Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.

Synthesis of the Biomimetic Polymer: Aliphatic Diamine and RGDS Modified Poly(d,l-lactic acid)

A novel poly（d, /-lactic acid） （PDLLA） based biomimetic polymer was synthesized by grafting maleic anhydride, butanediamine and arg-gly-asp-ser （RGDS） peptides onto the backbone of PDLLA, aiming to overcome the acidity and auto-accelerating degradation of PDLLA during degradation and to improve its biospecificity and biocompatibility. The synthetic copolymer was characterized by FTIR, ^13C NMR and amino acid analyzer （AAA）.

Preparation and Properties of Bio-Based Flame Retardant L-APP/Poly(L-lactic acid)Composites

Poly(L-lactic acid)(PLLA)is a thermoplastic material with complete degradability,high biocompatibility and excellent mechanical properties.It can replace petroleum-based polymers are currently being used in the fields of packaging,agriculture,textiles,medical and so on.However,PLLA’s extremely flammability greatly limits its wider application.An bio-based flame retardant L-APP/PLLA composites was prepared by melt blending of the L-APP and PLLA.The morphology,impact properties,thermal properties and flame retardant properties of composites were investigated by field emission scanning electron microscope(SEM),impact tester,differential scanning calorimeter(DSC),thermogravimetric analyzer(TGA),limiting oxygen indexer(LOI)and horizontalvertical burning tester.The results showed that the degree of crystallization(X_(c))and LOI of L-APP/PLLA composites increased as increasing of L-APP content.What’s more,the impact strength first increased and then decreased,the glass transition temperature(T_(g))and melting temperature(T_(m))do not changed significantly.The impact strength of composites was 9.1 kJ/m^(2) at a 5 wt%loading for L-APP,which was the highest level.When the content of L-APP was 20%,the LOI was 30.8%,the Xc was 42.3%and the UL-94 level was V-0.This research can promote the value-added utilization of lignin and the application of PLLA in the fields of flame retardant materials.

Synthesis and Characterization of Chitosan-g-poly- (D, L-lactic acid) Copolymer

Biodegradable chitosan-g-poly (D, L-lactic acid) copolymers were prepared via two methods. (1) The lactide was grafted onto hydroxyl groups of chitosan by using macromolecular initiator sodium of trimethylsilyl-chitosan, (2) poly (D,L-lactic acid)(PLA) with low molecular weight can be linked to the amino group by coupling activated PLA to trimethylsilyl-chitosan. Two graft copolymers had hydrophilic-hydrophobic character and can be applied as carriers for drug delivery.

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly（D,L-lactide-co-glycolic acid） has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly（D,L-lactide-co-glycolic acid） into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced ceils prus the poly（O,L-lactide-co-glycolic acid） scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly（D,L-lactide-co-glycolic acid） scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.

SURFACE OF GELATIN MODIFIED POLY(L-LACTIC ACID)FILM

In this paper, the surface structure of poly(L-lactic acid) (PLLA) film modified with gelatin was investigated. ThePLLA film specimens were treated directly with aqueous alkali solution to provide their surfaces with carboxyl groups, sothat these functional groups could become the reactive sites for gelatin immobilization. The functional groups of the PLLAfilms were identified by ATR-FTIR spectra and XPS spectra, the changes in surface morphology were observed by usingenvironmental scanning electron microscopy (ESEM), and the hydrophilicity of modified PLLA films was examined bywater contact angle measurement. Experimental results showed that the gelatin was immobilized with water-solublecarbodiimide (EDC) onto the PLLA film's surfaces, and the gelatin content on the polymer surface was related to carboxylicgroup formed in the controlled hydrolysis process. Rough surfaces caused by hydrolysis will predominantly favor the adhesion and growth of cell; and the hydrophilicity of these surfaces after the modification procedure is enhanced.

Design,synthesis and characterization of novel biodegradable macrodiols based on poly(DL-lactic acid) and poly(p-dioxanone)

Integrating poly（lactic acid） （PLA）, glycolic acid （GA） and ethylene glycol （EG） will hopefully result in a novel copolymer that combines such advantages as fastened and controllable release rate and improved flexibility together with good biocompatibility. In this study, p-dioxanone （PDO） was employed to copolymerize with DL-lactide （LA） via ring-opening melt polymerization using Sn（Oct）2 as an initiator and ethylene glycol as a co-initiator. The obtained degradable macrodiols （HO-P（LA-co-PDO）-OH） were just such a copolymer consisting of PLA, GA and EG. 1HNMR was employed to characterize the copolymers, and the effect of PDO/LA molar ratios in the feedstock on the molecular weights of HO-P（LA-co-PDO）-OH was investigated by means of endhydroxyl analysis, 1H NMR or GPC-MALLs. The results confirmed the successful synthesis of HO-P（LA-co-PDO）-OH and revealed that one end-hydroxyl of the micarodiols was donated by LA or PDO and the other one by the co-initiator EG. In addition, the molecular weights of HO-P（LA-co-PDO）-OH increased with decreasing PDO/LA ratios.

Melt Synthesis and Characterization of Poly(L-lactic Acid) Chain Linked by Multifunctional Epoxy Compound

High molecular weight（Mw） poly（L-lactic acid）s（PLLAs） were synthesized using multifunctional epoxy compound（Joncryl-ADR4370） as chain extender. The products were characterized by gel permeation chromatography（GPC） and spectroscopy（1HNMR and FTIR）. The results indicated that the Mw of PLLA increased with the increasing of the ratio of epoxy compound and the extending of reaction time. The highest Mw of PLLA reached 360 000 g/mol when the ratio of epoxy compound was 1.5 wt%. However, the reactants turned to cross-linking when the ratio of epoxy compound was over 1.5 wt%. Differential scanning calorimetry（DSC） measurements demonstrated that the glass transition（Tg） and melting temperatures（Tm） of products increased slightly as the increase of the molecular weight. Analysis of the hydrolytic degradation in vitro showed that the branched PLLA possessed the quicker degradability than that of the linear PLLA.

Effect of a Novel Nucleating Agent on Isothermal Crystallization of Poly（L-lactic acid）

The effect of a novel active nucleating agent(TBC8-eb) on the isothermal crystallization of poly(L-lactic acid) (PLLA) was studied by differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR) . The analysis on kinetics demonstrates that TBC8-eb can not only accelerate the crystallization rate but also transform most of the original spherulite crystals of PLLA into sheaf-like crystals. Furthermore,the free energy of folding(σe) of PLLA and PLLA with TBC8-eb is 0.15 and 0.06 J·m-2,respectively,which suggests that the addition of TBC8-eb favors the regular folding of molecule chains in the crystallization of PLLA,improv-ing its crystallization rate. The FTIR results show that TBC8-eb can accelerate the conformational ordering of PLLA in the isothermal crystallization. The conformational ordering of PLLA nucleated with TBC8-eb begins with the interchain interaction of CH3,and then a short helix emerges where a couple of CH3 groups interact.

Synthesis and Characterization of a Novel Biomaterial: Maleic Anhydride-modified Poly(dl-lactic acid)

A novel modified poly(dl-lactic acid) (PDLLA) was obtained by covalently grafting of maleic anhydride onto the backbone of PDLLA, attempting to improve PDLLA’s hydrophilicity and cell affinity and to provide reactive groups for further chemical modification. FTIR, 13C NMR and DSC were used to characterize the maleic anhydride-modified PDLLA.

Multi-porous electroactive poly(L-lactic acid)/ polypyrrole composite micro/nano fibrous scaffolds promote neurite outgrowth in PC12 cells

In this study, poly（L-lactic acid）/ammonium persulfate doped-polypyrrole composite fibrous scaffolds with moderate conductivity were produced by combining electrospinning with in situ polymerization. PC12 cells were cultured on these fibrous scaffolds and their growth following electrical stimulation （0-20.0 μA stimulus intensity, for 1-4 days） was observed using inverted light microscopy, and scanning electron microscopy coupled with the MTT cell viability test. The results demonstrated that the poly（L-lactic acid）/ammonium persulfate doped-polypyrrole fibrous scaffold was a dual multi-porous micro/nano fibrous scaffold. An electrical stimulation with a current intensity 5.0- 10.0 μAfor about 2 days enhanced neuronal growth and neurite outgrowth, while a high current intensity （over 15.0 μA） suppressed them. These results indicate that electrical stimulation with a moderate current intensity for an optimum time frame can promote neuronal growth and neurite outgrowth in an intensity- and time-dependent manner.

Composite Biomaterials Based on Poly(L-Lactic Acid)and Functionalized Cellulose Nanocrystals

The biocomposite films were prepared from poly(L-lactic acid)and cellulose nanocrystals.To improve interfacial compatibility of hydrophilic cellulose nanocrystals with hydrophobic matrix polymer as well as to provide the osteoconductive properties,cellulose was functionalized with poly(glutamic acid).The modified cellulose nanocrystals were better distributed and less aggregated within the matrix,which was testified by scanning electron,optical and polarized light microscopy.According to mechanical tests,composites filled with nanocrystals modified with PGlu demonstrated higher values of Young’s modulus,elongation at break and tensile strength.Incubation of composite materials in model buffer solutions for 30 weeks followed with staining of Ca^(2+)deposits with Alizarin Red S assay testified better mineralization of materials containing PGlu-modified cellulose nanocrystals as filler.As the result of in vivo experiment,the developed composite materials showed less level of inflammation in comparison with pure polymer matrix and composites filled with non-functionalized cellulose nanocrystals.

Sorption and Diffusion Behavior of Carbon Dioxide into Poly（l-lactic acid） Films at Elevated Pressures

Equilibrium sorption amount, desorption diffusion coefficients and sorption diffusion coefficients of CO2 in poly(l-lactic acid)(PLLA) films at elevated pressures were determined by the gravimetric method, in which the Fick's diffusion model was applied to analyze both the desorption and sorption processes. The equilibrium sorption amount of CO2 in PLLA increased with lowering temperature and elevating pressure at the temperature range from 40 to 60 °C and pressure from 104to 2×104kPa. Desorption diffusion coefficients were greatly influenced by the equilibrium sorption amount, and they were in the same order of magnitude as the sorption diffusion coefficients. The scan electron microscope(SEM) photos demonstrated that there was no foaming phenomenon of the PLLA film during desorption and sorption processes. The XRD spectra implied that the crystalline degree of PLLA film decreased after CO2 processing. It was concluded that PLLA polymer could be well swollen and plasticized by supercritical CO2.

High-performance and robust high-temperature polymer electrolyte membranes with moderate microphase separation by implementation of terphenyl-based polymers

Acid loss and plasticization of phosphoric acid(PA)-doped high-temperature polymer electrolyte membranes(HT-PEMs)are critical limitations to their practical application in fuel cells.To overcome these barriers,poly(terphenyl piperidinium)s constructed from the m-and p-isomers of terphenyl were synthesized to regulate the microstructure of the membrane.Highly rigid p-terphenyl units prompt the formation of moderate PA aggregates,where the ion-pair interaction between piperidinium and biphosphate is reinforced,leading to a reduction in the plasticizing effect.As a result,there are trade-offs between the proton conductivity,mechanical strength,and PA retention of the membranes with varied m/p-isomer ratios.The designed PA-doped PTP-20m membrane exhibits superior ionic conductivity,good mechanical strength,and excellent PA retention over a wide range of temperature(80–160°C)as well as satisfactory resistance to harsh accelerated aging tests.As a result,the membrane presents a desirable combination of performance(1.462 W cm^(-2) under the H_(2)/O_(2)condition,which is 1.5 times higher than that of PBI-based membrane)and durability(300 h at 160°C and 0.2 A cm^(-2))in the fuel cell.The results of this study provide new insights that will guide molecular design from the perspective of microstructure to improve the performance and robustness of HT-PEMs.

In vitro Degradation of Butanediamine-Grafted Poly(DL-Lactic acids)

The degradation of butanediamine-grafted poly（DL-lactic acid） polymers （BDPLAs） in vitro together with PDLLA and maleic anhydride-grafted poly（DL-lactic acid） polymers （MPLAs） was investigated by observation of the changes of the pH value of incubation media, and weight loss ratio during degradation duration of 12 weeks. The results reveal that the acidity of PDLLA degradation products was weakened or neutralized by grafting butanediamine onto PDLLA. A uniform degradation of BDPLAs was observed in comparison with an acidity-induced auto-accelerating degradation featured by PDLLA and MPLAs. The biodegradation behaviors of BDPLAs can be adjusted by controlling the content of BDA. BDPLAs might be a new derivative of PDLLA-based biodegradable materials for medical applications without acidity-caused irritations and acidity-induced auto-accelerating degradation behavior as that of PDLLA.

Preparation of Poly ( L-lactic acid ) / Vermiculites Composites by in situ Copolymerization of Lactic Acid and Hydroxylic Vermiculites

L-lactic acid (L-LA) based copolymer/hydroxylation vermiculites composites (PLLA-co-bis A/HVMTs) were prepared by in situ reaction among L-LA, adipic acid, and hydroxylation lamellar vermiculites (HVMTs) using bisphenol-A epoxy resin as chain extending agent. HVMTs were obtained by sulfuric acid-leaching of lamellar vermiculites (VMTs). The effects of sulfuric acid leaching on the VMTs structure were characterized by X-ray diffraction (XRD), 29Si magic-angle spinning nuclear magnetic resonance(29Si NMR), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). FTIR, FE-SEM, and TGA were used to characterize the reaction activity of HVMTs. The results indicated that VMTs with increased hydroxyl groups had been successfully obtained and could react with -COOH of the reaction system. The amount of L-LA based copolymer grafted on the surface of HVMTs was more than 22%. The onset decomposition temperature of L-LA based copolymer grafted on the surface of HVMTs was 30℃ higher than that of free L-LA based copolymer.

Biomechanical features of Poly-D,L-lactic acid (PDLLA) rods through the degradation in vitro and in vivo

Objective:To observe the changing of biomechanical features during the degradation course of poly-D,L-lactic acid (PDLLA) rods in vivo and in vitro and to evaluate its value as an internal fixation material. Methods:PDLLA rods were emerged into PBS simultaneous body fluid with constant temperature of 37 C and the rods were embedded into muscle tissue of 20 rabbits for degradation in vitro and in vivo . The rods were taken out in 2, 4, 6. 8 and 12 weeks. Biomechanical features of bending, shearing and axial compression strength, rigidity and elastic modulus were observed during the degradation course. Statistical method was used to test the changes of biomechanical parameters. Results: (1) There was similar changes of bending, compressive, shearing strength and bending, compressive and shearing rigidity of the PDLLA rods between in vivo and in vitro. (2)Bending, compressive, shearing strength decreased 33%, 18% and 43% respectively within the first stage of the degradation, and after 6 weeks of degradation, they decreased slowly. (3)Elastic modulus, bending, compressive and shearing rigidity.decreased sharply during the 6 weeks of degradation, with a drop of 22% , 39% and 30% respectively, and after 8 weeks, they decreased slowly. Even after 12 weeks of degradation, the strength of the rods was still higher than that of sponge bone. Conclusion: During the degradation of the material, the strength and rigidity of PDLLA rods can meet the need of fracture fixation of cancellous bones.