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）.

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 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.

The Effect of Annealing Treatments on Spherulitic Morphology and Physical Ageing on Glass Transition of Poly Lactic Acid (PLLA)

Spherulitic morphology of pure poly lactic acid (PLLA) PLLA have investigated after thermal annealing. The morphology of spherulite of pure poly lactic acid (PLLA) PLLA have investigated after thermal annealing. The effect of both annealing temperature and crystallization temperature on the formation of cracks was described by polarized optical microscope (POM). Non banded spherulite (fibrils) with cracks was detected in PLLA film after annealing at 160°C (180 min.) and isothermal crystallization temperatures at 140°C and 150°C. With increasing temperature after annealing treatment the size of spherulite is increased and more cracks are formed. The maximum growth rate of spherulites was found at 130°C. The physical ageing was carried out by annealing the PLLA sample at room temperature for several annealing time (ta) from 0 h to 720 h. The enthalpy relaxation has been studied by differential scanning calorimetry (DSC) through analysis of the endothermic peak of glass transition temperature, which increased and shifted towards higher temperature as the annealing time increased.

Effect of Process Parameters on Co-precipitation of Paclitaxel and Poly(L-lactic Acid) by Supercritical Antisolvent Process

Paclitaxel(PTX) is an effective anticancer drug with poor solubility in water.Recently,much effort has been devoted into alternative formulations of PTX for improving its aqueous solubility.In this study,PTX and poly(L-lactic acid)(PLLA) were co-precipitated by a supercritical antisolvent(SAS) process using dichloromethane(DCM) and the mixtures of DCM/ethanol(EtOH) or DCM/dimethyl sulfoxide(DMSO) as the solvent,with super-critical carbon dioxide as the antisolvent.The effects of solvent,solvent ratio,temperature,pressure,polymer con-centration and solution flow rate on particle morphology,mass median diameter(Dp50) and PTX loading were in-vestigated using single-factor method.The particle samples were characterized using X-ray diffraction(XRD),scanning electron microscopy(SEM),laser diffraction particle size analyzer and high pressure liquid chromatogra-phy(HPLC).XRD results indicate that the micronized PTX is dispersed into the PLLA matrix in an amorphous form.SEM indicates that the solvent and the solvent ratio have great effect on the particle morphologies,and particle morphology is good at the volume ratio of DCM/EtOH of 50/50.For the mixed DCM/EtOH solvent,Dp50 increases with the increase of the temperature,pressure,PLLA concentration and solution flow rate,and PTX loading in-creases with pressure.Suitable operating conditions for the experimental system are as follows:DCM/EtOH 50/50(by volume),35 ℃,10-12 MPa,PLLA concentration of 5 g·L-1 and solution flow rate of 0.5 ml·min-1.

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.

新型聚乳酸/β-磷酸三钙(PLLA/β-TCP)多孔支架材料的性能研究

选择含有70%β-磷酸三钙加入聚乳酸中,致孔剂含量为70%(质量分数),制作成孔径为200～400μm的复合多孔支架材料,将其压成直径为5 mm、高为5 mm的圆柱体形状。将大鼠的骨髓间充质干细胞(BMSCs,Bone Mesenchymal Stem Cells)经过体外分离培养、传代诱导后,与多孔聚乳酸/β-磷酸三钙支架材料在培养板内共同培养1、3、5、7、10、14 d。采用扫描电镜观察、MTT法及ALP检测试剂盒等方法检测BMSCs在材料表面的粘附、增殖和分化能力。检测结果显示:BMSCs能在该支架材料表面早期粘附和增殖,在体外共同培养时BMSCs大量增殖后维持其碱性磷酸酶活性。此种方法制造的多孔聚乳酸/β-磷酸三钙复合支架材料有望成为组织工程骨支架材料。

成骨诱导的大鼠骨髓间充质干细胞与不同比例的β-TCP/PLLA支架材料复合的研究

种子细胞、支架材料及二者的相互作用是骨组织工程需要解决的三大问题。骨髓间充质干细胞(Mesenchym al stem cells,MSCs)是一种很有潜力的种子细胞,但挑选什么样的MSCs作为种子细胞目前研究尚少;而材料方面,研制力学性能和生物相容性均好的可降解多孔支架材料一直是研究者努力的方向。为了挑选处于最佳时期的种子细胞以及最适比例的β- TCP/PL L A多孔支架材料,我们观察并检测了大鼠MSCs(r MSCs)成骨诱导后不同时期细胞的形态及功能,发现r MSCs成骨诱导后10 d左右开始进入增殖期,14 d左右进入基质合成期,2 0 d左右进入矿化结节期(但三者不是截然分开的) ,从而根据实验目的挑选出能作为骨组织工程用的最佳细胞。将该时期的种子细胞与不同比例的β- TCP/PL L A多孔支架材料复合后,通过荧光显微镜、扫描电镜以及MTT等方法初步比较了不同比例的材料对细胞生长状况的影响,结果显示不同比例的材料均具有一定的生物相容性,细胞生长良好。但以β- TCP/PL L A=2∶1的材料最好,对细胞的生长影响最小。

PLLA／CPC复合支架增强结构设计及制备

为制备用于负重部位骨缺损修复的人工植入体,提出了一种复合增强结构人工骨设计及制备方案,该方案 采用聚左旋乳酸支架(PLLA)为增强结构,以自凝固磷酸钙骨水泥(CPC)为复合填充材料,制备了复合增强结构人 工骨。研究了PLLA的棒材力学性能、支架设计和制作及其不同增强结构形式对人工骨力学性能的影响。力学试 验结果表明,所制作的人工骨有效提高了承载能力,并且该复合结构能有效弥补金属骨无法降解的缺陷。

RGD功能化HA/PLLA多孔复合材料的制备和表征

通过碳二亚胺法将精氨酸-甘氨酸-天冬氨酸(RGD)接枝到羟基磷灰石(HA)颗粒表面,增强HA颗粒识别细胞的功能,然后将其均匀地分布于左旋聚乳酸(PLLA)中制备多孔复合材料,分别用XPS和SEM等对HA颗粒和多孔复合材料进行了表征。结果表明:RGD成功地接枝到了HA颗粒表面,多孔复合材料中RGD功能化的HA颗粒是纳米尺寸的,且分布均匀;RGD功能化HA/PLLA多孔复合材料的细胞粘附率从普通HA/PLLA多孔复合材料的37.21%提高到了69.11%。

高分子量立构复合结晶的三枝化PPO-PDLA-PLLA嵌段共聚物

以三枝化低不饱和度聚环氧丙烷(PPO)引发D-丙交酯(D-LA)逐步开环聚合,合成了三枝化聚环氧丙烷-聚右旋乳酸(PPO-PDLA)共聚物.用辛酸亚锡Sn(Oct)2与PPO-PDLA端羟基反应进行Sn(Oct)封端,制备了三枝化PPO-PDLA-Sn(Oct)预聚物.再于130℃下,以其作为大分子引发剂与L-丙交酯(L-LA)开环聚合,合成了分子量>105的三枝化PPO-PDLA-PLLA嵌段共聚物.活性端基的引入,降低了聚合反应温度,从而降低了聚合中的酯交换或热降解反应发生的概率.实现了高分子量PPO-PDLA-PLLA嵌段共聚物的合成.结构测试结果表明,合成的嵌段共聚物具有分子结构易控及立构规整度高等特点.在结晶-熔融-再结晶重复热处理下,三枝化PPO-PDLA-PLLA嵌段共聚物仅发生立构复合聚乳酸结晶,且结晶能力稳定.

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.

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.

3D打印PLCL/PLLA复合材料支架的体外降解性能研究

目的探讨左旋聚乳酸(PLLA)与聚-L-丙交酯-己内酯(PLCL)的复合对PLCL的三维(3D)打印性能及其打印支架降解性能的影响。方法采用共混手段制备了系列不同比例的PLCL(100%、90%、80%、70%、60%、50%)为基质相、PLLA(10%、20%、30%、40%、50%、100%)为分散相的复合材料;利用熔融沉积成型(FDM)3D打印技术,制备不同比例、不同填充率(40%、50%、60%、70%)的PLCL/PLLA无边框3D多孔支架;通过支架宏/微观结构的观察及其体外加速降解实验,考察复合材料3D打印性能及其支架的降解性能。结果在研究条件下,复合材料均可打印成孔隙贯通的多孔支架,复合材料的孔径随填充率的增加而缩小,由40%时733μm缩小为70%时200μm。相对于单纯PLCL,复合PLLA更有利于支架结构成型。降解实验显示:PLCL支架降解较快,70%填充率打印支架60 d时降解达到88.58%,而PLLA的加入可以减慢支架降解速率;降解过程中,所有支架都较好地保持了原有结构的完整性,无明显断裂或崩解,但PLCL支架整体结构缩小、孔径增大明显,而复合PLLA明显改善了支架缩小和孔径增大的现象;微观形貌变化显示,PLCL支架表面在降解过程中出现了大量微孔结构,而PLCL/PLLA复合材料支架表面出现了微孔结构和微裂缝结构。结论复合PLLA不仅改善了PLCL的3D打印性能,而且也改变了复合材料支架的降解性能;通过改变PLCL和PLLA的比例及3D打印填充率,可以调控支架的孔径、孔隙率及降解速率,为多种组织、器官的工程化构建提供可选择的支架材料。