|Articles about Biomaterials|
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| Poly-L-lactic acid as a facial filler
Sterling, J. B. and C. W. Hanke (2005), Skin Therapy Lett 10(5): 9-11.
Abstract: Poly-L-lactic acid is a filler recently approved by the US FDA for the correction of facial lipoatrophy in patients infected with the human immunodeficiency virus (HIV). Currently, poly-L-lactic acid, sold under the brand name Sculptratrade mark (Dermik), is the only product approved by the FDA specifically for this indication. The market for poly-L-lactic acid will likely be larger than the HIV-infected population, as physicians use poly-L-lactic acid off-label to correct lipoatrophy associated with the normal aging process in non-HIV-infected patients. The benefits of poly-L-lactic acid are limited by the fact that multiple treatments are necessary to achieve the desired correction; its results are temporary and its cost is high.
| Poly-L-lactide surfaces subjected to long-term cell cultures: cell proliferation and polymer degradation
Guidoin, M. F., R. Guidoin, et al. (2005), Artif Cells Blood Substit Immobil Biotechnol 33(4): 411-22.
Abstract: Short term cell cultures are usually grown in contact with biomaterials to assess cytocompatibility. Depending on the rate of material degradation or corrosion, the time of culture can be a key-point in the method which, if too short, may not show any effect of the released material on the cells. A long term culture was therefore carried out with L929 fibroblast cells in contact with PLLA/PDLA samples for up to eight months. The degradation was measured in terms of shear-strength properties, intrinsic viscosity of the material and its cristallinity. The effect of the material on the cells was evaluated by measuring the growth rate of the cells. A significant decrease in the shear strength of the material was measured after three months. The rate of modification of the intrinsic viscosity was regular and decreased progressively throughout the culture period. Differential scanning calorimetry showed that the samples were initially essentially amorphous and that contact with the cell culture and its medium did not change its crystallinity level. The growth rate of the cells was not modified by the presence of the material when compared to the control. This study showed this material to be cytocompatible for a long period of time, even after detection of modifications of its physico-chemical properties.
| Polymer encapsulation of CdE (E = S, se) quantum dot ensembles via in-situ radical polymerization in miniemulsion
Esteves, A. C., A. Barros-Timmons, et al. (2005), J Nanosci Nanotechnol 5(5): 766-71.
Abstract: Cadmium sulfide and cadmium selenide/polymer nanocomposites were prepared via in-situ radical polymerization in miniemulsion. Organically capped CdE (E = S, Se) quantum dots (QDs) were used as the starting materials and ensembles of these dots were encapsulated with no need of further surface treatment. The use of two polymer matrices was investigated: polystyrene (PS) and poly(n-butyl acrylate) (PBA). In both cases, homogenous nanocomposites were obtained and their optical properties were investigated by visible absorption and photoluminescence spectroscopy. Quantum size effects were assigned to the nanocomposites, indicating the integrity of the individual QDs upon polymer encapsulation using the miniemulsion process.
| Polymer hollow particles with controllable holes in their surfaces
Hyuk Im, S., U. Jeong, et al. (2005), Nat Mater 4(9): 671-5.
Abstract: Colloidal particles with hollow interiors play important roles in microencapsulation-a process that has found widespread use in applications such as controlled release of drugs, cosmetics, inks, pigments or chemical reagents; protection of biologically active species; and removal of pollutants. The hollow particles are most commonly prepared by coating the surfaces of colloidal templates with thin layers of the desired material (or its precursor), followed by selective removal of the templates by means of calcination or chemical etching. This simple and straightforward approach works for a variety of materials that include polymers, ceramics, composites and metals. For polymers, methods such as emulsion polymerization, phase separation, crosslinking of micelles and self-assembly have also been demonstrated for generating hollow structures. However, diffusion through these closed shells with pores <10 nm is often a slow process. To solve this problem, macroporous capsules have been fabricated by organizing colloids around liquid droplets to form colloidosomes or by controlling the mixing of liquid droplets. Here we report the preparation of another class of macroporous capsules-polymer shells with controllable holes in their surfaces. After loading of functional materials, the holes can be closed by means of thermal annealing or solvent treatment.
| Polymer scaffolds fabricated with pore-size gradients as a model for studying the zonal organization within tissue-engineered cartilage constructs
Woodfield, T. B., C. A. Van Blitterswijk, et al. (2005), Tissue Eng 11(9-10): 1297-311.
Abstract: The zonal organization of cells and extracellular matrix (ECM) constituents within articular cartilage is important for its biomechanical function in diarthroidal joints. Tissue-engineering strategies adopting porous three-dimensional (3D) scaffolds offer significant promise for the repair of articular cartilage defects, yet few approaches have accounted for the zonal structural organization as in native articular cartilage. In this study, the ability of anisotropic pore architectures to influence the zonal organization of chondrocytes and ECM components was investigated. Using a novel 3D fiber deposition (3DF) technique, we designed and produced 100% interconnecting scaffolds containing either homogeneously spaced pores (fiber spacing, 1 mm; pore size, about 680 microm in diameter) or pore-size gradients (fiber spacing, 0.5-2.0 mm; pore size range, about 200-1650 microm in diameter), but with similar overall porosity (about 80%) and volume fraction available for cell attachment and ECM formation. In vitro cell seeding showed that pore-size gradients promoted anisotropic cell distribution like that in the superficial, middle, and lower zones of immature bovine articular cartilage, irrespective of dynamic or static seeding methods. There was a direct correlation between zonal scaffold volume fraction and both DNA and glycosaminoglycan (GAG) content. Prolonged tissue culture in vitro showed similar inhomogeneous distributions of zonal GAG and collagen type II accumulation but not of GAG:DNA content, and levels were an order of magnitude less than in native cartilage. In this model system, we illustrated how scaffold design and novel processing techniques can be used to develop anisotropic pore architectures for instructing zonal cell and tissue distribution in tissue-engineered cartilage constructs.
| Polymeric biomaterials: influence of phosphorylcholine polar groups on protein adsorption and complement activation
Yu, J., N. M. Lamba, et al. (1994), Int J Artif Organs 17(9): 499-504.
Abstract: The introduction to polymeric biomaterials of phosphorylcholine polar groups represents an approach towards the development of materials with improved blood compatibility. In this respect, two biomaterials, one a copolymer of butyl methacrylate and 2-methacryloyloxyethylphosphorylcholine (MPC), (poly(BMA-co-MPC) and the other, MPC-grafted Cuprophan, were examined with respect to their influence on protein adsorption and complement activation. Protein adsorption was studied by measurement of the adsorption of radiolabelled single proteins (albumin and fibrinogen), while complement activation was measured using radioimmunoassay for C3a des Arg. The investigation demonstrated that the polymers containing phosphorylcholine polar groups can achieve a marked reduction in protein adsorption and complement activation and supports the utilization of phosphorylcholine polar groups as a means of improving the compatibility of biomaterials for blood-contacting applications.
| Polymeric micelles for the solubilization and delivery of cyclosporine A: pharmacokinetics and biodistribution
Aliabadi, H. M., D. R. Brocks, et al. (2005), Biomaterials 26(35): 7251-9.
Abstract: The aim of this study was to assess the potential of polymeric micelles to modify the pharmacokinetics and tissue distribution of cyclosporine A (CsA). Drug-loaded methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) micellar solutions in isotonic medium were prepared and administered intravenously to healthy Sprague-Dawley rats. Blood and tissues were harvested and assayed for CsA, and resultant pharmacokinetic parameters and tissue distribution of CsA in its polymeric micellar formulation were compared to its commercially available intravenous formulation (Sandimmune). In the pharmacokinetic assessment, a 6.1 fold increase in the area under the blood concentration versus time curve (AUC) was observed for CsA when given as polymeric micellar formulation as compared to Sandimmune. The volume of distribution and clearance of CsA as PEO-b-PCL formulation were observed to be 10.0 and 7.6 fold lower, respectively, compared to the commercial formulation. No significant differences in t(1/2) or MRT could be detected. In the biodistribution study, analysis of tissue samples indicated that the mean AUC of CsA in polymeric micelles was lower in liver, spleen and kidney (1.5, 2.1 and 1.4-fold, respectively). Similar to the pharmacokinetic study in these rats, the polymeric micellar formulation gave rise to 5.7 and 4.9-fold increase in the AUC of CsA in blood and plasma, respectively. Our results show that PEO-b-PCL micelles can effectively solubilize CsA, at the same time confining CsA to the blood circulation and restricting its access to tissues such as kidney, perhaps limiting the onset of toxicity.
| Polymeric phospholipids as new biomaterials
Hayward, J. A., D. S. Johnston, et al. (1985), Ann N Y Acad Sci 446: 267-81.
Abstract: Phospholipid polymers form a new class of biomaterials with many potential applications in medicine and research. The development of these compounds is based upon the mimicry of cell surfaces and reflects our current understanding of the properties of membrane lipids. Physicochemical characterization of the monomeric, diacetylenic phospholipids illustrates the similarities to naturally occurring lipids, similarities that are confirmed by the capacity to enrich the membranes of A. laidlawii to the level of 90% diacetylenic lipid. Polymerization of diacetylenic phospholipids is easily attained by irradiation and produces a stable, crystalline array. The ability to link membrane lipids covalently permits the isothermal restriction in their motion, and is useful in basic studies of biomembranes. The thromboresistance of polymeric phosphatidylcholines in vitro may be a consequence of the inability of phosphatidylcholines to participate in coagulation. The restricted lateral diffusion of proteins along a polymeric lattice will also inhibit the formation of coagulation complexes. Existing polymers may be altered by a coating of polymeric lipid obtained by the Langmuir-Blodgett method. Polymerized vesicles display significant reductions in permeability and aggregation. Entrapment of soluble materials and reconstitution of membrane proteins may be exploited in controlled and site-directed drug delivery. Polymerization of cells in situ produces "cellular capsules" with entrapped membrane and cellular components. Polymeric hemosomes are capable of gas transport and may function as red cell surrogates. The hybrid qualities of biomembranes (polar surfaces, nonthrombogenic, low antigenic potential, and low permeability) and synthetic polymers (chemical and physical stability) suggest that polymeric phosphatidylcholines may serve as models for biomaterials design.
| Polymethacrylate-based nitric oxide donors with pendant N-diazeniumdiolated alkyldiamine moieties: synthesis, characterization, and preparation of nitric oxide releasing polymeric coatings
Zhou, Z. and M. E. Meyerhoff (2005), Biomacromolecules 6(2): 780-9.
Abstract: A series of new nitric oxide (NO) releasing copolymers have been prepared by covalently anchoring alkyldiamine side chains onto a polymethacrylate-based polymer backbone, followed by NO addition to form the desired pendant diazeniumdiolate structures. The resulting diazeniumdiolated copolymers were characterized via UV spectroscopy, and their proton-driven decomposition to release NO was also examined by UV and FTIR as well as chemiluminescence. Polymers with up to 22.1 mol % of incorporated amine sites that can be converted to corresponding diazeniumdiolates could be prepared, and such polymers release up to 0.94 micromol/mg of NO. Further, novel NO releasing polymeric coatings were formulated by doping one of the new polymethacrylate-based NO donors within inert polymeric matrixes. Biodegradable poly(lactide-co-glycolide) was employed as a film additive to greatly prolong the NO release of such coatings by continuously generating protons within the organic phase of the polymeric films, thereby driving decomposition of the diazeniumdiolates.
| Polymethylmethacrylate: one biomaterial for a series of membrane
Takeyama, T. and Y. Sakai (1999), Contrib Nephrol 125: 9-24.
| Polypeptide multilayer films
Haynie, D. T., L. Zhang, et al. (2005), Biomacromolecules 6(6): 2895-913.
Abstract: Research on polypeptide multilayer films, coatings, and microcapsules is located at the intersection of several disciplines: synthetic polymer chemistry and physics, biomaterials science, and nanoscale engineering. The past few years have witnessed considerable growth in each of these areas. Unexplored territory has been found at the borders, and new possibilities for technology development are taking form from technological advances in polypeptide production, sequencing of the human genome, and the nature of peptides themselves. Most envisioned applications of polypeptide multilayers have a biomedical bent. Prospects seem no less positive, however, in fields ranging from food technology to environmental science. This review of the present state of polypeptide multilayer film research covers key points of polypeptides as materials, means of polymer production and film preparation, film characterization methods, focal points of current research in basic science, and the outlook for a few specific applications. In addition, it discusses how the study of polypeptide multilayer films could help to clarify the physical basis of assembly and stability of polyelectrolyte multilayers, and mention is made of similarities to protein folding studies.
| Polyphosphazenes as biomaterials: surface modification of poly(bis(trifluoroethoxy)phosphazene) with polyethylene glycols
Lora, S., G. Palma, et al. (1993), Biomaterials 14(6): 430-6.
Abstract: Investigations were carried out on the metathetical exchange reaction between the -O-CH2CF3 moieties of poly(bis(trifluoroethoxy)phosphazene) (PTFP), in the state of slightly swollen films, and the alkoxide ions derived from methoxypolyethylene glycol (MPEG) of molecular mass ranging from 350 to 5000 g/mol. The substitution of these hydrophilic chains, mostly confined to thin surface layers, was revealed by means of optical microscopy and scanning electron microscopy observations, surface elemental analysis by energy-dispersive X-ray analysis (EDXA), FTIR-ATR analysis and water contact angle measurements. The surface biocompatibility was enhanced in all cases, whilst the mechanical properties of the original PTFP films were substantially retained in the modified samples exhibiting low substitutions. Such samples were obtained especially when the metathetical reaction was carried out with MPEG5000.
| Polysaccharide-poly(ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels
Yamaguchi, N. and K. L. Kiick (2005), Biomacromolecules 6(4): 1921-30.
Abstract: The production of polysaccharide-derivatized surfaces, polymers, and biomaterials has been shown to be a useful strategy for mediating the biological properties of materials, owing to the importance of polysaccharides for the sequestration and protection of bioactive proteins in vivo. We have therefore sought to combine the benefits of polysaccharide derivatization of polymers with unique opportunities to use these polymers for the production of bioactive, noncovalently assembled hydrogels. Accordingly, we report the synthesis of a heparin-modified poly(ethylene glycol) (PEG) star copolymer that can be used in the assembly of bioactive hydrogel networks via multiple strategies and that is also competent for the delivery of bioactive growth factors. A heparin-decorated polymer, synthesized by the reaction of thiol end-terminated four-arm star PEG (M(n) = 10 000) with maleimide functionalized low molecular weight heparin (LMWH, M(r) = 3000), has been characterized via (1)H NMR spectroscopy and size-exclusion chromatography; results indicate attachment of the LMWH with at least 73% efficiency. Both covalently and noncovalently assembled hydrogels can be produced from the PEG-LMWH conjugate. Viscoelastic noncovalently assembled hydrogels have been formed on the basis of the interaction of the PEG-LMWH with a PEG polymer bearing multiple heparin-binding peptide motifs. The binding and release of therapeutically important proteins from the assembled hydrogels have also been demonstrated via immunochemical assays, which demonstrate the slow release of basic fibroblast growth factor (bFGF) as a function of matrix erosion. The combination of these results suggests the opportunities for producing polymer-polysaccharide conjugates that can assemble into novel hydrogel networks on the basis of peptide-saccharide interactions and for employing these materials in delivery applications.
| Polysaccharide-protein surface modification of titanium via a layer-by-layer technique: characterization and cell behaviour aspects
Cai, K., A. Rechtenbach, et al. (2005), Biomaterials 26(30): 5960-71.
Abstract: To improve the surface biocompatibility of titanium films, a layer-by-layer (LBL) self-assembly technique, based on the polyelectrolyte-mediated electrostatic adsorption of chitosan (Chi) and gelatin (Gel), was used leading to the formation of multilayers on the titanium thin film surfaces. The film growth was initialized by deposition of one layer of positively charged poly(ethylene imine) (PEI). Then the thin film was formed by the alternate deposition of negatively charged Gel and positively charged Chi utilizing electrostatic interactions. The LBL film growth was monitored by several techniques. The chemical composition, surface topography as well as wettability were investigated by using X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), confocal laser scanning microscopy (CLSM) and water contact angle measurement, respectively. Quantitative XPS analysis showed the alternative change of C/N ratio after four sequential cycles coating of Ti/PEI/Gel/Chi/Gel, which indicated the discrete layer structure of coatings. Uncoated titanium (control sample) displayed a smooth surface morphology (root mean square (RMS) roughness was around 2.5 nm). A full coverage of coating with Gel/Chi layers was achieved on the titanium surface only after the deposition layers of PEI/(Gel/Chi)2. The PEI/Gel/(Chi/Gel)3 layer displayed a rough surface morphology with a tree-like structure (RMS roughness is around 82 nm). These results showed that titanium films could be modified with Chi/Gel which may affect the biocompatibility of the modified titanium films. To confirm this hypothesis, cell proliferation and cell viability of osteoblasts on LBL-modified titanium films as well as control samples were investigated in vitro. The proliferation of osteoblasts on modified titanium films was found to be greater than that on control (p<0.05) after 1 and 7 days culture, respectively. Cell viability measurement showed that the Chi/Gel-modified films have higher cell viability (p<0.05) than the control. These data suggest that Chi/Gel were successfully employed to surface engineer titanium via LBL technique, and enhanced its cell biocompatibility. The approach presented here may be exploited for fabrication of titanium-based implant surfaces.
| Polysulfone-graft-poly(ethylene glycol) graft copolymers for surface modification of polysulfone membranes
Park, J. Y., M. H. Acar, et al. (2006), Biomaterials 27(6): 856-65.
Abstract: Amphiphilic graft copolymers having polysulfone (PSf) backbones and poly(ethylene glycol) (PEG) side chains were synthesized via reaction of an alkoxide formed from PEG and a base (sodium hydride) with chloromethylated polysulfone. The resulting polysulfone-graft-poly(ethylene glycol), PSf-g-PEG, materials were hydrophilic but water insoluble, rendering them potentially useful as biomaterial coatings. PSf-g-PEG films exhibited high resistance to protein adsorption and cell attachment. When used as an additive in PSf membranes prepared by immersion precipitation, the graft copolymer preferentially segregates to the membrane surface, delivering enhanced wettability, porosity and protein resistance compared to unmodified PSf membranes. The surface properties of PSf-g-PEG modified membranes render them desirable candidates for hemodialysis.
| Polyurethane films seeded with embryonic stem cell-derived cardiomyocytes for use in cardiac tissue engineering applications
Alperin, C., P. W. Zandstra, et al. (2005), Biomaterials 26(35): 7377-86.
Abstract: Cardiomyocytes are terminally differentiated cells and therefore unable to regenerate heart tissue after infarction. The successful engraftment of various cell types resulting in improved cardiac function has been reported, however methods for improving the delivery of donor cells to the infarct site still need to be developed. The use of bioengineered cardiac grafts has been suggested to replace infarcted myocardium and enhance cardiac function. In this study, we cultured embryonic stem (ES) cell-derived cardiomyocytes on thin polyurethane (PU) films. The films were coated with gelatin, laminin or collagen IV in order to encourage cell adhesion. Constructs were examined for 30 days after seeding. Cells cultured on laminin and collagen IV, exhibited preferential attachment, as assessed by cellular counts, and viability assays. These surfaces also resulted in a greater number of contracting films compared to controls. A degradable elastomer seeded with embryonic stem cell-derived cardiomyocytes may hold potential for the repair of damaged heart tissue.
| Polyurethane scaffolds for meniscal tissue regeneration
de Groot, J. H. (2005), Med Device Technol 16(7): 18-20.
Abstract: More than 1 million procedures for the total or partial removal of the meniscus in the knee joint are performed in the United States and Europe each year. These meniscectomies lead to degenerative changes of the knee and to immobility of the patients. A polyurethane scaffold is described here, which has been developed as an alternative repair solution.
| Polyurethanes with radiopaque properties
James, N. R., J. Philip, et al. (2006), Biomaterials 27(2): 160-6.
Abstract: An aliphatic, commercially available, medical grade polyurethane, Tecoflex 80A was made radiopaque by coupling a 5-iodine-containing molecule, N-(2,6- diiodocarboxyphenyl)-3,4,5-triiodo benzamide (DCPTB) onto the polymer backbone. DCPTB was synthesized by coupling 4-amino-3,5-diiodobenzoic acid and 3,4,5-triiodobenzoic acid using dicyclohexyl carbodiimide. Radiopaque polyurethane thus obtained was characterized by IR, TGA, DSC and X-radiography. By optimizing the reaction conditions, it was possible to incorporate about 8% iodine in the polymer (wt/wt) to achieve radiopacity almost equivalent to that of a 2mm thick aluminium wedge. However, the products differed from the starting polymer in thermal characteristics. The starting polymer showed two endothermic transitions, the first one due to glass transition of the soft segment and the second one due to disruption of the hard segments. After modification, the second transition shifted to a lower temperature, while the first transition remained unaltered. Also, the modified polymers showed reduced thermal stability compared to the starting polymer. These observations could be explained on the basis of the reduced extent of intermolecular hydrogen bonding among the hard segments of the end product. Radiopaque polyurethanes are expected to have significant advantage over their non-radiopaque counterparts in many medical and related applications.
| Polyvinylidene fluoride (PVDF) as a biomaterial: from polymeric raw material to monofilament vascular suture
Laroche, G., Y. Marois, et al. (1995), J Biomed Mater Res 29(12): 1525-36.
Abstract: This study identified the effects of various manufacturing processes on the crystalline microstructure, mechanical properties, and biocompatibility of a polyvinylidene fluoride (PVDF) suture. To achieve this, changes in the crystalline microstructure and the tensile behavior of PVDF monofilaments were monitored in vitro after different thermal processing, coloration, and sterilization treatments. In addition, the in vivo biocompatibility of the manufactured and sterilized PVDF suture was assessed by using it to anastomose a preclotted polyester vascular prosthesis as a thoracoabdominal bypass in a series of dogs. The tissue response was followed by histologic and scanning electron microscopy over implantation periods ranging from 4 h to 6 months. Differential scanning calorimetry and infrared spectroscopy (FTIR-ATR) showed that thermal processing and the addition of a coloring agent had a direct effect on modifying the crystalline microstructure and hence changing the mechanical properties. For example, thermal processing converted some of the alpha phase into the beta and gamma polymorphs, whereas coloration led only to a major increase in the beta-to-alpha ratio. The tensile properties were found to be optimized when the relative proportion of the beta and gamma phases combined compared to the alpha form gave rise to an FTIR A509/A532 absorption ratio between 4.0 and 4.5. Sterilization was found to cause some modifications to the crystalline microstructure near the surface of the monofilaments, but it did not change their mechanical properties. Pathologic examination of the anastomotic regions after different periods of implantation revealed a minimal cellular response, with no mineralization, intimal hyperplasia, or excessive fibrous tissue reaction. This good biocompatibility, together with other desirable characteristics such as ease of manipulation and satisfactory mechanical strength, makes PVDF an attractive alternative monofilament suture material for cardiovascular surgery.
| Poor results after augmenting autograft with xenograft (Surgibone) in hip revision surgery: a report of 27 cases
Charalambides, C., M. Beer, et al. (2005), Acta Orthop 76(4): 544-9.
Abstract: BACKGROUND: Surgibone Unilab is prepared from bovine bone and contains hydroxyapatite and protein. It is supposed to be immunogenically inert but the protein could be antigenic in man. PATIENTS AND METHODS: We followed 27 patients for an average of 2.5 (1-5) years, all of whom had received Surgibone mixed with autograft to fill in defects in the acetabulum and the proximal femur in revision hip surgery. RESULTS: In 17 patients, there was apparently complete incorporation of the bone graft within 6 months. In 3 of these patients, the graft was incorporated after 3 months. In 3 patients, however, there was no incorporation of the graft as late as 3 years after the operation. 3 other patients appeared to have a type of graft rejection (pseudoinfection). 1 other patient suffered MRSA deep infection of the prosthesis which resulted in removal of the implants 1 month postoperatively. INTERPRETATION: Use of Surgibone xenograft in revision hip surgery, even in combination with autograft, resulted in failure and the need for rerevision in at least one quarter of the cases studied.
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