene transfectd into chondrocytes expresses TGF-beta1 protein stably in 3 weeks. The histological and immunohistochemical results confirmed that the primary chondrocytes cultured into the chitosan-gelatin scaffold maintained round and owned characters of high secretion of specific ECM. From this study, it can be concluded that this gene-activated chitosan-gelatins matrix has a potential in the application of cartilage defects regeneration.

Porous high-density polyethylene for orbital reconstruction
Lee, S., N. Maronian, et al. (2005), Arch Otolaryngol Head Neck Surg 131(5): 446-50.
Abstract: OBJECTIVE: To determine the safety and efficacy of using porous high-density polyethylene (PHDPE) in the repair of orbital defects. DESIGN: Retrospective case series. SETTING: Academic tertiary care trauma center.Patients One hundred seventy patients with orbital defects requiring surgical repair.Intervention Orbital defect repair with PHDPE.Main Outcome Measure Our review documents surgical results and complications associated with the use of PHDPE. RESULTS: There was a 6.4% complication rate associated with the use of PHDPE. The infection rate was 1.8%. The persistent orbital malposition rate was 3.5%. The extrusion rate was 0%. CONCLUSIONS: This report represents the largest case series in the literature using PHDPE for orbital reconstructions. The use of PHDPE resulted in a low complication rate and excellent functional and cosmetic reconstructive results. Because of our success with the use of PHDPE, we have changed our clinical practice to minimize the use of autologous graft material, thereby eliminating donor site morbidity in cases involving orbital reconstruction.

Porous poly (DL-lactic acid) modified chitosan-gelatin scaffolds for tissue engineering
Liu, H., F. Yao, et al. (2005), J Biomater Appl 19(4): 303-22.
Abstract: Chitosan-gelatin (Cs-Gel) scaffolds are modified with poly (DL-lactic acid) (PDLLA) dichloromethane solution of different concentrations (0.1, 0.5, and 1.0%) and immersed in water after the evaporation of the solvent. The swollen scaffolds are freeze dried. The concentration of PDLLA has significant effects on both the physicomechanical properties and the cytocompatibility. Data reveal that only the 0.1% concentration could increase the tensile strength fourfold in comparison with the pristine Cs-Gel scaffold, while maintaining the human fibroblast adhesion, migration, and proliferation just like the Cs-Gel scaffold.

Porous polyethylene for tissue engineering applications in diabetic rats treated with calcitonin: histomorphometric analysis
Claro, F. A., J. R. Lima, et al. (2005), Int J Oral Maxillofac Implants 20(2): 211-9.
Abstract: PURPOSE: The purpose of this work was to study the bone tissue reaction after porous polyethylene (Polipore) implantation into surgical defects in the parietal bones of rats with streptozotocin-induced diabetes, treated with salmon calcitonin. MATERIALS AND METHODS: Porous polyethylene implants were placed in bone defects created in 36 adult female rats. The rats were divided into 3 equal groups: diabetic treated with calcitonin (DCa), diabetic (D), and control (C). The animals of the DCa group received applications of salmon calcitonin on alternating days immediately after the surgery until sacrifice. The rats were sacrificed after 15, 30, 60, and 90 days, and the defects were examined histologically and statistically through histomorphometric analysis. RESULTS: Histomorphometric analysis showed that there was no statistically significant difference in the mean quantity of inflammatory cells among all study groups after 15 and 90 days. At 30 days, a statistically significant difference was observed between the D and C groups and the D and DCa groups. At 60 days, there was no statistically significant difference between the D and DCa groups. DISCUSSION: Porous polyethylene can be considered an option for implant material when there are investigations that prove its biocompatibility and stability in the host tissues. Salmon calcitonin positively aided the bone repair and attenuated the inflammatory response until 30 days after the surgery. CONCLUSION: Porous polyethylene was tolerated by the host tissues in all groups, and moderate chronic inflammatory reaction was observed up to the 90-day period. Salmon calcitonin attenuated the inflammatory response up until 30 days.

Porous scaffold design for tissue engineering
Hollister, S. J. (2005), Nat Mater 4(7): 518-24.
Abstract: A paradigm shift is taking place in medicine from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous material scaffolds integrated with biological cells or molecules to regenerate tissues. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and tissue regeneration. Little is known quantitatively about this balance as early scaffolds were not fabricated with precise porous architecture. Recent advances in both computational topology design (CTD) and solid free-form fabrication (SFF) have made it possible to create scaffolds with controlled architecture. This paper reviews the integration of CTD with SFF to build designer tissue-engineering scaffolds. It also details the mechanical properties and tissue regeneration achieved using designer scaffolds. Finally, future directions are suggested for using designer scaffolds with in vivo experimentation to optimize tissue-engineering treatments, and coupling designer scaffolds with cell printing to create designer material/biofactor hybrids.

Porous segmented polyurethanes--possible candidates as biomaterials
Wilkes, G. L. and S. L. Samuels (1973), J Biomed Mater Res 7(6): 541-4.

Positive patch-test reactions to gold: patients' perception of relevance and the role of titanium dioxide in cosmetics
Nedorost, S. and A. Wagman (2005), Dermatitis 16(2): 67-70; quiz 55-6.
Abstract: BACKGROUND: Positive patch-test reactions to gold that are without obvious clinical relevance are common. We speculate that titanium dioxide in cosmetics and sunscreens may adsorb gold particles in jewelry that occasionally contacts facial skin and cause contact dermatitis on this area despite the absence of dermatitis under gold jewelry worn on the hands. OBJECTIVE: To identify subgroups of gold allergic patients who improve with avoidance of gold. METHODS: A questionnaire was mailed to 102 gold-allergic patients. RESULTS: There were 49 responses, of which all but one were from women. When asked to evaluate the statement that patch testing with gold was useful to them, one-third of respondents agreed completely, one-third agreed in part, and one-third disagreed. The majority of patients reported that their dermatitis improved after patch testing, but most were avoiding other allergens in addition to gold. CONCLUSIONS: Avoidance of gold earrings did not appear to benefit patients with earlobe dermatitis, but total avoidance of gold jewelry on the hands and wrists did seem to benefit a subgroup of patients with facial and eyelid dermatitis who wore powder, eye shadow, or foundation on affected areas.

Positively charged biomaterials exert antimicrobial effects on gram-negative bacilli in rats
Gottenbos, B., H. C. van der Mei, et al. (2003), Biomaterials 24(16): 2707-10.
Abstract: Biomaterial-centered infection is a much-dreaded complication associated with the use of biomedical implants. Although positively charged biomaterial surfaces stimulate bacterial adhesion, it has been suggested that surface growth of adhering Gram-negative bacilli is inhibited on positively charged surfaces. In the present paper, we determined the infection rate of differently charged poly(methacrylates) in rats. To this end, 2 x 10(6)/cm(2) Escherichia coli O2K2 or 2 x 10(4)/cm(2) Pseudomonas aeruginosa AK1 were seeded on glass discs coated with three differently charged poly(methacrylates) coatings in a parallel plate flow chamber. Three rats received six subcutaneous discs (two discs of each charge variant) seeded with E. coli, while three other rats received discs seeded with P. aeruginosa. The numbers of viable bacteria on the surfaces were determined 48h after implantation. On 50% of all positively charged discs viable E. coli were absent, while the negatively charged discs were all colonized by E. coli. P. aeruginosa, however, were isolated from both positively and negatively charged discs. Probably, P. aeruginosa can circumvent the antimicrobial effect of the positive charge through the formation of extracellular polysaccharides.

Possibilities of application of composite bone-soft tissue complex in reconstructive surgery
Peradze, I. and T. Peradze (2005), Georgian Med News(9): 7-13.
Abstract: Hereby the method of formation of bone-soft tissue complex with its future application in reconstructive surgery is presented. Treatment of spacious defects of human body with soft tissue lost as well as with bone injury is considered as critical problem in contemporary surgery. Even today, there is no final reference regarding the particular sort of flat to be applied in each specific case. Method of formation and flap taking is one of the most complicated and crucial stages of the operation. Operation of free transplantation of compound composite flaps of soft tissues, muscles and bones, including microvascular anastomosis, was done for 66 patients; in total 68 transplantations were carried out. the patients were provided with clinic-laboratory analysis; identification of deficient tissues, X-ray, dopplerography, determination of various sorts of sensitivity, biomechanical examinations and tests, and bacteriological tests. 66 patients with grave injuries of bones and soft tissues were operated. In 86,8% of total good functional and esthetical effect was reached, and in 11,8%--the outcomes were estimated as satisfactory. While observance of all technical rules for flap formation precision during formation of vascular pedicle, accurate selections of form and flap dimension are of significant importance. During solution of this very problem, auto-transplantation of tissue flaps is deemed to be highly effective method of treatment. It is worthy to note, that value of micro-surgical transplantation, such as lack of lingering immobilization of extremities, is of crucial importance for children and adolescent as far as it prevents development of hard mobility of joints and saves from obligatory lingering confinement to bed during treatment with traditional methods (Italian plastics, Phylatov's stalk, etc.) The offered method of formation of bone-soft tissue complex facilitates technical sides of transplantation and monitoring. In case of serious bone-soft tissue defects, transplantation of rib-thoracodorsial complex is considered as method of choice.

Posterior capsule opacification in rabbit eyes implanted with 1-piece and 3-piece hydrophobic acrylic intraocular lenses
Werner, L., N. Mamalis, et al. (2005), J Cataract Refract Surg 31(4): 805-11.
Abstract: PURPOSE: To evaluate the outcome of posterior capsule opacification (PCO) after implantation in rabbit eyes of currently available 3-piece and 1-piece hydrophobic acrylic intraocular lenses (IOLs) with square optic edges. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: The 3-piece designs evaluated were the AR40e (Advanced Medical Optics Inc.) and the MA60AC (Alcon, Inc.); the 1-piece designs were the SA60AT and the SA30AT (Alcon, Inc.). Nine lenses of each type were implanted in a randomized manner by the same surgeon in 18 Dutch Belted pigmented rabbits. After a follow-up of 3 weeks, the rabbits were killed and analyses of the enucleated eyes were performed from the posterior or Miyake-Apple view. The intensity of central PCO, peripheral PCO, and Soemmering's ring formation was scored from 0 to 4. The area of Soemmering's ring formation was also scored from 0 to 4 based on the number of quadrants involved. Other parameters analyzed were capsulorhexis coverage of the IOL anterior surface, IOL centration, fixation, and presence of striae. Results from the posterior view were complemented by histopathologic evaluation of the eyes. RESULTS: No statistically significant difference was found between the 4 groups of IOLs in the parameters analyzed from the posterior view. When cell ingrowth occurred with the 1-piece designs, causing peripheral and central PCO formation, it was more likely to start at the optic-haptic junctions, as observed during the clinical follow-up with slitlamp examination and confirmed by gross and histopathologic analyses of the enucleated eyes. CONCLUSIONS: The square, truncated optic edge is the most important IOL design feature for PCO prevention. The optic-haptic junctions of the 1-piece designs appear to be sites where the barrier effect of the truncated optic edge is less effective.

Potent activation of antigen-specific T cells by antigen-loaded nanospheres
Wang, X., T. Uto, et al. (2005), Immunol Lett 98(1): 123-30.
Abstract: Polystyrene nanospheres (NS) were found to be efficiently taken up by murine antigen-presenting cells (APC), especially bone marrow-derived dendritic cells (DC), in vitro and in vivo. The efficiency of NS uptake was not affected by the maturation state of DC. Both immature and mature DC had similar ability to take up NS in a dose- and time-dependent manner. Uptake and intracellular localization of NS was clearly demonstrated by confocal laser microscopy, using NS with fluorescence. DC could efficiently take up ovalbumin (OVA), when loaded on the surface of NS (OVA-NS). Consequently, OVA-NS-pulsed DC activated antigen-specific interferon (IFN)-gamma-producing T cells much more strongly than OVA-pulsed DC in vitro. These results suggest that NS can be used as an efficient antigen delivery system to DC for a variety of vaccines, such as an anti-human immunodeficiency virus type 1 vaccine.

Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs
Morrissey, D. V., J. A. Lockridge, et al. (2005), Nat Biotechnol 23(8): 1002-7.
Abstract: The efficacy of lipid-encapsulated, chemically modified short interfering RNA (siRNA) targeted to hepatitis B virus (HBV) was examined in an in vivo mouse model of HBV replication. Stabilized siRNA targeted to the HBV RNA was incorporated into a specialized liposome to form a stable nucleic-acid-lipid particle (SNALP) and administered by intravenous injection into mice carrying replicating HBV. The improved efficacy of siRNA-SNALP compared to unformulated siRNA correlates with a longer half-life in plasma and liver. Three daily intravenous injections of 3 mg/kg/day reduced serum HBV DNA >1.0 log(10). The reduction in HBV DNA was specific, dose-dependent and lasted for up to 7 d after dosing. Furthermore, reductions were seen in serum HBV DNA for up to 6 weeks with weekly dosing. The advances demonstrated here, including persistence of in vivo activity, use of lower doses and reduced dosing frequency are important steps in making siRNA a clinically viable therapeutic approach.

Potential anti-cancer effects of virgin olive oil phenols on colorectal carcinogenesis models in vitro
Gill, C. I., A. Boyd, et al. (2005), Int J Cancer 117(1): 1-7.
Abstract: The traditional Mediterranean diet is thought to represent a healthy lifestyle; especially given the incidence of several cancers including colorectal cancer is lower in Mediterranean countries compared to Northern Europe. Olive oil, a central component of the Mediterranean diet, is believed to beneficially affect numerous biological processes. We used phenols extracted from virgin olive oil on a series of in vitro systems that model important stages of colon carcinogenesis. The effect the extract on DNA damage induced by hydrogen peroxide was measured in HT29 cells using single cell microgel-electrophoresis. A significant anti-genotoxic linear trend (p=0.011) was observed when HT29 cells were pre-incubated with olive oil phenols (0, 5, 10, 25, 50, 75, 100 microg/ml) for 24 hr, then challenged with hydrogen peroxide. The olive oil phenols (50, 100 microg/ml) significantly (p=0.004, p=0.002) improved barrier function of CACO2 cells after 48 hr as measured by trans-epithelial resistance. Significant inhibition of HT115 invasion (p<0.01) was observed at olive oil phenols concentrations of 25, 50, 75, 100 microg/ml using the matrigel invasion assay. No effect was observed on HT115 viability over the concentration range 0, 25, 50 75, 100 microg/ml after 24 hr, although 75 and 100 microg/ml olive oil phenols significantly inhibited HT115 cell attachment (p=0.011, p=0.006). Olive oil phenols had no significant effect on metastasis-related gene expression in HT115 cells. We have demonstrated that phenols extracted from virgin olive oil are capable of inhibiting several stages in colon carcinogenesis in vitro.

Potential pitfalls of radiolabel adsorption to ceramic biomaterials
Parker, T., Z. Upton, et al. (2005), J Biomed Mater Res A 72(4): 363-72.
Abstract: The use of radiolabeled precursor molecules for the metabolic analysis of cell functions is commonplace. Tritiated thymidine, in particular, has been used to quantitate cellular proliferation in numerous cells, including osteoblasts, when cultured on various biomaterials. Our aim was to assess cellular protein synthesis and proliferation, on a range of fluoride ion-substituted hydroxyapatites. Initially, we used a classical metabolic analysis strategy with radiolabeled tracer molecules. Our results suggested that these materials supported enhanced protein synthesis and proliferation of SaOS-2 human osteoblast-like cells. However, control samples also revealed enhanced adsorption of the radiolabeled tracer. We have shown that this arises because partially fluoride ion-substituted hydroxyapatite exhibits enhanced adsorptive characteristics of radiolabeled leucine and thymidine over tissue culture plastic, hydroxyapatite, and fluoroapatite. Moreover, manual cell count data obtained through SEM analysis showed no significant difference in cell proliferation between any of the materials, further indicating that our initial results were artifacts. These results highlight the use and reporting of appropriate cell-free controls are critical in bioassays examining functional responses of cells to biomaterials, and if absent, may confound accurate data interpretation. Our findings have general implications for investigations of cell function on other novel ceramic biomaterials.

Potentiation of infections by biomaterials: a comparison of three materials
Karlan, M. S., R. A. Mufson, et al. (1981), Otolaryngol Head Neck Surg 89(4): 528-34.
Abstract: Biomaterial implants frequently potentiate infections in patients, yet rarely have we considered the interactions between bacteria and biomaterials responsible for this. There is extensive literature concerning suture materials of various types and a few studies comparing porous and solid implants. We have developed a simple, relatively atraumatic model for comparing rates of infection surrounding a biomaterial implant in paired single animal observations. Statistically significant differences between silicone and fluorocarbon implants and between silicone and bioglass implants are demonstrated. The relatively greater rate of infection with silicones is consistent with a previous clinical study. The further use of this model for evaluation of material-surface interfacial effects is proposed.

Praziquantel-loaded PLGA nanoparticles: preparation and characterization
Mainardes, R. M. and R. C. Evangelista (2005), J Microencapsul 22(1): 13-24.
Abstract: Nanoparticles containing praziquantel made of poly (D,L-lactide-co-glycolide) were designed by an emulsion-solvent evaporation method. Two organic solvents were separately utilized as disperse phase: methylene chloride and ethyl acetate. The size of the particles prepared with the former solvent was bigger than the particles prepared with the latter. The entrapment efficiency was bigger when methylene chloride was used, 79.82% in comparison with 29.27% by using ethyl acetate. DSC and infrared studies showed that no strong chemical interaction between drug and polymer occurred. Release kinetics of praziquantel, used as a model drug, was governed not only by actual drug loading but also by particles size. The higher the drug content and the smaller the particle size resulted in faster drug release.

Precoated femoral component with proximal and distal centralizers: results at 5 to 12 years
Jarrett, S. D. and P. F. Lachiewicz (2005), J Arthroplasty 20(3): 309-15.
Abstract: One study, confounded by the use of crystalline polyethylene and ceramic heads, reported a high rate of early failure of a precoated femoral component with proximal and distal centralizers. The present study reports the prospective clinical and radiographic results, and 10-year survival data of 166 consecutive hybrid total hip arthroplasties using this femoral component. An A or B cement grade was obtained in 93% of hips. At a mean follow-up time of 7 years (range, 5-12 years), there were only 4 (2.4%) femoral failures. Ten-year survival of this component was 95% (confidence interval, 94%-99%). The rate of radiographic failure and revision of this component implanted with conventional polyethylene and cobalt chrome heads is similar to that reported with other "modern" femoral components.

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