Evaluation of hydrogels for soft tissue adhesives <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> analyses

In this study, natural materials (sodium alginate, dextran, gelatin and carboxymethyl chitosan) were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5-300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining (HE) and Masson’s trichrome staining (MTC) methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.     

A novel wound dressing material — fibrin–chitosan–sodium alginate composite sheet

The present study describes preparation and characterization of fibrin–chitosan–sodium alginate composite (F–C–SA) in sheet form. F–C–SA composite was prepared and characterized for its physicochemical properties like water absorption capacity, surface morphology, FTIR spectra and mechanical properties. The optimum quantities of fibrin, chitosan and sodium alginate to get better mechanical properties to composite were determined. FTIR spectrum confirmed the interaction between amino groups of chitosan, fibrin and sodium alginate and SEM studies revealed composite nature of the material.     

Preparation and characterization of oxidized alginate covalently cross-linked galactosylated chitosan scaffold for liver tissue engineering

Liver tissue engineering (LTE) requires a perfect extracellular matrix (ECM) for hepatocytes culture to maintain high level of liver-specific functions. Here, we reported a LTE scaffold derived from oxidized alginate covalently cross-linked galactosylated chitosan via Schiff base reaction, without employing any extraneous chemical cross-linking agent. The structure of galactosylated chitosan (GC) and oxidized alginate was confirmed by Fourier transformed infrared (FTIR) spectra, proton nuclear magnetic resonance (¹H-NMR) spectroscopy, X-ray diffraction (XRD) or thermogravimetric (TG) analysis. The structure and properties of a series of the scaffolds were characterized by FTIR, XRD, scanning electron microscopy (SEM), porosity, equilibrium swelling, mechanical properties, thermal stability and in vitro degradation. FTIR spectra confirmed the characteristic peak of Schiff base groups in the scaffolds and XRD indicated the scaffolds could be amorphous. SEM analysis showed that the scaffolds displayed highly porous surfaces with average pore size of 50-150 μm and interconnected pore structure in the internal structure with average pore size of 100-250 μm. Porosity measurement suggested the scaffolds had a porosity of about 70%. The compressive modulus of the scaffolds (hydrated) was in the range of 4.2-6.3 kPa. Further studies showed that, with the increase of the oxidized alginate content, the equilibrium swelling and in vitro degradation rate of the scaffolds decreased and the thermal stability slightly increased, which might mainly attribute to the difference of the degree of cross-linking and the nature properties of the raw materials. Additionally, the biocompatibility of the scaffolds was evaluated in vitro. The results showed that the hepatocytes cultured on the scaffolds had a typical spheroidal morphology, formed multi-cellular aggregates and presented perfect integration with the scaffolds, which suggested that the scaffolds may be potential candidates for LTE strategies.     

对氨基苯甲酸壳聚糖酯的制备、表征及抗菌活性

壳聚糖(CTS)经氨基保护合成席夫碱,再与由对氨基苯甲酸和氯化亚砜制备的对氨基苯甲酰氯反应,产物在一定pH下氨基去保护得到了对氨基苯甲酸壳聚糖酯(ABCTSE)。产物经FT-IR、1H NMR、13C NMR进行结构表征,证实为目标产物;由元素分析得到所制得壳聚糖酯的酯化度为16.8%、40.4%;室温下,壳聚糖衍生物在蒸馏水及有机试剂中的溶解性比壳聚糖更好;产物的TG和DTG分析结果表明所制得壳聚糖酯的稳定性稍低于壳聚糖。另外,由于分子结构中两个氨基的存在,其溶于弱酸性溶液后随着形成—NH3+的增多,使其在抑菌方面有更大优势。     

Non-decay type fast-setting calcium phosphate cement using chitosan

A non-decay type fast-setting calcium phosphate cement (nd-FSCPC) has been described, which did not decay but set within approximately 5–6 min even when the paste was immersed in serum immediately after mixing, and which forms hydroxyapatite as its end product. nd-FSCPC was produced by adding sodium alginate to the liquid phase of the base cement FSCPC. Sodium alginate forms a water-insoluble gel, and reduces the process of fluid penetration into the paste which is the cause of decay. The aim of this investigation was to confirm the mechanism of the non-decaying behaviour of nd-FSCPC proposed in a previous paper, using another chemical with properties similar to those of sodium alginate. Also, it was intended to further improve both the mechanical properties and tissue response of nd-FSCPC. Chitosan, which also forms a water-insoluble gel in the presence of calcium ions and has been reported to have pharmacologically beneficial effects on osteoconductivity, was added to the liquid phase of the base cement FSCPC. The cement thus prepared showed behaviour similar to that of nd-FSCPC using sodium alginate. The cement paste did not decay but set within approximately 5&amp;#x2013;6 min even when immersed in serum immediately after mixing. DTS value of the set mass was approximately 3&amp;#x2013;4 MPa, slightly lower than that of nd-FSCPC using sodium alginate, and no inhibitory effect was observed for the transformation of cement component to apatite within the range used in this investigation (up to 1.5%). Therefore, it was concluded that the mechanism of non-decaying behaviour was, at least in part, reduction of fluid penetration into the cement paste. nd-FSCPC using chitosan showed slightly poorer mechanical properties than that using sodium alginate. However, pharmacological effects such as osteoconductivity could be expected in nd-FSCPC using chitosan. Thus, this cement may be useful as a more sophisticated bioactive cement than nd-FSCPC using sodium alginate.     

Characterisation of a new bioadhesive system based on polysaccharides with the potential to be used as bone glue

Although gluing bone is in theory a very attractive alternative to classical fracture treatment, this method is not yet clinically established due to the lack of an adhesive which would meet all the necessary requirements. We therefore developed a novel two-component bioadhesive system with the potential to be used as a bone adhesive based on biocompatible and degradable biopolymers (chitosan, oxidised dextran or starch). After mixing in water, the two components covalently cross-link by forming a Schiff’s base. By the same mechanism, the glue binds to any other exposed amino group such as for example those exposed in fractured bone, even in the presence of water. Modified chitosan was synthesised from commercially available chitosan by deacetylation and was then reduced in molecular weight by heating in acid. The amount of free amino groups was analysed by IR. The molecular weight was determined by viscosimetry. Starch or dextran were oxidised with periodic acid to generate aldehyde groups, which were quantified by titration. l-Dopa was conjugated to oxidised dextran or starch in analogy to the gluing mechanism of mussels. Biomechanical studies revealed that the new glue is superior to fibrin glue, but has less adhesive strength than cyanoacrylates. In vitro cell testing demonstrated excellent biocompatibility, rendering this glue a potential candidate for clinical use.     

A novel hydrogel crosslinked hyaluronan with glycol chitosan

A novel hydrogel was prepared by crosslinking hyaluronan with glycol chitosan in aqueous solution using water soluble carbodiimide at nearly neutral pH and room temperature. The products can be easily formulated into injectable gels, various films, membranes and sponges for soft tissue augmentation, viscosupplementation, drug delivery, preventing adhesion of post operation, wound dressing and tissue engineering scaffolds. The said hydrogel has high water adsorption property and biostability. Rheololgical results of the gel showed a soft and viscoelastic structure. FTIR further confirmed the formation of amide bonds between carboxyl groups of hyaluronan and amine groups of glycol chitosan and no N-acylurea and other derivatives were identified.     

Comparison of bone marrow cell growth on 2D and 3D alginate hydrogels

Calcium cross-linked sodium alginate hydrogels have several advantageous features making them potentially suitable as tissue engineering scaffolds and this material has been previously used in many biomedical applications. 3D cell culture systems are often very different from 2D petri dish type cultures. in this study the effect of alginate hydrogel architecture was investigated by comparing rat bone marrow cell proliferation and differentiation on calcium cross linked sodium alginate discs and 1mm internal diameter tubes. It was found that bone marrow cell proliferation was diminished as the concentration of alginate in the 2D hydrogel substrates increased, yet proliferation was extensive on tubular alginate constructs with high alginate contents. Alginate gel thickness was found to be an important parameter in determining cell behaviour and the different geometries did not generate significant alterations in BMC differentiation profiles.     

海藻酸钙水凝胶/聚乳酸复合材料的制备与性能

通过化学发泡-冷冻干燥-粒子滤出复合法制备聚乳酸(PLLA)大孔支架, 然后在大孔内以海藻酸钠(SA)、碳酸钙、葡萄糖酸内酯(GDL)为原料, 通过原位相转变制备海藻酸钙水凝胶/聚乳酸复合材料(CA/PLLA); 分别利用SEM、压缩强度测试和细胞培养对CA/PLLA支架的形貌、力学性能及生物相容性进行了研究。结果表明: PLLA具有直径小于2 mm、孔道相互连通的孔洞, 且在大孔中能够形成均匀的CA。CA/PLLA复合材料的压缩强度(2.74 MPa)远大于单一的海藻酸钙水凝胶的压缩强度(0.10 MPa)。在CA/PLLA复合支架中, 软骨细胞呈簇状圆形生长状态, 与其在天然软骨陷窝里生长状态一致。这种软硬结合、天然与合成高分子杂化的CA/PLLA复合材料的力学强度和生物相容性同时得到提高, 可进一步作为骨和软骨修复材料研究。     

可按需释放抗生素并高效清除生物被膜的智能水凝胶

生物被膜相关感染在临床上的治疗难度极大,这是由于被包裹在被膜中的细菌对传统抗生素的抵抗力是浮游细菌的数十至数千倍.本文研究开发了一种由氨基糖苷类抗生素、果胶酶以及氧化葡聚糖组成的智能水凝胶,用于治疗与生物被膜相关的局部感染.氨基糖苷和果胶酶结构中的伯胺可与氧化葡聚糖的醛基形成对pH敏感的希夫碱键,从而形成凝胶.当发生感...     

Novel chitosan hydrogel formed by ethylene glycol chitosan, 1,6-diisocyanatohexan and polyethylene glycol-400 for tissue engineering scaffold: in vitro and in vivo evaluation

Traditional chitosan hydrogels were prepared by chemical or physical crosslinker, and both of the two kinds of hydrogels have their merits and demerits. In this study, researchers attempted to prepare one kind of chitosan hydrogel by slightly crosslinker, which could combine the advantages of the two kinds of hydrogels. In this experiment, the crosslinker was formed by a reaction between the isocyanate group of 1,6-diisocyanatohexan and the hydroxyl group of polyethylene glycol-400 (PEG-400), then the crosslinker reacted with the amidine and the hydroxyl group of ethylene glycol chitosan to form the network structure. Physical properties of the hydrogel were tested by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and biodegradation. Biocompatibility was assessed by cell implantation in vitro and the scaffold was used as a cartilage tissue engineering scaffold to repair a defect in rabbit knee joints in vivo. FTIR results show the formation of a covalent bond during thickening of the ethylene glycol chitosan. SEM and degradation experiments showed that the ethylene glycol chitosan hydrogel is a 3-D, porous, and degradable scaffold. The hydrogel contained 2 % ethylene glycol chitosan and 10 μl crosslinker was selected for the biocompatibility experiment in vitro and in vivo. After chondrocytes were cultured in the ethylene glycol chitosan hydrogel scaffold for 1 week cells exhibited clustered growth and had generated extracellular matrix on the scaffold in vitro. The results in vivo showed that hydrogel-chondrocytes promoted the repair of defect in rabbits. Based on these results, it could be concluded that ethylene glycol chitosan hydrogel is a scaffold with excellent physicochemical properties and it is a promising tissue engineering scaffold.     

Development of in situ-forming hydrogels for hemorrhage control

We report the preparation of in situ-forming hydrogels, composed of oxidized dextran (Odex) and amine-containing polymers, for their potential use as a wound dressing to promote blood clotting. Dextran was oxidized by sodium periodate to introduce aldehyde groups to form hydrogels, upon mixing in solution with different polymers containing primary amine groups, including polyallylamine (PAA), oligochitosan and glycol chitosan. A series of experiments were conducted to identify the optimum gelation condition for the Odex-PAA system. The polymer concentration appeared to have a major effect on gelation time and the polymer weight ratio affected the resulting gel content and swelling. Other influencing factors included pH of the buffer used to dissolve each polymer, PAA molecular weight, and the type of individual material. The latter also contributed significantly to gel content and swelling. Thromboelastography was used to examine the effects of the in situ gelation on blood coagulation in vitro, where the Odex-PAA combination was found to be most pro-hemostatic, as indicated by a decrease in clotting time and an increase in clot strength. The results of this study demonstrated that in situ-forming hydrogels could promote clotting in vitro; however, further studies are required to determine if the same hydrogel formulations are effective in controlling hemorrhage in vivo.     

Microcapsules for cell entrapment by template polymerization of a synthetic hydrogel coating around calcium alginate gel: preliminary development

Stable, water-soluble copolymers of glycidyl methacrylate with n-vinyl pyrrolidinone (I) were prepared by free-radical polymerization. Water-soluble copolymers of 2-hydroxyethyl methacrylate with methacrylic acid (II) were examined as co-reactants with (I) to form hydrogel matrices. Upon mixing of (I) and (II) in solution, a covalently crosslinked hydrogel was formed, presumably by etherification of epoxy functionality on (I) with hydroxyls on (II). Synthetic hydrogel-coated gel beads were prepared from an aqueous mixture of sodium alginate and (II) by treatment with solution containing (I) and calcium ion. An elastic, defect free and indefinitely stable covalently crosslinked hydrogel coating was formed around the calcium alginate by surface reaction of (I) and (II). Encapsulated guinea-pig red blood cells suffered minimal lysis over a 4 day period due to isolation and protection from the reacting species by the interior alginate gel matrix.     

Ⅰ型胶原/海藻酸钠/透明质酸复合水凝胶用于血管组织工程细胞负载与3D培养EI北大核心CSCD

胶原、海藻酸钠和透明质酸是天然来源的高分子材料,具有良好的细胞相容性与生物安全性,在细胞培养、组织工程、药物负载等方面具有广泛应用。单纯的胶原力学性能较差,将胶原与海藻酸钠制备成复合水凝胶材料后,可以通过调节海藻酸钠与Ca^(2+)交联程度来改变水凝胶支架的力学性能和孔隙率,模拟细胞培养的力学环境和细胞微环境。本研究通过PIUMA纳米压痕仪和DHR流变仪表征Ⅰ型胶原/海藻酸钠/透明质酸水凝胶的杨氏模量和溶胶-凝胶转变温度。并将内皮细胞与间充质干细胞在水凝胶微环境内进行3D培养,倒置荧光显微镜观察细胞培养0,3,5,7 d时细胞的活力情况,表征Ⅰ型胶原/海藻酸钠/透明质酸水凝胶的细胞相容性,并在内皮细胞与间充质干细胞培养0,1,4,6 d时,观察内皮细胞的迁移、成血管情况,在培养1,6,9 d时,观察内皮细胞的生长扩散情况。结果表明:水凝胶杨氏模量为(600±81)Pa,水凝胶的溶胶-凝胶转变温度为23.2℃。细胞培养0,3,5,7 d时,活力持续增强,培养4,6 d时,观测到共培养下内皮细胞的迁移,培养1,6,9 d时,水凝胶内的内皮细胞球体持续生长扩散。本工作表明,Ⅰ型胶原/海藻酸钠/透明质酸水凝胶对内皮细胞与间充质干细胞具有良好的细胞相容性,可用于细胞3D培养的理想支架材料。水凝胶的杨氏模量和溶胶-凝胶转变温度对细胞活力无损害,可作为研究血管新生的相关体外模型,在血管组织工程研究中具有重要的应用前景。     

PSY-g-PAA/APT/SA载药复合凝胶小球的制备及释药性能

采用离子凝胶法制备了欧车前胶-g-聚丙烯酸/凹凸棒黏土/海藻酸钠(PSY-g-PAA/APT/SA)载药复合凝胶小球,以双氯芬酸钠为模型药物,考察了pH敏感性和凹凸棒黏土含量对凝胶小球的包封率、载药率、溶胀性能和药物释放行为的影响。结果表明,当释放介质为模拟胃液(pH=1.2)时,药物基本不释放;而为模拟肠液(pH=6.8)时,5h后累积释放率超过90%,复合凝胶小球具有明显的pH敏感性。随着凝胶小球中凹凸棒黏土含量的增加,溶胀率和药物累积释放率均减小,表明凹凸棒黏土的引入可以减缓药物的突释效应。     

Coordinated Membrane Fusion of Proteinosomes by Contact‐Induced Hydrogel Self‐Healing

Controlled membrane fusion of proteinosome‐based protocells is achieved via a hydrogel‐mediated process involving dynamic covalent binding, self‐healing, and membrane reconfiguration at the contact interface. The rate of proteinosome fusion is dependent on dynamic Schiff base covalent interchange, and is accelerated in the presence of encapsulated glucose oxidase and glucose, or inhibited with cinnamyl aldehyde due to enzyme‐mediated decreases in pH or competitive covalent binding, respectively. The coordinated fusion of the proteinosomes leads to the concomitant transportation and redistribution of entrapped payloads such as DNA and dextran. Silica colloids with amino‐functionalized surfaces undergo partial fusion with the proteinosomes via a similar dynamic hydrogel‐mediated mechanism. Overall, the strategy provides opportunities for the development of interacting colloidal objects, control of collective behavior in soft matter microcompartmentalized systems, and increased complexity in synthetic protocell communities.     

可生物降解温敏凝胶PNMH-OSA的降解行为与释药性能

N-异丙基丙烯酰胺(NIPA)和丙烯酸甲酯(MA)通过自由基共聚形成线型大分子P(NIPA-MA),再用联胺取代MA嵌段上的甲氧基,得到一种多官能团的温敏大分子聚(N-异丙基丙烯酰胺-丙烯酸甲酯-丙烯酰肼)(PNMH),用它交联氧化的海藻酸钠(OSA),得到可生物降解的温敏凝胶PNMH-OSA。研究了PNMH的取代度(DS)、海藻酸钠的氧化程度(DO)、pH值和离子强度对PNMH-OSA凝胶降解性能的影响,同时以次甲基蓝(MB)和牛血清蛋白(BSA)为模拟药物,采用包埋法将药物载入凝胶中,研究了凝胶的释药行为。结果表明,凝胶降解速率随海藻酸钠的氧化程度、pH值增加而增加,随PNMH的取代度、离子强度增加而减慢;药物释放速率与药物的分子量和凝胶的降解速率有关。     

Cellulose-based hydrogels as body water retainers

In this work the possibility of using hydrogels as body water retainers for a therapeutic aid in pathologies such as oedemas of various origins was explored. For such a purpose, the material requires a good compatibility and a controlled swelling capacity without altering the body electrolyte homeostasis. The hydrogel was designed to meet the swelling requirements with the physiological constraints and its biocompatibility was assessed either in vitro or in vivo. Absorption tests were performed in order to define the swelling behavior by varying the pH and ion content of the external solution. The hydrogel swelling capacity was assessed in the presence of various solvents, in order to evaluate its absorption capacity in solutions similar to biological fluids. In addition, the capacity of the gel to modify electrolyte homeostasis by adsorbing ions such as calcium, potassium and sodium was tested. In order to assess the gel biocompatibility after contact of the hydrogel with intestinal cells, arachidonic acid relase was determined. No significant intracellular increase of free arachidonic acid was found in the cells after up to 2 h of contact with the gel. The results suggest that, as far as brief periods are concerned, the gel does not cause an inflammatory response in intestinal cells. ©2000 Kluwer Academic Publishers     

Sodium Alginate/Carboxyl-Functionalized Graphene Composite Hydrogel Via Neodymium Ions Coordination

A facile method for the preparation of sodium alginate(SA)/carboxyl-functionalized graphene(G-COOH)composite hydrogel was developed. Based on the coordination ability of lanthanide ions to the carboxyl groups, a series of hydrogel derived from different ratios of SA and G-COOH was fabricated by neodymium(Nd~(3+)) ions coordination. A relatively uniform layered structure was recorded by SEM at the interior of SA/G-COOH hydrogel. Several parameters such as water content, swelling ratio(SR), tensile test and solvent resistance were also investigated. The SA/G-COOH composite hydrogel showed excellent mechanical strength, and the tensile strength of SA/G-COOH composite hydrogel reaches 53.72 MPa at high water content. Due to the coordination ability of Nd~(3+) ions, the hydrogel also exhibited an excellent solvent resistance and stability.     

海藻酸钠-碳材料复合凝胶吸附水中污染物的研究进展

海藻酸钠的亲水性和其凝胶的三维网状结构赋予海藻酸钠水凝胶良好的吸附性能,成为处理水中污染物的理想吸附材料。碳材料如石墨烯、碳纳米管等因其具有较高的比表面积,常用于污染物的吸附,与海藻酸钠复合可进一步改善和丰富海藻酸钠凝胶的性能。针对海藻酸钠-碳材料复合凝胶吸附水中污染物的研究现状,以氧化石墨烯、碳纳米管和活性炭这3种碳材料为主线,简单总结了海藻酸钠-碳材料复合凝胶吸附水中污染物的研究进展,并提出需要解决的若干问题。