新型可完全降解材料聚外消旋乳酸-三亚甲基碳酸酯聚合物体内降解行为和组织相容性

背景：目前应用于临床的金属裸支架、金属药物洗脱支架、合金支架等置入心血管后会导致局部血管内膜增生、血栓形成,增加心血管不良事件发生率。因此,应用高分子聚合物材料研发和制备完全生物可降解血管支架逐渐成为研究热点。 目的：观察新型完全生物可降解材料聚外消旋乳酸-三亚甲基碳酸酯(PDLLA/TMC)(50/50)聚合物在机体内的降解行为和组织相容性。  方法：以课题组前期合成并研究的聚合物PDLLA/TMC(50/50)为实验对象,聚左旋乳酸-三亚甲基碳酸酯(PLLA/TMC)(50/50)和聚乳酸(PLLA)为对照,分别将其薄膜片植入144只6月龄Wistar大鼠,在不同的时间点,采用体积排除色谱、凝胶渗透色谱、核磁共振、环境扫描电镜研究其体内降解行为,并通过光镜下镜检及周围炎性细胞计数量化评价其组织相容性。 结果与结论：在植入机体前60 d,3组材料的失重率并没有太大的区别,降解速率均相对平稳缓慢,PDLLA/TMC的降解速率略快于其他两组聚合物材料,60 d后PDLLA/TMC的降解速率明显加快,其失重率显著高于另外两种聚合物材料,180 d后PDLLA/TMC大部分被降解,其余两种聚合物降解很少。3种聚合物材料包埋于生物体内即开始出现相对分子质量下降,初期下降速率较快,而后逐渐趋缓。3种材料的表面结构随着降解时间的延长,由初期的较为光滑整齐变为后期的皱褶、扭曲、紊乱、凹陷和孔洞,且PDLLA/TMC材料表面变化较明显。PDLLA/TMC和PLLA/TMC与PLLA比较,各个时间点均有相对较低的炎症细胞计数,差异均有显著性意义(P < 0.05);而PDLLA/TMC与PLLA/TMC比较,各个时间节点上的炎性细胞计数差异均无显著性意义(P > 0.05)。证实PDLLA/TMC聚合物是一种新型的完全生物可降解材料,具有良好的降解性能和组织相容性。     

应力对新型镁合金骨钉体外降解速率影响的实验研究

目的研究应力对新型镁合金骨钉体外降解速率的影响。方法根据逆向建模方法建立胫骨骨折三维模型设计体外降解实验装置,用有限元计算得到的骨钉应力分布加载实验载荷,有效提高实验的准确性及效率。实验共分为4组,A组作为对照组不加力,B、C和D组分别施加150、250、350 N轴向压力,研究不同力学环境对骨钉体外降解速率的影响程度。将应力分布与体外降解实验结果结合,得到应力与新型镁合金骨钉体外降解速率的变化曲线。结果体外降解实验表明,A组失重最小,产生氢气最少,平均降解速率为(0. 315±0. 005) mm/年;有应力组随着施加载荷的增大,失重、产氢量逐渐增加,B、C、D组平均降解速率分别为(0. 379±0. 006)、(0. 469±0. 007)、(0. 547±0. 009) mm/年。结论新型镁合金骨钉在力学环境中进行降解时,骨钉所受的应力越大,其降解速率越快;得到新型镁合金骨钉所受的最大应力与平均体外降解速率之间的关系曲线,为镁合金骨钉的选材、设计及临床应用提供数据支撑和理论指导。     

聚乳酸/聚乙二醇-聚乳酸新型亲水支架的制备与研究

利用热致相分离/粒子沥滤结合法,制备了聚乳酸(PDLLA)以及聚乳酸与聚乙二醇-聚乳酸共聚物(PELA)复合的PDLLA/PELA组织工程支架。讨论了聚乙二醇(PEG)分子量、PELA含量及组成比对于支架内部结构、力学性能、降解行为和细胞毒性的影响。结果表明,热致相分离/粒子沥滤结合法制备的支架,具有100~250μm大孔与5~40μm小孔兼备的特殊内部结构,PEG含量愈高、PEG分子量愈小,支架的孔隙率愈大。PDLLA/PELA比率的减小,PEG/PLA比率的增大会引起支架力学性能的下降和降解的加速。材料无细胞毒性。当支架中PDLLA/PELA为3∶1,PEG 5000/PLA为25∶75时,其内部孔形态最为理想。     

聚DL—丙交酯／羟基磷灰石（PDLLA／HA）复合材料（Ⅰ）：制备及力学性能

将羟基磷灰石（HA）与DL－丙交酯（DL－LA）按一定比例混合,在辛酸亚锡引发下开环聚合得到HA微粒填充的聚DL－丙交酯／羟基磷灰石（PDLLA／HA）复合材料。在一定引发剂浓度下,HA的含量越大,粒径越小,PDLLA的分子量越低,扫描电子显微镜观察HA微粒均匀分布在PDLLA基质中,当PDLLA的分子量在175000－245000范围内,HA含量（HAwt%）为30％时,复合材料的弯曲强度达90MPa,剪切强度为72MPa,模量为6．9GPa,均高于其它体系。HA的引入不仅提高了材料的初始力学强度。而且还延缓了PDLLA的降解速率。     

可吸收羟基磷灰石/聚DL-乳酸骨折内固定材料机械强度和生物降解性研究

目的评价自行研制的可吸收羟基磷灰石/聚DL-乳酸(HA/PDLLA)复合骨折内固定材料的机械强度和生物降解性。方法体外降解实验是把相同分子量的HA/PDLLA和单纯PDLLA试件分别置于PBS缓冲液中,于2、4、6、8、10、12周取材,测试生物降解率、吸水率、失重率、机械强度及降解液pH值,并作扫描电镜(SEM)观察;体内实验是用一枚HA/PDLLA棒内固定兔股骨髁松质骨部横形截骨,作X线摄片、组织学、机械强度及材料骨界面SEM观察。结果HA/PDLLA复合材料较单纯PDLLA材料降解速度减慢,机械强度提高,骨折正常愈合。结论HA/PDLLA材料具有足够的强度保证实验性松质骨骨折正常愈合。     

三维多孔牡蛎壳/消旋聚乳酸复合人工骨的研制及其相关性能的检测

研制性能优良的新型三维多孔复合人工骨材料,并评价其相关性能. 将牡蛎壳粉、消旋聚乳酸(PDLLA)按一定比例复合,采用热致相分离法(TIPS),制备多孔复合人工骨(OPCB)材料,检测其孔隙率、孔径、生物力学强度;将OPCB和纯PDLLA薄片浸泡于37℃的生理盐水中,观测不同时间点OPCB和纯PDLLA体外降解变化参数,对其结果进行统计学比较.所研制的OPCB材料平均孔隙率为85.1%;电镜下孔径测量大小为100～300 μm,孔隙之间的连通较好,孔隙形态、取向规则有序;压缩强度为2.12 MPa;在观测周期内,随着浸泡时间的延长,OPCB和纯PDLLA的质量损失率、PDLLA的分子量及浸泡液的pH值呈现出规律性变化,两组各时期的各项指标具有显著性差异(P<0.05).用TIPS法制得的OPCB材料,其孔隙率、孔径、生物力学强度、体外降解性能可满足骨替代材料的要求.     

聚DL-丙交酯/羟基磷灰石(PDLLA/HA)复合材料(I):制备及力学性能

将羟基磷灰石 (HA)与DL 丙交酯 (DL LA)按一定比例混合 ,在辛酸亚锡引发下开环聚合得到HA微粒填充的聚DL 丙交酯 /羟基磷灰石 (PDLLA/HA)复合材料。在一定引发剂浓度下 ,HA的含量越大 ,粒径越小 ,PDLLA的分子量越低。扫描电子显微镜观察HA微粒均匀分布在PDLLA基质中 ,当PDLLA的分子量在 175 0 0 0～ 2 45 0 0 0范围内 ,HA含量 (HAwt %)为 30 %时 ,复合材料的弯曲强度达 90MPa ,剪切强度为 72MPa,模量为 6 .9GPa ,均高于其它体系。HA的引入不仅提高了材料的初始力学强度 ,而且还延缓了PDLLA的降解速度。     

聚DL-丙交酯/羟基磷灰石(PDLLA/HA)复合材料(I):制备及力学性能

将羟基磷灰石(HA)与DL-丙交酯(DL-LA)按一定比例混合,在辛酸亚锡引发下开环聚合得到HA微粒填充的聚DL-丙交酯/羟基磷灰石(PDLLA/HA)复合材料.在一定引发剂浓度下,HA的含量越大,粒径越小,PDLLA的分子量越低.扫描电子显微镜观察HA微粒均匀分布在PDLLA基质中,当PDLLA的分子量在175000～245000范围内,HA含量(HAwt%)为30%时,复合材料的弯曲强度达90MPa,剪切强度为72MPa,模量为6.9GPa,均高于其它体系.HA的引入不仅提高了材料的初始力学强度,而且还延缓了PDLLA的降解速度.     

羟基磷灰石/聚DL-乳酸复合内固定材料对成骨细胞活性影响的体外研究

目的 :与单纯聚DL 乳酸 (PDLLA)材料比较研究羟基磷灰石 /聚DL 乳酸 (HA/PDLLA)复合内固定材料的降解产物对成骨细胞增殖和分化的影响。方法 :检测HA/PDLLA材料和PDLLA材料体外降解过程中降解液 pH值、钙离子、无机磷浓度的变化 ;通过四甲基偶氮唑盐 (MTT)酶反应比色法检测成骨细胞在材料降解产物作用下的增殖情况 ,通过检测碱性磷酸酶 (ALP)活性了解其分化情况 ,扫描电镜 (SEM)观察成骨细胞在材料直接作用下的形态学表现。结果 :体外自然降解时 ,HA/PDLLA材料降解液 pH值下降较PDLLA材料慢 ,HA/PDLLA材料降解时有钙磷成分溶出。与对照组比较 ,HA/PDLLA材料所设全部七个浓度的浸提液及PDLLA材料从 1∶2 5 6到 1∶16这四个浓度的浸提液对成骨细胞增殖均无抑制 (P >0 .0 5 ) ,PDLLA材料 1∶4及 1∶1两个浓度的浸提液抑制了成骨细胞增殖 (P <0 .0 5及P <0 .0 1)。作用 1d和 4d后的成骨细胞ALP活性在HA/PDLLA材料组与同期对照组相比均无显著性差异(P >0 .0 5 ) ,在PDLLA材料组与同期对照组及HA/PDLLA材料组相比均有显著性升高 (P <0 .0 1)。HA/PDLLA材料表面的成骨细胞呈纺锤形及延展为多角状 ;PDLLA材料表面的成骨细胞呈球形及延展不充分 ,且数量较少 ;HA/PDL LA材料表面可见HA颗粒。结论 :HA/PDLLA材料降     

压缩载荷下猪腰椎间盘髓核摘除后力学行为的实验研究

为研究退变及摘除髓核后腰椎间盘的力学行为,对猪腰椎间盘进行压缩实验。髓核摘除并经胰蛋白酶处理后的椎间盘作为实验组,正常椎间盘作为对照组。考虑载荷大小及加载速率的影响,得到椎间盘应力和应变关系、瞬时弹性模量及蠕变性能,并建立了蠕变本构模型。结果发现:随着压缩载荷和加载速率的增大,实验组的应变及蠕变与对照组相比均明显增大,瞬时弹性模量与对照组相比则明显减小,这表明髓核摘除后,椎间盘的承载能力受压缩载荷大小及加载速率的影响明显大于正常椎间盘。实验组仍可以采用Kelvin三参量固体模型描述其蠕变性能,预测腰椎间盘去核后的蠕变行为。研究结果可为椎间盘疾病的临床治疗及术后康复提供理论基础。     

Reflections on the mechanical structure of the base of the skull and on the face

Using thick sections of the base of the skull and face their mechanical structure is viewed from the engineering aspect and the anatomic solutions evolved are compared with those selected by Aerospatiale engineers for the concept and development of the Airbus. It is concluded that the anterior and middle cranial fossae, together with the face, constitute an inseparable mechanical assembly each of whose component units participate in the rigidity of the others. Since this mechanical assembly must provide maximal rigidity for minimal weight, this suggests that aeronautical solutions should throw much light on the detail of construction of the skull and face. Indeed, the rigidity and lightness of the latter are obtained by means of solutions familiar in aeronautics: the reliance on thin-shelled beams with a honeycomb filling, the diploe analogous to a preconstrained composite or sandwich structure, a system of frames, struts and stiffeners, and the use of fillets at the sites of junction of struts.     

邻苯二甲酸二丁酯对巨噬细胞吞噬能力的影响研究

目的:近期台湾地区食品及饮料中添加邻苯二甲酸酯类(塑化剂)的安全问题受到广泛关注,已有研究证实邻苯二甲酸酯类物质能影响人类生殖系统发育,但其对人体免疫系统影响尚不清楚。本文研究邻苯二甲酸二丁酯对巨噬细胞吞噬能力的影响,以期揭示其对人类健康的危害。方法:使用不同浓度邻苯二甲酸二丁酯体外处理小鼠腹腔巨噬细胞24小时,然后进行巨噬细胞对细菌E.coli以及诱导凋亡的小鼠胸腺细胞的吞噬实验,并检测其吞噬率和吞噬指数,从而评价其对巨噬细胞吞噬能力的影响。用流式细胞仪检测邻苯二甲酸二丁酯对巨噬细胞表面吞噬相关分子CD11b、CD54、CD36、TLR4和CD64的影响;利用siRNA技术对吞噬相关受体CD36进行表达干扰,验证其在邻苯二甲酸二丁酯抑制巨噬细胞吞噬能力中的作用。结果:经过24小时体外处理,不同浓度邻苯二甲酸二丁酯对巨噬细胞吞噬能力均有抑制作用,并且具有剂量依赖性。此外,邻苯二甲酸二丁酯能显著降低巨噬细胞清道夫受体CD36的表达。结论:研究结果证实邻苯二甲酸二丁酯通过降低细胞膜表面CD36表达从而抑制巨噬细胞吞噬能力。     

Studies on the influence of the structural modifications in the tracer on the immunoassay of progesterone

The main objective of the present study was to examine the influence of different bridges in radioiodinated tracers on the assay performance of progesterone using antibodies. Three homologous and two heterologous immunoassay systems for the measurement of progesterone in human serum are described. Using an antiserum raised against progesterone-11alpha-hemisuccinate-bovine serum albumin (BSA), assays with homologous radioligands, namely progesterone-11alpha-hemisuccinate-125I-tyrosine methyl ester (TME) and progesterone-11alpha-hemisuccinate-125I-histamine, heterologous bridge radioligand, namely progesterone-11alpha-hemiphthalate-125I-TME, and a heterologous site radioligand namely progesterone-3-(O-carboxymethyl) oxime (CMO)-125I-histamine were optimized. A homologous assay system, using antiserum raised against progesterone-3-carboxymethyl oxime-BSA and progesterone-3-CMO-125I-histamine as the radioligand was also optimized to develop a radio-immunoassay (RIA) for serum progesterone. Amongst the two homologous radioligands, viz., progesterone-11alpha-hemisuccinate-125I-histamine and the corresponding TME conjugate tracer, the former yielded a standard curve with a higher slope (-0.6) as compared to the latter (-0.5). The heterologous bridge system with progesterone-11alpha-hemiphthalate-125I-TME resulted in a more sensitive assay (slope of -0.8) than the homologous tracers, whilst the heterologous site radioligand, viz., progesterone-3-CMO-125I-histamine gave the most sensitive assay (slope of -1.2). The homologous assay with antiserum against progesterone-3-CMO-BSA and progesterone-3-CMO-125I-histamine tracer gave a standard curve having a slope of -0.97. The two antibodies developed against progesterone, viz., progesterone-11alpha-hemisuccinate-BSA and progesterone-3-CMO-BSA were characterized for their titre, sensitivity, and specificity. Considering the slope, sensitivity, cross-reactivity, and the quality of tracer, the assay system using antiserum against progesterone-11alpha-hemisuccinate-BSA and progesterone-3-CMO-125I-histamine was found to be suitable for the development of RIA for serum progesterone. The bridges used in an immunogen for production of antibodies, as well as in the preparation of tracer, have a great influence on the assay characteristics.     

Study on the interference of ticlopidine on the immune system

In-vitro and ex-vivo studies have been performed in order to investigate the possible interference of ticlopidine on different lymphocyte parameters. In vitro, ticlopidine displays a dose-dependent inhibition of both spontaneous and lectin-induced 3H-thymidine incorporation by normal lymphocytes. Moreover the highest drug concentrations also reduce the in-vitro PWM-stimulated Ig synthesis. Lymphocyte tests performed in healthy volunteers after a 10-day oral treatment (250 mg/day) show only a slight reduction of PHA- and ConA-induced proliferative responses and in-vitro PWM-stimulated Ig synthesis. The values found after treatment however remain within the normal range, excluding a clear interference of ticlopidine on the immune parameters tested. In addition the treatment does not affect the white blood cells nor the lymphocyte subset distribution identified by the monoclonal antibodies OKT3, OKT4 and OKT8.     

Experimental studies on the effect of duodenal contents on the epithelium of the esophagus

10 male BD IX rats and 15 male and female Wistar rats weighing between 250 and 300 g had an esophago-jejunostomy according to the method described by Levrat et al. (1962). Four weeks after surgery all 40 animals were sacrificed and examined macroscopically as well as histologically. All animals had deep ulcerative lesions in the lower half of the esophagus associated with hyperplasia, hyperkeratosis and akanthosis.