Morphological evaluation of bioartificial hydrogels as potential tissue engineering scaffolds

Poly(vinyl alcohol) hydrogels prepared by freeze-thawing procedure represent synthetic systems widely investigated as non-biodegradable scaffolds for tissue regeneration. In order to improve the biocompatibility properties of pure poly(vinyl alcohol) (PVA) hydrogels, blends of PVA with different biological macromolecules, such hyaluronic acid, dextran, and gelatin were prepared and used to produce bioartificial hydrogels. The porosity characteristics of these hydrogels were investigated by scanning electron microscopy and mercury intrusion porosimetry. The morphology of bioartificial hydrogels was evaluated and compared with that of pure PVA hydrogels. In particular the effect exerted by each biological component on pore size and distribution was investigated. The obtained results indicate that when a natural macromolecule is added to PVA the internal structure of the material changes. A small amount of biopolymer induces the structural elements of PVA matrix to take on a well evident lamellar appearance and an apparent preferential orientation. Comparing the results of SEM and mercury intrusion porosimetry it was concluded that hydrogels containing 20% of biological component have the most regular structure and at the same time the lowest total porosity. On the contrary samples with the highest content of natural polymer (40%) show the less regular structure and the highest total porosity.     

Effect of chitosan and dextran on the properties of poly(vinyl alcohol) hydrogels

Hydrogels are three-dimensional polymeric networks very similar to biological tissues and potentially useful as drug delivery systems. Poly(vinyl alcohol)-based hydrogels containing different amounts of dextran or chitosan were prepared using the freezing–thawing method. Repeated freezing–thawing cycles of a poly(vinyl alcohol) (PVA) aqueous solution lead to the formation of crystallites which act as cross-linking sites, and a hydrogel with a high capacity to swell is obtained. The effects of the two different polysaccharides on the properties of the obtained materials were investigated by differential scanning calorimetry, dynamic mechanical analysis and scanning electron microscopy. In addition the release with time of poly(vinyl alcohol) in aqueous medium, was monitored and evaluated. On the basis of the obtained results it seems that the presence of dextran favors the crystallization process of PVA, allowing the formation of a more ordered and homogeneous structure. Instead, chitosan seems to perturb the formation of PVA crystallites leading to a material with a less regular structure. © 1999 Kluwer Academic Publishers     

Release of dexamethasone from PLGA nanoparticles entrapped into dextran/poly(vinyl alcohol) hydrogels

Hydrogels based on blends of poly(vinyl alcohol) (PVA) with dextran were prepared by a physical cross-linking procedure and used as matrices for the entrapment of biodegradable nanoparticles loaded with dexamethasone. The nanoparticles were prepared, by a solvent evaporation technique, using biodegradable copolymers of poly(lactic acid)–poly(glycolic acid) (PLGA). Size, morphology and surface characteristics of the nanoparticles were evaluated by scanning electron microscopy. The mechanism of drug release from the nanoparticles entrapped into the PVA-based matrices was studied and compared to that from free nanoparticles. The effect of dextran on the in vitro release profile of dexamethasone from the hydrogels was investigated. The obtained results indicate that PLGA nanoparticles are able to release dexamethasone following a diffusion-controlled mechanism. The entrapment of the nanoparticles into the hydrogels affects only slightly this mechanism of drug release. In addition, dextran/PVA hydrogels release a higher amount of drug with respect to pure PVA hydrogels and by increasing dextran content in the hydrogels, the amount of drug released increases.     

聚乙二醇改性纳米纤维素/聚乙烯醇复合水凝胶的制备及性能

通过酸碱处理和机械研磨结合的方法制备纳米纤维素(CNFs),并利用冻融循环法分别制备了聚乙烯醇(PVA)和纳米纤维素/聚乙烯醇(CNFs/PVA)复合水凝胶,以及聚乙二醇(PEG)改性PVA和CNFs/PVA复合水凝胶。考察不同配方下复合水凝胶的微观形貌变化,并对复合水凝胶的溶胀性能、压缩强度及热稳定性能进行研究。结果表明,CNFs与PEG对PVA水凝胶的微观形貌均有改善作用,加入PEG后形成的PEG/PVA凝胶产生明显的三维网络结构。当PEG与CNFs同时加入到PVA凝胶后形成的CNFs-PEG/PVA凝胶具有均匀的互穿孔洞结构,此时复合水凝胶的孔隙率最高((67.5±4.3)%),溶胀度最好(980%),且压缩强度较PVA水凝胶也有所提升。PEG对复合凝胶的热稳定性无影响,而加入CNFs后,CNFs-PEG/PVA复合凝胶的初始热分解温度从235℃上升至300℃,显著提高了PVA凝胶的热稳定性。     

微波原位合成2D Ni-Fe MOF/硅藻土复合材料及其改性聚乙烯醇水凝胶不锈钢筛网油水分离性能

如何高效处理含油污水的问题,是如今世界科研人员共同关注的问题。聚乙烯醇(PVA)水凝胶作为高含水量及具有三维亲水网络的软材料在油水分离领域引起了广泛的关注。但是,和大多数具有超润湿性质的水凝胶一样,PVA水凝胶类油水分离材料不仅力学性能差,同时也存在化学稳定性差的问题。基于此,通过微波法制备了2D Ni-Fe金属-有机框架材料(MOF)-硅藻土(Dia)纳米材料及其PVA复合水凝胶。同时,不锈钢网经过浸泡2D Ni-Fe MOF-Dia/PVA水凝胶溶液得到2D Ni-Fe MOF-Dia/PVA水凝胶不锈钢筛网,表现出超亲水-水下超疏油性质。利用SEM、XPS分析2D Ni-Fe MOF-Dia及其复合水凝胶的化学组成和表面形貌。研究了2D Ni-Fe MOF-Dia/PVA复合水凝胶的力学性能及2D Ni-Fe MOF-Dia/PVA复合水凝胶不锈钢筛网的油水分离与乳液分离的分离效率及水通量,并对其耐盐性、耐酸耐碱性油水分离性能进行了测试。结果表明:2D Ni-Fe MOF-Dia/PVA复合水凝胶具有优异的力学性能,拉伸与压缩强度分别达到1.49 MPa及0.58 MPa,同时表现出超亲水-水下超疏油性质,2D Ni-Fe MOF-Dia/PVA不锈钢筛网的油水分离与乳液分离效率与通量分别可达99.2%和742.7 L·m?2·h?1。在酸性、碱性、盐性环境下均保持优异的分离效率与通量,并且在5次循环后,依旧保持稳定的分离效率与通量。      

Novel PVP/PVA hydrogels for articular cartilage replacement

Poly(vinyl alcohol) (PVA) hydrogel has been considered as a very interesting and promising material for articular cartilage replacement. The most vital shortcoming of PVA hydrogels is that their mechanical properties are difficult to meet the requirements of articular cartilage. In the present work, blend hydrogels based on PVA and poly (vinyl pyrrolidone) (PVP) were prepared by repeated freezing and thawing method. Such hydrogel had similar internal three-dimensional structure and water content (approximately 75%) as nature articular cartilage. The mechanical and tribological properties were investigated to find out that change of mechanical and tribological properties of PVP/PVA hydrogels were significantly dependent on PVP content and freezing–thawing cycles. The blend hydrogel with 1 wt.% PVP had the best mechanical properties and the friction system consisting of such blend hydrogel and stainless steel ball exhibited a mixed lubrication regime especially under bovine serum lubrication. The results established that such hydrogel would be a novel attractive material for articular cartilage replacement.     

Preparation of collagen modified photopolymers: a new type of biodegradable gel for cell growth

In this study a new branched methacrylated poly(propylene glycol-co-lactic acid) (PPG–PLA–IEM) and methacrylated cellulose acetate butyrate resin (CAB–IEM) were synthesized. Hydrogels with various amounts of PPG–PLA–IEM and CAB–IEM (25, 50 and 75 wt% IEM modified) were prepared by photopolymerization. Collagen tethered PEG–monoacrylate (PEGMA–collagen) was prepared and introduced as a bioactive moiety to modify the hydrogel in order to enhance cell affinity. In vitro attachment and growth of 3T3 mouse fibroblasts and human umbilical vein endothelial cells (HUVEC) on the hydrogels with and without collagen were also investigated. It was observed that, the collagen improves the cell adhesion onto the hydrogel surface. With the increasing amount of collagen, cell viability increased by 28% for ECV304 (P < 0.05) and 30% for 3T3 (P < 0.05).     

聚乙烯醇水凝胶与聚乙烯薄膜的表面粘接

用铬酸氧化方法处理聚乙烯(PE)薄膜,得到了表面刻蚀均匀的化学改性薄膜;利用XPS、IR表征了薄膜表面的化学变化,采用SEM、AFM、接触角表征了薄膜表面微观结构和物理性能。制备可化学交联及物理交联成水凝胶的聚乙烯醇(PVA)溶液,与表面刻蚀的PE薄膜复合,得到了PVA水凝胶与PE薄膜的表面复合材料。通过剥离强度测定、SEM观察,表明PVA水凝胶与PE薄膜很好地粘接在一起。     

Topographical heterogeneity in transparent PVA hydrogels studied by AFM

Physically crosslinked poly (vinyl alcohol) (PVA) hydrogels have a wide range of biomedical applications. Transparent and stable PVA hydrogels synthesized by freeze-thawing method are potential candidates to be used as tissue engineering scaffolds provided they exhibit suitable topographical roughness and surface energy. The effect of processing parameters i.e., polymer concentration and number of freeze-thaw cycles on the resulting topography of the freeze-thawed transparent hydrogels has been studied and quantified using non-contact mode of an atomic force microscope (AFM) and image analysis. Simultaneously captured phase contrast images have revealed significant information about morphological changes in the topographical features and crystallinity of the hydrogels. Topographical roughness was found to decrease as a function of number of freeze-thaw cycles.     

Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea

Each approach for artificial cornea design is toward the same goal: to develop a material that best mimics the important properties of natural cornea. Accordingly, the selection and optimization of corneal substitute should be based on their physicochemical properties. In this study, three types of polyvinyl alcohol (PVA) hydrogels with different polymerization degree (PVA1799, PVA2499 and PVA2699) were prepared by freeze-thawing techniques. After characterization in terms of transparency, water content, water contact angle, mechanical property, root-mean-square roughness and protein adsorption behavior, the optimized PVA2499 hydrogel with similar properties of natural cornea was selected as a matrix material for artificial cornea. Based on this, a biomimetic artificial cornea was fabricated with core-and-skirt structure: a transparent PVA hydrogel core, surrounding by a ringed PVA-matrix composite skirt that composed of graphite, Fe-doped nano hydroxyapatite (n-Fe-HA) and PVA hydrogel. Different ratio of graphite/n-Fe-HA can tune the skirt color from dark brown to light brown, which well simulates the iris color of Oriental eyes. Moreover, morphologic and mechanical examination showed that an integrated core-and-skirt artificial cornea was formed from an interpenetrating polymer network, no phase separation appeared on the interface between the core and the skirt.     

Rheological and thermal characteristics of a two phase hydrogel system for potential wound healing applications

Hydrogels fabricated from single polymers have been extensively investigated for wound healing applications. However, in many cases a single polymer cannot meet divergent demands in terms of both properties and performance. In this work, a two phase hydrogel was prepared by physically imbedding a xerogel in the core of a freeze thawed hydrogel. The outer hydrogel was prepared by freeze thawing poly (vinyl alcohol) (PVA) and poly (acrylic acid) (PAA) while the xerogels were prepared by UV polymerisation of 1-vinyl-2-pyrrolidinone (NVP). The rheological results indicated that the two phase hydrogels over a period of 2 weeks formed a strong interface and demonstrated greater physical strength. This suggested that the inner gel containing PVP diffused into the PVA/PAA hydrogel, which in turn increased hydrogen bonding, resulting in the overall increase in the stiffness of the gel. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirmed hydrogen bonding had occurred between the constituents of the two phase hydrogels. Thermal analysis suggested that T _g of each of the samples was above 80 °C, which indicated no impact on the behaviour of the gel at body temperature, but did however, give an indication of the stiffness of the dry polymer.     

Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles

Poly(vinyl alcohol) (PVA) hydrogels prepared by a freeze-thawing procedure were evaluated as matrices for the release of water-insoluble drugs such as dexamethasone. As it is impossible to directly entrap a lipophilic drug into a hydrophilic matrix, a novel mechanism has been designed based on producing biodegradable nanoparticles loaded with the drug, that could then be entrapped into the hydrogels. Nanoparticles were prepared by a solvent evaporation technique using a biodegradable copolymer of poly(lactic acid)-poly(glycolic acid) (PLGA). The effects of several processing parameters on particle properties were investigated. The drug release from free nanoparticles was compared to that from the nanoparticles entrapped into the PVA matrices. It was observed that the release profile of the drug is not significantly affected by the PVA matrix. A correlation was found between the amount of drug released and the PVA concentration in the hydrogels: the percentage of drug released, as a function of time, decreased by increasing PVA concentration, indicating that PVA concentration can be used as a tool in modulating the release of the drug.     

Non cell adhesive photopolymerized cross-linked layers (I): synthesis and characterization

The aim of this study is to design an effective hydrogel, which has good potential for application in the field of tissue regeneration. Ultimately, the polymeric biomaterial will be used as a bottom, non-cell adhering layer of a polymeric scaffold, which will inhibit the adhesion and proliferation of fibroblast cells. A series of terpolymer hydrogels were prepared from MMA/HPOEM/MePOEM monomers based on varying formulations. The gels were polymerized via free radical polymerization under UV and characterized by TGA, DSC and FTIR studies. Furthermore, the double bond conversion, gel content and swelling properties of the polymer were analyzed and correlated to its crosslinking density, which revealed details about the hydrogels character. Finally, cell culture experiments were used to compare the UV-cured polymer to its thermally derived non-functionalized polymer of the same formulation. Inverted optical microscopy was used to demonstrate cell-resistance of both materials with respect to a control Tissue Culture PolyStyrene plate. ©2003 Kluwer Acadamic Publishers     

磺胺嘧啶银/聚乙烯醇水凝胶复合材料的制备及性能表征

采用e-Beam电子辐射和冻融循环相结合的方法制备了磺胺嘧啶银(SD-Ag)/聚乙烯醇(PVA)水凝胶。研究了制备工艺对PVA水凝胶的性能的影响。通过拉伸性能测试、吸水率检测、SEM和FT-IR等表征,考察了PVA浓度(占总质量5%~15%)、冻融与辐射处理等对PVA水凝胶拉伸强度、断裂伸长率、吸水性、凝胶含量和微观结构等的影响。结果表明:随着PVA浓度增大,PVA水凝胶的拉伸强度提高。当PVA浓度为15%、辐射剂量为25kGy时,单独辐射、辐射后冻融及冻融后辐射三种工艺制备的PVA水凝胶拉伸强度分别为0.023 MPa、0.048MPa、0.028MPa,吸水率分别为为95%、45%、63%,说明经冻融处理的水凝胶力学强度提高,吸水率有所下降。然后,选择适当的制备工艺并在PVA水凝胶中加入SD-Ag,考察了SD-Ag/PVA水凝胶的抑菌性能,抑菌活性测试结果显示,随着SD-Ag含量的增加,SD-Ag/PVA水凝胶的抑菌效果增强,而且其对革兰式阴性菌(大肠杆菌)的抑菌效果优于其对革兰式阳性菌(金黄色葡萄球菌)的抑菌效果。     

Physico-chemical and mechanical characterization of hydrogels of poly (vinyl alcohol) and hyaluronic acid

Hydrogels are three-dimensional polymeric networks very similar to biological tissues and potentially useful as soft tissue substitutes and drug delivery systems. Many synthetic polymers can be used to make hydrogels: poly (vinyl alcohol) is widely employed to make hydrogels for biomedical applications. Improvements in the biocompatibility characteristics of synthetic materials could be achieved by the addition of biological macromolecules. The resulting materials named bioartificial polymeric materials could possess the good mechanical properties of the synthetic component and adequate biocompatibility due to the biological component. We have used poly (vinyl alcohol) to make hydrogels containing various amounts of hyaluronic acid. These bioartificial materials were studied to investigate the effect of the presence of the hyaluronic acid on the structural properties of the hydrogels. Thermal, mechanical, morphological and X-ray analyses were performed. A close correspondence between the network consistency and the degree of crystallinity developed in the matrix suggested that the hyaluronic acid, when its content is about 20%, could provide heterogeneous crystallization nuclei for poly (vinyl alcohol) thus increasing the crystallization degree, and consequently, the storage modulus.     

Physically cross-linked polyvinyl alcohol for the topical delivery of fluconazole

The aim of this study was to develop fluconazole in an ultrapure polyvinyl alcohol (PVA) hydrogel able to deliver the drug in a sustained release pattern for local treatment of skin fungal infections. The topical fluconazole hydrogels were prepared using PVA hydrogels physically cross-linked by freeze-thaw technique. Polyethylene glycol (PEG) was added as a hydrophilic excipient as a release enhancer of fluconazole. The effects of PVA molecular weight, PEG molecular weight, and PEG concentration were studied using a 2 x 4 x 2 factorially designed experiment. The selected fluconazole hydrogel proved to be physically stable over a period of 6 months and to be effective in the topical treatment of cutaneous candidiasis. Therefore, it could be concluded that the formula composed of 10% PVA 205000 and 1.5% PEG 4000 and 2% fluconazole and prepared by three cycles of freezing, and thawing is very promising in the local treatment of skin fungal infection as an alternative to the systemic use of fluconazole.     

Graphite/poly (vinyl alcohol) hydrogel composite as porous ringy skirt for artificial cornea

Graphite/poly (vinyl alcohol) (PVA) hydrogel composites, which were designed as the porous ringy skirt surrounding the transparent core of a novel artificial cornea, were prepared by using the freeze/thawing process and the particle-leaching technique. The properties of the composites, including the water content, the mechanical strength, the porous architecture and the interactions between the graphite and PVA, were investigated. The tissue responses to the composite and pure PVA hydrogel were studied by in vivo implantation in the dorsal muscles of mice. The results showed that chemical interactions were present between the graphite and PVA in the composite, which benefited the combination of the two phases and enhanced the uniform distribution of graphite particles in the PVA matrix. However, the present of graphites in the PVA hydrogels reduced the tensile strength, elongation at break and water content of the composite. Moreover, the porous graphite/PVA hydrogel composite had interconnective pore structure with high porosity and enough mechanical strength. According to the histological analysis of 1 week and 12 weeks post-implantation, the graphite/PVA hydrogel composites showed less inflammatory reactions than the PVA hydrogels at the 1 week post-implantation. Moreover, compared to pure PVA hydrogel, the graphite/PVA hydrogel composite exhibited enhanced migration and infiltration of cells, and more neovascularization and tissue ingrowth. These in vivo characteristics will be beneficial for the long-term biofixation of artificial cornea. Therefore, the porous graphite/PVA hydrogel composite has a potential to be used as novel artificial cornea skirt.     

Facile preparation of low swelling,high strength,self-healing and pH-responsive hydrogels based on the triple-network structure

A polyacrylic acid(PAA)/gelatin(Gela)/polyvinyl alcohol(PVA)hydrogel was prepared by copolymerization,cooling,and freezing/thawing methods.This triplenetwork(TN)structure hydrogel displayed superior mechanical properties,low swelling ratio and self-healing properties,The superior mechanical properties are attributed to the triple helix association of Gela and PVA crystallites by reversible hydrogen bonding.The characterization results indicated that the fracture stress and the strain were 808 kPa and 370% respectively,while the compression strength could reach 4443 kPa and the compressive modulus was up to 39 MPa under the deformation of 90%.The hydrogen bonding in PVA contributed to maintain and improve the self-healing ability of hydrogels.Every type of hydrogels exhibited a higher swelling ratio under alkaline conditions,and the swelling ratios of PAA,PAA/PVA and PAA/Gela hydrogels were 27.71,12.30 and 9.09,respectively.The PAA/Gela/PVA TN hydrogel showed the lowest swelling ratio(6.57)among these hydrogels.These results indicate that the novel TN hydrogels possess good environmental adaptability and have potential applications in the biomedical engineering and sensor field.     

Non-destructive characterization of hydrogels

Hydrogels have been prepared by a freezing–thawing procedure and investigations made of the effect of both number of freezing–thawing cycles and different content of hyaluronic acid (HA) on the mechanical properties of the PVA-HA hydrogels using non-destructive testing. The bulk elastic modulus K of hydrogels has been determined by pulse-echo measurements. It is noted that hydrogel elastic properties improve with the number of the cycles in PVA-HA 100/0; on the other hand samples with a high HA (1000000 molecular weight) content, beyond the third cycle, seem to be unaffected by the number of cycles. A bulk elastic modulus fall-off is then observed in samples submitted to an additional overnight freezing between two subsequent cycles. K increases in hydrogels with the highest HA content, when samples undergo pulse-echo measurements soon after their preparation. When hydrogels reach equilibrium, after having been kept in deionized water for 12 h, K values are lower, showing a nearly constant behaviour with different PVA-HA ratios and cycles. Furthermore, by means of scanning laser acoustic microscopy (SLAM) defects have been detected in the hydrogels. In samples which have reached equilibrium, SLAM images show that these defects disappear in PVA-HA hydrogels.     

A high strength semi-degradable polysaccharide-based hybrid hydrogel for promoting cell adhesion and proliferation

Traditionally, practical applications of polysaccharide hydrogels have been limited for their weak mechanical properties under physiological conditions. In this study, we constructed a novel polysaccharide-based semi-degradable hydrogel whose network was constructed by chemical cross-linking of glycidyl methacrylate-modified laminarin and the hydrogen bonded physical cross-linking of poly(N-acryloyl glycinamide). In addition, the introduction of 1-vinyl-1,2,4-triazole content could increase the equilibrium water content of hydrogels and endow hydrogels with anti-bacterial and anti-inflammatory abilities. The prepared hydrogels exhibited comprehensive high mechanical properties up to 0.63 MPa tensile strength, 650% stretchability, and maximum 3.2 MPa compressive strength at swelling equilibrium state. The hydrogen bond interactions could well support the three-dimensional network of hydrogel after the degradation of modified laminarin. Meanwhile, the content of laminarin could facilitate cell adhesion and proliferation on the surface of hydrogel. It is anticipated that this high strength semi-degraded hydrogel may find a promising application as articular cartilage replacement.