Biosynthetic hydrogel scaffolds made from fibrinogen and polyethylene glycol for 3D cell cultures

Tissue engineering scaffolds are fabricated from either biological materials, which provide biofunctional signals and interact well with cells, or from synthetic polymers, which provide precise control over their structural properties. We describe a biosynthetic hybrid scaffold comprised of a fibrinogen backbone and crosslinked with difunctional polyethylene glycol (PEG) side chains. Denatured fibrinogen fragments are PEGylated with PEG-diacrylates, mixed with photoinitiator and exposed to UV light to form a hydrogel material in the presence of a cell suspension. This unique hydrogel material provides a distinct advantage over other scaffold materials because its mechanical properties are highly malleable while the biological functionality is maintained by the backbone of the polymeric network. The elastic modulus of the PEG-fibrinogen hydrogel is dependent on the molecular weight of the PEG constituent and proportional to the percent polymeric composition. The biological domains in the fibrinogen backbone provide attachment motifs for endothelial cell and smooth muscle cell adhesion as well as proteolytic sensitivity for biodegradation. Smooth muscle cells demonstrate the ability to proteolytically penetrate through the hydrogel material and form interconnecting networks of cells. Our efforts to develop novel biodegradable scaffolds for cultivating cells in a 3D environment are beneficial for tissue regeneration therapies.     

Covalent stabilization of alginate hydrogel beads via Staudinger ligation: assessment of poly(ethylene glycol) and alginate cross-linkers

Cellular encapsulation within alginate hydrogel capsules has broad applications in tissue engineering. In seeking to improve the inherent instability of ionically cross-linked alginate hydrogels, we previously demonstrated the covalent stabilization of Ba(2+) cross-linked alginate-azide beads via chemoselective Staudinger ligation using a 1-methyl-2-diphenylphosphino-terephthalate (MDT) terminated poly(ethylene glycol) (PEG) linker. In this study, we functionalized variant PEG, linear and branched, and alginate polymers with MDT groups to evaluate the effect of size, structural design, number of functional groups, and charge on the resulting hydrogel bead. All cross-linkers resulted in enhanced covalent stabilization of alginate beads, with significant decreases in swelling and resistance to dissolution via Ba(2+) chelation. The MDT-functionalized alginate resulted in the most stable and homogeneous bead, with the most restrictive permeability even after EDTA exposure. Co-encapsulation of MIN6 cells within the cross-linked alginate hydrogel beads resulted in minimal effects on viability, whereas the degree of proliferation following culture varied with cross-linker type. Altogether, the results illustrate that manipulating the cross-linker structural design permits flexibility in resulting alginate beads characteristics. Covalent stabilization of alginate hydrogel beads with these chemoselective alginate and PEG-based cross-linkers provides a unique platform for cellular encapsulation.     

The effect of polyethylene glycol structure on paclitaxel drug release and mechanical properties of PLGA thin films

Thin films of poly(lactic acid-co-glycolic acid) (PLGA) incorporating paclitaxel typically have slow release rates of paclitaxel of the order of 1 μg day(-1) cm(-2). For implementation as medical devices a range of zero order release rates (i.e. 1-15 μg day(-1) cm(-2)) is desirable for different tissues and pathologies. Eight and 35 kDa molecular weight polyethylene glycol (PEG) was incorporated at 15%, 25% and 50% weight ratios into PLGA containing 10 wt.% paclitaxel. The mechanical properties were assessed for potential use as medical implants and the rates of release of paclitaxel were quantified as per cent release and the more clinically useful rate of release in μg day(-1) cm(-2). Paclitaxel quantitation was correlated with the release of PEG from PLGA, to further understand its role in paclitaxel/PLGA release modulation. PEG release was found to correlate with paclitaxel release and the level of crystallinity of the PEG in the PLGA film, as measured by Raman spectrometry. This supports the concept of using a phase separating, partitioning compound to increase the release rates of hydrophobic drugs such as paclitaxel from PLGA films, where paclitaxel is normally homogeneously distributed/dissolved. Two formulations are promising for medical device thin films, when optimized for tensile strength, elongation, and drug release. For slow rates of paclitaxel release an average of 3.8 μg day(-1) cm(-2) using 15% 35k PEG for >30 days was achieved, while a high rate of drug release of 12 μg day(-1) cm(-2) was maintained using 25% 8 kDa PEG for up to 12 days.     

Influence of cell-adhesive peptide ligands on poly(ethylene glycol) hydrogel physical,mechanical and transport properties

Synthetic three-dimensional scaffolds for cell and tissue engineering routinely utilize peptide ligands to provide sites for cell adhesion and to promote cellular activity. Given the fact that recent studies have dedicated great attention to the mechanisms by which cell behavior is influenced by various ligands and scaffold material properties, it is surprising that little work to date has been carried out to investigate the influence of covalently bound ligands on hydrogel material properties. Herein we report the influence of three common ligands utilized in tissue engineering, namely RGD, YIGSR and IKVAV, on the mechanical properties of cross-linked poly(ethylene glycol) (PEG) hydrogels. The effect of the ligands on hydrogel storage modulus, swelling ratio, mesh size and also on the diffusivity of bovine serum albumin through the hydrogel were investigated in detail. We identified conditions under which these ligands strikingly influence the properties of the material. The extent of influence and whether the ligand increases or decreases a specific property is linked to ligand type and concentration. Further, we pinpoint mechanisms by which the ligands interact with the PEG network. This work thus provides specific evidence for interactions between peptide ligands and cross-linked PEG hydrogels that have a significant impact on hydrogel material and transport properties. As a result, this work may have important implications for interpreting cell experiments carried out with ligand-modified hydrogels, because the addition of ligand may affect not only the scaffold’s biological properties, but also key physical properties of the system.     

Chemical and physical properties of a hydrogel wound dressing

Geliperm hydrogel provides optimal physiological conditions for wound healing. The material is composed of two interlaced networks, one of polyacrylamide and one of agar, and contains about 96% firmly bound water. It is supplied in smooth, elastic, transparent sheets which are impermeable to bacteria but permeable to gases, salts, metabolites and proteins. Geliperm is nontoxic and has no irritative properties. Mechanical properties, water retention and diffusion of dyes and proteins are reported. Bacterial size should preclude penetration of the gel. The hydrogel in granular form represents a coherent material which could be used in deep fissured wounds and for the treatment of injuries with a large amount of exudation and contamination.     

Maintaining dimensions and mechanical properties of ionically crosslinked alginate hydrogel scaffolds in vitro

Ionically crosslinked alginate hydrogels are attractive scaffolds because of their biocompatibility and mild gelation reaction that allows for gentle cell incorporation. However, the instability of ionically crosslinked hydrogels in an aqueous environment is a challenge that limits their application. This report presents a novel method to control the dimensions and mechanical properties of ionically crosslinked hydrogels via control of the ionic concentration of the medium. Homogeneous calcium-alginate gels were incubated in physiological saline baths adjusted to specific calcium ion concentrations. Swelling and shrinking occurred at low and high ionic concentrations of the medium, respectively, while an "optimal" intermediate calcium ion concentration of the medium was found to maintain original size and shape of the hydrogel. This optimal calcium ion concentration was found to be a function of crosslinking density and polymer concentration of the hydrogel and chemical composition of the alginate. The effects of optimal and high calcium ion concentrations of the medium on swelling behavior, calcium content, dry weight, and mechanical properties of the immersed hydrogels were investigated. It was found that the resulting hydrogel composition and mechanical properties depended on not only the calcium concentration of the medium, but also the crosslinking density and polymer concentration of the gel. In an 8-week experiment, controlled dimensions and mechanical properties of alginate gels in an aqueous environment were demonstrated. This new technique significantly enhances the potential of alginate hydrogels for tissue engineering and other biomedical applications.     

Lubricin: A versatile,biological anti-adhesive with properties comparable to polyethylene glycol

Lubricin is a glycoprotein found in articular joints which has been recognized as being an important biological boundary lubricant molecule. Besides providing lubrication, we demonstrate, using a quartz crystal microbalance, that lubricin also exhibits anti-adhesive properties and is highly effective at preventing the non-specific adsorption of representative globular proteins and constituents of blood plasma. This impressive anti-adhesive property, combined with lubricin's ability to readily self-assemble to form dense, highly stable telechelic polymer brush layers on virtually any substrates, and its innate biocompatibility, makes it an attractive candidate for anti-adhesive and anti-fouling coatings. We show that coatings of lubricin protein are as effective as, or better than, self-assembled monolayers of polyethylene glycol over a wide range of pH and that this provides a simple, versatile, highly stable, and highly effective method of controlling unwanted adhesion to surfaces.     

Incorporation of phosphate group modulates bone cell attachment and differentiation on oligo(polyethylene glycol) fumarate hydrogel

In this work, we have investigated the development of a synthetic hydrogel that contains a negatively charged phosphate group for use as a substrate for bone cell attachment and differentiation in culture. The photoreactive, phosphate-containing molecule, bis(2-(methacryloyloxy)ethyl)phosphate (BP), was incorporated into oligo(polyethylene glycol) fumarate hydrogel and the mechanical, rheological and thermal properties of the resulting hydrogels were characterized. Our results showed changes in hydrogel compression and storage moduli with incorporation of BP. The modification also resulted in decreased crystallinity as recorded by differential scanning calorimetry. Our data revealed that incorporation of BP improved attachment and differentiation of human fetal osteoblast (hFOB) cells in a dose-dependent manner. A change in surface chemistry and mineralization of the phosphate-containing surfaces verified by scanning electron microscopy and energy dispersive X-ray analysis was found to be important for hFOB cell attachment and differentiation. We also demonstrated that phosphate-containing hydrogels support attachment and differentiation of primary bone marrow stromal cells. These findings suggest that BP-modified hydrogels are capable of sustaining attachment and differentiation of both bone marrow stromal cells and osteoblasts that are critical for bone regeneration.     

Investigation of a new microcapsule membrane combining alginate, chitosan, polyethylene glycol and poly-L-lysine for cell transplantation applications

Microencapsulation of living cells may serve as an alternative therapy for patients requiring organ transplants. One of the limiting factors in the progress of such therapy is attaining a biocompatible and mechanically stable polymer. The current study investigates the potential of a novel membrane combining alginate, chitosan, polyethylene glycol (PEG) and poly-L-lysine (PLL) with the objective of proposing a membrane suitable for cell entrapment that may overcome some of the shortcomings of the widely studied alginate-poly-L-lysine-alginate (APA) capsules. The novel microcapsule was formulated using a 1.5% alginate solution coated with 0.05% chitosan, 0.1% PEG and 0.05% poly-L-lysine with a final layer of 0.1% alginate. Microcapsules having a diameter of 450 +/- 30 microm were prepared. Upon citrate treatment, the membrane remained intact and retained its spherical structure. The membrane was able to support liver cell proliferation and the encapsulated cells were capable of secreting proteins. The study demonstrated that the new membrane can be used for cell entrapment. However, further investigations are needed to assess its potential for long term transplantation and usage in the development of bioartificial organs.     

Structured drug-eluting bioresorbable films: microstructure and release profile

Bioresorbable drug-eluting films can be used in many biomedical applications. Examples for such applications include biodegradable medical support devices which combine mechanical support with drug release and antibiotic-eluting film coatings for prevention of bacterial infections associated with orthopedic implants or during gingival healing. In the current study, bioresorbable drug-loaded polymer films are prepared by solution processing. Two film structures are studied: A polymer film with large drug crystals located on its surface (A-type) and a polymer film with small drug particles and crystals distributed within the bulk (B-type). The basic mode of drug dispersion/location in the film (A or B-type) is found to be determined mainly by the process of film formation and depends mainly on the solvent evaporation rate, whereas the drug's hydrophilicity has a minor effect on this structuring process. Most release profiles from A-type films exhibit a burst effect of approximately 30% and a second release stage that occurs at an approximately constant rate and is determined mainly by the polymer weight loss rate. An extremely high burst release is exhibited only by a very hydrophilic drug. The matrix (monolithic) nature of the B-type film enables release profiles that are determined mainly by the host polymer's degradation profile, with a very low burst effect in most of the studied systems. In addition to the drug location/ dispersion in the film, the host polymer and drug type also strongly affect the drug's release profile from the film. It has been demonstrated that appropriate selection of the process parameters and film components (polymer and drug) can yield film structures with desirable drug release behaviors. This can lead to the engineering of new bioresorbable drug-eluting film-based implants for various applications.     

Polypyrrole-polysaccharide thin films characteristics: electrosynthesis and biological properties

Polypyrrole-polysaccharide thin films were electropolymerized from starting solutions containing pyrrole and a polysaccharide, namely, heparin, chondroitin-4-sulphate or hyaluronic acid. The synthesized samples showed good chemical and physicochemical properties determined by the synthesis parameters such as the current density and time. For instance, the sample morphology was strictly correlated to the current density as follows: a smooth surface morphology was observed when the current density was in the range of 100-700 microA/cm(2), whereas high current (I > 1.0 mA/cm(2)) or longer time (synthesis charge > 100 mC/cm(2)) led to rough surfaces. The presence of polysaccharide within the polymeric matrix assured proper hydrophilicity to the samples. The optimized surface chemistry due to the presence of a polysaccharide and the controllable morphology allowed positive cell/substrate interactions and these are proved by cellular tests using MC3T3-E1 osteoblast cultures.     

Alginate/polyethylene glycol blend fibers and their properties for drug controlled release

Fibers of alginate and polyethylene glycol (PEG), with salicylic acid (SA) as model drug incorporated in different concentrations, were obtained by spinning their solution through a viscose-type spinneret into a coagulating bath containing aqueous CaCl(2) and ethanol. Chemical, morphological, and mechanical properties characterization were carried out, as well as the studies of the factors that influence the drug releasing from alginate/PEG fibers. These factors included the component ratio of alginate and PEG, the loaded amount of SA, the pH, and the ionic strength of the release solution and others. The best values of the tensile strength at 13.41 cN/tex and breaking elongation at 23.13% of blend fibers were obtained when the PEG content was 5 wt %; the water swelling ratio (WSR) of blend fibers increased as the composition of PEG was raised. The results of controlled release tests showed that the amount of SA released increased with an increase in the proportion of PEG present in the fiber. Moreover, the release rate of drug decreased as the amount of drug loaded in the fiber increased, but the cumulative release amount is increasing. The alginate/PEG fibers were also sensitive to pH and ionic strength. For pH 7.4 the drug release was faster compared to pH 1.0, being simultaneously accelerated by a higher ionic strength. All the results indicated that the alginate/PEG fiber was potentially useful in drug delivery systems.     

Chitosan/polyethylene glycol blend fibers and their properties for drug controlled release

Fibers of chitosan and polyethylene glycol (PEG), with salicylic acid as model drug incorporated in different concentrations, were obtained by spinning their solution through a viscose-type spinneret into a coagulating bath containing aqueous tripolyphosphate and ethanol. Chemical, morphological, and mechanical properties characterization were carried out, as well as the studies of the factors that influence the drug releasing from chitosan/PEG fibers. These factors included the component ratio of chitosan and PEG, the loaded amount of salicylic acid, the pH and the ionic strength of the release solution and others. The diameter of the fibers is around 15 +/- 3 microm. The best values of the tensile strength at 12.86 cN/tex and breaking elongation at 21.13% of blend fibers were obtained when the PEG content was 8 and 5 wt %, respectively; the water-retention value of blend fibers increased as the composition of PEG was raised. The results of controlled release tests showed that the amount of salicylic acid released increased with an increase in the proportion of PEG present in the fiber. Moreover, the release rate of drug decreased as the amount of drug loaded in the fiber increased, but the cumulative release amount is increasing. The chitosan/PEG fibers were also sensitive to pH and ionic strength. The release rate was being accelerated by a lower pH and a higher ionic strength, respectively. All the results indicated that the chitosan/PEG fiber was potentially useful in drug delivery systems.     

The effect of incorporating RGD adhesive peptide in polyethylene glycol diacrylate hydrogel on osteogenesis of bone marrow stromal cells

Advances in tissue engineering require biofunctional scaffolds that can not only provide cells with structural support, but also interact with cells in a biological manner. To achieve this goal, a frequently used cell adhesion peptide Arg-Gly-Asp (RGD) was covalently incorporated into poly(ethylene glycol) diacrylate (PEODA) hydrogel and its dosage effect (0.025, 1.25 and 2.5 mm) on osteogenesis of marrow stromal cells in a three-dimensional environment was examined. Expression of bone-related markers, osteocalcin (OCN) and Alkaline phosphatase (ALP), increased significantly as the RGD concentration increased. Compared with no RGD, 2.5 mm RGD group showed a 1344% increase in ALP production and a 277% increase in OCN accumulation in the medium. RGD helped MSCs maintain cbfa-1 expression when shifted from a two-dimensional environment to a three-dimensional environment. Soluble RGD was found to completely block the mineralization of marrow stromal cells, as manifested by quantitative calcium assay, phosphorus elemental analysis and Von Kossa staining. In conclusion, we have demonstrated that RGD-conjugated PEODA hydrogel promotes the osteogenesis of MSCs in a dosage-dependent manner, with 2.5 mm being optimal concentration.     

Investigation of the material properties of alginate for the development of hydrogel repair of dura mater

The collagenous dura mater isolates the brain from the external environment and requires a secure closure following invasive neurosurgery. This is typically accomplished by approximation of the dura mater via sutures and adhesives. In selected cases, however, large portions of dura mater require excision, necessitating a tissue replacement patch. The mild reaction conditions and long-term biocompatibility of alginate evince strong candidacy for these applications. This study investigates the potential of diffusion and internally gelled alginates for these applications. Specifically, we quantified the viscosity, gel rate, syneresis level, compressive strength, compressive modulus, complex modulus and loss angle in the context of dura mater repair. The ideal sealant would have a rapid cross-link speed, while the ideal dura mater replacement would have a low level of syneresis. Both applications require a compressive modulus of 20-100 kPa and a complex modulus of 1-24 kPa. The data collected in this study suggests that the use of 1.95 wt% 43 mPa?s alginate with 200?mM?CaCl(2) is sufficient for approximating the dural membrane for closure alone or in conjunction with suture. Alternatively, the use of 1.95 wt% 43 mPa?s alginate with 100?mM?CaCO(3) is sufficient for tissue replacement in large dural defects.     

A quantitative examination of the light scattering properties of immune complexes in polyethylene glycol

The effect of polyethylene glycol on the light scattering properties of immune complexes prepared in vitro was examined. Immune complexes were prepared in the zone of antigen excess from purified rabbit anti-ovalbumin and ovalbumin at 2-32 times (X) the equivalence ratio. Immune complex concentration was determined by analytical ultracentrifugation. Immune complexes were then incubated for 1 h in solutions containing 0, 1, 2, 3 and 4% polyethylene glycol (PEG), and examined in a laser nephelometer. The effect of PEG on light scattering (%RLS) was different for each immune complex combining ratio, although for each immune complex combining ratio, there was a linear relationship between the light scattered and immune complex concentration. To evaluate the effect of serum proteins on the light scattered by the immune complexes, immune complexes made at 4X and 16X the equivalence ratio were placed in serum and the sera containing these immune complexes were examined in the nephelometer. The ratio of the %RLS of the immune complexes in serum to the sum of the %RLS of the same immune complexes in saline plus the %RLS of serum alone was determined. This ratio varied systematically with changes in combining ratio and PEG concentration, as well as the concentration of the immune complexes themselves. Depending on the combination of these 3 factors, serum could increase, decrease or have no effect on the quantity of light scattered by the immune complexes. Discrimination between serum alone and serum containing immune complexes was best in 3% PEG.     

甲基丙烯酸钠修饰光交联海藻酸盐水凝胶支架的制备和表征

文题释义：甲基丙烯酸钠：是一种具有双功能的化学基团的有机小分子,一端含有2-甲基丙烯酰基,该基团具有良好的化学活性,可与化合物中的多种基团反应而修饰化合物;另一个功能集团就是拥有负电荷基团,能给修饰过的化合物材料表面带来稳定的负电荷。 光引发剂：又称光敏剂,是一类能在紫外光区(250-420 nm)或可见光区(400-800 nm)吸收一定波长的能量,产生自由基、阳离子等,从而引发单体聚合交联固化的化合物。引发剂分子在紫外光区(250-400 nm)或可见光区(400-800 nm)有一定吸光能力,在直接或间接吸收光能后,引发剂分子从基态跃迁到激发单线态,经系间窜跃至激发三线态;在激发单线态或三线态经历单分子或双分子化学作用后,产生能够引发单体聚合的活性碎片,这些活性碎片可以是自由基、阳离子、阴离子等。按照引发机制不同,光引发剂可分为自由基聚合光引发剂与阳离子光引发剂,其中以自由基聚合光引发剂应用最为广泛。 背景：光交联海藻酸盐水凝胶因具有良好的生物相容性、可微创注射等优势已为热门的组织工程研究材料,但是仍然存在强度不足、细胞黏附能力不足等问题。 目的：构建载负电荷的光交联海藻酸盐水凝胶材料,探索其物理性能和细胞黏附性能变化。 方法：利用海藻酸钠和2-氨乙基甲基丙烯酸酯盐酸盐制备甲基丙烯酸酯化海藻酸盐后,再与光引发剂和不同浓度甲基丙烯酸钠(0,20,40,60 mmol/L)混合制备载负电荷光交联海藻酸盐水凝胶,利用傅里叶红外光谱仪分析水凝胶的功能基团变化情况,扫面电镜观察水凝胶的表面形态,并测量其溶胀率。将MC3T3-E1细胞与各组水凝胶共培养48 h,采用活死染色与CCK-8法分析水凝胶的细胞毒性;接种MC3T3-E1细胞于4组水凝胶表面,在第4小时活死染色观察细胞早期黏附情况,第3天活死染色观察细胞伸展情况。 结果与结论：①傅里叶红外光谱分析显示,甲基丙烯酸钠的引入可在水凝胶红外波普波数1 600 cm^-1左右处出现来自甲基丙烯酸钠的新波峰;②扫描电镜显示随着甲基丙烯酸钠浓度的增加,光交联海藻酸盐水凝胶的致密度增加,孔径减小;③溶胀率测试显示随着甲基丙烯酸钠浓度的升高,光交联海藻酸盐水凝胶的溶胀率逐渐降低;④活死染色显示4种水凝胶表面的细胞生长状态良好,细胞活性均在95%以上;CCK-8检测显示,载负电荷的光交联海藻酸盐水凝胶材料无细胞毒性;⑤随着甲基丙烯酸钠引入量的增加,载负电荷光交联海藻酸盐水凝胶表面的早期细胞黏附率逐渐增加,细胞伸展状态明显改善;⑥结果表明,甲基丙烯酸钠修饰的引入调节了光交联海藻酸盐水凝胶物理性能,并明显提高了其细胞黏附性能。 ORCID: 0000-0002-1054-6002(赵德路) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Degradative properties and cytocompatibility of a mixed-mode hydrogel containing oligo[poly(ethylene glycol)fumarate] and poly(ethylene glycol)dithiol

Our laboratory is currently exploring synthetic oligo(poly(ethylene glycol)fumarate) (OPF)-based biomaterials as a means to deliver fibroblasts to promote regeneration of central/partial defects in tendons and ligaments. In order to further modulate the swelling and degradative characteristics of OPF-based hydrogels, OPF crosslinking via a radically initiated, mixed-mode reaction involving poly(ethylene glycol) (PEG)-diacrylate and PEG-dithiol was investigated. Results demonstrate that mixed-mode hydrogels containing OPF can be formed and that the presence of 20 wt.% PEG-dithiol increases swelling and decreases degradation time vs. 10 wt.% PEG-dithiol and non-thiol-containing hydrogels (20% thiol fold swelling 28.7+/-0.8; 10% thiol fold swelling 11.6+/-1.4; non-thiol 8.7+/-0.2; 20% thiol-containing hydrogels degrade within 15 days in vitro). After encapsulation, tendon/ligament fibroblasts remained largely viable over 8 days of static culture. While the presence of PEG-dithiol did not significantly affect cellularity or collagen production within the constructs over this time period, image analysis revealed that the 20% PEG-dithiol gels did appear to promote cell clustering, with greater values for aggregate area observed by day 8. These experiments suggest that mixed-mode OPF-based hydrogels may provide an interesting alternative as a cell carrier for engineering a variety of soft orthopedic tissues, particularly for applications when it is important to encourage cell-cell contact.     

Swelling characteristics and drug delivery properties of nifedipine-loaded pH sensitive alginate-chitosan hydrogel beads

The aim of the present work was to investigate the swelling behavior and in vitro release of nifedipine from alginate-chitosan hydrogel beads. Structure and surface morphology of the hydrogel were characterized by FTIR and SEM, respectively. Alginate-chitosan mixed beads and alginate-chitosan coated beads were prepared by ionic gelation method. The swelling ability of the beads and in vitro release of nifedipine in simulated gastric fluid (pH 1.5) and different phosphate buffer solutions (pH 2.5, 5.0, 6.8, 7.4, and 8.0) were found to be dependent on the presence of the polyelectrolyte complex between chitosan and alginate. The amount of nifedipine released from the mixed beads at pH 1.5 was relatively low (42%), whereas this value approached to 99% at pH 6.8. In comparison with the mixed beads, the released nifedipine from the coated beads was minimal at pH 1.5 (18%), whereas approximately 99% nifedipine was released at pH 6.8. The results suggested that the coated beads can hold drug better at low pH than the mixed beads and show excellent pH sensitivity. Therefore, the alginate-chitosan coated beads could be a suitable polymeric carrier for drug delivery in the intestinal tract.     

The histopathological effects of reabsorbable polyethylene glycol hydrogel (Coseal) on epidural fibrosis in an experimental postlaminectomy model in rats

Background/aimTo investigate the histopathological effects of reabsorbable polyethylene glycol hydrogel (RPGH, Coseal) on epidural fibrosis (EF) following laminectomy in rats.Materials and methodsA total of 24 rats were equally divided into three groups. In the first group, no treatment was applied after laminectomy (control group, Group 1). In the second group, hemostasis was achieved after laminectomy, and 2 mm absorbable gelatin sponge soaked in saline was placed over the epidural space and the wound was closed (Group 2). In the third group, hemostasis was achieved following laminectomy, and 0.5 mL RPGH (Coseal, Group 3) was squeezed over the dura mater, and the wound was closed. A histopathological examination was undertaken to evaluate arachnoidal invasion and EF.ResultsThe results of EF in the Group 2 and Group 3 were significantly lower compared to the Group 1 (p = 0.023 and p = 0.002, respectively). No statistically significant difference was found between the Group 2 and Group 3 in terms of EF (p = 0.957). There was also no statistically significant difference between the mean arachnoidal invasion of the three groups (p > 0.171). However, the rate of arachnoidal invasion was the lowest in the Group 3.ConclusionIntraoperative Coseal, a polyethylene glycol polymer, tends to reduce the risk of epidural fibrosis, although this is not statistically significant.