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）.

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.

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.

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.

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.

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.

Superior Toughened Biodegradable Poly(L-lactic acid)-based Blends with Enhanced Melt Strength and Excellent Low-temperature Toughness via In situ Reaction Compatibilization

The toughened poly(L-lactic acid)/poly(butylene succinate-butylene terephthalate)(PLLA/PBST) blend with enhanced melt strength and excellent low temperature toughness and strength was prepared by melt compounding through in situ compatibilization reaction in presence of multifunctional epoxy compound(ADR).The PLLA/PBST blend was an immiscible system,and the compatibility of the PLLA/PBST blend was improved after adding ADR.FTIR and GPC curves confirmed the formation of the PLLA-g-PBST copolymer,which improved the interfacial bonding of the blend and therefore the PLLA/PBST/ADR blend showed excellent melt strength and mechanical properties.For the PLLA/PBST/ADR blend with 70/30 PLLA/PBST content,the complex viscosity increased significantly with increasing ADR content.Moreover,the tensile strength,elongation at break and impact strength all increased obviously with increasing the ADR content.The elongation at break of the blend reached the maximum value of 392.7%,which was 93.2 times that of neat PLLA.And the impact strength of the blend reached the maximum value of 74.7 k J/m~2,which was 21.3 times that of neat PLLA.Interestingly,the PLLA/PBST/ADR blend exhibited excellent lowtemperature toughness and strength.At –20 ℃,the elongation at break of the PLLA/PBST/ADR blend was as high as 93.2%,and the impact strength reached 18.8 k J/m~2.Meanwhile,the tensile strength of the blend at low temperature was also high(64.7 MPa),which was beneficial to the application of PLA in the low temperature field.In addition,the PLLA/PBST/ADR blend maintaind good biodegradability,which was of great significance to the wide application of PLLA.

Microwave-assisted Polymerization of D,L-Lactide with Stannous Octanoate as Catalyst

Poly (lactic acid) (PLA) was synthesized by microwave-assisted ring-opening polymerization of D, L-lactide with stannous octanoate (SnOct(2)) as catalyst. Its weight-average molar mass (M-w) ranged from 39000 to 67000 and the polydispersity index from 1.3 to 1.7. The polymerization rate was much faster than that of the conventional thermal polymerization. A degradation of newly formed PLA in reaction mixture by microwave irradiation was observed.

Preparation and Degradation Characteristics of Poly(d,1-laetide) Composite Films

PDLLA/CHI/β-TCP/NGF composite films were prepared by a solvent evaporation method. The degradation characteristics of the poly （d, l-lactide） composite films were studied in vitro and in vivo. The acidity produced by poly （d, l-lactide） materials was not obvious. Adding chitosan and β-TCP can relieve the acidity problem and improve strength performance of films. The NGF has influences on the degradation characteristics of films. It is verified that PDLLA/CHI/β-TCP/NGF composite films prepared by solvent evaporation method have excellent degradation characteristics. It can be used as a perfect biomaterial for repairing nerve injuries.

Biocorrosion resistance and biocompatibility of Mg-AI layered double hydroxide/poly(L-lactic acid) hybrid coating on magnesium alloy AZ31

A Mg-AI layered double hydroxide(Mg-AI-LDH)coating was firstly synthesized via an in-situ steam coating growth method on the AZ31 Mg alloy,and then was modified with poly(L-lactic acid)(PLLA)via dipping and vacuum freeze-drying.The microstructure and composition of LDH/PLLA hybrid coating were analyzed by XRD,SEM,EDS and FT-IR.The biocorrosion behavior of hybrid coating was evaluated by potentiodynamic polarization,electrochemical impedance spectroscopy(EIS)and hydrogen evolution test in the Hank's solution.The results showed that LDH/PLLA coatings exhibited a much dense layer compared to the unmodified Mg-AI-LDH coating with unobvious boundary between PLLA and LDH coatings.The corrosion current density of the LDH/PLLA-10 hybrid coating decreased three orders of magnitude in comparison to its substrate.It was proven that the existence of the PLLA coating further prolonged the service life of the Mg-AI-LDH coating.What's more,the MTT assay and livel dead staining showed that the LDH/PLL A-10 coating had good biocompatibility for Mouse NIH3T3 fibroblasts.The formation mechanism and the anti-corrosion mechanism of hybrid coatings were proposed.

PREPARATION AND CHARACTERIZATION OF ELECTROSPUN FIBERS BASED ON POLY(L-LACTIC ACID)/CELLULOSE ACETATE

PLLA/CA mixtures of different compositions were successfully electrospun to obtain composite nanofibrous membranes. The microstructures of the membrances changed from homogeneous to heterogeneous with the addition of CA, which was observed by FE-ESEM. The PLLA/CA fabric membranes were characterized by mechanical testing, DSC and contact angle measurements. The tensile stress of the composite fibrous membranes increased obviously with the increase of CA content. DSC results indicated that the CA component was the main factor for the changes of enthalpies in the composite fibers. Contact angle measurements showed the hydrophilicity of the electrospun nanofiber membranes was improved with the addition of CA.

Replicated Banded Spherulite:Microscopic Lamellar-assembly of Poly(L-lactic acid)Crystals in the Poly(oxymethylene)Crystal Framework

The morphologies of poly（L-lactic acid） （PLLA） spherulites, when crystallized within the pre-existed poly（oxymethylene） （POM） crystal frameworks, have been investigated. PLLA/POM blend is a melt-miscible crystalline/crystalline blend system. Owing to the lower melting point but much faster crystallization rate than PLEA, POM crystallized first upon cooling from the melt state and then melted first during the subsequent heating process in this blend system. Lamellar assembly of PLLA crystals within the pre-existed POM spherulitic frameworks was directly observed with the polarized light microscopy by selectively melting the POM frameworks. The investigation indicated that PLLA crystals fully replicated the spherulitic morphology and optical birefringence of the POM crystal frameworks, which was independent of To. On the other hand, POM could also duplicate the pre-existed PLLA morphologies. The result obtained provides us a possibility to design the lamellar assembly and crystal structures of polymer crystals in miscible crystalline/crystalline polymer blends.

Superiority of poly(L-lactic acid)microspheres as dermal fillers

The demand for injectable dermal filler has unde rgone significant growth with the rapid development of the beauty industry.Poly(lactic acid)(PLA) as a benefit of excellent biocompatibility and long-term promotion of collagen regeneration has been favored as a commonly used filler.However,the effects of chirality and particle size of PLA on the efficacy of dermal filler have not been studied.In this study,we prepared three kinds of microspheres(MSs) consisting of poly(D-lactic acid)(PDLA MS),poly(L-lactic acid)(PLLA MS),or meso-PLA(PDLLA MS)at 5,10 and 20 μmto reveal the different biological functions as dermal filler.Following intradermal injection into guinea pig,it was found that PLLA MS induced the slightest inflammation,and the level of pro-inflammatory cytokine IL-1β induced by PLLA MS is only 0.3 or 0.7-fold of that induced by PDLA or PDLLA MS,respectively.More importantly,PLLA MS significantly stimulated the regeneration of collagen,which was 1.4 or 1.1 times higher than those stimulated by PDLA MS or PDLLA MS,respectively.The size of PLA MSs did not affect the levels of inflammation and collagen regeneration.The results confirmed the superiority of PLLA as a dermal filler.

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)in rat

Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)(PEG-PLA)is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier(nanocarrier)in drug delivery.Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems.However,acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA.In this study,the pharmacokinetics,biodistribution,metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration.The results show that unchanged PEG-PLA is mainly distributed to spleen,liver,and kidney before being eliminated in urine over 48 h mainly(>80%)in the form of its PEG metabolite.Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientifc design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.

Poly(methyl methacrylate)-induced Microstructure and Hydrolysis Behavior Changes of Poly(L-lactic acid)/Carbon Nanotubes Composites

Poly(L-lactic acid)(PLLA)-based composites exhibit wide applications in many fields.However,most of hydrophilic fillers usually accelerate the hydrolytic degradation of PLLA,which is unfavorable for the prolonging of the service life of the articles.In this work,a small quantity of poly(methyl methacrylate)(PMMA)(2 wt%-10 wt%)was incorporated into the PLLA/carbon nanotubes(CNTs)composites.The effects of PMMA content on the dispersion of CNTs as well as the microstructure and hydrolytic degradation behaviors of the composites were systematically investigated.The results showed that PMMA promoted the dispersion of CNTs in the composites.Amorphous PLLA was obtained in all the composites.Largely enhanced hydrolytic degradation resistance was achieved by incorporating PMMA,especially at relatively high PMMA content.Incorporating 10 wt%PMMA led to a dramatic decrease in the hydrolytic degradation rate from 0.19%/h of the PLLA/CNT composite sample to 0.059%/h of the PLLA/PMMA-10/CNT composite sample.The microstructure evolution of the composites was also detected,and the results showed that no crystallization occurred in the PLLA matrix.Further results based on the interfacial tension calculation showed that the enhanced hydrolytic degradation resistance of the PLLA matrix was mainly attributed to the relatively strong interfacial affinity between PMMA and CNTs,which prevented the occurrence of hydrolytic degradation at the interface between PLLA and CNTs.This work provides an alternative method for tailoring the hydrolytic degradation ability of the PLLA-based composites.

Electrospun poly(L-lactic acid)/gelatine membranes loaded with doxorubicin for effective suppression of glioblastoma cell growth in vitro and in vivo

Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading.In this study,the electrospun membrane was loaded with doxorubicin(DOX)via electrostatic adsorption for long-term drug delivery.DOX loading process was optimized by varying temperature,time,drug concentration,pH and ionic strength of solutions.The loading process did not impair the structural properties of the membrane.Next,we investigated the drug release kinetics using spectroscopic techniques.The composite membranes released 22%of the adsorbed DOX over the first 48 h,followed by a slower and sustained release over 4 weeks.The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4.The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92%to 25.49%from 24 to 72 h of coincubation.These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33%compared with blank membrane-treated group on Day 20.In conclusion,we have developed an effective approach to load DOX within a clinically approved poly(L-lactic acid)/gelatine membrane for local and longterm delivery of DOX for the treatment of glioblastoma.

聚乳酸-聚乙醇酸共聚物的合成及其结构与性能研究

以左旋乳酸（ L－LA ）为原料，以氯化亚锡（SnCl2）和对甲苯磺酸（TSA）为复合催化剂直接熔融缩聚制备不同相对分子质量（ Mw ）的聚左旋乳酸（ PLLA）；将不同 Mw 的 PLLA 与 Mw 为4620的聚乙醇酸（PGA）按摩尔比为4：1，催化剂SnCl2：TSA摩尔比为1：1，在170℃，小于100 Pa的条件下反应4 h，制得PLLA－PGA共聚物（ PLGA）；通过用丙酮、三氯甲烷等多步溶解－离心沉淀进行分离，对PLGA的结构与性能进行表征。结果表明：共聚物为PLGA及PGA共混物；共聚物中PLGA组分的含量随着PLLA的 Mw 变化而变化，当PLLA的Mw 在20000左右时，共聚物中PLGA的质量分数大于90％，共聚物具有2个熔融峰，熔程分别为120．19～140．74℃，196．28～202．94℃，其热性能优于PLLA。

In Vitro Characterizations of PLLA/β-TCP Porous Matrix Materials and RMSC-PLLA-β-TCP Composite Scaffolds

To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, i.e. solventcasting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behaviorof the porous scaffold, e.g. weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP,the particle size of β-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporatedinto the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold weredetermined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Resultsshow that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strengthneeded for surgery. RMSCs seeding on porous PLLA/β-TCP composite behaves good seeding efficacy, biocompatibility andosteoinductive potential. Osteoprogenitor cells could well penetrate into the material matrix and begin cell proliferation andosteogenic differentiation. Osseous matrix could be formed on the surface of the composite after culturing in vitro. It isexpected that the PLLA/β-TCP porous composites are promising scaffolds for bone tissue engineering in prosthesis surgery.