体外研究聚合物P（DLLA—co—TMC）的降解性能与释药行为

目的 研究P（DLLA—CO-TMC）聚合物的体外降解性能与释药行为,且探讨该聚合物作为长效避孕释放载体的可行性。方法以PBS溶液为溶媒研究P（DLLA-CO-TMC）的降解性能;以P（DLLA—CO—TMC）聚合物为载体制备含孕二烯酮的载药片,并通过蒸馏水浸泡载药片研究载药体系的体外释药行为。结果P（DLLA-CO-TMc）聚合物前期降解较慢,第30天和第90天失重率分别为10．0％和12．3％,后期降解速率较快,第120天的失重率为59．3％;P（DLLA-CO-TMC）的载药片前期释药速率较大,出现“暴释现象”,后期释药速率减缓并逐渐趋于平稳,第100天时累计释放率为5．64％。结论P（DLLA-co-TMC）聚合物降解性能良好、释药效果明显,有望通过体内研究使含孕二烯酮的P（DLLA—CO—TMC）聚合物载药系统应用于长效埋植避孕。     

含有(聚)乙二醇侧链的丙烯酸酯类聚合物的体外血小板黏附研究

目的对含有(聚)乙二醇侧链的丙烯酸酯类聚合物的血液相容性进行研究。方法采用自由基共聚合成了若干种具有不同结构聚乙二醇侧链的丙烯酸酯类(EOMA)与甲基丙烯酸丁酯(BMA)无规共聚物。测量水接触角来考察所得不同组成结构的共聚物表面的亲水性；通过扫描电镜(SEM)观察血小板在各系列共聚物表面的吸附及变性情况；并且分析了共聚物结构对其亲水性、血小板吸附状况的影响。结果与结论该类材料具有优良的血液相容性，是一种有着很好应用前景的生物医用材料。     

可降解金属Mg-Nd-Zn-Zr镁合金的降解行为

背景：添加合金元素是改变镁合金微观结构和控制镁合金降解行为的有效方法。 目的：探讨Mg-Nd-Zn-Zr镁合金体内外的降解行为。 方法：①体外静态浸泡实验：在(37.0±0.5) ℃条件下,将Mg-Nd-Zn-Zr镁合金和纯镁各6个样品分别浸入 250 mL模拟体液中,浸泡过程中不搅拌振荡。静态浸泡第3,7,30天后从模拟体液中取出试样,扫描电镜及能谱分析分析Mg-Nd-Zn-Zr镁合金在模拟体液中的降解行为。②体内植入实验：在成年新西兰兔左侧股骨钻孔,实验组植入Mg-Nd-Zn-Zr镁合金,对照组植入钛合金,空白对照组不植入任何内植物。植入后1,2,4,8周,通过X射线观察内植物的位置及降解行为;植入后4,8周,通过扫描电镜观察Mg-Nd-Zn-Zr镁合金表面腐蚀产物,通过元素能谱分析腐蚀产物的成分,并计算材料降解速率。 结果与结论：①Mg-Nd-Zn-Zr镁合金浸泡于模拟体液中不同时间点的降解速率均低于纯镁组;浸泡30 d后,沉积于Mg-Nd-Zn-Zr镁合金表面的腐蚀产物主要是氧、碳、钠、镁、钙、磷和氯,去除腐蚀产物后Mg-Nd-Zn-Zr镁合金和纯镁表面均有腐蚀坑,但Mg-Nd-Zn-Zr镁合金表面腐蚀坑体积更小,分布更均匀,表明Mg-Nd-Zn-Zr镁合金和纯镁存在不同的腐蚀形式。②Mg-Nd-Zn-Zr镁合金植入动物体内后随时间延长逐渐降解,材料表面腐蚀产物及成分类似于体外浸泡实验。     

聚羟基磷酸钙钠的骨细胞相容性体外研究

聚羟基磷酸钙钠（Ｈｙｄｒｏｘｙｌ ｐｏｌｙｃａｌｃｉｕｍｓｏｄｉｕｍ ｐｈｏｓｐｈａｔｅ,ＨＰ）是一种新的人人体硬组织替代。本实验选用Ｓ．Ｄ乳鼠颅顶细胞,采用体外细胞培养技术,从细胞水平评价聚羟基磷酸钙钠的骨细胞相容性体外研究。结果表明细胞在ＨＰ表面正常粘附、伸展、增殖,具有良好的细胞附着形态及细胞增殖率,其增殖速度较羟基磷灰石,生物玻璃陶瓷快,表明ＨＰ更有利于细胞的粘附生长,容易形成早期骨性结合     

降解材料聚乳酸－聚乙二醇生物相容性的研究

作者对国产新型生物医用可降解材料ＤＬ—聚乳酸—聚乙二醇共聚物（ＰＥＬＡ）进行了系统的生物学评价。结果表明：降解材料ＰＥＬＡ无全身毒性、无热原和细胞毒性、无溶血（溶血率小于５％）、对皮肤和眼粘膜无刺激、不引起致敬反应、对骨髓多染红细胞无影响。体内植入２８０天，材料基本降解完全，材料周围纤维囊壁厚度逐渐变薄，炎症细胞反应减轻。因此，可认为降解材料ＰＥＬＡ有良好的生物相容性。     

超声可控释药体系研究进展

超声可控释药体系是一种新兴的靶向给药及基因转运方法。以超声敏感材料作为药物或基因转送的载体,当超声辐照于靶组织或靶器官时, 靶体内载体可定向释放出包裹或附着的基因或药物, 实现对负载药物的定时定量定点释放和提高药物输送效率或基因转染率的目的。文中对超声可控释药体系的作用机制、超声敏感载体材料及生物医学应用等方面进行综述,最后对该领域目前存在的问题和今后的发展方向提出了一些看法。     

生物可降解载药纤维的制备、特征表征及释药特性的研究

为了研发一种可供脂溶性药物上载的长效释放植入生物可降解纤维载体,采用有机相分离法制备左旋聚乳酸(PLLA)纤维,扫描电镜(SEM)观察结构,差示扫描热分析(DSC)以及红外光谱分析(FTIR)分析药物载体状态,高效液相(HPLC)方法测定载药纤维的载药量,紫外分光光度法(UV)测定药物释放情况.结果表明制备出了成形性良好的空白PLLA纤维及载药纤维,药物包合入纤维中;药物与载体的结合形式为微晶分散与非晶态分散相结合,该纤维制剂在体外可以长效可调地释放.有机相分离法可以用来成功制备作为缓释植入药物载体的微米级别的左旋聚乳酸载药(PLLA)纤维.     

丙戊酸镁缓释片体外释药特性及体内相对生物利用度的研究

目的:研制丙戊酸镁缓释片,并评价其体外释药特性及体内生物等效性。方法:以释放度为主要指标筛选片剂处方及制备工艺,并对12名健康男性受试者进行体内生物利用度研究。结果:以优选的处方,工艺制备的片剂,体外释药性能良好,符合Higuchi方程,持续释药达8h以上。且释药性能稳定,不受溶出介质pH值的影响。其体内药代动力学参数为:Cmax,30.0±4.6ug·ml-1;Tmax,11.5±4.8h;T1/2。17.8±4.6h;F,95±8％。结论:丙戊酸镁缓释片与普通片相比具有缓释特性。相对生物利用度为95±8％。     

聚乳酸支架材料与角膜上皮样细胞的体外生物相容性

目的观察聚乳酸支架材料与角膜上皮样细胞的体外生物相容性。方法通过热压法与流延法分别制作聚乳酸支架材料。复苏培养前期实验获得的角膜上皮样细胞,免疫荧光化学法鉴定,将第三代角膜上皮样细胞分别种植于上述2种聚乳酸支架材料,显微镜下观察此两种支架材料上细胞的存活与生长情况;采用伊红染色观察支架材料上细胞数量与形态,噻唑蓝法检测细胞活力。结果热压法聚乳酸支架材料为纤维交织立体结构,而流延法材料为实性结构,无孔隙。细胞种植于支架材料后,细胞种植4d后镜下可见热压法聚乳酸支架材料组大量细胞存活,且紧贴着支架材料生长并向支架材料内伸展,伊红染色可见材料上大量着色的细胞;流延法组细胞存活极少,伊红染色仅见极少细胞附着在材料上。结论热压法聚乳酸支架材料具备纤维孔隙结构,支持角膜上皮样细胞的存活与生长,具备与角膜上皮样细胞有较好的生物相容性,有进一步开发角膜上皮样细胞移植支架的前景。     

盐酸多柔比星缓释植入剂体外释药与体外降解的研究

以聚（乳酸-羟基乙酸）共聚物（PLGA）为载体制备盐酸多柔比星缓释植入剂,测定植入剂的释放度和PLGA失重率,结果表明PLGA体外降解曲线呈＂S＂形,起初的迟缓期后降解速率加快,5周时失重率达80%。植入剂表现出趋于零级的药物释放模式（r=0.9880）,在0~25 d日均释放度达3.26%,35 d时累积释放度达90%以上。植入剂可持续释药1个月,释药速率主要取决于PLGA降解速率,通过调节PLGA降解速率可以很好地控制药物的释放度。     

In vitro degradation of insulin-loaded poly (n-butylcyanoacrylate) nanoparticles

Poly (n-butyl cyanoacrylate) (PBCA) nanoparticles were prepared by a dispersion polymerisation process in water at pH 3 and using dextran as a stabilising agent. The drug insulin was introduced during the latter stages of particle synthesis and was found not to interfere with the polymer structure, molecular weight, and the particle size. Nanoparticles were exposed to the enzyme esterase in phosphate buffered saline solution at 37 degrees C for time periods up to 4h. Esterase catalyses the degradation of the PBCA through hydrolysis of the side chain on the repeat unit with the release of butanol, and this was monitored as an indicator of degradation. The release of both butanol and insulin occurred via similar biphasic processes, with an initial burst release from the surface, followed by a slower diffusionally hindered release associated with particle erosion. Hydrolysis of the nanoparticle polymer was confirmed by infrared spectroscopy. Particle size reduces with time of exposure to esterase, but is greatest in the first 30 min of exposure. Despite the hydrolysis reaction, and reduction in particle size, there was no reduction in residual polymer molecular weight suggesting a progressive loss of entire chains from the active surface. Polymer loss is thought to occur through either solvation of degradation residue or through complete depolymerisation of hydrolysed chains.     

Porous hybrid structures based on P(DLLA-co-TMC) and collagen for tissue engineering of small-diameter blood vessels

Poly (D,L-lactide)-7co-(1,3-trimethylene carbonate) [P(DLLA-co-TMC)] (83 mol % DLLA) was used to produce matrices suitable for tissue engineering of small-diameter blood vessels. The copolymer was processed into tubular structures with a porosity of approximately 98% by melt spinning and fiber winding, thus obviating the need of organic solvents that may compromise subsequent cell culture. Unexpectedly, incubation in culture medium at 37 degrees C resulted in disconnection of the contact points between the polymer fibers. To improve the structural stability of these P(DLLA-co-TMC) scaffolds, a collagen microsponge was formed inside the pores of the synthetic matrix by dip coating and freeze drying. Hybrid structures with a porosity of 97% and an average pore size of 102 mum were obtained. Structural stability was preserved during incubation in culture medium at 37 degrees C. Smooth-muscle cells (SMCs) were seeded in these hybrid scaffolds and cultured under pulsatile flow conditions in a bioreactor (120 beats/min, 80-120 mmHg). After 7 days of culture in a dynamic environment viable SMCs were homogeneously distributed throughout the constructs, which were five times stronger and stiffer than noncultured scaffolds. Values for yield stress (2.8 +/- 0.6 MPa), stiffness (1.6 +/- 0.4 MPa), and yield strain (120% +/- 20%) were comparable to those of the human artery mesenterica.     

In vitro degradation and biocompatibility of poly(DL-lactide-epsilon-caprolactone) nerve guides

Bridging nerve gaps by means of autologous nerve grafts involves donor nerve graft harvesting. Recent studies have focused on the use of alternative methods, and one of these is the use of biodegradable nerve guides. After serving their function, nerve guides should degrade to avoid a chronic foreign body reaction. The in vitro degradation, in vitro cytotoxicity, hemocompatibility, and short-term in vivo foreign body reaction of poly((65)/(35) ((85)/(15) (L)/(D)) lactide-epsilon-caprolactone) nerve guides was studied. The in vitro degradation characteristics of poly(DLLA-epsilon-CL) nerve guides were monitored at 2-week time intervals during a period of 22 weeks. Weight loss, degree of swelling of the tube wall, mechanical strength, thermal properties, and the intrinsic viscosity of the nerve guides were determined. Cytotoxicity was studied by measuring the cell proliferation inhibition index (CPII) on mouse fibroblasts in vitro. Cell growth was evaluated by cell counting, while morphology was assessed by light microscopy. Hemocompatibility was evaluated using a thrombin generation assay and a complement convertase assay. The foreign body reaction against poly(DLLA-epsilon-CL) nerve guides was investigated by examining toluidine blue stained sections. The in vitro degradation data showed that poly(DLLA-epsilon-CL) nerve guides do not swell, maintain their mechanical strength and flexibility for a period of about 8-10 weeks, and start to lose mass after about 10 weeks. Poly(DLLA-epsilon-CL) nerve guides were classified as noncytotoxic, as cytotoxicity tests demonstrated that cell morphology was not affected (CPII 0%). The thrombin generation assay and complement convertase assay indicated that the material is highly hemocompatible. The foreign body reaction against the biomaterial was mild with a light priming of the immunesystem. The results presented in this study demonstrate that poly((65)/(35) ((85)/(15) (L)/(D)) lactide-epsilon-caprolactone) nerve guides are biocompatible, and show good in vitro degradation characteristics, making these biodegradable nerve guides promising candidates for bridging peripheral nerve defects up to several centimeters.     

In vitro degradation of porous poly(L-lactic acid) foams

This study investigated the in vitro degradation of porous poly(L-lactic acid) (PLLA) foams during a 46-week period in pH 7.4 phosphate-buffered saline at 37 degrees C. Four types of PLLA foams were fabricated using a solvent-casting, particulate-leaching technique. The three types had initial salt weight fraction of 70, 80, and 90%, and a salt particle size of 106-150 microm, while the fourth type had 90% initial weight fraction of salt in the size range 0-53 microm. The porosities of the resulting foams were 0.67, 0.79, 0.91, and 0.84, respectively. The corresponding median pore diameters were 33, 52, 91, and 34 microm. The macroscopic degradation of PLLA foams was independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. However, decrease in melting temperature and slight increase in crystallinity were observed at the end of degradation. The foam half-lives based on the weight average molecular weight were 11.6+/-0.7 (70%, 106-150 microm), 15.8+/-1.2 (80%, 106-150 microm), 21.5+/-1.5 (90%, 106-150 microm), and 43.0+/-2.7 (90%, 0-53 microm) weeks. The thicker pore walls of foams prepared with 70 or 80% salt weight fraction as compared to those with 90% salt weight fraction contributed to an autocatalytic effect resulting in faster foam degradation. Also, the increased pore surface/volume ratio of foams prepared with salt in the range 0-53 microm enhanced the release of degradation products thus diminishing the autocatalytic effect and resulting in slower foam degradation compared to those with salt in the range 106-150 microm. Formation and release of crystalline PLLA particulates occurred for foams fabricated with 90% salt weight fraction at early stages of degradation. These results suggest that the degradation rate of porous foams can be engineered by varying the pore wall thickness and pore surface/volume ratio.     

In vitro degradation and in vivo biocompatibility study of a new linear poly(urethane urea)

Segmented poly(urethane urea)s (PUUs) with hard segments derived only from methyl 2,6-diisocyantohexanoate (LDI) without the use of a chain extender have previously been described. These materials, which contain hard segments with multiple urea linkages, show exceptionally high strain capability (1600-4700%). In the study reported here, the rate and effect of hydrolysis of these materials were determined for gamma-sterilized and nonsterilized samples. Materials investigated contained PCL, PTMC, P(TMC-co-CL), P(CL-co-DLLA), or P(TMC-co-DLLA) as soft segments and, as well as their mechanical properties, changes in mass, inherent viscosity (I.V.), and thermal properties were studied over 20 weeks. Results showed that the degradation rate was dependant on the soft segment structure, with a higher rate of degradation for the polyester-dominating PUUs exhibiting a substantial loss in I.V. A tendency of reduction of tensile strength and strain hardening was seen for all samples. Also, loss in elongation at break was detected, for PUU-P(CL-DLLA) it went from 1600% to 830% in 10 weeks. Gamma radiation caused an initial loss in I.V. and induced more rapid hydrolysis compared with nonsterilized samples, except for PUU-PTMC. A cytotoxicity test using human fibroblasts demonstrated that the material supports cell viability. In addition, an in vivo biocompatibility study showed a typical foreign body reaction after 1 and 6 weeks.     

In vitro enzymatic degradation of poly (glycerol sebacate)-based materials

Enzymatic degradation is a major feature of polyester implants in vivo. An in vitro experimental protocol that can simulate and predict the in vivo enzymatic degradation kinetics of implants is of importance not only to our understanding of the scientific issue, but also to the well-being of animals. In this study, we explored the enzymatic degradation of PGS-based materials in vitro, in tissue culture medium or a buffer solution at the pH optima and under static or cyclic mechanical-loading conditions, in the presence of defined concentrations of an esterase. Surprisingly, it was found that the in vitro enzymatic degradation rates of the PGS-based materials were higher in the tissue culture medium than in the buffered solution at the optimum pH 8. The in vitro enzymatic degradation rate of PGS-based biomaterials crosslinked at 125°C for 2 days was approximately 0.6-0.9 mm/month in tissue culture medium, which falls within the range of in vivo degradation rates (0.2-1.5mm/month) of PGS crosslinked at similar conditions. Enzymatic degradation was also further enhanced in relation to mechanical deformation. Hence, in vitro enzymatic degradation of PGS materials conducted in tissue culture medium under appropriate enzymatic conditions can quantitatively capture the features of in vivo degradation of PGS-based materials and can be used to indicate effective strategies for tuning the degradation rates of this material system prior to animal model testing.     

In vitro degradation of a poly(ether urethane) by trypsin

In vitro enzymatic degradation of non-porous films of segmented poly(ether urethane) (Pellethane 2363-80AE) was investigated by incubating the biomaterial in concentrated trypsin solutions for 5 months at room temperature. Chemical degradation of films was monitored by surface analysis techniques such as Fourier transform infrared spectroscopy-attenuated total reflectance and electron spectroscopy for chemical analysis. This latter technique proved to be much superior in detecting chemical changes. Extraction of films with methanol and characterization of the extracts by gel permeation chromatography revealed the presence of low-molecular-weight polymers. Results have shown that trypsin has the ability to induce degradation in PEU, the soft segment being most affected, particularly the CH2-O bond of the ether linkages.     

In vitro degradation of thin poly(DL-lactic-co-glycolic acid) films.

This study was designed to investigate the in vitro degradation of thin poly(DL-lactic-co-glycolic acid) (PLGA) films for applications in retinal pigment epithelium transplantation and guided tissue regeneration. PLGA films of copolymer ratios of 75:25 and 50:50 were manufactured with thickness levels of 10 microm (thin) and 100 microm (thick). Degradation of the films occurred during sample processing, and thin films with a higher surface area to volume ratio degraded faster. Sample weight loss, molecular weight loss, dimensional, and morphological changes were analyzed over a 10-week period of degradation in 0.2 M of phosphate-buffered saline (PBS), pH 7.4, at 37 degrees C. All PLGA films degraded by heterogeneous bulk degradation. Sample weights remained relatively constant for the first several weeks and then decreased dramatically. The molecular weights of PLGA films decreased immediately upon placement in PBS and continued to decrease throughout the time course. PLGA 50:50 films degraded faster than 75:25 films due to their higher content of hydrophilic glycolic units. The results also demonstrated that thick films degrade faster than corresponding thin films with the same composition. This was attributed to the greater extent of the autocatalytic effect, which further was confirmed by heterogeneous gel permeation chromatograms. These studies suggest that the degradation rate of thin films can be engineered by varying film thicknesses.     

In vitro bioactivity and degradation behavior of silica xerogels intended as controlled release materials

Room temperature-processed silica-based sol-gel, termed silica xerogel, is a novel type of controlled release material. As shown previously, these materials are porous, degradable and can release biologically functional molecules in a controlled manner. It was also demonstrated that these materials are biocompatible in vivo. Herein we report on the ability of silica-based xerogels to form a bioactive, apatite-like (AP) surface and the effect of AP surface on the xerogel stability in vitro. Formation of a crystalline, carbonated AP (c-AP) was found on all silica xerogels studied, with or without Ca- and P-oxides. Calcium and phosphate (Ca-P) free xerogels showed long times to Ca-P precipitation and to formation of a detectable AP-layer (up to 2 weeks). In contrast, the times to precipitation were reduced by 2-3 orders of magnitude, and the c-AP layer was formed within 24 h on all Ca-P containing xerogels. Mechanisms of the c-AP formation on these xerogels were similar to those typical for Ca-P based ceramics: dissolution of calcium and phosphate ions, solution oversaturation with respect to AP and subsequent precipitation of bone-like minerals. The presence of the c-AP surface film produced a remarkable surface stabilizing effect: the rates and the amounts of Si release were significantly reduced in comparison to those for xerogels without the film. This evidence of in vitro bioactivity and controlled degradation, combined with previous in vitro and in vivo reports, suggests that silica xerogel is a promising controlled release material.     

In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams

This study investigated the in vitro degradation of porous poly(DL-lactic-co-glycolic acid) (PLGA) foams during a 20-week period in pH 7.4 phosphate-buffered saline (PBS) at 37 degrees C and their in vivo degradation following implantation in rat mesentery for up to 8 weeks. Three types of PLGA 85 : 15 and three types of 50 : 50 foams were fabricated using a solvent-casting, particulate-leaching technique. The two types had initial salt weight fraction of 80 and 90%, and a salt particle size of 106-150 microm, while the third type had 90% initial weight fraction of salt in the size range 0-53 microm. The porosities of the resulting foams were 0.82, 0.89, and 0.85 for PLGA 85 : 15, and 0.73, 0.87, and 0.84 for PLGA 50 : 50 foams, respectively. The corresponding median pore diameters were 30, 50, and 17 microm for PLGA 85: 15, and 19, 17, and 17 microm for PLGA 50 : 50. The in vitro and in vivo degradation kinetics of PLGA 85: 15 foams were independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. The in vitro foam half-lives based on the weight average molecular weight were 11.1 +/- 1.8 (80%, 106-150 microm), 12.0 +/- 2.0 (90%, 106-150 microm), and 11.6 +/- 1.3 (90%, 0-53 microm) weeks, similar to the corresponding values of 9.4 +/- 2.2, 14.3 +/- 1.5, and 13.7 +/- 3.3 weeks for in vivo degradation. In contrast, all PLGA 50 : 50 foams exhibited significant change in foam weight, water absorption, and pore distribution after 6-8 weeks of incubation with PBS. The in vitro foam half-lives were 3.3 +/- 0.3 (80%, 106-150 microm), 3.0 +/- 0.3 (90%, 106-150 microm), and 3.2 +/- 0.1 (90%, 0-53 microm) weeks, and the corresponding in vivo half-lives were 1.9 micro 0.1, 2.2 +/- 0.2, and 2.4 +/- 0.2 weeks. The significantly shorter half-lives of PLGA 50: 50 compared to 85: 15 foams indicated their faster degradation both in vitro and in vivo. In addition, PLGA 50: 50 foams exhibited significantly faster degradation in vivo as compared to in vitro conditions due to an autocatalytic effect of the accumulated acidic degradation products in the medium surrounding the implants. These results suggest that the polymer composition and environmental conditions have significant effects on the degradation rate of porous PLGA foams.