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Lactoferrin: an important host defence against microbial and viral attack
Valenti, P. and G. Antonini (2005), Cell Mol Life Sci 62(22): 2576-87.
Abstract: The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf. In mucosal secretions, iron and Lf modulate the motility and aggregation of pathogenic bacteria. Lf inhibits bacterial adhesion on abiotic surfaces through ionic binding to biomaterials, or specific binding to bacterial structures or both. Lf inhibition of bacterial adhesion to host cells requires Lf binding to bacteria and/or host cells. Lf hinders microbial internalization by binding to both glycosaminoglycans and bacterial proteins which can be degraded by Lf-mediated proteolysis. Moreover, Lf internalisation and localisation to the host cell nuclei could modulate bacterial entry into cells through gene regulation. Finally, the capability of Lf to exert antiviral activity, through its binding to host cells and/or viral particles, strengthens the idea that it is an important brick in the mucosal wall, effective against both microbial and viral attacks.

Laparoscopic augmentation cystoplasty using the novel biomaterial Surgisis: small-intestinal submucosa
Calvano, C. J., M. E. Moran, et al. (2000), J Endourol 14(2): 213-7.
Abstract: BACKGROUND AND PURPOSE: Urinary bladder augmentation is indicated for diverse conditions, including neurogenic bladder, cancer resection, spinal cord injury, and congenital anomalies. The ideal cystoplasty material is yet to be described. Native gastrointestinal segments commonly used are limited by leakage and small-bowel obstruction, metabolic/nutritional abnormalities, calculi, and malignancy. This study assessed laparoscopic bladder augmentation with porcine small intestinal submucosa (SIS). MATERIALS AND METHODS: Five female pigs (<25 kg) were prepared for surgery under general anesthesia. After Veress needle insufflation, a main 10-mm trocar was placed in the midline for the laparoscope, with two lateral 10-mm ports added for operative instruments. The bladder dome was incised, and a patch of SIS was sewn into the bladder using running 2-0 Vicryl. Three animals served as technical studies. Two additional sows underwent long-term survival surgery: one undiverted and one diverted via a Stamey suprapubic catheter. RESULTS: There were no operative losses. The mean operative time was 140 minutes. The SIS graft held the sutures without tearing. Laparoscopic survey revealed no urine leaks at bladder closure. All five animals voided postoperatively. Urinary extravasation was evident in the three undiverted technique animals. In the other two sows, cystoscopy at 7 days showed intact suture lines without evidence of urinary extravasation and with normal vesicular volumes. Tissue growth was evident, but the graft margins were still discernible. CONCLUSIONS: Laparoscopic bladder augmentation was possible using SIS but at minimal volumes. There were no operative complications; however, the material was difficult to deploy and may benefit from application of an absorbable scaffold. Postoperative urinary drainage is necessary. Further studies will optimize the graft configuration for maximal augmentation.

Large deformation compression induced crystallinity degradation of conventional and highly crosslinked UHMWPEs
Sobieraj, M. C., S. M. Kurtz, et al. (2005), Biomaterials 26(33): 6430-9.
Abstract: The effect of a large compressive plastic deformation on the melt temperature (Tm), lamellar thickness, crystallinity, and density of four UHMWPEs (two conventional and two highly crosslinked) was examined. The materials were prepared from a single batch of medical grade GUR 1050 resin (Ticona, Bayport, TX, USA). The two conventional UHMWPEs were as-received (virgin) and gamma radiation sterilized at 30 kGy in a nitrogen atmosphere (radiation sterilized). The two highly crosslinked UHMWPEs were each irradiated at 100 kGy and then post-processed with one of either two thermal treatments: annealing, which was done below the melt transition temperature (Tm), at 110 degrees C for 2h (110 degrees C-annealed); and, remelting, which was done above Tm, at 150 degrees C (150 degrees C-remelted). Differences in changes upon compression between the materials were examined using ANCOVA analyses. The 150 degrees C-remelted material showed a significant change in Tm and lamellar thickness upon compressive plastic deformation whereas the other three UHMWPE materials did not. However, all of the materials showed significantly decreased crystallinity and density upon compressive deformation. The findings of this study support that microstructural evolution during compressive deformation is a function of UHMWPE formulation, as affected by irradiation and post-irradiation heat treatment.

Large-scale propagation of four undifferentiated human embryonic stem cell lines in a feeder-free culture system
Sjogren-Jansson, E., M. Zetterstrom, et al. (2005), Dev Dyn 233(4): 1304-14.
Abstract: We describe an improved and more robust protocol for transfer and subsequent propagation of human embryonic stem cells under feeder-free conditions. The results show that mechanical dissociation for transfer of the human embryonic stem cells to Matrigel resulted in highest survival rates. For passage of the cultures on the other hand, enzymatic dissociation was found to be most efficient. In addition, this method reduces the time, work, and skills needed for propagation of the human embryonic stem cells. With the present protocol, the human embryonic stem cells have been cultured under feeder-free conditions for up to 35 passages while maintaining a normal karyotype, stable proliferation rate, and high telomerase activity. Furthermore, the feeder-free human embryonic stem cell cultures express the transcription factor Oct-4, alkaline phosphatase, and cell surface markers SSEA-3, SSEA-4, Tra 1-60, Tra 1-81, and formed teratomas in severe combined immunodeficient mice. This method provides distinct advantages compared with previous protocols and make propagation of human embryonic stem cells less laborious and more efficient.

Laser deposition of polymer and biomaterial films
Chrisey, D. B., A. Pique, et al. (2003), Chem Rev 103(2): 553-76.

Laser technology in orthopedics: preliminary study on low power laser therapy to improve the bone-biomaterial interface
Guzzardella, G. A., P. Torricelli, et al. (2001), Int J Artif Organs 24(12): 898-902.
Abstract: Low Power Laser (LPL) seems to enhance the healing of bone defects and fractures. The effect of LPL in other orthopedic areas such as osteointegration of implanted prosthetic bone devices is still unclear. In the present study, 12 rabbits were used to evaluate whether Ga-Al-As (780 nm) LPL stimulation has positive effects on osteointegration. Hydroxyapatite (HA) cylindrical nails were drilled into both distal femurs of rabbits. From postoperative day 1 and for 5 consecutive days, the left femura of all rabbits were given LPL treatment (Laser Group-LG) with the following parameters: 300 Joule/cm2, 1 Watt, 300 Hertz, pulsating emission, 10 minutes. The right femura were sham-treated (Control Group-CG). At 4 and 8 weeks after implantation, histologic and histomorphometric investigations evaluated bone-biomaterial-contact. Histomorphometry showed a higher degree of osteointegration at the HA-bone interface in the LG Group at 4 (p < 0.0005) and 8 weeks (p < 0.001). These preliminary positive results seem to support the hypothesis that LPL treatment can be considered a good tool to enhance the bone-implant interface in orthopedic surgery.

Laser-guided direct writing for three-dimensional tissue engineering
Nahmias, Y., R. E. Schwartz, et al. (2005), Biotechnol Bioeng 92(2): 129-36.
Abstract: One of the principal limitations to the size of an engineered tissue is oxygen and nutrient transport. Lacking a vascular bed, cells embedded in an engineered tissue will consume all available oxygen within hours while out branching blood vessels will take days to vascularize the implanted tissue. One possible solution is to directly write vascular structures within the engineered tissue prior to implantation, reconstructing the tissue according to its native architecture. The cell patterning technique, laser-guided direct writing (LGDW), can pattern multiple cells types with micrometer resolution on arbitrary surfaces, including biological gels. Here we show that LGDW can pattern human umbilical vein endothelial cells (HUVEC) in two- and three-dimensions with micrometer accuracy. By patterning HUVEC on Matrigel, we can direct their self-assembly into vascular structures along the desired pattern. Finally, co-culturing the vascular structures with hepatocytes resulted in an aggregated tubular structure similar in organization to a hepatic sinusoid. This capability can facilitate studies of tissue architecture at the single cell level, and of heterotypic interactions underlying processes such as liver and pancreas morphogenesis, differentiation, and angiogenesis.

Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q-switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. I. A review
Chirila, T. V., I. J. Constable, et al. (1990), Biomaterials 11(5): 305-12.
Abstract: The use of short-pulsed lasers in ophthalmic surgery inspired and called for research on the damage inflicted by the laser radiation upon the acrylic polymers from which artificial intraocular lenses are made. The possible release of toxic monomers by laser-induced depolymerization is of great concern but past investigations of this phenomenon have been very limited. The present knowledge of various types of laser-induced damage to transparent polymers is reviewed with particular emphasis on the acrylic materials and intraocular lenses.

Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q-switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. II. Study of monomer release from artificial intraocular lenses
Chirila, T. V., G. D. Barrett, et al. (1990), Biomaterials 11(5): 313-20.
Abstract: Commercial intraocular lenses and polymer specimens, both poly(methyl methacrylate) (PMMA) and poly(2-hydroxyethyl methacrylate) p(HEMA), were subjected to various levels of irradiation from a Q-switched Nd:YAG laser, and then to extraction and sample-enrichment techniques. The extracts were analysed by capillary gas chromatography. In PMMA samples, residual contents of 0.05-0.89% (wt) MMA were found and it appeared that the laser radiation did not cause a detectable increase of the monomer content. No residual HEMA could be found in p(HEMA) samples before or after laser bombardment. It is concluded that the accidental exposure of lenses to Nd:YAG laser cannot produce a significant release of monomers. Depolymerization induced by laser is a process unlikely to occur at the energy levels used in ophthalmic surgery.

Laser-perforated membranous biomaterials induced pore size-dependent bone induction when used as a new BMP carrier
Kuboki, Y., M. Kikuchi, et al. (2003), Connect Tissue Res 44 Suppl 1: 318-25.
Abstract: Previously we found that laser perforation of a collagen membrane (35 microm thickness, Koken Co., Tokyo) produced an effective bone morphogenetic protein (BMP) carrier, if the created pore sizes were larger than 0.5 mm. In this study we applied the same technique to create pores of 0.2 and 1.0 mm in a thicker (1.2 mm thickness) porous biodegradable membrane made of polylactic acid and an epsilon-caprolactone copolymer (PLA-CL) to obtain an effective membranous BMP carrier with higher mechanical strength. Pieces of PLA-CL (0.5 x 1.0 x 0.12 cm) combined with rhBMP-2 (5 microg) were implanted subcutaneously into rats and processed for analyses at 1-3 weeks. The laser-perforated PLA-CL membranes equipped with 1.0 mm pores induced mineralization beginning from the margins of the pores judging from the X-ray patterns, but bone formation seemed to proceed irregularly inside the pores. In the perforated PLA-CL membrane with 1.0-mm pores bone formation did not significantly increase compared with the nonperforated one. This was due to the fact that the PLA-CL membrane was already a porous structure (85% porosity). In contrast with laser-perforated PLA-CL 0.2 mm pores, bone was induced on the collagen fibers and fiber bundles inside the pores. The different patterns of bone formation between the PLA-CL membranes with 1.0 and 0.2 mm pores seemed to be related to the active formation of perpendicular collagen fibers through the 0.2 mm pores.

Late infection of a Dacron carotid endarterectomy patch--a case report
Byer, A., R. C. Keys, et al. (2001), Vasc Surg 35(6): 469-72.
Abstract: This unique case reports the nonsurgical management of a late (2 years) methicillin-resistant Staphylococcus aureus neck infection around a Dacron-patched carotid endarterectomy. Because the patient was elderly with multiple serious risk factors and no drainable material, IV and oral antibiotics were selected as initial management. Follow-up computed tomography of the neck, however, documented complete resolution of the phlegmon. While the authors remain uncertain of the long-term outcome the patient is free of local infection 2 years after diagnosis and nonoperative treatment.

Late Paraplegia After Scoliosis Treatment: An Uncommon Diagnosis
Vialle, R., S. Wolff, et al. (2005), J Spinal Disord Tech 18(6): 531-534.
Abstract: We report the case of a young girl treated at age 16 for a progressive scoliosis by posterior instrumented arthrodesis. Ten years later, she suddenly developed lumbar pain and paraplegia. The surgical procedure showed a mass infiltrating the vertebral canal and the dural sheath following a supralaminar hook. Histology revealed a diagnosis of leiomyosarcoma. The outcome was poor with a rapid and fatal extension of the tumor. There is nothing to justify a causal link between the scoliosis and the late onset of a malignant tumor. Nevertheless, we discuss the potential role of diagnostic irradiation consecutive to scoliosis monitoring during growth and the potential role of environmental carcinogens like metallic biomaterials. Finally, rapid intrusion of this extraspinal tumor into the dural sheath resulted in a confusing clinical picture and delayed the diagnosis and treatment of the tumor.

Late thrombosis following treatment of in-stent restenosis with drug-eluting stents after discontinuation of antiplatelet therapy
Waters, R. E., D. E. Kandzari, et al. (2005), Catheter Cardiovasc Interv 65(4): 520-4.
Abstract: Drug-eluting stent usage has become commonplace for the percutaneous treatment of de novo coronary lesions, but the safety and efficacy profile for their evolving usage in restenotic lesions is largely unknown. We report three cases of angiographically confirmed drug-eluting stent thrombosis following treatment of restenotic lesions that occurred late (193, 237, and 535 days) and shortly after interruption of antiplatelet therapy. All three patients suffered ST elevation myocardial infarction, and there was one death. Further studies are necessary to better define the associated risk and ideal duration of antiplatelet therapy necessary in this cohort of patients with restenotic lesions.

Late thrombosis of sirolimus-eluting stents following noncardiac surgery
Nasser, M., M. Kapeliovich, et al. (2005), Catheter Cardiovasc Interv 65(4): 516-9.
Abstract: We describe two patients with in-stent thrombosis occurring 4 and 21 months after implantation of sirolimus-eluting stents. Both cases occurred following noncardiac surgery. In both cases, aspirin had been stopped prior to surgery. Both patient sustained a severe myocardial infarction; one died. The occurrence of late thrombosis of sirolimus-eluting stents is of concern.

Lateral ridge augmentation by the use of grafts comprised of autologous bone or a biomaterial. An experiment in the dog
Araujo, M. G., M. Sonohara, et al. (2002), J Clin Periodontol 29(12): 1122-31.
Abstract: OBJECTIVE: The present investigation was performed to determine if a block of Bio-Oss used as an onlay graft can be used as a scaffold for new bone formation. MATERIAL AND METHODS: Five mongrel dogs were used. The mandibular premolars were extracted. On both sides of the mandible, the buccal bone plate was resected and defects, about 25 mm long, 8 mm high and 5 mm wide, were produced After 3 months of healing, a second surgical procedure was performed. In the left side, a block of Bio-Oss was adjusted to the buccal bone wall. The graft had the shape of a cylinder and was retained with a miniscrew and covered with a collagen membrane. In the contra-lateral side of the mandible, a block biopsy was first obtained from the ascending ramus. This bone graft had the shape of a cylinder that was 8 mm in diameter and 3 mm thick. The graft was transferred to the experimental site, adjusted to the buccal wall, retained with a miniscrew, and covered with a membrane. The flaps were repositioned and closed with sutures to ensure a complete coverage of the experimental sites. After 6 months of healing, the dogs were sacrificed and the experimental sites dissected. The biopsies were processed for ground sectioning. The sections were stained in toluidine blue, examined in the microscope, and a number of histo- and morphometric assessments made. RESULTS: The study demonstrated that cortical bone used as an onlay graft in the lateral aspect of the alveolar ridge, during a 6-month period of healing integrated with the host bone but underwent marked peripheral resorption. Thus, close to 30% of the height and 50% of the length of the graft was replaced with connective tissue. It was further observed that while the dimensions of a graft which contained a scaffold of cancellous bovine bone mineral remained unchanged, only moderate amounts of new bone formed at the base of this graft. CONCLUSION: Grafts of autologous cortical bone, placed on the surface of a one-wall defect, may undergo marked resorption during healing. A similar graft of Bio-Oss may retain its dimension, and limited amounts of new bone will form within the biomaterial.

Lateral window sinus augmentation using bone replacement grafts: a biologically sound surgical technique
Wallace, S. S. (2005), Alpha Omegan 98(2): 36-46.

Latin American randomized trial of balloon angioplasty vs coronary stenting for small vessels (LASMAL): immediate and long-term results
Rodriguez, A., M. Rodriguez Alemparte, et al. (2005), Am J Med 118(7): 743-51.
Abstract: PURPOSE: To assess the potential role of coronary stent to improved acute success and reduce late restenosis in lesions with reference diameter <2.9 mm using a bare metal stent specifically designed for small coronary vessels. There is controversy on the results among previous studies comparing bare metal stent implantation with conventional balloon percutaneous transluminal coronary angioplasty (PTCA). Differences in baseline characteristics, inclusion and exclusion criteria, and stent design may account for these discrepancies. METHODS: The population of this multicenter, multinational randomized study (LASMAL) consisted of 246 patients undergoing percutaneous coronary intervention of small vessel reference diameter. They were randomized into 2 strategies of percutaneous revascularization: elective primary stent (n = 124) or conventional balloon PTCA with provisional stenting (n = 122) in the presence of acute, threatened closure or flow-limiting dissections. RESULTS: The clinical success rate was significantly better for the stent group (98.3% vs 91.8%; P = 0.038). At 30 days follow-up, requirements of target vessel revascularization (TVR) (6.6% vs 0.8%; P = 0.018) and incidence of major adverse cardiac and cerebrovascular events (MACCE) (9.8% vs 2.4%; P = 0.01) was significantly lower in the stent strategy. Postpercutaneous coronary intervention minimal luminal diameter (MLD) was significantly larger in the stent group (2.3 +/- 0.2 mm vs 2.2 +/- 0.2 mm; P = 0.003). At follow-up, MLD in the stent group was larger than with PTCA (1.7 +/- 0.7 mm vs 1.5 +/- 0.7 mm, respectively; P = 0.035). Net gain was also significantly better with stent strategy (1.1 +/- 0.7 mm vs 0.8 +/- 0.7 mm, respectively; P = 0.002). Stenting resulted in a significant lower angiographic binary restenosis (20% vs 31%; P = 0.02) than PTCA. Furthermore, patients treated with stent were more frequently free from MACCE at 9-month follow-up (death, acute myocardial infarction [AMI], stroke, repeat revascularization procedures) than those treated initially with PTCA (82.2% vs 72% of PTCA, P = 0.046). CONCLUSIONS: The use of a specifically designed bare metal coronary phosphoril choline-coated stent as primary device during percutaneous interventions in small coronary arteries was associated with high procedural success and low in-hospital and 30-day follow-up complications. At long-term follow-up, patients initially treated with stents had lower angiographic restenosis rate and were more frequently free from major adverse cardiac events.

Layer-by-Layer assembly of TiO2 nanoparticles for stable hydrophilic biocompatible coatings
Kommireddy, D. S., A. A. Patel, et al. (2005), J Nanosci Nanotechnol 5(7): 1081-7.
Abstract: Stable, super-hydrophilic (water contact angle approximately equal to 0 degrees) titanium dioxide nanoparticle thin films have been obtained on substrates with different initial wettability such as glass, poly(methyl methacrylate) and poly(dimethyl siloxane) using layer-by-layer nano-assembly method. Titanium dioxide nanoparticles were alternated with poly(styrene sulfonate) to form films of thickness ranging from 11 nm to 220 nm. The hydrophilicity of these thin films increases with increasing number of deposited PSS/TiO2 bilayers. It was found that 2, 5 and 20 layers were needed to form super-hydrophilic TiO2 coating on glass, PMMA and PDMS respectively. Oxygen plasma treatment of substrate surfaces enhanced the formation of homogeneous TiO2 films and accelerated the formation of hydrophilic layers. Super-hydrophilicity has been shown to be unique to PSS/TiO2 films as compared with other polyelectrolyte/nanoparticle layers, and UV irradiation may restore hydrophilicity even after months of storing of the samples. Biocompatibility of TiO2 nanoparticle films has been demonstrated by the successful cell culture of human dermal fibroblast.

Lead electrocapture on hydroxyapatite coated electrodes
Zejli, H., K. Temsamani, et al. (2005), Chemosphere 60(8): 1157-61.
Abstract: Hydroxyapatite coated electrodes were made by a hydrolysis reaction involving silanes and hydroxyapatite particles on stainless steel. Aqueous lead ions were captured on the coatings with or without electromigration. Results depend on coating thickness, supporting electrolyte and the presence of the electric field. It was found that this new electrocapture method can remove lead from solutions down to ppb levels.

Legal requirements for the preclinical toxicological evaluation of biomaterials
Leuschner, J. (1992), Clin Mater 10(1-2): 51-7.
Abstract: Biomaterials intended for use in humans must, by law, be tested preclinically before the products can be placed on the market. Such preclinical studies should be guided by the recommendations for testing proprietary medical products. The biomaterial employed should in most cases be tested or evaluated at three levels: (1) toxicity tests with the various ingredients used to manufacture the basic biomaterial; (2) toxicity tests with the final biomaterial; and (3) toxicity tests with the final device. This article discusses the legal requirements and preclinical studies for biomaterials, suggesting that the type of test conducted, its design, and the extent of testing should depend upon the risks associated with that biomaterial.


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