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Medium term results in keratoprostheses with biocompatible and biological haptic.

PURPOSE: Corneal grafts or limbal stem cell transplantation are often unsuccessful in patients with severe ocular surface disorders such as severe dry eye syndrome, symblepharon or diffuse vascularisation. In those patients, a keratoprosthesis (KPro) may be an alternative for the recovery of vision. Various KPro differ from each other in the material of the haptic that supports the optic cylinder. The haptic may be made of biocompatible or biological material such as tibia bone (TKPro) or dentine and alveolar bone (osteo-odonto-keratoprosthesis, OOKP). On the basis of our experience, we wanted to comment on the value of different KPro. METHODS: Over the last 10 years we have implanted a total of 35 KPro, 29 with biological haptic (25 OOKP and four TKPro), and six KPro with biocompatible haptic (one Legais KPro, five Pintucci KPro). A follow up examination was carried out approximately every6 months. RESULTS: The patients gained a visual acuity of > or =0.9 in 20.6%, of > or =0.5 in 52.9%, of > or =0.2 in 61.8% and a significant improvement in visual acuity in 76.5%, respectively. There was no significant difference between the various types of KPro concerning the best postoperative visual acuity. All patients showing poor improvement had a pre-existing end stage secondary glaucoma or other retinal damage. The median follow-up was 2.9 years (maximum 8) for OOKP, 1 year for TKPro, 1 year (maximum 2) for Pintucci Kpro and 6 month for Legeais KPro. During this period, only one of the KPro with biological haptic was lost (one TKPro after 1 year), compared with four out of six of the KPro with biocompatible haptic (P<0.0001). CONCLUSIONS: Fixation of the KPro by a root of the patient s own tooth (OOKP) leads to the best results in the long-term follow up, as our results as well as the literature demonstrate. As long as a KPro is in place, the visual acuity is as good as the retinal function. For the ranking of different types of KPro, the percentage and the duration of the anatomic success are most important. The comparability of the various KPro results may be limited, since the patients were not randomised and the four groups differ in number.

Adult↗

Lower esophageal sphincter injection of a biocompatible polymer: accuracy of implantation assessed by esophagectomy.

BACKGROUND: Endoscopic lower esophageal sphincter (LES) implantation of a biocompatible polymer is undergoing clinical trial as an alternative to pharmacologic and laparoscopic treatments for gastroesophageal reflux disease. The safety and efficacy of LES augmentation depend on accurate placement of the implant into the wall of the esophagus. To date, no study has demonstrated the prevalence and location of the intended implant. METHODS: The study group consisted of nine patients with underlying esophageal disease severe enough to warrant esophagectomy. Three or four implants of 1 or 2 cc of Enteryx (a biocompatible ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide with micronized tantalum as a radiopaque marker) were placed at the squamocolumnar junction of each patient via a 4-mm, 23-gauge needle under endoscopic guidance. Fluoroscopy was utilized in all patients to facilitate endoscopic placement. Outcome measures included the prevalence and location of successful implantation into the wall of the esophagus. RESULTS: Thirty of 34 implants (88%) were successfully placed into the wall of the esophagus. The remaining 4 were found lying subserosally or attached to the exterior of the gastroesophageal junction (GEJ). Fluoroscopically, the implants often tended to coalesce, forming arcs or a ring around the GEJ. Histologic examination revealed implantation into the deep submucosa contiguous with the circular muscle and within the muscularis propria in all patients, with implants occasionally extending into the subserosa. There were no untoward reactions identified. CONCLUSIONS: Endoscopically directed implantation of a biocompatible polymer into the esophageal wall can be accomplished with a high degree of accuracy. Injection via a 4-mm needle results in the placement of material along and within the muscular layers of the esophagus.

Biocompatible Materials↗

A lightweight polypropylene mesh (TiMesh) for laparoscopic intraperitoneal repair of abdominal wall hernias: comparison of biocompatibility with the DualMesh in an experimental study using the porcine model.

BACKGROUND: Despite numerous experimental studies, conducted most often with the open small-animal model, the ideal structure for a mesh with maximum biocompatibility in the intraabdominal region has yet to be found. To date, few experimental models have been concerned with the laparoscopic intraabdominal implantation of meshes. Numerous experimental and clinical studies appear to have identified expanded polytetrafluoroethylene (ePTFE), in the form of DualMesh, as the gold standard. Since publications have reported fistula formation and marked adhesions to be associated with the use of polypropylene meshes, only few studies have investigated meshes made of this material. It is known, however, that a reduction in the amount of material and an increase in pore size results in better mesh biocompatibility. METHODS: Six pigs each underwent laparoscopic intraabdominal placement of either a TiMesh or a DualMesh, both of which were prepared for implantation in standardized fashion. After 87 +/- 2 days, the pigs were killed, and postmortem laparoscopy was performed, followed by the removal of the tissue embedding the mesh for assessment of adhesions and shrinkage, and for histologic workup. The specimens were processed both histologically and immunohistochemically. RESULTS: In all but one case, the greater omentum adhered, usually over discrete areas, to the mesh. In every case the omentum was separable from the mesh surface only by sharp dissection. With the titanium-coated polypropylene meshes, the average total adhesion area was only 0.085, as compared with 0.25 for the GoreTex meshes (p = 0.055). The GoreTex meshes showed an average shrinkage to almost half of the original surface area (median, 0.435). The average shrinkage of the TiMesh, was to 0.18 of the original area (p = 0.006), which thus was significantly smaller. Determination of the partial volume of the inflammatory cells showed significantly lower median figures for the TiMesh (p = 0.009). Measurements of the proliferation marker Ki67 showed significantly higher values for ePTFE than for TiMesh (p = 0.011). The apoptosis index was significantly higher for the ePTFE membranes (p = 0.002). CONCLUSIONS: Titanium-coated polypropylene mesh (TiMesh) is clearly superior to the DualMesh in terms of biocompatibility, and is thus suitable for the laparoscopic intraperitoneal repair of abdominal wall and incisional hernias.

Abdominal Wall↗

Concepts in biocompatibility testing of dental restorative materials.

Due to the diversity of adverse biological effects which might be caused by dental restorative materials, biocompatibility assessment cannot rely on a single test but has to be based on a planned and structured approach (concept). First, the possible harm evoked by the material, the known data, and suitable biological and other test methods available must be taken into consideration. Modern regulatory concepts require for this purpose the services of experts to propose the appropriate set of required tests for a given material. The use of standards is generally emphasized because of better comparability of the data. Other tests may be chosen if more appropriate. Modern scientific concepts of biocompatibility testing are based on the need for rapid and cost-effective test methods, avoiding animal tests whenever possible. While formerly in vitro experiments did not take into account the special clinical situation in which the material would be used, modern concepts try to simulate important parameters of the in vivo situation as closely as possible. This may be achieved, for example, by including suitable barriers between the material and the target cells, by constructing appropriate target cells, and by choosing clinically relevant markers for measuring the biological effects caused by the material. There are indications so far that through this approach the number of animal tests can be reduced. The use of these methods may also lead to a better understanding of the mechanisms behind the biological reactions (mechanistic approach) in describing the biocompatibility of dental restorative materials.

Animals↗

Biocompatibility testing of a silicone maxillofacial prosthetic elastomer: soft tissue study in primates.

Little information exists on the biocompatibility of maxillofacial prosthetic materials. Cosmesil material is a purpose-designed facial prosthetic elastomer that has an established clinical profile in humans but results of biocompatibility testing have not been published. Cosmesil, acrylic resin (positive control), black surgical gutta-percha (negative control), and Silastic 382 material (Dow Corning, Midland, Mich.) (reference control) were processed as custom-designed implants. The implants were inserted into five chacma baboons for a 12-week period in intraosseous, subperiosteal, submucosal, and intramuscular sites. The histologic assessment was based on a modified form of the FDI-ISO Technical Report 7405 for subcutaneous implants. An evaluation was made of capsule formation and inflammatory response. The statistical analysis involved a three-way ANOVA and a Tukey-Kramer Student range test. The critical level of statistical significance chosen was p less than 0.05. The study found that gutta-percha provoked a statistically significantly thicker capsule and a severe inflammatory response. Acrylic resin, Cosmesil material, and Silastic 382 material produced capsule formations and an inflammatory response that did not differ significantly. Cosmesil material is not manufactured as an implant material, but from the present findings it is considered acceptably biocompatible for its intended use where there may be contact with internal tissue spaces that are contiguous to external surfaces.

Acrylic Resins↗

Biocompatibility of a prolonged-action antialcohol preparation.

Acid and alkaline phosphatase activities in liver lysosomes and liver mitochondria, respectively, as well as in connective tissue capsule were studied for an antialcohol preparation (polyurethane carrier and disulfiram at 150, 300 and 625 mg/kg body weight) implanted subcutaneously. Increased acid phosphatase activity was observed in connective tissue capsule on days 14, 30 and 90 after implantation and in liver lysosome fraction on days 14 and 30 with preparation containing disulfiram at 300 and 625 mg/kg body weight. Alkaline phosphatase activity increased both in connective tissue capsule and in liver mitochondria up to day 30 only when sample with maximal disulfiram dose was implanted. Acid phosphatase activity is an adequate indicator for biocompatibility of prolonged-action medicine preparations. The data obtained show that the suggested medical form containing disulfiram 150 mg/kg body weight is biocompatible. Interaction between acid and alkaline phosphatase activity changes and biocompatibility and destruction of polymer implants is discussed.

Acid Phosphatase↗

Modification of the biocompatible and haemocompatible properties of polymer substrates by plasma-deposited fluorocarbon coatings.

The polymerization of gases present in a low temperature plasma is a technique particularly well suited for biomedical material processing. Therefore, the possibilities this technique offers to increase the biocompatibility and haemocompatibility of polysulphone and poly(hydroxybutyrate) membranes to be used in a new bioartificial pancreas device were studied. The deposition of thin fluorocarbon coatings from an argon plasma containing perfluorohexane gave very smooth and hydrophobic surfaces without affecting the filtering properties of the treated membranes. Adding hydrogen increased the reaction yield, but gave rougher and less hydrophobic coatings. We characterized the biological properties of the treated surfaces and discussed the influence of the modified surface properties on the biological behaviour of the treated polymers. The good biocompatibility of the deposited coatings was established by following in vitro the insulin secretion of Langerhans islets cultured on the treated membranes and by examining the fibrous capsule that developed on plasma-treated polymer disks after three months of in vivo incubation in the peritoneum of Wistar rats. Rough and haemocompatible films of poly(hydroxybutyrate) and smoother, but more thrombogenic, polysulphone films were treated by perfluorohexane and perfluorohexane + H2 plasmas to study the relative influence of surface roughness and surface energy on polymer thrombogenicity. In vitro protein adsorption and total blood clotting tests proved that the surface roughness influences the thrombogenicity more than the other surface properties. This study seems to show that the plasma deposition of smooth and hydrophobic fluorocarbon coatings can increase the biocompatibility and reduce the surface thrombogenicity of the treated membranes without affecting their filtering properties.

Animals↗

Biocompatibility and in vivo morphine diffusion into a placebo morphine-triggered naltrexone delivery device in rabbits.

Two key factors in developing a clinically useful triggered naltrexone delivery system are device biocompatibility and ability of morphine to diffuse from the blood into the device in concentrations useful to trigger delivery. Two types of devices were implanted subcutaneously into rabbits and their biocompatibility was investigated. One device consisted of the outer semipermeable regenerated cellulose acetate tubing, closed at both ends with double knots and filled with poly(N-vinyl pyrrolidone) as osmotic filler. The other device was a placebo device that contained within the regenerated cellulose acetate tubing, also closed at both ends with double knots, all device components except naltrexone. Both devices were biocompatible. When the regenerated cellulose acetate device filled with osmotic filler was implanted in rabbits which were subsequently dosed at day 7 and day 14 post-implant with 150 mg kg(-1) morphine sulphate, the concentration of morphine in the device was only about 10-fold less than that measured in rabbit blood. Thus, enough morphine diffuses into the device to make triggering in a real-life situation feasible.

Animals↗

Biocompatibility of chemical-vapour-deposited diamond.

The biocompatibility of chemical-vapour-deposited (CVD) diamond surfaces has been assessed. Our results indicate that CVD diamond is as biocompatible as titanium (Ti) and 316 stainless steel (SS). First, the amount of adsorbed and 'denatured' fibrinogen on CVD diamond was very close to that of Ti and SS. Second, both in vitro and in vivo there appears to be less cellular adhesion and activation on the surface of CVD diamond surfaces compared to Ti and SS. This evident biocompatibility, coupled with the corrosion resistance and notable mechanical integrity of CVD diamond, suggests that diamond-coated surfaces may be highly desirable in a number of biomedical applications.

Absorption↗

An albumin-coated polyester arterial graft: in vivo assessment of biocompatibility and healing characteristics.

The albumin-coated vascular graft (ACG) and its uncoated polyester substrate, the Vascular II (V-II), were evaluated in terms of biocompatibility and biofunctionality using two in vivo animal studies. Biocompatibility and immunoreactivity were assessed by implanting intraperitoneally in the rat small segments of the ACG and the V-II graft and harvesting them with their surrounding tissue 3d, 1, 2 and 4 weeks later. Cytofluorometric determination of total T cells (CD3), the ratio of CD4/CD8 subsets and the percentage of IL-2 receptor-positive T cells in the peripheral blood has revealed that no significant difference in any of the T cell populations was found between the ACG and the V-II graft. The cellular reactivity of the ACG in terms of acid phosphatase activity at the implant side was significantly greater at 3 d but not at longer periods. Biofunctionality was evaluated by implanting both grafts as a thoracoabdominal vascular bypass in dogs for 11 different periods ranging from 4 h to 6 months. The rate of albumin resorption was such that traces were still present at 1 month, but no longer observable at 2 months. Tissue incorporation into the graft wall was earlier for the V-II (2 weeks) than for the ACG (4 weeks), which showed complete encapsulation, tissue incorporation and endothelialization after 2 months in vivo. Only small differences were observed between both grafts in terms of platelet and fibrin uptake on the luminal surface. The prostacyclin/thromboxane A2 ratio increased to a level higher that 1.0 aorta within 1 month for the V-II and 4 months for the ACG. In conclusion, the Bard ACG has demonstrated excellent biocompatibility in terms of blood T cell behaviour and acid phosphatase activity at the implant site. Finally, its healing response is equivalent to that of the uncoated Dacron prosthesis once the albumin coating has been resorbed.

Acid Phosphatase↗

Evaluation of the effect of three surface treatments on the biocompatibility of 316L stainless steel using human differentiated cells.

AISI 316L stainless steel (SS) is widely used in orthopaedic implantology, although biological complications may result from its insufficient mechanical and tribological properties. In order to improve the wear and corrosion resistance as well as the hardness of 316L SS, three surface treatments, derived from those applied in mechanical engineering industries, were investigated: (1) glow discharge nitrogen implantation, (2) carbon-doped stainless steel coating sputtering and (3) low temperature plasma nitriding. Surface characterization according to the different heat treatments showed that corrosion and wear resistance were strongly improved, especially by ion implantation or carbon-doped SS coating sputtering. In the same way, microhardness was significantly increased after the three treatments. The effect of such treatments on the biocompatibility of 316L SS was studied with human osteoblast and fibroblast cultures. Basic and specific features of the cells showed that ion-implanted and carbon-doped stainless steels were biocompatible, whereas dramatic cellular reactions were noted when contacted with nitrided stainless steel. A hypothesis is given to explain this observation but further experiments are needed to optimize the nitriding process. Nitrogen implantation and carbon-doped layer deposition could be efficient means for improving the physical properties of stainless steel without affecting its biocompatibility. Such surface treatments may have relevance for increasing the life time of 316L biomedical devices.

Alkaline Phosphatase↗

Processing, characterisation and biocompatibility of iron-phosphate glass fibres for tissue engineering.

Iron-phosphate glass fibres based on the CaO-Na2O-Fe2O3-P2O5 system have been processed and characterised via thermal, XRPD, dissolution rates, diameter and biocompatibility studies. The compositions investigated were fixed at 50mol% P2O5, and the CaO content was varied between 30, 35 and 40mol%. The Fe2O3 was added in low amounts from 1-5mol%, substituting it for the Na2O mol%. The number of Tc (crystallisation temperature) peaks detected from the thermal analysis traces only showed correlation with XRPD analysis, for five out of the 15 compositions investigated. It has been suggested that either the crystalline phases had very similar Tc temperatures or that the other phase(s) were present in very small quantities. There was a good match seen with number of Tm (melting temperature) peaks picked up from the DTA traces, with the number of phases identified from XRPD analysis. The main phases identified from XRPD were NaCa(PO3)3, CaP2O6 and NaFeP2O7. Using network connectivity (NC), predictions on Qn species present within the compositions investigated were made. The predicted species (metaphosphates) matched with phases identified from XRPD analysis. A decrease in dissolution rates for the bulk glass and glass fibres was seen with an increase in CaO mol%, along with an increase in Fe2O3 mol%. An increase in fibre dissolution rates was seen with a decrease in diameter size. The biocompatibility studies were conducted using a conditionally immortal muscle precursor cell line derived from the H-2Kb-tsA58 immortomouse. It was found that iron-phosphate glass fibres containing 4-5mol% Fe2O3 was sufficient for cell attachment and differentiation. It was seen that myotubes formed along the axis of the fibres (which was indicative of differentiation). The biocompatibility of these compositions was attributed to the enhanced chemical durability of the glass fibres.

Animals↗

Long-term in vivo biomechanical properties and biocompatibility of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) nerve conduits.

Artificial grafts are promising alternatives to nerve grafts for peripheral nerve repair because they obviate the complications and disadvantages associated with autografting such as donor site morbidity and limited tissue availability. We have synthesized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their efficacy in vivo. Specifically, we studied the short- and long-term stability and biocompatibility of 12 mm long tubes for the repair of surgically created 10 mm nerve gaps in rat sciatic nerves. Prior to implantation, tubes were analyzed in vitro using a micro-mechanical tester to measure displacement achieved with load applied. These results served as a calibration curve, y = 6.8105 x -0.0073 (R2 = 0.9750, n = 28), for in vivo morphometric tube compression measurements. In vivo, most of the PHEMA-MMA conduits maintained their structural integrity up to 8 weeks, but 29% (4/14) of them collapsed by 16 weeks. Interestingly, the tube wall area of collapsed 16-week tubes was significantly lower than those of patent tubes. Tubes were largely biocompatible; however, a small subset of 16-week tubes displayed signs of chronic inflammation characterized by "finger-like" tissue extensions invading the inner tube aspect, inflammatory cells (some of which were ED1+macrophages) and giant cells. Tubes also demonstrated signs of calcification, which increased from 8 to 16 weeks. To overcome these issues, future nerve conduits will be re-designed to be more robust and biocompatible.

Animals↗

Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics.

Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.

Animals↗

The mechanical properties and in vitro biodegradation and biocompatibility of UV-treated poly(3-hydroxybutyrate-co-3-hydroxyhexanoate).

Strong mechanical properties and controllable biodegradability, together with biocompatibility, are the important requirement for the development of medical implant materials. In this study, an ultraviolet (UV) radiation method was developed to achieve controlled degradation for bacterial biopolyester poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) which has a low biodegradation rate that limits its application for many implant applications required quick degradation. When UV radiation was applied directly to PHBHHx powder, significant molecular weight (Mw) losses were observed with the powder, Mw reduction depended on the UV radiation time. At the same time, a broad PHBHHx Mw distribution was the result of inhomogeneous radiation. Interestingly, this inhomogeneous radiation helped maintain the mechanical properties of films made of the UV-radiated powder. In comparison, the PHBHHx films subjected to direct UV radiation became very brittle although their degradation was faster than that of the PHBHHx powders subjected to direct UV radiation. After 15 weeks of degradation in simulated body fluid (SBF), films prepared from 8 and 16h UV-treated PHBHHx powders maintained 92% and 87% of their original weights, respectively, while the untreated PHBHHx films lost only 1% of its weight. Significant increases in growth of fibroblast L929 were observed on films prepared from UV-radiated powders. This improved biocompatibility could be attributed to increasing hydrophilic functional groups generated by increasing polar groups C-O and CO. In general, UV-treated PHBHHx powder had a broad Mw distribution, which contributed to fast degradation due to dissolution of low Mw polymer fragments, and strong mechanical property due to high Mw polymer chains. Combined with its improved biocompatibility, PHBHHx is one more step close to become a biomedical implant material.

3-Hydroxybutyric Acid↗

Biocompatibility of alginate-poly-L-lysine microcapsules for cell therapy.

Cell microencapsulation holds promise for the treatment of many diseases by the continuous delivery of therapeutic products. The biocompatibility of the microcapsules and their biomaterials components is a critical issue for the long-term efficacy of this technology. The objective of this paper is to provide detailed information about the principal factors affecting the biocompatibility of alginates and alginate-poly-l-lysine microcapsules, which are the most frequently employed biomaterials and encapsulation devices for cell immobilization, respectively. Some of these factors include the alginate composition and purification, the selection of the polycation, the interactions between the alginates and the polycation, the microcapsule fabrication process, the uniformity of the devices and the implantation procedure. Improved knowledge will lead to the production of standardized transplantation-grade biomaterials and biocompatible microcapsules.

Alginates↗

Development and evaluation of biocompatible films of polytetrafluoroethylene polymers holding lithium phthalocyanine crystals for their use in EPR oximetry.

Electron paramagnetic resonance (EPR) oximetry is a powerful technology that allows the monitoring of oxygenation in tissues. The measurement of tissue oxygenation can be achieved using lithium phthalocyanine (LiPc) crystals as oxygen reporters. In order to have biocompatibility for the sensing system and to assure long-term stability in the responsiveness of the system, we developed films of Teflon AF 2400 with embedded LiPc crystals. These systems can be used as retrievable inserts or parts of an implantable resonator or catheter. Atomic force microscopy studies revealed that the surface of the films was regular and planar. The response to oxygen of the sensor (EPR linewidth as a function of pO(2)) remained unchanged after implantation in mice, and was not affected by sterilization or irradiation. The use of resonators, holding LiPc embedded in Teflon AF 2400, implanted in the gastrocnemius muscle of rabbits allowed the monitoring of oxygen during several weeks. Several assays also demonstrated the biocompatibility of the system: (1) no hemolytic effect was noted; (2) no toxicity was found using the systemic injection test of extracts; (3) histological analysis in rabbit muscle in which the films were implanted for 1 week or 3 months was similar to standard polyethylene biocompatible devices. These advanced oxygen sensors are promising tools for future pre-clinical and clinical developments of EPR oximetry. These developments can be applied for other applications of biosensors where there is a need for oxygen permeable membranes.

Absorption↗

Improved biocompatibility of a viscous bioerodible poly(ortho ester) by controlling the environmental pH during degradation.

The poly(ortho ester), POE, used in this investigation, is a viscous bioerodible polymer (8 kDa), which rapidly degrades into a triol and an acidic by-product, acetic acid. In order to improve biocompatibility, we have evaluated the addition of various basic excipients, such as sodium acetate, hydroxyapatite, calcium carbonate and magnesium hydroxide, which buffered and neutralized the acidic degradation product and prolonged the polymer lifetime and drug release. This decrease of POE degradation rate results in a decreased rate of formation of the acidic by-product. Similarly, a POE of higher molecular weight (14 kDa) has been tested. Sodium acetate was too hydrophilic to affect the drug release and the biocompatibility of the polymer, whereas the presence of magnesium hydroxide markedly prolonged the drug release and improved the acceptability of the polymer. The increased molecular weight POE did not improve biocompatibility and a similar but delayed, inflammatory reaction was observed.

Animals↗