Polyamine-Polymeric Micelle Hybrid Hydrogel: Microscopic Properties of Crosslinkers Affecting Macroscopic Rheological Properties of Hydrogel

We have developed a hybrid hydrogel that is formed from a crosslinkable polymeric micelle and a polyamine. Under optimal conditions, the hydrogel rapidly formed in one second after a crosslinkable polymeric micelle solution was mixed with a polyamine solution. We could change the hydrogel’s gelation properties, such as the storage modulus and gelation time by tuning the molecular weights of block copolymers and by tuning the pH of the dissolving-solvent of the hydrogel’s constituent components. Furthermore, we have clarified here that the structural difference among the micelles acting as crosslinkers can affect the gelation properties of the hydrogel. According to our findings, the hydrogel that was formed from the polymeric micelles possessing a highly packed (i.e., well-entangled or crosslinked) inner core exhibited a higher storage modulus than the hydrogel that was formed from the polymeric micelles possessing a lowly packed structure. Our results demonstrate that a microscopic structural difference among crosslinkers can induce a macroscopic change in the properties of the resulting hydrogels. For medical applications, the hydrogel proposed in the present paper can encapsulate the hydrophobic compounds in crosslinkers (polymeric micelles) so that the hydrogel can be available as the biomaterial for their sustained release.

Detecting early changes in choroidal vascularity and thickness using optical coherence tomography in patients with corneal crosslinking for keratoconus

AIM:To investigate changes in choroidal thickness and vascularity in keratoconus patients treated with corneal crosslinking.METHODS:This study evaluated 28 eyes of 22 patients with keratoconus who underwent corneal crosslinking.The choroidal thicknesses were evaluated on enhanced depth imaging optical coherence tomography at the preoperative and postoperative 3d,1,and 3mo.Choroidal thickness in the four cardinal quadrants and the fovea were evaluated.The choroidal vascularity index was also calculated.RESULTS:There was no significant difference in central choroidal thickness between the preoperative and postoperative 3d,1mo(P>0.05).There was a significant increase in the 3mo(P=0.034)and a significant decrease in the horizontal choroidal vascularity index on the postoperative 3d(P=0.014),there was no statistically significant change in vertical axes and other visits in horizontal sections(P>0.05).CONCLUSION:This study sheds light on choroidal changes in postoperative corneal crosslinking for keratoconus.While it suggests the procedure’s relative safety for submacular choroid,more extensive research is necessary to confirm these findings and their clinical significance.

Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK:a case series

●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis(FS-LASIK).●METHODS:A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo.The lenticules were collected from patients undertaking small incision lenticule extraction(SMILE)for the correction of myopia.Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength.●RESULTS:All surgeries were conducted successfully with no significant complications.Their best corrected visual acuity(BCVA)ranged from 0.05 to 0.8-2 before surgery.The pre-operational total corneal thickness ranged from 345-404μm and maximum keratometry(Kmax)ranged from 50.8 to 86.3.After the combination surgery,both the corneal keratometry(range 55.9 to 92.8)and total corneal thickness(range 413-482μm)significantly increased.Four out of 5 patients had improvement of corneal biomechanical parameters(reflected by stiffness parameter A1 in Corvis ST).However,3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze.Despite the onset of corneal edema right after SLAK,the corneal topography and thickness generally stabilized after 3mo.●CONCLUSION:SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia.Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

3D打印中空管道双交联水凝胶组织工程支架

背景:在培养对结构、氧需求度较高的细胞时,需要构建一个具有中空管道结构的立体生物支架来保证细胞得到足够的营养与氧气。近年来,具有中空管道结构的水凝胶组织工程支架受到广泛关注。目的:以海藻酸钠为基础的生物支架材料结合同轴打印技术制备具有中空管道结构的组织工程支架,通过灌注方式接种细胞验证其生物相容性。方法:制备海藻酸钠-丙烯酰胺混合打印溶液,控制同轴打印过程中的内外层打印速度、海藻酸钠浓度、接收皿中氯化钙浓度等参数实现打印具有中空管道组织工程支架——海藻酸钠-聚丙烯酰胺双交联水凝胶,表征支架的微观形貌与弹性模量;将小鼠成纤维细胞灌注至组织工程支架中空管道内,利用活死细胞染色观察支架的细胞相容性。结果与结论:①通过探究打印过程中的打印参数,当内层打印速度不变时,中空管道的外径随着外层打印溶液的流速提升而提升,内径有略微提升;当外层打印溶液流速不变、内层溶液流速提升时,中空管道支架的外径基本不变,内径有明显提升;②实验结果显示海藻酸钠的最佳浓度为2.5%,过高的浓度不利于多层结构层与层之间的融合,过低的浓度制备出的水凝胶机械性能不足;③海藻酸钠-聚丙烯酰胺双交联水凝胶的弹性模量较高,普遍高于200 kPa,并且随着氯化钙浓度的提升而增大,在内层氯化钙浓度为2%、接收皿氯化钙浓度为0.3%时双交联水凝胶的弹性模量达到最大值(375 kPa);④组织工程支架灌注细胞体外培养后的活死细胞染色显示,细胞沿着中空管道轴向分布且具有较高的存活率,但细胞浓度小于灌注时的细胞浓度;⑤结果表明,海藻酸钠-聚丙烯酰胺双交联水凝胶具有较强的机械性能与良好的生物相容性,可应用在构建具有中空管道的组织工程支架中,并且“先制备支架、后接种细胞”的方式也避免了传统“细胞与打印溶液混合再进行制备”方式对支架材料及加工方式的限制。

交联透明质酸钠凝胶对近距离放射治疗中危及器官的隔离防护作用

背景:交联透明质酸钠凝胶具备良好的力学性能、生物相容性与降解性,可作为肿瘤放射治疗中的隔离防护材料,用于保护危及器官免受多余辐照剂量的损伤。目的:探究交联透明质酸钠凝胶在近距离放射治疗中减少危及器官受照剂量等方面的安全性及有效性。方法:取周龄相同、体质量相近的无特定病原体级昆明小鼠作为实验对象,共16只,采用随机数字表法分为实验组与对照组,每组8只。在实验组小鼠背部皮下植入125Ⅰ放射性粒子,随后环绕放射性粒子周边注射交联透明质酸钠凝胶,在对照组小鼠背部皮下仅植入125Ⅰ放射性粒子。注射完成后,采用螺旋CT扫描测量放射性粒子与表皮的距离,采用辐射剂量仪检测体表辐射剂量;注射后10周内,观察小鼠生长状态及存活率、皮肤放射损伤情况及凝胶存留量。结果与结论:①螺旋CT扫描显示植入的凝胶相对集中,并且使放射性粒子与表皮之间产生有效的间隔距离。实验组小鼠体表辐射剂量明显低于对照组(P<0.01)。②在实验观察期内,两组小鼠均存活,对照组小鼠在实验观察后期出现明显烦躁等不稳定表现,部分实验组小鼠出现类似行为;两组小鼠日摄食量无明显变化,体质量呈现相同的增长趋势。植入放射性粒子后两组小鼠均出现不同程度的放射性皮肤损伤,自注射后第23天开始至实验结束,实验组小鼠皮肤放射损伤评分均低于对照组(P<0.01)。植入后第10周,实验组6只小鼠皮下无明显凝胶残留,2只小鼠皮下存在极少量散在的凝胶状样品。③结果表明,注射交联透明质酸钠凝胶可通过物理占位作用增加125Ⅰ放射性粒子放射靶区和靶外危及器官的间隔空间,有效降低危及器官的受照剂量,对危及器官起到隔离防护作用。

Metal cation crosslinking of Ti O_2-alginate hybrid gels

In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation was applied for the preparation of hybrid gels while Ca2＋ Ce3＋ Ni2＋Cu2＋and Fe3＋were employed as the crosslinkers.Papain was selected as the model enzyme. UV-Vis spectroscopy was employed to investigate the activity of papain to evaluate kinetics and stability.Analysis results show that the highest affinity the lowest Michaelis-Menten constant Km =11.0 mg/mL and the highest stability are obtained when using Cu2＋as the crosslinker.The effect of the mass ratio of TiO2 to papain on the stability and leakage of papain is also investigated and the results show that 10∶1 TiO2∶papain is optimal because the proper use of TiO2 can reduce enzyme leakage and ensure enzyme stability.Preparing Cu/alginate/TiO2 hybrid gels via ionotropic gelation can provide a satisfactory diffusion capability and enzyme stability.

Study on Tribological Properties of Irradiated Crosslinking UHMWPE Nano-Composite

Ultra High Molecular Weight Polyethylene(UHMWPE)has been widely used as a bearing material for artificial joint replacement over forty years.It is usually crosslinked by gamma rays irradiation before its implantation into human body.In this study,UHMWPE and UHMWPE/nano-hydroxyapatite(n-HA)composite were prepared by vacuum hot-pressing method.The prepared materials were irradiated by gamma rays in vacuum and molten heat treated in vacuum just after irradiation.The effect of filling n-HA with gamma irradiation on tribological properties of UHMWPE was investigated by using friction and wear experimental machine(model MM-200)under deionized water lubrication.Micro-morphology of worn surface was observed by metallographic microscope.Contact angle and hardness of the materials were also measured.The results show that contact angle and hardness are changed by filling n-HA and gamma irradiation.Friction coefficient and wear rate under deionized water lubrication are reduced by filling n-HA.While friction coefficient is increased and wear rate is reduced significantly by gamma irradiation.The worn surface of unfilled material is mainly characterized as adhesive wear and abrasive wear,and that of n-HA filled material is mainly characterized as abrasive wear.After gamma irradiation,the degrees of adhesive and abrasive wear for unfilled material and abrasive wear of n-HA filled material are significantly reduced.Unfilled and filled materials after irradiation are mainly shown as slight fatigue wear.The results indicate that UHMWPE and UHMWPE/n-HA irradiated at the dose of 150 kGy can be used as bearing materials in artificial joints for its excellent wear resistance compared to original UHMWPE.

Procyanidins Inhibit Tumor Angiogenesis by Crosslinking Extracellular Matrix

Objective： Procyanidins （PC） are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix （ECM） and preventing proteolysis by matrix metalloproteinases （MMPs）. Methods： Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. Results： PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC （0.75-100 μg/mL） did not inhibit vascular and tumor cells proliferation. PC injections （30 mg PC/kg bodyweight） in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. Conclusion： The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.

Crosslinked P84 copolyimide/MXene mixed matrix membrane with excellent solvent resistance and permselectivity

MXene is a novel 2D lamellar material with excellent hydrophilicity and permselectivity. MXene was introduced in the P84 polymer matrix and the matrix was crosslinked with triethylenetetramine(TETA) to improve the permselectivity and solvent resistance of the polyimide membrane. The membrane was characterized with SEM, AFM and ATR-FTIR, and effects of MXene content on the membrane morphology and separation performance are investigated. The membrane prepared with 18% P84 and 1% MXene shows high rejection(100%) to gentian violet(408) and high flux(268 L·m^-2·h^-1) at 0.1 MPa and ambient temperature. MXene endows the membrane with much water channel and denser functional layer which improves the membrane performance obviously. The membrane shows excellent solvent resistance to dimethylformamide(DMF), acetone and methanol after crosslinking with TETA during the 18 days of immersion.

Corneal collagen crosslinking for corneal ectasia of post-LASIK: one-year results

AIM: To evaluate the efficacy and safety of corneal collagen crosslinking (01) to prevent the progression of post-laser in situ keratomileusis (LASIK) corneal ectasia. METHODS: In a prospective, nonrandomized, single-centre study, CXL was performed in 20 eyes of 11 patients who had LASIK for myopic astigmatism and subsequently developed keratectasia. The procedure included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation. The eyes were evaluated preoperatively and at 1-, 3-, 6-, and 12-month intervals. The complete ophthalmologic examination comprised uncorrected visual acuity, best spectacle-corrected visual acuity, endothelial cell count, ultrasound pachymetry, corneal topography, and in vivo confocal microscopy. RESULTS: CXL appeared to stabilise or partially reverse the progression of post-LASIK corneal ectasia without apparent complication in our cohort. UCVA and BCVA improvements were statistically significant (P<0.05)beyond 12 months after surgery (improvement of 0.07 and 0.13 logMAR at 1 year, respectively). Mean baseline flattest meridian keratometry and mean steepest meridian keratometry reduction (improvement of 2.00 and 1.50 diopters (D), respectively) were statistically significant (P < 0.05) at 12 months postoperatively. At 1 year after 01, mean endothelial cell count did not deteriorate. Mean thinnest cornea pachymetry increased significantly. CONCLUSION: The results of the study showed a long-term stability of post-LASIK corneal ectasia after crosslinking without relevant side effects. It seems to be a safe and promising procedure to stop the progression of post-LASIK keratectasia, thereby avoiding or delaying keratoplasty.

COORDINATION CROSSLINKING OF NITRILE RUBBER FILLED WITH COPPER SULFATE PARTICLES

By incorporating copper sulfate （CuSO4） particles into acrylonitrile butadiene rubber （NBR） followed by heat pressing, a novel vulcanization method is developed in rubber through the formation of coordination crosslinking. This method totally differs from traditional covalent or non-covalent vulcanization approaches of rubber. No other vulcanizing agent or additional additive is involved in this process. By analyzing the results of DMA, XPS and FT-IR, it is found that the crosslinking of CuSO4 particles filled NBR was induced by in situ coordination between nitrogen atoms of nitrile groups （-CN） and copper ions （Cu^2＋） from CuSO4. SEM and EDX results revealed the generation of a core （CuSO4 solid particle）- shell （adherent NBR） structure, which leads to a result that the crosslinked rubber has excellent mechanical properties. Moreover, poly（vinyl chloride） （PVC） and liquid acrylonitrile-butadiene rubber （LNBR） were used as mobilizer to improve the coordination crosslinking of CuSO4/NBR. The addition of PVC or LNBR could lead to higher crosslink density and better mechanical properties of coordination vulcanization. In addition, crystal water in CuSO4 played a positive role to coordination crosslinking of rubber because it decreased the metal point of CuSO4 and promoted the metal ionization.

Effect of Crosslink Structure of Bridge Polycarboxylate Superplasticizers on Dispersion Ability

Bridge polycarboxylate superplasticizers（PCs） with crosslink structure were synthesized by using polyethyleneglycol di-acrylate（PEGdA）, replacing partial polyethyleneglycol mono-acrylate （PEGmA） as crosslinking agent. Structures of bridge PCs were analyzed by gel permeation chromatography, and dispersion ability was evaluated by cement paste dispersity variation on time and rheology test. The experimental results showed that, molecular weight（MW） of bridge PCs increased with increase of PEGdA proportion, and MW distribution curve changed from Gaussian to fiat like, which meant notable increase of highly crosslinked copolymer. Bridge PCs led to decreased initial cement paste dispersity and better dispersity retention due to slow releasing. Further research showed that, PEGdA proportion had slight effect on polymerization degree of backbone, MW distribution of backbone deviated from Gaussian distribution and shoulder peaks appeared on distribution curve when PEGdA increased.

Fabrication of high-performance PVA/PAN composite pervaporation membranes crosslinked by PMDA for wastewater desalination

The pyromellitic dianhydride（PMDA） crosslinked poly（vinyl alcohol）（PVA） was coated on top of the PAN ultrafiltration membrane to form a PVA/PAN composite PV membranes for wastewater desalination. The composite membranes have high application value in industrial wastewater treatment. By varying the membrane fabrication parameters including the weight percent（wt%） of the PMDA, the crosslink temperature and duration, membrane with the best desalination performance was obtained. The composite membrane with a 2-lm-thick PVA selective layer containing 20 wt% of PMDA and being crosslinked at 100 °C for 2 h showed the highest Na Cl rejection of 99.98% with a water flux of 32.26 L/（m^2 h）at 70 °C using the 35,000 ppm Na Cl aqueous solution as feed. FTIR spectroscopy, wide-angle X-ray diffraction, thermogravimetric analysis and scanning electron microscope have been used to characterize the structures and properties of both the crosslinked PVA dense films and PVA/PAN composite membranes. The effects of the concentrations of PMDA,the crosslinking time and temperature to the membrane water contact angle, swelling degree, salt rejection and water flux were systematically studied.

CHARACTERIZATION OF RADIATION CROSSLINKING DENSITY OF F-40

In this paper, radiation-induced crosslinking mechanism and characterization of the crosslinking density of F-40 and F-4 by X-ray photoelectron spectroscopy （XPS） have been studied. The dose of gelation of F-40 obtained from XPS is 4.1×10;Gy. It is found that crosslinking density is the largest in the range of certain dose for F-40 and F-4.

Evaluation of the in vitro antimicrobial properties of ultraviolet A/riboflavin mediated crosslinking on Candida albicans and Fusarium solani

AIMTo evaluate the antimicrobial properties of ultraviolet A (UVA) (365 nm)/riboflavin against Candida albicans and Fusarium solani.

Allyl-containing Poly(aryl ether sulfone): Synthesis and Crosslinking

A novel type of crosslinkable poly（aryl ether sulfone）（PAES） bearing an allyl pendant（PES-OAllyl） was synthesized by a grafting reaction of hydrophenyl-containing PAES（PES-OH） and allyl bromide. PES-OH was prepared by a demethylation reaction of a methoxyphenylated PAES（PES-OCH3） in the presence of pyridine/hydrochlo- ride. The PES-OCH3 was synthesized by an aromatic nucleophilic substitution of bis（4-chlorophenyl）sulfone and （p-methoxy）phenylhydroquinone. Both DSC and solubility investigation were used to study the crosslinking behavior of PES-OAllyl. After heat treatment, the glass transition temperature（Tg） value of PES-OAllyl sharply increased from 165 ℃ to 227 ℃. Meanwhile, PES-OAllyl changed from a soluble polymer to an insoluble thermoset. In addition, TGA（thermogravimetric analysis） result suggests that the thermal stability of the crosslinked product was improved. All the data prove that the crosslinked PES-OAllyl could be a potential solvent-resistance high-performance material.

Impact of crosslinking/riboflavin-UVA-photodynamic inactivation on viability,apoptosis and activation of human keratocytes in vitro

Riboflavin-UVA photodynamic inactivation is a potential treatment altemative in therapy resistant infectious keratitis. The purpose of our study was to determine the impact of riboflavin-UVA photodynamic inactivation on viability, apop- tosis and activation of human keratocytes in vitro. Primary human keratocytes were isolated from human corneal buttons and cultured in DMEM/Ham＇s F12 medium supplemented with 10% fetal calf serum. Keratocytes underwent UVA light illumination （375 nm） for 4.10 minutes （2 J/cm2） during exposure to different concentrations of riboflavin. Twenty-four hours after treatment, cell viability was evaluated photometrically, whereas apoptosis, CD34 and alpha-smooth muscle actin （α-SMA） expression were assessed using flow cytometry. We did not detect significant changes in cell viability, apoptosis, CD34 and α-SMA expression in groups only treated with riboflavin or UVA light. In the group treated with riboflavin-UVA-photodynamic inactivation, viability of keratocytes decreased significantly at 0.1% riboflavin （P〈0.01） while the percentage of CD34 （P〈0.01 for both 0.05% and 0.1% riboflavin） and alpha-SMA positive keratocytes （P〈0.01 and P〈0.05 for 0.05% and 0.1% riboflavin, respectively） increased significantly compared to the controls. There was no significant change in the percentage of apoptotic keratocytes compared to controls at any of the used ribo- flavin concentrations （P=0.09 and P=0.13）. We concluded that riboflavin-UVA-photodynamic-inactivation decreases viability of myofibroblastic transformation and multipotent haematopoietic stem cell transformation; however, it does not have an impact on apoptosis of human keratocytes in vitro.

PREPARATION OF MONODISPERSE CROSSLINKED POLYMER MICROSPHERES HAVING CHLOROMETHYL GROUP BY DISTILLATIONPRECIPITATION POLYMERIZATION

Monodisperse crosslinked poly(chloromethylstyrene-co-divinylbenzene)(poly(CMSt-co-DVB))microsphereswere prepared by distillation-precipitation copolymerization of chloromethylstyrene(CMSt)and divinylbenzene(DVB)inneat acetonitrile.The polymer particles had clean surfaces due to the absence of any added stabilizer.The size of the particlesranges from 2.59 μm to 3.19 μm and with mono-dispersity around 1.002-1.014.The effects of monomer feed incopolymerization on the microsphere formation were described.The polymer microspheres were characterized by SEM andchlorinity elemental analysis.

SYNTHESIS, CROSSLINKING MECHANISM AND PROPERTIES OF A POLYACRYLATE/POLYURETHANE COMPOSITE COATING

A polyacrylate/polyurethane (P(A)/P(U)) composite coating has been prepared by crosslinking an acetoacetylated polyacrylate with a vinylic group terminated polyurethane at room temperature. A model Michael reaction between ethyl acetoacetate (EAA) and methyl acrylate (MA) was designed to study the crosslinking mechanism. It was found that the two active hydrogen atoms in acetoacetyl group can both add to vinylic groups and the yield of mono-and bis-adducts are much affected by the molar ratio of acetoacetyl to vinylic groups. Higher crosslinking degree and better properties could be obtained with decreasing the molar ratio of the two active groups from 1/1 to 0.6/1 in the composite coatings.

Preparation and Dyeing Performance of a Novel Crosslinking Polymeric Dye Containing Flavone Moiety

A yellow crosslinking polymeric dye was prepared by grafting the flavone moiety containing azo chromophore onto polyvinylamine backbone.The λ max of this polymeric dye in water is 382 nm.The polymeric dye is fixed to silk and cotton with a crosslinking agent,2-chloro-4,6-di(aminobenzene-4'-β-sulphatoethylsulphone)-1,3,5-s-triazine,which acts as a bridge between the fiber and dye molecules.The fixation of this polymeric dye reaches 99% and the dyed samples exhibit excellent rubbing and washing fastness.