聚(D,L-乳酸)/羟基磷灰石复合材料的体外降解行为

将用取向模压增强的聚 ( D,L-乳酸 ) /羟基磷灰石 ( PDLLA/ HA)复合物圆棒 ( 3.2 mm)在37℃的生理盐水中进行降解试验 ,结果显示 HA对 PDL LA的降解有显著的抑制作用 ,圆棒的力学强度保持时间比纯 PALL A棒长。讨论了 PDL LA在 HA存在下的降解机理     

骨组织工程用聚DL—乳酸多孔三维结构的制备与表征

采用“溶剂浇铸——颗粒滤沥”方法制备了分子量为 3.9× 10 4道尔顿的聚 DL-乳酸 ( PDL LA)多孔支架并对其进行了表征 ,结果表明 ,其孔隙率高达 88% ,其中孔径为 80～ 150 μm的有效孔占 70 % ;SEM结果进一步显示 ,该三维多孔支架的孔呈均匀分布且相互连通 ,适用于骨组织工程     

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。     

HA/PDLLA复合材料体内植入的组织学观察

可吸收骨折内固定材料要求具有较高的初始强度及良好的生物相容性。对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进行骨内植入实验。大体观察结果表明:HA/PDLLA 材料强度良好,周围无明显的炎性反应。结论:HA/PDLLA复合材料强度较好,适用于松质骨骨折的固定, 且生物相容性良好。     

优化磷酸三钙/聚磷酸钙纤维/聚乳酸软骨组织工程支架材料的配比

背景：前期实验显示,聚乳酸存在刚度差,降解缓慢,降解后期降解液明显偏于酸性,易在细胞培养时引起无菌性炎症反应等缺点。 目的：在前期工作的基础上,优化聚乳酸支架材料实验方案和配比。 方法：自制聚磷酸钙纤维和β-磷酸三钙为添加材料,聚左旋乳酸为基体材料,采用溶媒浇铸/粒子滤取技术与气体发泡相结合制备配比20/30/50磷酸三钙/聚磷酸钙纤维/聚乳酸软骨组织工程支架复合材料。 结果与结论：①磷酸三钙/聚磷酸钙纤维/聚乳酸支架材料具有三维、连通、微孔网状结构,孔隙率在70%~95%。②孔隙率相近时,该支架材料的压缩模量比纯聚乳酸支架的压缩模量有了明显提高。③支架材料的降解率可通过加入聚磷酸钙纤维和支架的孔隙率加以调控。④β-磷酸三钙的加入使降解液pH值保持在6.0~7.0之间,避免了酸性降解产物引起的无菌性炎症反应。说明磷酸三钙/聚磷酸钙纤维/聚乳酸支架材料的物理力学性能和降解性能基本满足软骨组织工程的要求。     

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     

聚磷酸钙纤维增强聚右旋乳酸软骨组织工程支架材料的制备及性能

背景:传统的支架材料聚乳酸、聚乙醇酸及二者的共聚物,具有良好的生物相容性,并已广泛用于制造细胞传递和组织工程支架。但还存在易变形、降解时间长等缺点。目的:在前期工作的基础上,制备了聚磷酸钙纤维增强聚右旋乳酸软骨组织工程支架复合材料,对其物理、力学及降解性能进行了实验研究和理论分析,旨在验证前期优化配方的可行性。方法:以自制聚磷酸钙纤维为增强材料,聚右旋乳酸为基体材料,纤维与基体的配比为67/33,采用溶媒浇铸/粒子滤取技术与气体发泡相结合的方法制备了聚磷酸钙纤维增强聚右旋乳酸软骨组织工程支架复合材料,测试了该复合材料的物理力学性能和降解性能。结果与结论:聚磷酸钙/聚右旋乳酸支架材料具有高的孔隙率,孔隙率在80%～93%之间,压缩模量比纯聚乳酸支架的压缩模量有了明显提高,具有可控的降解性能,能为细胞的培养提供三维空间环境。结果提示聚磷酸钙纤维增强聚右旋乳酸支架复合材料的力学性能和生物降解特性基本满足软骨组织工程的要求,故可用作软骨组织工程支架材料。     

低强度脉冲超声波作用下羟基磷灰石/磷酸三钙三维支架上成骨细胞的生物学行为的研究

目的评价低强度脉冲超声波对羟基磷灰石(HA)/磷酸三钙(TCP)三维多孔支架材料上的MC3T3-E1成骨细胞的生物学行为的影响。方法将鼠MC3T3-E1成骨细胞与HA/TCP支架材料复合培养4 d和7 d。超声组每天接受20 min的低强度脉冲(1 MHz)超声波辐照,对照组为不开功率源的假辐照。通过观察成骨细胞在支架材料上的附着和细胞活力,检测细胞长入支架深度、DNA含量等指标评价低强度脉冲超声波对成骨细胞生物学行为的影响。结果 14 d和7 d时超声组HA/TCP支架材料上成骨细胞生长密度高于对照组。24 d和7 d时超声组HA/TCP支架材料上成骨细胞长入深度较对照组分别增加了34.45%和23.45%,4 d时二者差异无统计学意义(P=0.057),而7 d差异有统计学意义(P=0.032)。34 d和7 d时超声组较对照组DNA含量分别增加了27.54%(P=0.000)和24.39%(P=0.000),差异均有显著统计学意义。结论加载低强度脉冲超声波有利于成骨细胞在HA/TCP支架材料上的生长与增殖。     

聚左旋乳酸/壳聚糖纳米纤维三维多孔支架复合骨髓间充质干细胞修复兔骨缺损**△

背景：骨髓间充质干细胞具有向多种间质细胞谱系分化的能力,且支架材料的性能对骨缺损的修复有重要影响。 目的：观察聚左旋乳酸/壳聚糖纳米纤维三维多孔支架复合骨髓间充质干细胞治疗骨缺损。 方法：对骨缺损模型兔分别采用空白植入、髂后上棘自体松质骨移植、聚左旋乳酸/壳聚糖纳米纤维多孔支架移植和复合了骨髓间充质干细胞的聚左旋乳酸/壳聚糖纳米纤维多孔支架移植修复缺损部位。 结果与结论：至移植12周,移植复合了骨髓间充质干细胞的聚左旋乳酸/壳聚糖纳米纤维多孔支架的实验兔的缺损处有骨组织生成,支架材料降解,已完成缺损修复,其修复情况接近松质骨组;髂后上棘自体松质骨移植的实验兔的缺损修复完好,新形成的骨组织较规则;只植入聚左旋乳酸/壳聚糖纳米纤维多孔支架的实验兔有少量骨组织形成,材料部分降解;空白植入的实验兔缺损处无新生骨组织生成,主要由纤维结缔组织填充。说明新型的生物支架材料聚左旋乳酸/壳聚糖纳米纤维三维多孔支架与来源于新西兰大白兔的骨髓间充质干细胞复合培养后,植入同种异体兔股骨髁缺损处,使骨缺损的修复速度加快,表现为较好的体内诱导成骨的作用。     

聚L乳酸/β-磷酸三钙可吸收材料体内降解过程中的生物力学特性

背景：临床应用的金属内固定材料初始弯曲强度及弹性模量约为皮质骨的4倍及20倍,其力学性能不能随骨愈合过程动态变化,出现医学上的“应力遮挡效应”,影响骨愈合且需要二次手术取出。 目的：观察β-磷酸三钙与聚L乳酸复合可吸收内固定材料在动物体内降解后的生物力学特性。 方法：在30只新西兰大白兔腰背部左侧皮下植入聚L乳酸可吸收棒状材料为对照组,右侧植入聚L乳酸/β-磷酸三钙可吸收棒状材料作为实验组。于术前及术后4,8,12,16,24周观察两组材料的弯曲强度、剪切强度及扭转强度。 结果与结论：降解过程中两组材料的弯曲强度、剪切强度及扭转强度随时间的延长呈逐步下降趋势;术后12,16,24周实验组材料弯曲强度均高于对照组材料(P < 0.05)。术后4,8,12,16,24周实验组材料剪切强度均高于对照组材料(P < 0.05)。术后各时间点实验组材料扭转强度均稍高于对照组材料,但差异无显著性意义(P > 0.05)。说明聚L乳酸/β-磷酸三钙可吸收材料的体内降解速度较纯聚L乳酸慢,其力学强度能维持较长时间,可满足松质骨骨折的固定及骨组织愈合的要求。     

Effect of in vitro degradation of poly(D,L-lactide)/beta-tricalcium composite on its shape-memory properties

The in vitro degradation characteristic and shape-memory properties of poly(D,L-lactide) (PDLLA)/beta-tricalcium phosphate (beta-TCP) composites were investigated because of their wide application in biomedical fields. In this article, PDLLA and crystalline beta-TCP were compounded and interesting shape-memory behaviors of the composite were first investigated. Then, in vitro degradation of the PDLLA/beta-TCP composites with weight ratios of 1:1, 2:1, and 3:1 was performed in phosphate buffer saline solution (PBS) (154 mM, pH 7.4) at 37 degrees C. The effect of in vitro degradation time for PDLLA/beta-TCP composites on shape-memory properties was studied by scanning electron microscopy, differential scanning calorimetry, gel permeation chromatography, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The changes of structural morphology, glass transition temperature (T(g)), molecular weight, and weight loss of composites matrix and pH change of degradation medium indicated that shape-memory effects at different degradation time were nonlinearly influenced because of the breaking down of polymer chain and the formation of degradation products. Furthermore, the results from XRD and FTIR implied that the degradation products, for example, hydroxyapatite (HA), calcium hydrogen phosphate (CaHPO(4)), and calcium pyrophosphate (Ca(2)P(2)O(7)) phases also had some effects on shape-memory properties during the degradation.     

Development and in vitro characterisation of novel bioresorbable and bioactive composite materials based on polylactide foams and Bioglass for tissue engineering applications

Bioactive and bioresorbable composite materials were fabricated using macroporous poly(DL-lactide) (PDLLA) foams coated with and impregnated by bioactive glass (Bioglass) particles. Stable and homogeneous Bioglass coatings on the surface of PDLLA foams as well as infiltration of Bioglass particles throughout the porous network were achieved using a slurry-dipping technique in conjunction with pre-treatment of the foams in ethanol. The quality of the bioactive glass coatings was reproducible in terms of thickness and microstructure. Additionally, electrophoretic deposition was investigated as an alternative method for the fabrication of PDLLA foam/Bioglass composite materials. In vitro studies in simulated body fluid (SBF) were performed to study the formation of hydroxyapatite (HA) on the surface of PDLLA/Bioglass composites. SEM analysis showed that the HA layer thickness rapidly increased with increasing time in SBF. The high bioactivity of the PDLLA foam/Bioglass composites indicates the potential of the materials for use as bioactive, resorbable scaffolds in bone tissue engineering.     

Proliferation of chondrocytes on porous poly(DL-lactide)/chitosan scaffolds

Porous poly(DL-lactide)(PDLLA)/chitosan scaffolds with well-controlled pore structures and desirable mechanical characteristics were fabricated via a combination of solvent extraction, phase separation and freeze-drying. These scaffolds were further evaluated for the proliferation of isolated rabbit chondrocytes in vitro for various incubation periods up to 4 weeks in order to finally use them for the cartilage tissue engineering. MTT assay data revealed that the number of cells grown on PDLLA/chitosan scaffolds measurably increased with the weight ratio of the chitosan component and was significantly higher than those collected from pure PDLLA scaffolds for the entire incubation period. Scanning electron microscopy examinations, histological observations and proteoglycan measurements indicated that the resulting PDLLA/chitosan scaffolds exhibited increasing ability to promote the attachment and proliferation of chondrocytes, and also helped seeded chondrocytes spread through the scaffolds and distribute homogeneously inside compared to pure PDLLA scaffolds. Immunohistochemical staining verified that these PDLLA/chitosan scaffolds could preserve the phenotype of chondrocyte and effectively support the production of type II collagen.     

Preparation and characterization of porous PDLLA/HA composite foams by supercritical carbon dioxide technology

A composite poly(D,L)lactic acid (PDLLA)/hydroxyapatite (HA) biomaterial was prepared by in situ polymerization of D,L-lactide monomer and HA. Supercritical CO2 (SC CO2) technology was developed to prepare the biodegradable composite foams for use in tissue regeneration. In this technology, NaCl particles were used as porogen to produce an open-pore structure. Organic solvents were not used and high temperature was not necessary. The problem with pore interconnectivity was resolved. High-porosity composite foams (up to 90% +/- 2% porosity) were obtained with pore sizes ranging from 100 to 300 microm suitable for cell seeding. The microstructure and morphology of the composite foams could be controlled by saturation pressure, saturation time, and temperature as well as amount of NaCl particles. The compressive strength and water absorbability of the composite foams were also determined. With an increase in HA amount, the molecular weight of PDLLA/HA composite foams decreased, but the mechanical strength and hydrophilicity increased slightly.     

In vitro evaluation of novel bioactive composites based on Bioglass-filled polylactide foams for bone tissue engineering scaffolds

Highly porous poly(DL-lactic acid) (PDLLA) foams and Bioglass-filled PDLLA composite foams were characterized and evaluated in vitro as bone tissue engineering scaffolds. The hypothesis was that the combination of PDLLA with Bioglass in a porous structure would result in a bioresorbable and bioactive composite, capable of supporting osteoblast adhesion, spreading and viability. Composite and unfilled foams were incubated in simulated body fluid (SBF) at 37 degrees C to study the in vitro degradation of the polymer and to detect hydroxyapatite (HA) formation, which is a measure of the materials' in vitro bioactivity. HA was detected on all the composite samples after incubation in SBF for just 3 days. After 28 days immersion the foams filled with 40 wt % Bioglass developed a continuous layer of HA. The formation of HA for the 5 wt % Bioglass-filled foams was localized to the Bioglass particles. Cell culture studies using a commercially available (ECACC) human osteosarcoma cell line (MG-63) were conducted to assess the biocompatibility of the foams and cell attachment to the porous substrates. The osteoblast cell infiltration study showed that the cells were able to migrate through the porous network and colonize the deeper regions within the foam, indicating that the composition of the foams and the pore structures are able to support osteoblast attachment, spreading, and viability. Rapid formation of HA on the composites and the attachment of MG-63 cells within the porous network of the composite foams confirms the high in vitro bioactivity and biocompatibility of these materials and their potential to be used as scaffolds in bone tissue engineering and repair.     

Biocompatibility of bioresorbable poly(L-lactic acid) composite scaffolds obtained by supercritical gas foaming with human fetal bone cells

The aim of this investigation was to test the biocompatibility of three-dimensional bioresorbable foams made of poly(L-lactic acid) (PLA), alone or filled with hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP), with human primary osteoblasts, using a direct contact method. Porous constructs were processed by supercritical gas foaming, after a melt-extrusion of ceramic/polymer mixture. Three neat polymer foams, with pore sizes of 170, 310, and 600 microm, and two composite foams, PLA/5 wt% HA and PLA/5 wt% beta-TCP, were examined over a 4-week culture period. The targeted application is the bone tissue-engineering field. For this purpose, human fetal and adult bone cells were chosen because of their highly osteogenic potential. The association of fetal bone cells and composite scaffold should lead to in vitro bone formation. The polymer and composite foams supported adhesion and intense proliferation of seeded cells, as revealed by scanning electron microscopy. Cell differentiation toward osteoblasts was demonstrated by alkaline phosphatase (ALP) enzymatic activity, gamma-carboxylated Gla-osteocalcin production, and the onset of mineralization. The addition of HA or beta-TCP resulted in higher ALP enzymatic activity for fetal bone cells and a stronger production of Gla-osteocalcin for adult bone cells.     

模压挤出条件对聚(D,L-乳酸)及其复合材料力学性能的影响

在辛酸亚锡的催化下由丙交酯开环聚合制备了聚（D，L）-乳酸（PDLLA），并用二苯基甲烷二异氰酸酯（MDI）作为扩链剂分别合成了MDI扩链聚（D，L）-乳酸（PDLLA/MDI）和MDI扩链聚（D，L）-乳酸/羟基磷灰石（PDLLA/HA/MDI）复合材料，采用自行设计的模压挤出设备着重研究了成型加工条件对这两类可生物降解材料力学性能的影响，实验结果表明，在最佳条件下PDLLA和PDLLA/MDI的弯曲强度分别为35.1MPa和51.3MPa，弯曲模量分别为2413.6MPa和1830.9MPa,PDLLA/HA和PDLLA/HA/MDI复合材料的弯曲强度分别为31.2MPa和55.4MPa。弯曲模量分别为1735.0MPa和2068.5MPa，可见，MDI扩链可显著提高PDLLA和PDLLA/HA复合材料的力学性能。     

Poly(D,L-lactide) foams modified by poly(ethylene oxide)-block-poly(D,L-lactide) copolymers and a-FGF: in vitro and in vivo evaluation for spinal cord regeneration

The first goal of this study was to examine the influence that poly(ethylene oxide)-block-poly(D,L-lactide) (PELA) copolymer can have on the wettability, the in vitro controlled delivery capability, and the degradation of poly(D,L-lactide) (PDLLA) foams. These foams were prepared by freeze-drying and contain micropores (10 microm) in addition of macropores (100 microm) organized longitudinally. Weight loss, water absorption, changes in molecular weight, polymolecularity (Mw/Mn) and glass transition temperature (Tg) of PDLLA foams mixed with various amounts of PELA were followed with time. It was found that 10wt% of PELA increased the wettability and the degradation rate of the polymer foams. The release of sulforhodamine (SR) was compared for PDLLA and PDLLA-PELA foams in relation with the foam porosity. An initial burst release was observed only in the case of the 90:10 PDLLA/PELA foam. The ability of the foam of this composition to be integrated and to promote tissue repair and axonal regeneration in the transected rat spinal cord was investigated. After implantation of ca. 20 polymer rods assembled with fibrin-glue, the polymer construct was able to bridge the cord stumps by forming a permissive support for cellular migration, angiogenesis and axonal regrowth.     

聚DL-乳酸/羟基磷灰石复合材料修复长骨缺损的实验研究

目的 :评价羟基磷灰石 (HA)复合聚DL 乳酸 (PDLLA )制备的材料体内成骨能力。方法 :将PDLLA和PDLLA/HA( 2 0wt % )材料采用盐结晶颗粒沥滤法制成三维多孔材料 ,45例 1cm兔桡骨去骨膜缺损分为三组 ,分别植入 2种材料和作空白对照 ,术后 2 ,4,8,12周行X线、组织学及扫描电镜观察骨生成状况 ,8、12周行生物力学测试 (三点折弯强度 )。结果 :泡沫状PDLLA/HA ( 2 0wt % )材料比纯PDLLA成骨更好 (P <0 .0 5 ) ,实验组与对照组相比差异有显著性 (P <0 .0 5 )。结论 :PDLLA具有良好的生物相容性 ,制成多孔状具有较好的骨传导性能 ,HA( 2 0wt % )的加入促进了多孔PDLLA的骨传导能力 ,提高了骨生成的质量。PDLLA/HA( 2 0wt % )复合材料是一种有临床应用前景的骨移植材料。