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Polyurethanes with radiopaque properties
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.
... It is noteworthy to mention that most polymers are not intrinsically radiopaque, which makes visualization in the human body difficult. The reason is that most polymers are composed of atoms with low electron density and low specific gravity, such as carbon, hydrogen, and nitrogen; hence, the resulting image is radiolucent (transparent to X-rays or other forms of radiation) [13]. To improve the radiopacity of polymers, the average electron density and the specific gravity of the atoms must also be increased by incorporating heavier atoms (iodine or barium) in the polymer backbone through synthesis or by adding ceramic/metallic particles into the polymeric matrix [13]. ...
... The reason is that most polymers are composed of atoms with low electron density and low specific gravity, such as carbon, hydrogen, and nitrogen; hence, the resulting image is radiolucent (transparent to X-rays or other forms of radiation) [13]. To improve the radiopacity of polymers, the average electron density and the specific gravity of the atoms must also be increased by incorporating heavier atoms (iodine or barium) in the polymer backbone through synthesis or by adding ceramic/metallic particles into the polymeric matrix [13]. An alternative is to mix nanoparticles (such as barium sulfate) with the polymer (such as polyurethane) in the process and obtain the radiopaque material. ...
... The material has cytocompatibility with L929 mouse fibroblast cells and has reasonable tissue compatibility, even after 12 weeks of implantation. James et al. [13] added a 5iodine-containing molecule, N-(2,6-diiodocarboxyphenyl)-3,4,5-triiodobenzamide, onto the polymer backbone of a medical-grade aliphatic polyurethane, Tecoflex ® 80A. The authors claimed an equivalent radiopacity to that of a 2 mm-thick aluminum wedge by incorporating about 8% iodine in the polymer backbone. ...
Radiopaque polyurethanes are extensively used in biomedical fields owing to their favorable balance of properties. This research aims to investigate the influence of particle concentration on various properties, including rheological, radiopacity, structural, thermal, and mechanical attributes, with a thorough analysis. The findings are benchmarked against a commercial product (PL 8500 A) that contains 10% weight barium sulfate. Two more thermoplastic polyurethanes (TPU) were formulated with two different concentrations of barium sulfate (10 wt.% and 20 wt.%) and compared to the commercially available product. FTIR demonstrated similar absorption bands among all samples, indicating that the fabrication method did not impact the TPU matrix. DSC indicated a predominantly amorphous structure for PL 8500 A compared to the other samples, while the kinetic degradation was more influenced by the higher barium sulfate content. The rheological analysis showed a decrease in the complex viscosity and storage modulus with the radiopacifier and an increase in the radiopacity, as demonstrated by the X-radiography. X-ray microtomography showed a more spherical particle format with a heterogeneous particle structure for PL 8500 A compared to the other polyurethanes. These findings enhance the comprehension of the structure–property relationships inherent in these materials and facilitate the development of customized materials for targeted applications.
... 72 Aliphatic Polyurethane: Tecoflex (Lubrizol Advanced Materials) Tecoflex is commercially available medical-grade polyurethane that is used in a wide range of medical implants (artificial hearts, wound dressings, and pacemaker leads) due to minimal inflammatory response and good hemocompatibility. 73,74 This SMP is prepared using poly(tetramethylene glycol), 4,4 0 -methylenebis(cyclohexyl isocyanate) and butanediol. 73 James et al. functionalized Tecoflex with iodinecontaining compounds for medical applications that require radiopaque materials. ...
... 73,74 This SMP is prepared using poly(tetramethylene glycol), 4,4 0 -methylenebis(cyclohexyl isocyanate) and butanediol. 73 James et al. functionalized Tecoflex with iodinecontaining compounds for medical applications that require radiopaque materials. 73 Their study confirmed 8 wt % iodine loading was possible for the material, however, significant reduction in the thermal properties were observed. ...
... 73 James et al. functionalized Tecoflex with iodinecontaining compounds for medical applications that require radiopaque materials. 73 Their study confirmed 8 wt % iodine loading was possible for the material, however, significant reduction in the thermal properties were observed. Macossay et al. enhanced the mechanical properties of Tecoflex by incorporating multiwalled carbon nanotubes into the polymer matrix. ...
Porous shape memory polymers (SMPs) exhibit geometric and volumetric shape change when actuated by an external stimulus and can be fabricated as foams, scaffolds, meshes, and other polymeric substrates that possess porous three-dimensional macrostructures. These materials have applications in multiple industries such as textiles, biomedical devices, tissue engineering, and aerospace. This review article examines recent developments in porous SMPs, with a focus on fabrication methods, methods of characterization, modes of actuation, and applications. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016
... In addition, biodegradable implants require radiopacity to facilitate the evaluation of their degradation during healing. However, native biodegradable polymers cannot be detected by commonly used Xradiography techniques because they exhibit low specific gravity and electron density, which results in low X-ray absorption [3]. ...
... Increasing the specific gravity of a polymer by incorporating heavy elements is the primary strategy for improving radiopacity [3]. Among the radiopaque polymers, iodine is the most commonly used element to enhance the contrast of a polymer because it can be incorporated into various polymers. ...
... Among the radiopaque polymers, iodine is the most commonly used element to enhance the contrast of a polymer because it can be incorporated into various polymers. For example, it has been used to fabricate radiopaque polyurethanes [3], polyester [4], and polymethylmethacrylate [5]. In addition to iodine, researchers also used barium sulfate and bismuth bromide to produce radiopaque polyurethanes [6][7]. ...
Nanosized iron oxide particles exhibit osteogenic and radiopaque properties. Thus, iron oxide (Fe3O4) nanoparticles were incorporated into a biodegradable polymer (poly-L-lactic acid, PLLA) to fabricate a composite bone screw. This multifunctional, 3D printable bone screw was detectable on X-ray examination. In this study, mechanical tests including three-point bending and ultimate tensile strength were conducted to evaluate the optimal ratio of iron oxide nanoparticles in the PLLA composite. Both injection molding and 3D printing techniques were used to fabricate the PLLA bone screws with and without the iron oxide nanoparticles. The fabricated screws were implanted into the femoral condyles of New Zealand White rabbits. Bone blocks containing the PLLA screws were resected 2 and 4 weeks after surgery. Histologic examination of the surrounding bone and the radiopacity of the iron-oxide-containing PLLA screws were evaluated. Our results indicated that addition of iron oxide nanoparticles at 30% significantly decreased the ultimate tensile stress properties of the PLLA screws. The screws with 20% iron oxide exhibited strong radiopacity compared to the screws fabricated without the iron oxide nanoparticles. Four weeks after surgery, the average bone volume of the iron oxide PLLA composite screws was significantly greater than that of PLLA screws without iron oxide. These findings suggested that biodegradable and X-ray detectable PLLA bone screws can be produced by incorporation of 20% iron oxide nanoparticles. Furthermore, these screws had significantly greater osteogenic capability than the PLLA screws without iron oxide.
... Polymers have been utilized as medical implants for the last 30 years with much success. [1,2] Some natural and synthetic polymers are known to be biocompatible, indicating their ability to perform with appropriate host response for biomedical applications. [1] These biocompatible polymers, commonly referred to as polymeric biomaterials, are known to have a wide range of applications because of their wide availability, ease of manufacturing, and tunable mechanical and thermal properties. ...
... [1,4] Most polymeric materials lack radiopacity because their elements possess low electron density and low specific gravity. [2,5,6] Several steps have been taken to improve radiopacity of polymers by incorporating heavy-metal fillers as physical mixtures, attaching heavy-metal salts to the polymer backbone via chelation, and by covalently binding radiopaque elements to monomers prior to their polymerization. [2,5] Radiopaque polymeric blends consisted of heavy metal fillers physically mixed into the polymer matrix thus imparting radiopacity to the whole system because of the high Z-element nature of the filler. ...
... [2,5,6] Several steps have been taken to improve radiopacity of polymers by incorporating heavy-metal fillers as physical mixtures, attaching heavy-metal salts to the polymer backbone via chelation, and by covalently binding radiopaque elements to monomers prior to their polymerization. [2,5] Radiopaque polymeric blends consisted of heavy metal fillers physically mixed into the polymer matrix thus imparting radiopacity to the whole system because of the high Z-element nature of the filler. [5] Most commonly used fillers for this technique include iodine, barium, bismuth, zircon, and tantalum. ...
Shape memory polymer (SMP) foams have been developed for use in neurovascular occlusion applications. These materials are predominantly polyurethanes that are known for their biocompatibility and tunable properties. However, these polymers inherently lack X-ray visibility, which is a significant challenge for their use as implantable materials. Herein, low density, highly porous shape memory polyurethane foams were developed with tungsten nanoparticles dispersed into the foam matrix, at increasing concentrations, to serve as a radiopaque agent. Utilizing X-ray fluoroscopy sufficient visibility of the foams at small geometries was observed. Thermal characterization of the foams indicated altered thermal response and delayed foam actuation with increasing nanoparticle loading (because of restricted network mobility). Mechanical testing indicated decreased toughness and strength for higher loading because of disruption of the SMP matrix. Overall, filler addition imparted x-ray visibility to the SMP foams and allowed for tuned control of the transition temperature and actuation kinetics for the material. Copyright © 2015 John Wiley & Sons, Ltd.
... One promising and feasible approach to synthesize radiopaque PUs is to covalently incorporate an iodinated chain extender into segmented PU backbone. Jayakrishnan and coworkers [17] reported synthesis of a radiopaque PU by coupling a molecule containing 5 iodine atoms onto the polymer backbone, and the effect of reaction temperature on thermal stability of iodinated polyurethanes (I-PUs) was discussed. In a following study, 4,4 0 -isopropylidenedi-(2,6diiodophenol) (IBPA) with four iodine per molecule was incorporated into segmented PU as chain extender using three different diols as soft chain segment, with the goal of preparing I-PUs of different mechanical properties for wide range of biomedical applications [18,19]. ...
... Synthesis of iodine-containing polyurethanes (I-PUs) 4,4 0 -isopropylidene-(2,6-diiodophenol) (IBPA) was synthesized at first according to the procedure reported in previous work [17,23]. I-PUs with two molar ratios of PCL2000 diol/IPDI/IBPA (1:2:1, 1:3:2) were synthesized. ...
... The EDX spectra analysis was semi-quantitative and may have slight deviation of the iodine content due to gold-spraying treatment and undetected elements such as nitrogen and hydrogen. Similar results were also reported in earlier reports [17]. ...
Biodegradable radiopaque iodinated polyurethanes (I-PUs) based on poly(ε-caprolactone) diol (PCL) as soft segment have been synthesized using 4,4′-isopropylidene-(2,6-diiodophenol) (IBPA) as chain extender. In order to elucidate the effect of iodinated chain extender on degradation properties of I-PUs, a control polyurethane with bisphenol A as chain extender was also synthesized. The enzymatic degradation study of these I-PUs was carried out using phosphate-buffered solution (pH 7.4) at 37 °C. The mass loss, surface morphology, iodine content, radiopacity, hydrophilicity and thermal properties of the samples during degradation were characterized with scanning electron microscopy (SEM), energy-dispersive X-ray detector (EDX), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and static contact angle. Results of enzymatic degradation during 3 months indicated that the incorporation of iodinated chain extender greatly hindered the in vitro degradation of I-PUs compared with the control PU-C sample. The reason for the retarded degradation was attributed to the bulky iodine atoms on IBPA chain extender with steric hindrance, which decreased the surface hydrophilicity of I-PUs and slowed water/lipase diffusion rate. Moreover, the radiopacity of I-PUs does not sharply attenuate after long-time degradation, which is useful for interventional biomedical applications.
... Polyurethanes particularly can be synthesized to be intrinsically radiopaque. This avoids problems in the manufacturing of the product by incorporation of particles in the polymer/particle mixture stage which would speed up the process, avoiding the lixiviation of the material and potentially lower the cost of production [109][110][111]. Since one of the main characteristics of radiopaque materials is the high electron density, one of the main alternatives (and more appropriate) is incorporating heavy atoms (such as barium or iodine) through physical blends or polymer salt complexes. ...
... James et al. [111] produced an aliphatic polyurethane (Tecoflex 80A) with 5-iodine-containing molecule, N-(2,6-diiodocarboxyphenyl)-3,4,5-triiodo benzamide (DCPTB). The optimal reaction mechanism was obtained by incorporating 8% iodine (wt/wt) in the polymer. ...
It's been a growing concern that many microbes are developing resistance against many antibiotics, lowering the effectiveness and progress expected from that treatment option. To overcome the re-sistance developed by microbes, metallic and non-metallic-based nanoparticle treatments are starting to present a very promising approach. Furthermore, polyurethanes are used in a wide range of biomedical applications due to their variety of physical-chemical, mechanical, and structural properties, and biotic and abiotic degradation. They are widely used in bio-imaging procedures when metallic-based filler particles are incorporated, making the final product radiopaque. It would be advantageous, however, if polyurethanes with intrinsic radiopacity could be produced in their synthesis, avoiding a series of disadvantages in the processing and final product and also presenting potential antimicrobial activities. This review’s objective was to study the radiopacifying charac-teristics of nanoparticles as well as the physical principles of radiopacity and the variety of medical applications of polyurethanes with nanoparticles. It was found in this study that the synthetization of radiopaque polyurethanes is not only possible but also that the efficiency of synthetization was improved when using atoms with high electron density as part of the back chainbone or grafted, making them great multipurpose materials.
... In response to comment "In the "Introduction" part, many discussions should be respective with the relevant references, such as sentences [8][9][10][11][12][13][14][15][18][19][20][21][22], and 54-60." from the reviewer, I have revised the introduction part of the paper to ensure that the discussions have relevant references respectively. ...
... James et al. prepared polyurethane elastomer with cyclohexyl isocyanate and butanediol. Subsequently, the amino group of the polyurethane is reacted with the acid chloride group, and an iodine atom-containing monomer was introduced on the side group of the polyurethane to obtain a polyurethane elastomer containing an iodine side group [13,14]. Unfortunately, in the process of introducing iodine-containing side groups, the molecular weight also 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 was subjected to ring-opening reaction with iodine to obtain a copolymer with an iodine side group, and at the same time, the ring-opening reaction of the epoxy group also added a side hydroxyl group, which improved the hydrophilicity of the material. ...
Polymeric materials implanted in the human body are usually invisible under X-ray, and the mixing of heavy metal salts into polymeric materials by physical compounding often poses compatibility problems. We have synthesized a new iodine-containing cyclic carbonate monomer IBTMC, which has a degradable carbonate group as its basic structural unit and iodine atoms attached to the side chain in the form of covalent bonds. The ring-opening polymerization of IBTMC was achieved at room temperature under the catalysis of the solid superbase DBU. The structure and X-ray developing ability of the synthesized polycarbonate were characterized by ¹H-NMR, XPS, EDS, GPC and Micro-CT. The iodine atoms remained bound to the polymer as covalent bonds after a series of reactions and exhibited a high level of X-ray opacity. In vitro degradation experiments of the polymer proved that the polymer is degradable.
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... Bismuth, the filling used in catheters to render them radiopaque 37 , was detected on the surface of catheters subjected to LPD treatment (>15 atom %). In contrast, bismuth was not detected on the surface of catheters coated using the CVD method. ...
... With LPD treatment a high atomic concentration of bismuth (>15 atom %) is evident on the surface of the catheters while with CVD treatment no bismuth was detected. Bismuth is introduced to render the catheters radiopaque so that they can be visualized on x-rays during and after insertion 37 . It is likely that hydrochloric acid produced during the liquid treatment process partially degraded the outer polymeric layer of the catheter, thus exposing the bismuth on the surface. ...
Abstarct
Catheter associated thrombosis is an ongoing problem. Omniphobic coatings based on tethering biocompatible liquid lubricants on self-assembled monolayers of hydrophobic organosilanes attenuate clotting on surfaces. Herein we report an efficient, non-invasive and robust process for coating catheters with an antithrombotic, omniphobic lubricant-infused coating produced using chemical vapor deposition (CVD) of hydrophobic fluorine-based organosilanes. Compared with uncoated catheters, CVD coated catheters significantly attenuated thrombosis via the contact pathway of coagulation. When compared with the commonly used technique of liquid phase deposition (LPD) of fluorine-based organosilanes, the CVD method was more efficient and reproducible, resulted in less disruption of the outer polymeric layer of the catheters and produced greater antithrombotic activity. Therefore, omniphobic coating of catheters using the CVD method is a simple, straightforward and non-invasive procedure. This method has the potential to not only prevent catheter thrombosis, but also to prevent thrombosis on other blood-contacting medical devices.
... Incorporating iodine-containing moieties in the polymer chain is an excellent approach to impart X-ray shielding property to polymers. [17][18][19][20][21][22][23][24][25][26][27] Iodine is preferred to impart X-ray opacity for two reasons. First the greater mass attenuation coefficient of iodine atom, and second iodinated compounds are well accepted as the X-ray opacifying agents of modern nonionic X-ray contrast media. ...
... It may be noted that grafting technique would be effective only if the polymer possesses sufficient reactive functional group to which the X-ray opacifying molecule can be attached. [17,18] Even though the incorporation of iodinated chain extender is considered as the best option for imparting X-ray opacity to polyurethanes, this method was found to be more effective in the case of aromatic diisocyanate-based polyurethanes. [28][29][30][31] The literature reveals that up to 10-15% iodine content could be achieved with aliphatic diisocyanates. ...
Synthesis and characterization of X-ray shielding thermoplastic polyurethane elastomers which are capable of blocking harmful radiation emitted by various sources are reported. X-ray shielding capability was generated in the polymer by covalently binding iodine atoms in a monomer and polymerizing it with other monomers such that the resultant polymer has the capability of shielding X-radiation. For rendering X-ray shielding capability to the polyurethane, Bisphenol-A [BPA] was iodinated to 4,4′-isopropylidinedi-[2,6-diiodophenol] [IBPA] and used it as a chain extender during the synthesis of polyurethane. Polyurethanes were synthesized by reacting 1,6-Diisocyanatohexane [HDI] and IBPA with two different polyols, namely, poly [tetramethylene glycol] [PTMG] and poly [hexamethylene carbonate] diol [PHCD]. X-ray shielding polyurethanes [XPU] were characterized by infrared spectroscopy, thermogravimetry, dynamic mechanical analysis, energy dispersive X-ray analysis, gel permeation chromatography and X-radiography. Studies showed that by effectively changing polyol from polyether to polycarbonate, XPUs having different physico-mechanical properties could be manufactured. Furthermore, these polyurethanes were also found to be non-cytotoxic to L929 fibroblast cell lines. X-ray images revealed that incorporation of IBPA has rendered X-ray opacity to the polyurethanes which are several times higher than aluminium wedge of equivalent thickness. The materials are sufficiently flexible and rubbery so that it can be used as coatings, films or sheets for applications in energy sector, power generating nuclear power plants, defense sector (bunkers for army personnel), medical applications (X-ray diagnostic and CT scanner rooms, gamma radiation therapy of cancer), etc.
... PUs can be synthesized to be intrinsically radiopaque by inserting a contrast agent in the chain backbone or by the incorporation of metallic or ceramic particles in the blend processing. When the contrast agent is inserted in the chain backbone, it obtains some advantages such as avoiding problems in the manufacturing of the product by incorporating particles in the polymer/particle mixture stage, which would speed up the process, avoiding the lixiviation of the material and potentially lowering the cost of production [45][46][47]. Since one of the main characteristics of radiopaque materials is the high electron density, one of the main alternatives (and more appropriate) is incorporating heavy atoms (such as barium or iodine) through physical blends or polymer salt complexes. ...
Polyurethanes are used in a wide range of biomedical applications due to their variety of physical–chemical, mechanical, and structural properties, and biotic and abiotic degradation. They are widely used in bio-imaging procedures when metallic-based filler particles are incorporated, making the final product radiopaque. It would be advantageous, however, if polyurethanes with intrinsic radiopacity could be produced in their synthesis, avoiding a series of disadvantages in the processing and final product and also presenting potential antimicrobial activities. This review’s objective was to study the radiopacifying characteristics of nanoparticles, the physical principles of radiopacity, and the variety of medical applications of polyurethanes with nanoparticles. It was found in this study that the synthetization of radiopaque polyurethanes is not only possible but the efficiency of synthetization was improved when using atoms with high electron density as part of the backbone or when grafted, making them great multipurpose materials.
... Even though different approaches were considered to impart radiopacity to the polymer matrix, covalently attaching halogen atoms is a promising method for attaining radiopacity without further deteriorating polymer bulk properties. Iodine has been the atom of choice for imparting radiopacity since it has been extensively employed as a contrast agent without any side effects and higher electron density [9][10][11][12][13][14][15][16]. However, most of the reported attempts to impart radiopacity to polyurethanes either involve the usage of halogenated derivatives of BPA, which is known to possess estrogenic activities [12,[17][18][19][20], or the use of aromatic isocyanate which could result in the release of toxic aromatic di-amines during degradation [10,12,14,16,[20][21][22][23]. ...
The ease of real-time visibility of biomedical implants and minimally invasive medical devices is indispensable in radiological imaging to avoid complications and assess therapeutic success. Herein, we prepared a series of polyurethane elastomers with inherent radiopacity, enabling them to be imaged under fluoroscopy. Through an appropriate selection of less toxic intermediates such as 1,6-Diisocyanatohexane (HDI), poly (tetramethylene glycol) (PTMG), and a chain extender, iodinated hydroquinone bis(2-hydroxyethyl) ether (IBHE), new radiopaque polyether urethanes (RPUs) containing about 10.8 to 20.6 % iodine contents were synthesized. RPUs were characterized for the physicochemical, thermomechanical and radiopacifying properties. It was observed that the concentration of IBHE had a profound impact on the radiopacity of polyurethanes. RPUs exhibited similar or better radiopacity than an aluminum wedge of equivalent thickness. In-vivo imaging revealed that the RPUs were easily distinguishable from the surrounding tissues. Irrespective of iodine content, all the RPUs were cytocompatible, indicating the suitability of these materials for medical and allied applications.
... Therefore, radiopaque polyurethanes are an advantageous material in the development of CVCs. Conventional techniques for imparting radiopacity to polymeric medical devices include incorporation of metal powders or metal salts by blending with polymers or by coating halogen moieties onto the polymeric materials surface (JAMES et al., 2006;Kiran et al., 2012). Some silicone is also widely used in the composition of catheters because this polymer is thermostable and has high resistance to bending, causing less damage to the vessel walls. ...
Central venous catheter (CVC) is a medical device widely used in therapeutics to avoid repetitive venipuncture. Although its use is advantageous, it is possible to highlight limitations, such as the risk of catheter-related bloodstream infections, caused by excessive manipulation and even the urgency at the time of insertion. These factors lead to an expensive treatment, often hampered by resistance to antimicrobial agents, exposing the patient the risk and even leading to death. The use of CVC impregnated with free drugs or incorporated with nanoparticles is a promising strategy for preventing the adherence of microorganisms in these devices and consequently in the prevention of the infections. Although most of the nanoparticles registered by the FDA for medical use are organic, several studies have reported the potential of inorganic nanoparticles for this purpose. Therefore, the present review seeks to highlight the current scenario of hospital infections related to the use of CVC and the importance of CVCs impregnated with drugs or incorporated with inorganic nanoparticles as an interesting strategy in combating infections assigned to the use of this medical device.
... A myriad of reports in the literature indicates the importance of developing radiopaque compounds for imaging applications. 1−17 Radiopaque compounds along with some polymers find applications in imaging body organs, 2−9 detection or diagnosis of various diseases, monitoring embolization processes, 1,10,11 construction of implants used in surgery, 1,12,13 and dental compositions. 1,14 Lei et al. reported the development of a radiopaque thermoreversible hydrogel for preventing postoperative adhesions. ...
A radiopaque compound, namely, 4,4-bis(4-hydroxy-3,5-diiodophenyl)pentanoic acid, was synthesized by the electrophilic aromatic iodination of 4,4-bis(4-hydroxyphenyl)pentanoic acid using sodium iodide and sodium hypochlorite. The active iodines created by hypochlorite were selectively bound to the ortho positions of the diphenolic acid and obtained a tetraiodo compound. Characterization of this iodinated compound was accomplished by routine methods such as Fourier transform infrared (FTIR) spectroscopy, ¹H nuclear magnetic resonance (NMR) spectroscopy, energy-dispersive X-ray spectroscopy, mass spectroscopy, UV–Vis spectroscopy, and thermogravimetry. The iodine content in the compound was as high as 64% by weight and therefore expected to possess substantial radiopacity. A 5% solution of the compound in dimethyl sulfoxide exhibited radiopacity of 885 ± 7 Hounsfield Units when tested with computed tomography (CT) scanner. In vitro cytotoxicity test performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that the compound was noncytotoxic to L929 fibroblast cells up to the level of 0.8 mg/mL concentration. Overall results indicate that this highly radiopaque compound has the potential to be used for X-ray imaging in the clinical scenario.
... In other approaches, iodo-atoms are covalently attached to the polymer chain, for example by developing radiopaque monomers or by capping or postmodification of prepared polymers. Reported materials include, polyether-polyurethanes, [24] poly(meth)acrylates, [25][26][27] biodegradable polycarbonates, [28,29] polyanhydrides, [30] polyester hydrogels, [31] and poly(ester-urethane)s. [32] Aldenhoff et al. have reported that the 4-iodo benzoate CA groups that they have incorporated in their polymethacrylates are stable except when exposed to γ-irradiation. ...
For in situ tissue engineering (TE) applications it is important that implant degradation proceeds in concord with neo‐tissue formation to avoid graft failure. It will therefore be valuable to have an imaging contrast agent (CA) available that can report on the degrading implant. For this purpose, a biodegradable radiopaque biomaterial is presented, modularly composed of a bisurea chain‐extended polycaprolactone (PCL2000‐U4U) elastomer and a novel iodinated bisurea‐modified CA additive (I‐U4U). Supramolecular hydrogen bonding interactions between the components ensure their intimate mixing. Porous implant TE‐grafts are prepared by simply electrospinning a solution containing PCL2000‐U4U and I‐U4U. Rats receive an aortic interposition graft, either composed of only PCL2000‐U4U (control) or of PCL2000‐U4U and I‐U4U (test). The grafts are explanted for analysis at three time points over a 1‐month period. Computed tomography imaging of the test group implants prior to explantation shows a decrease in iodide volume and density over time. Explant analysis also indicates scaffold degradation. (Immuno)histochemistry shows comparable cellular contents and a similar neo‐tissue formation process for test and control group, demonstrating that the CA does not have apparent adverse effects. A supramolecular approach to create solid radiopaque biomaterials can therefore be used to noninvasively monitor the biodegradation of synthetic implants. Computed tomography (CT) imaging noninvasively shows the degradation of an electrospun aortic implant graft that is modularly composed of an elastomer and a novel iodinated (purple) contrast agent (CA). Both synthetic components contain supramolecularly interacting bis‐urea units (blue), ensuring their intimate mixing. The supramolecular approach to creating radiopaque biomaterials is applied to porous implants for in situ cardiovascular tissue engineering .
... [11] To introduce radiopacity to hydrogels, polymers are either chemically modified with contrast agents or the contrast agents are directly embedded within the hydrogel. A number of hydrogels have emerged with radiopaque properties for hydrogel tracking in vivo for applications such as implants, [12] catheters, [13] embolization procedures, [14] and dental prosthetics. [15,16] Bakker et al. functionalized supramolecular ureidopyrimidinone-based hydrogels with a modified Gadolinium(III)−DOTA complex for contrast enhanced magnetic resonance imaging. ...
Injectable hydrogels are being widely explored for treatment after myocardial infarction (MI) through mechanical bulking or the delivery of therapeutics. Despite this interest, there have been few approaches to image hydrogels upon injection to identify their location, volume, and pattern of delivery, features that are important to understand toward clinical translation. Using a hyaluronic acid (HA) hydrogel as an example, the aim of this study is to introduce radiopacity to hydrogels by encapsulating a clinically used contrast agent (Omnipaque Iohexol, GE Healthcare) for imaging upon placement in the myocardium. Specifically, iohexol is encapsulated into shear‐thinning and self‐healing hydrogels formed through the mixing of HA‐hydrazide and HA‐aldehyde. Upon examination of a range of iohexol concentrations, a concentration of 100 mg mL⁻¹ iohexol is deemed optimal based on the greatest contrast, while maintaining hydrogel mechanical properties and acceptable injection forces. In an acute porcine model of MI, hybrid single‐photon emission computed tomography/computed tomography (SPECT/CT) perfusion imaging is performed immediately and 3–4 days after hydrogel delivery to assess radiopacity and verify the hydrogel location within the perfusion defect. Hybrid SPECT/CT imaging demonstrates excellent radiopacity of the hydrogel within the perfusion defect immediately after intramyocardial hydrogel injection, demonstrating the feasibility of this method for short‐term noninvasive hydrogel monitoring.
... Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are the most common types (Alie et al., 2015). At present, radionuclide-labeled nanomaterials can be used to monitor the embolization process and the distribution of nanomedicine to achieve targeted imaging (Mottu et al., 2002;Okamura et al., 2002;Torchilin, 2002;James et al., 2006). For example, the researchers used 186 Re-BMEDA (Bao et al., 2003) and 99 m Tc-PEGylate-labeled (Bao et al., 2004) doxorubicin liposomes to perform SPECT, which can trace the distribution of drugs in the body, and also promote drug release. ...
Cardiovascular diseases (CVDs) have become a serious threat to human life and health. Though many drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of CVDs, they are still far from satisfactory due to poor water solubility, low biological efficacy, non-targeting, and drug resistance. Nano-drug delivery systems (NDDSs) provide a new drug delivery method for the treatment of CVDs with the development of nanotechnology, demonstrating great advantages in solving the above problems. Nevertheless, there are some problems about NDDSs need to be addressed, such as cytotoxicity. In this review, the types and targeting strategies of NDDSs were summarized, and the new research progress in the diagnosis and therapy of CVDs in recent years was reviewed. Future prospective for nano-carriers in drug delivery for CVDs includes gene therapy, in order to provide more ideas for the improvement of cardiovascular drugs. In addition, its safety was also discussed in the review.
... Generally speaking, two main strategies are utilized to synthesize iodine-containing polymer. One approach involves the copolymerization of iodinated monomer with other monomers, including iodinated polycarbonate, iodinated cellulose, iodinated methacrylate (I-MMA) [24][25][26][27][28]. Another method to achieve radiopacity involved mildly graft iodine-containing moieties onto the polymer backbones [29][30][31][32][33]. The second method is usually employed to obtain iodinated polyurethanes, with specific functional groups provided by diisocyanate segment. ...
Non-invasive micro-CT imaging functionalized biodegradable polymeric microspheres for interventional embolization are gaining increasing attention recent years. We herein report a facile method of end-group modification to prepare X-ray opaque poly(lactic acid) (PLA) using triiodobenzoic acid (TIBA) as end-capping agent, and develop the inherently radiopaque poly(lactic acid) materials towards embolic microspheres traceable with non-invasive micro-CT imaging. Two types, that is, linear 2-arm and star 4-arm, of TIBA terminated PLA were designed and successfully synthesized by ¹H NMR characterization. Then these PLA materials were used to fabricate polymeric microspheres with well-controlled size (100–200 μm) by W/O emulsification method. As expected, the star 4-arm TIBA terminated poly(lactic acid) (I-S-PLA) microspheres possessed higher iodine content and exhibited greater radiopacity compared with linear 2-arm analogue (I-L-PLA). Both these microspheres showed low cytotoxicity and controllable micro-CT imaging. Furthermore, the effects of linear and star structure of I-PLA microspheres on in vitro degradation behavior was investigated by GPC, micro-CT, SEM and EDS. The degradable results revealed that iodine content of I-L-PLA decreased faster than that of I-S-PLA, which resulted in a further attenuation in micro-CT imaging. Consequently, CT-imaging of I-S-PLA microspheres did not drop sharply over degradation period, exhibiting higher HU values than aluminum wedge of 2 mm. These findings suggested that the biodegradable radiopaque poly(lactic acid) microspheres could be traceable by non-invasive micro-CT imaging, which are promising embolic agents.
... Among these techniques, copolymerization of iodinated vinyl monomers with the non-iodinated ones such as methyl methacrylate [15,16] or grafting iodinated substituents on the main backbone of high molecular weight polymers via covalent bonding is the most common method used for the preparation of radiopaque polymers. The copolymers with iodine-containing acrylate and methacrylate moieties show an excellent X-radiopacity property [17][18][19]. ...
New radiopaque nanocomposites were prepared using iodinated copolymers and cloisite 20A, as reinforcement agent. Iodinated copolymers were prepared through copolymerization of Methyl methacrylate and acrylic acid and subsequently modification of the P(MMA-co-AA) via 4-iodophenyl isocynate and 3,4,5-triiophenyl isocyanate for synthesis of 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA) respectively. Preparation of the nanocomposites was carried out by the solution method using various amounts of organoclay. In order to investigate the effect of iodinated substituents on the morphology and thermal characteristics of the composite samples, the P(MMA-co-AA) was modified via phenyl isocyanate (PIC-P(MMA-co-AA)) and then the nanocomposites were prepared using cloisite 20A. All the nanocomposite samples were characterized by X-ray diffraction (XRD), scanning electron microscopoy (SEM), and thermogravimetric analysis (TGA). The X-ray visibility of the radiopaque nanocomposites was also explored using X-radiography. The results obtained indicated that the iodinated nanocomposites had an excellent radiopacity, and due to their biocompatibility, they could be used for medical applications.
... Researchers have added various contrast agents to enhance the radiopacity of polymeric devices. Most investigators reported that these compounds reduced the thermal stability of the polymer [11,28,29]. However, our results showed a different trend. ...
The aim of this study was to fabricate biodegradable poly-L-lactic acid (PLLA) bone screws containing iron oxide (Fe3O4) nanoparticles, which are radiopaque and 3D-printable. The PLLA composites were fabricated by loading 20%, 30%, and 40% Fe3O4 nanoparticles into the PLLA. The physical properties, including elastic modulus, thermal properties, and biocompatibility of the composites were tested. The 20% nano-Fe3O4/PLLA composite was used as the material for fabricating the 3D-printed bone screws. The mechanical performance of the nano-Fe3O4/PLLA bone screws was evaluated by anti-bending and anti-torque strength tests. The tissue response and radiopacity of the nano-Fe3O4/PLLA bone screws were assessed by histologic and CT imaging studies using an animal model. The addition of nano-Fe3O4 increased the crystallization of the PLLA composites. Furthermore, the 20% nano-Fe3O4/PLLA composite exhibited the highest thermal stability compared to the other Fe3O4 proportions. The 3D-printed bone screws using the 20% nano-Fe3O4/PLLA composite provided excellent local tissue response. In addition, the radiopacity of the 20% nano-Fe3O4/PLLA screw was significantly better compared with the neat PLLA screw.
... For this purpose, the contrast agent is covalently bonded to the polymer backbone, and thus the radiopaque polymers made via this method have permanent radiopacity. 1,12,[27][28][29] Over the years, the covalent binding of iodine atoms to monomers or preformed polymers has received great attention. Among the reactive halogens, iodine is the best choice due to its safety, low cost, and the largest mass attenuation coefficient. ...
New radiopaque acrylic copolymers were prepared via the copolymerization of methyl methacrylate (MMA) and acrylic acid (AA). The copolymers were made radiopaque through the reaction of carboxylic acid groups with 4-iodophenyl isocyanate and 3,4,5-triiodophenyl isocyanate moieties, as radiopacifying agents. The iodinated copolymers were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR), energy dispersive X-ray (EDAX), gel permeation chromatography (GPC), elemental analysis, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The composition and iodine content of the copolymers were demonstrated via acid-base and potentiometric titrations, respectively. The radiopacity of the copolymers was investigated by X-radiography. To evaluate the biocompatibility of the iodinated copolymers, a direct MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was carried out on Swiss mouse embryonic stem tissue fibroblast-like cells (NIH3T3 cell line) according to the ISO10993-5 standard. The results indicated that the new iodinated copolymers are thermally stable and have high radiopacity. It was also found that the newly radiopaque copolymers have no cytotoxicity, and could be useful for biomedical applications.
... [40] Because the polar hard segments are hardly miscible with the less polar soft segments, two separate phase transition points can be frequently observed as two clearly different glassy temperatures for soft and hard segments. [41] The broad temperature range (T g2 ) was attributed to the different degree of phase mixing of hard and soft segments. In addition, a weak endothermic peak at ~97 °C was observed only in thermograms of SPU-I, which was attributed to the melting of hard domains. ...
This study describes the preparation and properties of a novel aliphatic cost-effective segmented polyurethanes (SPUs) based on poly(ether ester) (poly-(ε-caprolactone-co-L-lactide)-poly(ethylene glycol)-poly-(ε-caprolactone-co-L- lactide), PECLA) and uniform-size diurethane diisocyanates (HDI-BDO-HDI). PECLA was synthesized via bulk ring-opening polymerization with poly(ethylene glycol) (PEG) as an initiator and ε-caprolactone, L-lactide as monomers. By chain extension of PECLA diol with HDI-BDO-HDI, three SPUs with different hydrophilic segments content and hard segments content were obtained. The chemical structures of the chain extender, PECLA and SPUs were confirmed by (1)H NMR, (13)C NMR, FT-IR, HR-TOF-MS and GPC. The influences of PEG content and uniform-size hard segments on in vitro degradability and mechanical properties of SPU films were researched. Similar thermostability observed in TGA curves of SPU films indicated that the hard segments and PEG content had little influence on the thermostability. The formation of microsphase-separated morphologies, which were demonstrated by the results of DSC and XRD, and physical-linking (H-bonds) network structures led to better mechanical properties of SPU films (ultimate stress: 23.1-17.9 MPa; elongation at break: 840-1130%). The results of water absorption and water contact angle showed that the bulk and surface hydrophilicity were closely related with the hydrophilic PEG content in SPU backbone. And the water absorption being less than 10 wt% indicated that the SPU films had low swelling property. In vitro hydrolytic degradation studies showed that the time of the SPU films becoming fragments was 34-19 days and the degradation rate increased with the increasing content of hydrophilic segments in SPUs, indicating that the degradation rate of SPU films could be controlled by adjusting PEG content. Cytotoxicity test of film extracts were conducted using L929 cells, and the relative growth rate exceeded 90% after incubation for 24, 48 and 72 h, showing excellent cytocompatibility. The acceptable mechanical properties, controllable biodegradability and excellent cytocompatibility of the polyurethanes can make them good candidates for further biomedical applications.
... 16 These medical grade polymers are expected to have application as embolic agents and vascular or urethral stents where radio-opacity has an added advantage. 17,18 Polymerization of aromatic iodine-containing ethenyl monomers like triiodophenyl methacrylate, 3-(methacryloy-lamidoaceta-mido)-2,4,6-triiodobenzoic acid, 2-(4-iodobenzoyloxy)ethyl methacrylate , 2-methacryloyloxyethyl(2,3,5triiodobenzoate) [MAOETIB] and 2-hydroxy-3-methacryloyloxy-propyl (2,3,5-triiodobenzoate) with monomers like methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) by the introduction of a spacer arm between the bulky halogenated aromatic nucleus and ethenyl group is another method of imparting radio-opacity. 19−25 Polymers formed are nonbiodegradable and hydrophobic and their exposure is reported to cause hypersensitive reactions, peripheral neurological and cardiovascular symptoms. ...
The purpose of the study is to develop a method of imparting radio-opacity to silk fibers by step-wise 2,5-Dimethoxy-2,5-Dihydro-Furan (DMDF) - Iodine cross-linking reaction for suture fabrication with mechanical properties abiding with US pharmacopeia guidelines along with non invasive imaging advantage in post operative follow-up. Silk fibers isolated for Bombyx mori were crosslinked with suitable concentration of DMDF linked with Iodine under elevated temperature and pressure. Crosslinked fibers knitted into sutures were subjected to further testing. Computed tomography (CT) images on day 28 of in vivo studies showed mean radio-opacity value of 213±19.46 compared to vertebral bone having value of 254.66±0.51. Modified silk sutures demonstrated several advantages like high tensile strength (626±23.3MPa) and knot strength (388.6±16.8) besides antimicrobial property. Encouraging preliminary in vitro and in vivo biocompatibility studies advocate the potential use of modified suture material in cardiac surgery, aneurysmal embolization surgeries, arterio-venous occlusion surgeries.
... Incorporation of BaSO 4 particles to polymer matrices enables surgeons to accurately place and to monitor any migration of the implant over time [11,12]. Regarding the mechanical properties of the resulting composites, several studies have investigated the effect of BaSO 4 on the mechanical properties of polymethylmethacrylate [13][14][15], polypropylene [16], or polyurethane [17], concluding that a large amount of BaSO 4 (30-40%) is detrimental for both static and fatigue strength of the bone cement [14]. Such formulations are used for spine reconstructive surgery, while bone cement used to fix joint prostheses contains between 9% and 13% BaSO 4 [18,19]. ...
... Other strategies have focused on the covalent attachment of iodine or iodine-containing molecules to the polymer chains, particles, or matrix. [26][27][28][29][30][31][32] Various polymeric structures and architectures such as dendrimers, linear, block, graft, and hyperbranched polymers are also being investigated. These materials can differ in the placement of the radiolabels, with some having the contrast within main chain/backbone of the polymer, [33][34][35][36][37] at the chain end, 38 or as a side group on the Additional Supporting Information may be found in the online version of this article. ...
Since two of the most common technologies for imaging the human body are X-ray radiography and computed tomography (CT), researchers are focused on developing biodegradable and biocompatible polymeric molecules as an alternative to the traditional small molecule contrast agents. This report highlights the synthesis of novel biodegradable iodinated poly(ε-caprolactone) copolymers by oxime “Click” ligation reactions. A series of ketone-bearing materials are built by tin (II)-mediated ring-opening polymerization followed by a postpolymerization deprotection step. The intended X-ray opacity is imparted through acid-catalyzed oxime postpolymerization modification of the resultant polymers with an iodinated hydroxylamine. All small molecules and polymeric materials are characterized using proton nuclear magnetic resonance (NMR) for purity, functional group stoichiometry, and number-averaged molecular weight calculations. Additionally, the polymers are evaluated with gel permeation chromatography (GPC) to determine polymer sample polydispersity and general molecular weight distribution shapes and by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) for thermal properties. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015
... or oligomers have been reported: various polymethacrylates, [6][7][8][9][10][11] iodinated poly(ethylene glycol) acrylates, 12,13 poly(anhydride esters), 14 and polyurethanes. 15,16 Recent work also dealt with derivatization of preformed polymers: iodinated cellulose mixed esters, 17,18 polyurethanes, 19,20 natural rubber, 21,22 poly(methyl methacrylate-co-glycidyl methacrylate), [23][24][25] esters of poly(vinyl alcohol), [26][27][28] polyphosphazenes, 29 and poly(allylamine). 30 Early studies on liquid embolics [31][32][33][34] focused on common waterinsoluble polymers dissolved in water-miscible organic vehicles (mostly dimethylsulfoxide, DMSO) and added with an insoluble contrast agent. ...
Leachable-free radiopaque iodinated polymers were designed as long-lived embolization materials visible by X-ray tomography. This is a definite improvement over liquid embolics incorporating either radiopaque inorganic particles or iodinated polymers having hydrolysable ester bonds. Grafting 4-iodobenzyl or 2,3,5-triiodobenzyl groups to poly(vinyl alcohol) (PVAL) yields iodobenzyl ethers of PVAL having iodine contents in the range 40–70 wt %. Their solubility in solvents accepted for medical devices (DMSO and NMP), viscosity of concentrated solutions, precipitation behavior, radiopacity, and stability with respect to sterilization and hydrolysis were assessed. The solvent NMP allows the preparation of concentrated solutions of suitable viscosity for their application as liquid embolics. Precipitation in water yields a cohesive mass of material that can plug vascular malformations. A rationale to the properties is given in terms of the Hansen contributions to the Hildebrand solubility parameters. Iodobenzyl ethers of PVA resist hydrolysis whereas their corresponding iodobenzoyl esters leach iodinated fragments. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41791.
... [14][15][16][17][18][19][20][21][22][23] There are a few reports on the synthesis and characterization of X-ray opaque polyurethanes in the literature. [24][25][26] However, studies have shown that substantially better approach to impart X-ray opacity in polyurethanes is by incorporating iodinated chain extenders in polymer chain during synthesis. [27][28][29][30] Polyurethanes generated using aliphatic diisocyanate monomers were reported to have better biocompatibility than their aromatic counterparts. ...
An inherently radiopaque poly(carbonate urethane) containing fluorine and iodine atoms in the polymer chain was synthesized and characterized. Radiopaque polyurethane was synthesized from 1,6-diisocyanatohexane (HDI), poly (hexamethylene carbonate)diol (PHCD) and a newly synthesized chain extender having fluorine and iodine in the molecule, namely, 4,4’-(1,1,1,3,3,3-hexafluoropropane-2,2-
diyl)bis(2,6-diiodophenol) (IBAF). IBAF monomer imparted radiopacity and improved the hemocompatibility of the resultant polymer. For comparative evaluation, polyurethanes (PU) were synthesized by reacting monomers HDI and PHCD without any chain extender and also by reacting HDI and PHCD along with noniodinated, but fluorine containing, version of the above chain extender, namely, 4,40-(Hexafluoroisopropylidene) diphenol (BAF). Chain extended PUs showed improved mechanical and thermal properties, and hemocompatibility compared to the nonchain extended PU. Radiopacity measurements by fluoroscopy showed that IBAF incorporated PU of 200 mm thickness had radiopacity equivalent to that of 25% barium sulfate filled noniodinated PU of same thickness and to that of 0.6-mm thick aluminum wedge. In vivo imaging using a rabbit cadaver model showed clearly distinguishable image of IBAF incorporated PU sample. All the PU materials were noncytotoxic to L929 mouse fibroblast cells. Preliminary results obtained from blood-material interaction studies showed that incorporation of fluorinated chain extenders in the PUs resulted in significant reduction in the adhesion of white blood cells onto the PU material surface and also resulted in prolonged partial thromboplastin time. Results suggest that incorporation of fluorine and iodine containing chain extenders would lead to the development PU with improved hemocompatibility and radiopacity.
... We are interested in using Tecoflex® as the PU since it is also blood compatible [61,62] and is currently used in several cardiovascular devices [63,64]. PU is more compliant than PCL, and therefore inclusion of PU into the blend may provide better compliance matching to the mechanical environment of the implant. ...
Polymers as biomaterials possess favorable properties, which include corrosion resistance, light weight, biocompatibility, ease of processing, low cost, and an ability to be easily tailored to meet specific applications. However, their inherent low X-ray attenuation, resulting from the low atomic numbers of their constituent elements, i.e., hydrogen (1), carbon (6), nitrogen (7), and oxygen (8), makes them difficult to visualize radiographically. Imparting radiopacity to radiolucent polymeric implants is necessary to enable noninvasive evaluation of implantable medical devices using conventional imaging methods. Numerous studies have undertaken this by blending various polymers with contrast agents consisting of heavy elements. The selection of an appropriate contrast agent is important, primarily to ensure that it does not cause detrimental effects to the relevant mechanical and physical properties of the polymer depending upon the intended application. Furthermore, its biocompatibility with adjacent tissues and its excretion from the body require thorough evaluation. We aimed to summarize the current knowledge on contrast agents incorporated into synthetic polymers in the context of implantable medical devices. While a single review was found that discussed radiopacity in polymeric biomaterials, the publication is outdated and does not address contemporary polymers employed in implant applications. Our review provides an up-to-date overview of contrast agents incorporated into synthetic medical polymers, encompassing both temporary and permanent implants. We expect that our results will significantly inform and guide the strategic selection of contrast agents, considering the specific requirements of implantable polymeric medical devices.
The addition of inorganic fillers has been reported to increase the toughness of poly(l-lactide) (PLLA), but the effect of physical aging in such composites has been neglected. The present work discusses the effect of the still ongoing segmental relaxation in PLLA-based composites filled with BaSO4 inorganic particles in regard of the filler quantity. By means of differential scanning calorimetry, X-ray diffraction, and tensile testing of progressively aged PLLA filled with particles ranging from 0.5–10 wt %, we observed an increase in the mechanical energy required to activate the plastic flow of the primary structure in the PLLA matrix, which resulted in the embrittlement of the majority of composites upon enough aging. Results further clarify the role of debonding in the activation process of PLLA, and the behavior of the composite is described at the segmental level. Only an addition of 10% of particles has effectively preserved a ductile behavior of the samples beyond 150 aging days; therefore, we strongly remark the significance of studying the effect of physical aging in such composites.
Bonding iodine atoms to polymer is a common means of obtaining polymer with X-ray imaging ability. However, it is generally not possible to obtain degradable polymers with both high molecular weight and high iodine content. We propose a novel method for combining iodine atoms to polymers, which has a degradable carbonate group as its basic structural unit and iodine atoms attached to the backbone in the form of covalent bonds. First, cyclic carbonate monomers with a carbon-carbon double bond is synthesized, the monomers are purified and then polymerized to obtain polycarbonates containing carbon-carbon double bonds. Subsequently, the iodine atoms were successfully introduced into the polymer chains by the addition reaction. The iodinated polycarbonate exhibited high level of X-ray opacity. The structure and X-ray developing ability of the polycarbonates were characterized by ¹H-NMR, IR, XPS, EDS, GPC and Micro-CT. In vitro degradation experiments of the iodinated polycarbonate proved that the polymer is degradable.
The field of biomaterials has grown rapidly over the past decades. Within this field, porous biomaterials have played a remarkable role in: (i) enabling the manuface of complex three-dimensional structures; (ii) facilitating interconnected structures for the transport of macromolecules and cells; (iii) recreating mechanical properties close to those of the host tissues; and (iv) behaving as biocompatible inserts, tailored to either interact or not with the host body. This review outlines a brief history of the development of biomaterials, before discussing current materials proposed for use as porous biomaterials, and exploring the state-of-the-art in their manufacture. The wide clinical applications of these materials are extensively discussed, drawing on specific examples of how the porous features of such biomaterials impact their behaviours, as well as the advantages and challenges faced for each class of materials.
Biodegradable polyesters with X-ray visibility for biomedical applications have attracted increasing attention. We herein reported a facile method of end-chain functionalization to prepare highly branched linear-comb poly (lactic acid) (Lc-PLA) using triiodobenzoic acid (TIBA) as end-capping and X-ray contrast agent. Three branch lengths of iodinated linear-comb poly (lactic acid) (I-Lc-PLA30k, I-Lc-PLA50k, and I-Lc-PLA70k) were successfully synthesized and then microspheres with well-controlled size (average size ∼180 μm) were prepared. By micro-CT testing, the results showed that shorter branch length of PLA contributed more iodinated end-group functionalized sites, leading a relatively high iodine content and excellent radiopacity. After terminated with TIBA, glass transition temperature and thermal stability of I-Lc-PLA polymers were greatly improved. During the in vitro hydrolytic degradation of three months, the molecular weight, iodine content, surface microstructure and micro-CT radiopacity of these microspheres were investigated. The degradation results showed that I-Lc-PLA50k possessed sufficient iodine content and high household unit values, suggesting a well-maintained radiopacity of I-Lc-PLA. Therefore, this work proposed a highly branched I-Lc-PLA microspheres with promising CT-imaging capacity, which could be used as a long-term embolic material.
Medical polyurethane was treated with 20 keV nitrogen ions with a fluence of 10¹⁴–10¹⁶ ions/cm². The modified polyurethane has a layered structure consisting of a 70-nm carbonized layer and a partly depolymerized layer below the carbonized layer. The high level of activity of the polyurethane due to free radicals provides stable adhesion of protein molecules to the surface layer of the polyurethane. The high level of hydrophilicity of the modified polyurethane surface preserves the biological activity of the attached proteins. This contributes to the attachment of endothelial cells to the polyurethane surface and their proliferation. Thus, this modified polyurethane can be used as a material for soft-tissue medical implants.
The patency capsule is a radiopaque, dissolvable diagnostic tool, similar in shape and size to small bowel capsule endoscopes. It was developed to offer a simple, safe, efficient, and accurate evaluation of small bowel functional patency. Although unable to provide direct visual information regarding the presence and location of strictures, masses, or luminal narrowing of the small bowel, a successful patency test minimizes the risk of retention and allows the safe administration of a capsule endoscope. However, its use entails a low risk of potentially harmful adverse events, which in their majority are indolent and resolve spontaneously. Abdominal pain and symptomatic retention are accountable for the majority of reported adverse events, whereas a limited number of reports describe life-threatening complications, namely intestinal obstruction, perforation, and intestinal ischemia. Computed tomography is the modality of choice for the identification of the exact position of an impacted patency capsule, whilst the use of plain abdominal radiographs should be avoided for the evaluation of the patency capsule position, as they provide false information. Hereby, we present a comprehensive review of the available literature regarding the characteristics, indications, clinical use, effectiveness, and adverse events of the patency capsule.
In order to develop a methodology of synthesizing a family of radiopaque biodegradable polymers, a new iodinated trimethylene carbonate monomer, 5,5-bis(iodomethyl)-1,3-dioxan-2-one (ITMC), was designed and synthesized from a commercially available 2,2-bis(bromomethyl)-1,3-propanediol by halogen exchange with sodium iodine followed by cyclization with ethyl chloroformate using triethylamine as an acid binding agent. The multigram-scale production of the ITMC monomer was facilely fulfilled and the good stability of the ITMC monomer allowed convenient storage under room temperature conditions. The ring-opening copolymerization of ITMC with other common monomers was successfully carried out in the presence of a small molecule initiator or macro-initiator using diphenyl phosphate as the catalyst. The physico-chemical and thermal properties of the generated aliphatic polycarbonates were measured by ¹H NMR, GPC, DSC and TGA. Their radiopacity was assessed by both in vitro and ex vivo tests, and appeared high enough to be of interest for biomedical applications. Considering the good repeatability and versatility of polymerization, ITMC is a very promising carbonate monomer to synthesize various aliphatic polycarbonates with strong and adjustable radiopacity. This methodology opens an appealing way to develop a variety of radiopaque polymers by direct transformation of the iodide group.
The design of polymeric biomaterials with long-lasting X-ray contrast could advance safe and effective implants and contrast agents. Herein, a new set of wholly aliphatic, iodinated polyesters are synthesized and evaluated as high-contrast biomaterials and nanoparticle contrast agents for general computed tomography imaging. A single iodinated monomer is used to synthesize a variety of aliphatic polyesters with tunable thermal and mechanical properties. These iodinated polyesters are end-functionalized with a photocurable methacrylate group, which allows easy processability. The resulting materials exhibit no cytotoxicity and are radiopaque, containing over 40% iodine by weight after processing. The polymers can be formulated into lipid–polymer hybrid nanoparticles using a modified nanoprecipitation method. Initial studies indicate that these nanoparticles show good continual contrast over 60 minutes with no uptake into the kidneys. The work presented here illustrates a novel platform for iodinated polyesters that exhibit high radiopacity and processability, low cost, and no cytotoxicity. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017
A series of radiopaque polyurethanes used for prosthetic disc nucleus were prepared via polycondensation between polyurethane prepolymer and N, N'-bis (1 , 3-dihydroxypropyl ) -2 , 3 , 5 , 6-tetra iodoterephthalamide (BDTIP) ,which was synthesized as crosslinker and X-ray contrast agent. The structure of BDTIP was characterized by 1H-NMR. Infrared spectroscopy was used to monitor the reaction degree of BDTIP. The developing effect of modified polyurethane was characterized by X-radiography. Meanwhile,the cytotoxicity was tested by the method of thiazolyl blue tetrazolium bromide (MTT) colorimetric assay using mouse fibroblast, and the mechanical properties of radiopaque polyurethanes with different iodine contents were also studied. The results of 1H-NMR showed that the hydrogen atoms on benzene ring were replaced by iodine completely and expected structure was obtained. Polyether polyurethane structure, demonstrated by FTIR, was also obtained. The X-radiography results showed that polymer had a good radiopacity which is almost equivalent to that of a 2 mm thick aluminum wedge when the iodine content was very small, while the mechanical properties were still excellent. There was nearly no change of compression modulus when the iodine content is low and within half an hour after the compression test the shape of prosthetic disc nucleus were restored to the state before compression, which demonstrated that the addition of BDTIP had little effect on the mechanical properties of prosthetic disc nucleus of polyurethane. The cell proliferation rate ( RGR ) of all modified polyurethanes was more than 75% ,they were all biomaterials without cytotoxicity. This study provides a new modification way for preparing radiopaque polyurethane used for prosthetic disc nucleus.
Medical imaging is a cornerstone of modern medicine. In that context the development of innovative imaging systems combining biomaterials and contrast agents (CAs)/imaging probes (IPs) for improved diagnostic and theranostic applications focuses intense research efforts. In particular, the classical aliphatic (co)polyesters poly(lactide) (PLA), poly(lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL), attract much attention due to their long track record in the medical field. This review aims therefore at providing a state-of-the-art of polyester-based imaging systems. In a first section a rapid description of the various imaging modalities, including magnetic resonance imaging (MRI), optical imaging, computed tomography (CT), ultrasound (US) and radionuclide imaging (SPECT, PET) will be given. Then, the two main strategies used to combine the CAs/IPs and the polyesters will be discussed. In more detail we will first present the strategies relying on CAs/IPs encapsulation in nanoparticles, micelles, dendrimers or capsules. We will then present chemical modifications of polyesters backbones and/or polyester surfaces to yield macromolecular imaging agents. Finally, opportunities offered by these innovative systems will be illustrated with some recent examples in the fields of cell labeling, diagnostic or theranostic applications and medical devices.
Calcium alginate microspheres embedded with silver nanoparticles were prepared by dripping mixed solution of sodium alginate and silver nanoparticles, which were synthesized by reduction of silver nitrate (AgNO3) with sodium alginate as stabilizing agent and sodium borohydride as chemical reducing agent, into a crosslinking bath of calcium chloride solution. The concentration of sodium alginate and sodium borohydride used in synthesis step were found to have effect on the formation and growth of the silver nanoparticles as revealed by UV-visible spectroscopy. The TEM image indicated that uniform silver nanoparticles with particle size range from 20 to 60 nm are fabricated. The XRD spectrums showed that the silver nanoparticles embedded in calcium alginate microspheres exhibit crystalline state. The EDS showed that the higher the ration of AgNO3, the more silver nanoparticles embedded in calcium alginate microspheres. Moreover, X-ray images showed the calcium alginate microspheres embedded with silver nanoparticles exhibited better radiopaque properties than the pure calcium alginate microspheres and the microspheres with higher concentration of AgNO3 solution show sharper X-ray image. All the above facts indicated that these calcium alginate microspheres embedded with silver nanoparticles could therefore be used in embolization.
Implantable polymeric medical devices suffer from a lack of visibility under current clinical imaging techniques. To circumvent this problem, poly(ε-caprolactone-co-α-triiodobenzoate-ε-caprolactone)s (PCL-TIB) containing from 3.5% to 24% of triiodobenzoate-ε-caprolactone units were synthesized as new X-ray macromolecular contrast agents. Physico-chemical and thermal properties of PCL-TIBs were evaluated by 1H NMR, SEC, DSC and TGA. Their potential as radio-opacifying additive for medical devices was evaluated by preparing polymeric blends of PCL-TIB with various (co)polyesters. At first, in vitro X-ray visibility of PCL/PCL-TIB blends was evaluated. A more in depth characterization was then carried out based on PCL/PLA50-PEG-PLA50 blends. The impact of PCL-TIB content on the mechanical properties of blends was evaluated by tensile tests. Stability of X-ray visibility was evaluated by ex vivo implantation of non-degraded blends and of blends degraded for 6 weeks in vitro. Finally, cytocompatibility was assessed by evaluating the proliferation of L929 fibroblasts on the blends.
Iodinated polyurethanes (IPUs) with radiopaque property were prepared using poly(oxytetramethylene) glycol, 4,4′-diphenylmethane diisocyanate, and a novel chain extender. The chain extender, described as N-(1,3-dihydroxypropan-2-yl)-2,3,5-triiodobenzamide, was synthesized in two steps from 2-aminopropane-1,3-diol and 2,3,5-triiodobenzoic acid with a high yield. A thorough study on the chemical structure, mechanical properties, radiopacity, and physiological properties of the IPUs was conducted. It is revealed that with increasing content of chain extender, the molecular weights of IPUs decreased slightly while the tensile modulus and breaking strength of IPUs increased significantly, illustrating an excellent comprehensive performance. With iodine content high to about 16 wt %, the IPU sample is equal to the aluminum plate with the same thickness in X-ray radiopacity, meaning that the synthesized polyurethanes are promising as radiopaque materials. The oxidative degradation and cytotoxicity tests illustrated a good performance of stability and biocompatibility for the IPUs. It confirmed that the as-synthesized IPUs are promising for biomedicine applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42693.
A series of radiopaque iodinated polyurethanes (I-PUs) used for embolic agents were synthesized via coupling reaction between poly(butylene succinate) PBS and iodinated bisphenol-A (IBPA) with varying compositions using isophorone diisocyanate (IPDI). The IBPA with four iodine atoms per molecule was applied as a chain extender and X-ray contrast agent. The chemical structure and composition of I-PUs were characterized by FTIR and H-1-NMR. The effects of IBPA on crystallization and thermal properties of I-PUs were systematically studied by means of differential scanning calorimetry (DSC), thermogravimetry analysis (TGA) and wide-angle X-ray diffraction (WAXD). The results showed that the crystallization behavior and thermal stability were restrained with the introduction of IBPA,which was also confirmed by WAXD. However, in the X-radiography analysis, all the synthesized I-PUs and their microspheres exhibited high radiopacity compared with an aluminum wedge of equivalent thickness. As expected,the X-ray visibility was increased with the iodine content increased. Basic cytotoxicity test was conducted by the method of thiazolyl blue tetrazolium bromide (MTT) colorimetric assay and fluorescent live/dead staining. Cells proliferating well on the polymer-coated coverslips demonstrated that all the synthesized I-P Us were noncytotoxic biomaterials. This study presents a facile synthetic route of radiopaque polyurethanes with high iodine contents, which are expected to possess significantly advantage over the traditional polymer counterparts used for embolic agents and other related biomedical applications.
Biocompatible shape-memory polymers are of high significance for application in medical devices or instruments for minimally invasive surgery. To follow the medical device placement or changes in shape of the device in vivo by imaging methods like X-ray techniques, radiopacity of the polymer is required. In this work, we explored the shape-memory properties of radiopaque polymer composites prepared by incorporation of barium sulphate micro-particles in a biomedical grade polyether urethane (PEU) by co-extrusion technique. The filler content was varied from 5 wt% to 40 wt%, which was confirmed by thermal gravimetric analysis (TGA) measurements, while the particle distribution was visualized by scanning electron microscopy (SEM). The thermal and mechanical properties of the composites were investigated by means of dynamic mechanical analysis at varied temperature (DMTA) and tensile tests. The shape-memory properties of PEU composites were quantified in cyclic, thermomechanical experiments.
A significant increase in Young’s modulus and a decrease in elongation at break were observed for PEU composites with increasing content of BaSO4, while the DMTA results were not affected by incorporation of the fillers. All samples exhibited excellent shape-memory properties with shape fixity rates (Rf) above 98% and values for shape recovery rate (Rr) in the range of 81% to 93%. The maximum stress (σmax) obtained under constant strain recovery conditions increased from 0.6 MPa to 1.4 MPa with raising amount of BaSO4, while the corresponding temperature (Tσ,max) as well as the switching temperature (Tsw) determined under stress-free conditions remained constant for all polymer composites.
Radiopaque polymers can be used in medicine. Conventional protective shields against radiation X contain harmful lead compounds that are heavy and fragile. The aim of this work was to study the check the properties of selected fillers as X-radiation absorbing substance and them use in natural rubber (NR) composites. Fillers and simultaneously active substances were bismuth (III) oxide (Bi2O3), gadolinium (III) oxide (Gd2O3), tungsten (III) oxide (WO3) and antimony (III) oxide (Sb2O3). The polymeric matrix consisted of NR and sulfuric cross-linking system was applied. The properties of the fillers were determined from zeta potential and particle size measurements. X-ray absorption measurements were carried out using isotopic source 57Co (122 keV). The mechanical properties of the thin 1 mm composite plates were examined.
The synthesis and characterization of iodine-functionalized phenylalanine-based poly(ester urea)s (PEUs) are reported. 4-Iodo-L-phenylalanine and L-phenylalanine were separately reacted with 1,6-hexanediol to produce two monomers, bis-4-I-L-phenylalanine-1,6-hexanediol-diester (1-IPHE-6 monomer) and bis-L-phenylalanine-1,6-hexanediol-diester (1-PHE-6 monomer). By varying the feed ratio of the 1-IPHE-6 and 1-PHE-6 monomers, the copolymer composition was modulated resulting in a wide variation in thermal, mechanical and radiopacity properties. Micro-computed tomography (µ-CT) projections demonstrate that increasing iodine content results in greater X-ray contrast. Compression tests of dry and wet porous scaffolds indicate that the poly(1-IPHE-6)0.24-co-poly(1-PHE-6)0.76 material results in the highest compression modulus. As most medical device procedures require placement verification via fluoroscopic imaging, materials that possess inherent X-ray contrast are valuable for a number of applications.
Radiopaque polyurethanes are used for medical applications as it allows post-operative assessment of the biomaterial devices using X-ray. Inherently, radiopaque polyurethanes based on polytetramethylene glycol (PTMG), polypropylene glycol, 4,4'-methylenebis(phenyl isocyanate), and a new iodinated chain extender 4,4'-isopropylidenebis[2-(2,6-diiodophenoxy)ethanol] with flexible spacers were synthesized and characterized. The iodinated polyurethanes were clear, optically transparent, and had high molecular weights. The polyurethanes also possessed excellent radiopacity and high thermal stability. The biocompatibility of the most promising iodinated polyurethane was evaluated both in vitro (cytotoxicity evaluation by direct contact and MTT assay, using L929 mouse fibroblast cells) and in vivo (toxicology studies in rabbits and subcutaneous implantation in rats). The material was nontoxic and well tolerated by the animals. Thus, these radiopaque and transparent polyurethanes are expected to have potential for various biomedical applications.
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In this study, a strategy of using iodine-containing cyclophosphazenes as radiopacifiers for dental composite resin was evaluated. It was hypothesized that cyclophosphazenes bearing both iodine and acrylate group swere able to endow composite resins radiopacity without compromising mechanical properties. The cyclophosphazene compounds were synthesized by subsequently nucleophilic substitution of hexachlorocyclotriphosphazene with hydroxyethyl methacrylate (HEMA) and 4-iodoaniline. Cyclotriphosphazenes containing two different molar ratios of HEMA to 4-iodoaniline (1:5 and 2:4) were obtained, and were identified with (1)H NMR, FT-IR, UV and mass spectroscopy. The iodine-containing cyclophosphazenes were able to dissolve well in bisphenol A glycidyl methacrylate (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA) resin, and were added at two contents (10 or 15%wt. of the resin). The resins were photo-cured and post-thermal treated before characterizations. The resulting composite resins demonstrated the ability of blocking X-ray. And the addition of HEMA-co-iodoaniline substituted cyclotriphosphazenes caused minor adverse effect on the mechanical properties of the resins because the cyclotriphosphazenes could mix well and react with the resins. The presence of rigid phosphazene rings between resin backbones displayed an effective function of decreasing polymerization shrinkage. In summary, soluble and reactive iodine-containing cyclotriphosphazenes demonstrated advantages over traditional heavy metals or metal oxides in being used as additives for producing radiopaque dental resins.
Poly(glycidyl methacrylate‐co‐ethyl methacrylate) and poly(glycidyl methacrylate‐co‐butyl methacrylate) random copolymers (with 50–50 mol % of monomers) were made radiopaque by grafting iodine moieties through the ring opening reaction of the epoxy groups. The percentage weight of grafted iodine in the copolymers was found to be as high as 19%. The iodinated copolymers showed higher glass transition temperature and thermal stability in comparison with the parent copolymers. Iodinated copolymer of poly(glycidyl methacrylate‐co‐ethyl methacrylate) has improved glass transistion temperature than iodinated poly(glycidyl methacrylate‐co‐butyl methacrylate). Radiographic analysis of these iodinated copolymers showed excellent radiopacity. The in vitro cytotoxicity tests revealed cytocompatibility with cells. These radiopaque copolymers are expected to find application as dental and orthopedic cements. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Poly(vinyl alcohol) (PVA) microspheres impregnated with barium sulphate and methyl iothalamate, having diameters raning from 100 to 1500 μm were prepared by the glutaraldehyde cross-linking of an aqueous dispersion of PVA containing the radiopaques in paraffin oil using dioctyl sulfosuccinate (DOS) as the stabilizing agent and thionyl chloride as the catalyst. while the use of thionyl chloride allowed the formation of spherical, nonaggregatory beads, other catalysts such as magnesium chloride and hydrochloric acid gave rise to an agglomerated product. The radiopaques were found to be firmly trapped inside the microspheres as they did not leach out on prolonged standing in water, on sonication, or on steam sterilization. Microspheres with pores and channels were also made by incorporating a fine powder of methyl methacrylate along with barium sulphate during their preparation and washing out the polymer after the microspheres were formed. The porous nature of such microspheres was confirmed by transmission electron microscopy (TEM). Microspheres containing the radiopaques exhibited hydrophilicity, swelling ability, and compressibility to a significant extent. the radiopaque nature of the microspheres was confirmed by their x-ray images. In vitro tests using heparinized calf blood showed that the microspheres were nonhaemolytic in nature. These microspheres may find application as radiopaque emboli in particulate embolization.
Polyurethane microspheres having diameters in the range 150-1500 microns were prepared by condensation polymerization of toluene diisocyanate (TDI) with poly(tetramethylene glycol) (PTMG) of average mol wt 990 in an aqueous dispersion medium containing dioctyl sulphosuccinate (DOS) as the suspension stabilizer and 1,4-diazabicyclo[2.2.2]octane (DABCO) as the catalyst for polymerization. Incorporation of tantalum powder in the polymerizing phase led to the formation of Ta-loaded microspheres with good radiopacity. Microspheres were surface-modified by grafting methacrylic acid (MA) on to them using gamma-radiation from a Co60 source. Conversion of the grafted MA into its sodium salt imparted hydrophilicity and slipperiness to the microspheres enabling them to pass through Teflon catheters without obstructing the catheter lumen. These microspheres may find application as radiopaque embolization agents.
Highly porous poly(2-hydroxyethyl methacrylate) (PHEMA) microspheres prepared by suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) in presence of polymeric diluents such as poly(methyl methacrylate) (PMMA) in toluene and poly(tetramethylene glycol) (PTMG) were made radiopaque by esterification of the reactive hydroxyl groups with iothalamic acid and iopanoic acid, two radiopaque substances clinically used. Of the various solvents and catalysts examined, tetrahydrofuran (THF) and N,N'-dimethyl paratoluidine (DMPT) were found to be best for obtaining a high degree of conversion. More than 30 wt% iodine could be bound to the microspheres which made them sufficiently radiopaque to be imaged radiographically. Microspheres retained their porosity, swelling ability, hydrophilicity, and surface morphology to a significant extent after iodination. Preliminary implantation studies of such microspheres subcutaneously in rats have shown no adverse tissue reactions over a 6-month period. It is suggested that these microspheres would prove to be useful as particulate emboli in endovascular embolization.
The preparation of miscible systems containing poly(methyl methacrylate) and cupric nitrate, manganese chloride, praseodymium chloride, and uranyl nitrate is described. The salt was dissolved in the monomer, which was subsequently polymerized. The heavy metal salts impart radiopacity to these plastics and this renders them useful for X-ray imaging in applications such as medical implants. The polymer–salt systems are characterized on the basis of their infrared spectra, thermal, and radiographic properties, and the formation of complexes between the cations and the carbonyl function of the polymer is discussed. The glass transition temperatures of the salt-containing polymers are higher than those of the salt-free polymers, the elevation being dependent on the nature and concentration of the metal salt. Miscible PMMA–uranyl nitrate systems are transparent, glassy plastics and approximately 11 wt % of uranyl nitrate hexahydrate imparts a radiopacity equivalent to that of aluminum.
A number of miscible metal salt–polymer systems of acrylated phosphonates derived from various polyols such as glycerol, D-mannitol, D-sorbitol, pentaerythritol, and dipentaerythritol are described. The salt–monomer systems could be polymerized radically to form homogeneous transparent glassy polymers. Incorporation of heavy metal salts in polymers imparts radiopacity on otherwise radiolucent materials rendering them useful for X-ray imaging. The polymer–salt systems have been characterized with the aid of infrared spectroscopy and thermal and radiographic analyses. In these salt–polymer systems, salts are bonded to the polymers predominantly through the phosphoryl's oxygen. The results indicate that about 11 wt % of uranyl nitrate hexahydrate and 12.5 wt % of bismuth bromide impart a radiopacity equivalent to that of aluminum. The glass transition temperatures (Tg) of the salt-containing polymers are substantially higher than the salt-free polymers. The Tg values seem to depend on the chemical nature of the polymers, concentration of metal salts, and the extent of crosslinking induced through chelation. The analysis indicated complete solubility in the polymer matrices. No melting point endotherms of free salt crystals were detected. Some preliminary adhesion measurements revealed that acrylated phosphonates are excellent adhesion promoters for hard tissues.
Triiodophenol and iothalamic acid (5-acetamido-2,4,6-triio-N-methyl isophthalamic acid) were converted to their acrylic derivatives by esterfication with methacryloyl chloride and 2-hydroxyethyl methacrylate (HEMA), respectively. The monomers due to presence of heavy iodine atoms were expected to be radiopaque in nature. The monomers were characterized using TLC, IR, and 1H-NMR spectroscopy. Both monomers were highly resistant to homopolymerization and copolymerization with other acrylic monomers such as methyl methacrylate (MMA) or HEMA by initiators such as 2,2′-azobis isobutyronitriie (AIBN) or benzoyl peroxide (BPO) yielding only polymers of low molecular weight. The polymers obtained were charactrized by gel permeation chromatography (GPC) and differential thermal analysis (DTA). The resistance to polymerization is presumably due to the presence of bulky iodine atoms in the monomers sterically hindering the propagation step. The decomposition temperatures of the homopolymers and copolymers were close to 300°. Copolymers of HEMA with both radiopaque monomers incorporated to the extent of 25 wt % in the feed, however, produced polymers with good radiopacity. Copolymers with HEMA were also prepared in the form of microspheres by a solvent evaporation method with the aim of using them as particles in therapeutic embolization. While the polymer based on triiodophenol was found to cause extensive blood haemolysis in in vitro tests, polymer based on iothalamic acid was found to be nonhemolytic in character suggesting that copolymers based on iothalamic acid would be suitable for implantation in the living tissue.
A new iodine-containing methacrylate monomer, 3,4,5-triiodobenzoyloxyethyl methacrylate (TIBEM), was synthesized by coupling 2-hydroxyethyl methacrylate (HEMA) with 3,4,5-triiodobenzoic acid. The monomer was characterized by 1H nuclear magnetic resonance, infrared (IR), and ultraviolet spectra. Homopolymerization and copolymerization of the monomer with methyl methacrylate (MMA) were carried out using 2,2′-azobis isobutyronitrile as the initiator. A terpolymer of TIBEM, MMA, and HEMA was also synthesized. The copolymers were characterized by IR, gel permeation chromatography, differential thermal analysis, and thermogravimetric analysis (TGA). High molecular weight polymers were produced with MMA at different feed compositions of TIBEM. The polymers were found to be freely soluble in common solvents for acrylic polymers. TGA showed little decomposition of the copolymer below 280°C. Copolymers showed good radiopacity at 25 wt % of TIBEM in the feed. These copolymers could find applications in medical and dental areas where radiopacity is a desirable feature of the implants. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2580–2584, 2003
A coating of polyurethaneurea was made from a solution on the surface of metal stents. The influence of cleaning, etching, chemical and ion beam modification (plasma immersion ion implantation) of the metal surface on the adhesion strength of the polyurethaneurea was analysed. Polyurethaneurea films imbedded with tantalum particles as a radiopaque filler maintained their strength and elasticity and produced clear X-ray contrast images of vascular stents.
Poly(2-hydroxyethyl methacrylate) p(HEMA) microspheres of good spherical geometry (diameter 90-1500 microns) encapsulated with 40-50% barium sulphate to impart radiopaque properties were prepared by a solvent evaporation process. These microspheres were cross-linked by reacting with hexamethylene diisocyanate (HMDI) or by gamma-irradiation in the presence of ethylene glycol dimethacrylate (EGDM) in n-heptane. Microspheres with a porous structure and a rough surface were also made by the incorporation of NaCl along with BaSO4. The effects of concentration of the polymer solution, concentration of the stabilizing agent, concentration of BaSO4, viscosity of the dispersion medium and ratio of the dispersed phase to the dispersion medium on the formation, stability and particle size distribution of the microspheres were investigated.
The synthesis and properties of spherical radiopaque hydrogel particles designed for endovascular occlusion are reported. These particles were prepared by the hydroxyl acylation of low crosslinked poly (2-hydroxyethyl methacrylate) beads with a nontoxic radiopaque compound based on triiodobenzoic acid, without affecting their properties which are advantages in medical practice. The effect of the iodine content on the size of dry and swollen particles is discussed. It has been found that an iodine content of about 25-30 wt% is desirable in order to obtain an easily recognizable X-ray image. These particles make the immediate control of embolus application easy and enable periodical inspection of the polymer to check the successful blockage of the vessel. They also open up the method of endovascular occlusion to further improvement.
Two new polymeric materials (polymers A and B) containing covalently bound iodine were prepared. These polymers were evaluated with respect to their possible use as radiopaque implant biomaterials--that is, materials that are visible in a noninvasive manner using routine X-ray absorption imaging techniques. Polymer A is a copolymer of methyl methacrylate (MMA) and 1 (80 and 20 mol%, respectively). Polymer B was prepared from MMA, 1, and 2-hydroxyethyl methacrylate (HEMA) (mol ratio 65:20:15, respectively). Compound 1 was synthesized from 4-iodophenol and methacryloyl chloride. The resulting polymers were characterized with GPC, DSC, NMR, and by measuring both the advancing and receding contact angles. Thrombogenicity of the polymers was determined by an in vitro thrombin generation test procedure. The maximum concentration of free thrombin was 76 +/- 1 nM for polymer A, and 64 +/- 3 nM for polymer B. The lag times (i.e., time onset of thrombin generation) were 392 seconds for polymer A and 553 seconds for polymer B. For PVC-T, which is known as a passive material, a lag time of 583 seconds was found. This indicates that polymer B is comparable to PVC-T, and more passive than polymer A. Polymer A exhibited minor activation of platelets. Polymer B did not induce platelet activation at all. The polymers exhibited, even as fibers with a diameter of ca. 0.3 mm, good radiopacity with routine imaging X-ray techniques in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS)
A methacrylic monomer containing three iodine atoms, 2- [2',3',5'-triiodobenzoyl]-ethyl methacrylate (compound 1), was prepared in pure form. Compound 1 can be reacted with other methacrylates, such as methyl methacrylate (MMA), and 2-hydroxyethyl methacrylate (HEMA) with high conversion. Typically, less than 0.5% of free monomer is left after polymerization. For example, compound 1 was reacted with MMA and HEMA in the molar ratio 7:73:20, respectively. This yielded a terpolymer with Tg = 86 degrees C, Mw = 47,000 g/ mol and Mn = 22,800 g/mol. This material was characterized by various physicochemical techniques, including gel permeation chromatography, differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance (NMR) spectroscopy (1H at 400 MHz, DMSO-d6 solution). In addition the material was found to exhibit low surface thrombogenicity in vitro and a low propensity to activate contacting blood platelets. Furthermore it was found that the terpolymer is markedly radiopaque: even thin objects (< 0.5 mm) could be easily visualized using X-ray fluoroscopic techniques as are routinely used in the clinic, e.g., during coronary angiography. The combined results obtained with the present terpolymer (particularly its in vitro hemocompatibility and its radiopacity) leads to the suggestion that this type of polymer could be used as cardiovascular biomaterials, for instance for the construction of a new type of endovascular stents. These would be expected to show improved biocompatibility if compared with metallic stents which are currently used, for instance in conjunction with percutaneous transluminal coronary angioplasty (PTCA). A stent prototype, constructed from the present radiopaque terpolymer, is shown and discussed briefly.
The purpose of this study was to evaluate novel iodinated methacrylate copolymers as X-ray opaque denture base resins.
The synthesis of specific monomers and suspension copolymerization with methyl methacrylate to produce copolymer beads. The resulting beads were processed in an identical manner to standard PMMA to produce test-pieces for mechanical testing.
Samples prepared from beads containing 25 wt% of the iodinated copolymer exhibited an X-ray opacity equivalent to that exhibited by a similar thickness of aluminium. Furthermore, the appearance and mechanical properties were comparable to standard PMMA, while thermal stability proved superior.
These novel iodinated methacrylate monomers show promise not only as polymerizable additives to methyl methacrylate to produce an X-ray opaque denture base but also as thermally stable copolymerizable additives to other applications where X-ray opacity would be advantageous.
A novel iodine-containing methacrylate, 2,5-diiodo-8-quinolyl methacrylate, has been synthesized and used in the preparation of acrylic radiopaque cements. The effect of incorporation of this monomer to the self-curing resins, on the curing parameters, swelling behaviour and mechanical properties was studied. The incorporation of the radiopaque compound 2,5-diiodo-8-hydroxyquinoline to the solid phase was also carried out for comparative experiments. A decrease in the peak temperature and an increase in the setting time was observed with the addition of the radiopaque monomer, however, the curing parameters did not appreciably change with the addition of the radiopaque compound to the solid phase. Swelling of the modified cements was in the same range as that of the radiolucent cement; however, the diffusion coefficients calculated according to the Fick's law were higher for the iodine-containing materials. The addition of 5 wt% of the iodine-containing methacrylate provided a significant increase in the tensile properties with respect to either control radiolucent formulations or BaSO4-containing formulations. Biocompatibility of the modified cements was studied by implantation of rods of the cements into rats and histological analysis of the surrounding tissue.
In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc).
Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation.
None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs.
The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.
The present study deals with the synthesis and characterization of radiopaque polymers which could, when solubilized in an appropriate water-miscible solvent, be useful embolic materials for the treatment of cerebral aneurysms and arteriovenous malformations. For this purpose cellulose (both microcrystalline and powdered) and partially substituted cellulose acetate (two different viscosity grades) were selected as starting materials to prepare iodine-containing polymers through various synthetic routes. The materials obtained were characterized by IR and NMR spectroscopy, molecular weight, iodine content, radiopacity and solubility in selected injectable organic solvents. The embolic liquids were evaluated for their precipitation behavior in a phosphate buffer solution (pH 7.4) mimicking physiological conditions using an in vitro aneurysm model. A sheep model was also used to assess in vivo the radiopacity and precipitation properties of a highly concentrated solution of a cellulose acetate 2,3,4-triiodobenzoate mixed ester. All materials with 4-iodo- and 2,3,5-triiodobenzoyl groups gave sufficient radiopacity to be regarded as possible embolization materials, whereas iododeoxycellulose and iododeoxycellulose acetate were not radiopaque because of their low iodine content. Esters synthesized using cellulose as starting material were not soluble in the selected organic solvents due to the presence of many residual hydroxyl groups, but could be used for other biomedical applications where insoluble radiopaque materials are used. In contrast, solubility of the materials as well as satisfactory precipitation properties were ensured using cellulose acetate as the starting material. In conclusion, cellulose acetate iodobenzoate mixed esters dissolved in diglyme or dimethyl isosorbide (dimethyl sulfoxide is probably less appropriate because of its toxicity and hemolytic properties) could be useful embolic liquids for the treatment of cerebral aneurysms or arteriovenous malformations.
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