聚-L-乳酸/β-磷酸三钙多孔支架材料的制备及性能研究

以氯化钠为致孔剂,采用溶液浇铸致孔剂—粒子滤出复合法制备了不同比例梯度(9∶1,8∶2,7∶3)的聚-L-乳酸/β-磷酸三钙(PLLA/β-TCP)复合材料多孔支架,研究了PLLA/β-TCP多孔支架的孔隙率、力学性能、生物相容性。研究结果表明,随着制备过程中致孔剂用量的增加,多孔支架的孔隙率逐渐增加,而与致孔剂的颗粒大小基本无关;致孔剂的颗粒大小只影响多孔支架的孔径;材料的压缩强度和压缩模量随孔隙率的增大而降低;PLLA/β-TCP多孔复合支架材料具有良好的生物相容性。     

磷酸钙骨水泥/明胶微球复合支架的力学性能

选用α-磷酸三钙(tricalcium phosphate,TCP)系磷酸钙骨水泥(calcium phosphate based cements,CPC)和明胶微球(gelatin microspheres,GMS)复合体系,制备了仿生CPC/GMS多孔支架。比较了戊二醛交联对GMS溶胀度的影响,并考察了支架在模拟体液中降解引起的抗压强度变化。用扫描电镜、X射线衍射分析了支架不同降解时期的表面形貌和晶相组成。结果表明:GMS降解后可获得水化产物羟基磷灰石,具有贯通性通孔,孔径范围在100～500μm之间的多孔骨水泥支架;明胶的加入对骨水泥水化过程有促进作用;随GMS加入量的增加,支架的孔隙率从37%增大到84%,其相应抗压强度由28.7MPa逐渐降到2.5MPa。     

羟基磷灰石涂层的生物仿生法研究进展

羟基磷灰石的生物复合涂层具有很高的外科应用价值.制备羟基磷灰石复合材料的方法有很多种,其中仿生法模仿了自然界生理磷灰石的矿化机制,在类似于人体组织内环境条件的水溶液中自然沉积出磷灰石层.仿生法具有许多其它方法无可比拟的优越性.本文对近年来文献报道中出现的生物仿生法进行了综述,阐述了各种仿生法中包括对基体进行预处理使其表面官能团化,再将基体在模拟体液中浸泡从而使磷灰石自然沉积的模拟生物矿化的4个阶段的工艺过程及其仿生机理.     

聚乳酸/壳聚糖/氧化石墨烯载阿司匹林仿生支架的制备与表征

单纯的支架仿生结构在调节细胞行为和骨组织再生方面有一定的局限性，因此将仿生支架与纳米给药相结合成为一种提高支架功能的有效解决方案。本文采用相分离法成功制备了不同ASA （阿司匹林）含量的三维多孔PLA/CS/GO/ASA载药仿生复合支架。ASA的添加破坏了PLA球晶结构的形成，但对仿生微、纳米纤维结构的影响不大；实验范围内随ASA含量的增加，载药支架亲水性能有所改善，但孔隙率呈先减后增的趋势，均大于80%；溶血率和血小板黏附实验表明，控制ASA含量在5%以下可获得具有良好血液相容性的支架材料；体外细胞增殖实验则表明所制备的载药支架具有细胞相容性；低ASA含量可以促进MC3T3-E1细胞增殖，高含量的ASA对MC3T3-E1细胞有一定的抑制作用；药物缓释实验表明PLA/CS/GO/ASA载药仿生复合支架具有良好的ASA缓释性能。     

可注射nHA/PU复合多孔骨修复支架制备及表征

兼具良好孔隙率和原位任意塑形固化的可注射复合多孔骨修复材料在临床不规则骨缺损的治疗方面显示出巨大的优势。本研究通过优化双组分设计,以水为发泡剂制备可注射纳米羟基磷灰石/聚氨酯（nHA/PU）复合多孔支架。利用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、力学测试及Gillmore针测试等手段对制备的支架进行结构形貌、化学组成、力学性能和固化时间表征。结果表明,本研究制备的可注射nHA/PU复合多孔支架孔隙率高、孔隙贯通性好,孔径分布在100~700μm,适宜细胞和组织向孔内生长;添加20% nHA显著提高了PU支架的力学强度,但降低了支架的孔隙率;可注射支架在8h固化,适宜临床操作。本研究制备的可注射nHA/PU复合多孔支架在不规则骨缺损修复领域具有较大的应用潜力。     

气体发泡法制备PLLA/BCP多孔复合支架及其性能研究

用气体发泡法制备的聚乳酸(PLLA)多孔支架,力学性能通常随着孔隙率的增加而降低,且支架表面的疏水性限制着其在骨支架中的应用。通过共混PLLA与双相磷酸钙(BCP)陶瓷粉末,以碳酸氢铵(AB)作为致孔剂,采用气体发泡法制备了PLLA/BCP多孔复合支架,分析了AB粒径对支架孔径的影响以及AB和BCP的含量对PLLA支架力学性能及亲水性能的影响。结果表明,随着AB粒径的增大,支架的孔径尺寸也相应增大;随着AB含量的增加,PLLA/BCP复合支架的孔隙率相应增大、力学性能呈下降趋势;BCP的加入对PLLA支架的孔隙率影响不大,随着BCP含量的增加,支架的力学性能和亲水性能整体上升。通过调节AB的粒径和含量、BCP的含量,控制支架材料的孔隙率(52.2%~82.1%)、力学性能(压缩强度0.52~1.24MPa)以及亲水性能,制备的PLLA/BCP多孔复合支架能更好地满足骨组织工程的要求。     

壳聚糖/生物活性玻璃多孔复合支架的制备及界面增强作用

采用卵磷脂作为表面活性剂对溶胶-凝胶生物玻璃进行表面改性,并采用冷冻干燥法制备用于骨和软骨组织工程的壳聚糖/生物活性玻璃复合多孔支架(chitosan/bioglass porous composite scaffolds,CS/BGS),观察CS/BGS的显微形貌并测定抗压强度,探讨生物玻璃的表面改性对CS/BGS显微结构及力学强度的影响。研究表明:采用冷冻干燥法可以制备具有一定强度的三维连通的CS/BGS,且孔隙率达到90%以上。通过对生物玻璃表面改性可以在一定程度上提高CS/BGS的抗压强度。     

体外构建壳聚糖/β-甘油磷酸钠/明胶仿生梯度支架

针对软骨特定结构缺损后不能自我修复的特点,通过调控单层原料质量比,构建具有复杂分层结构的壳聚糖/β-甘油磷酸钠/明胶(chitosan/β-sodium glycerophosphates/gelatin,Cs/GP/Gel)仿生复合梯度支架。通过对比物理性能优选适宜比例的支架材料,并将骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)接种到梯度支架上考察其生物相容性。结果表明,Cs/GP/Gel复合梯度支架具有良好的吸水性能[(584.24±3.79)%～(677.47±1.70)%]、孔隙率[(86.34±5.10)%～(95.20±2.86)%]和降解性能[(86.09±2.46)%～(92.48±3.86)%]。扫描电镜(SEM)结果表明,支架材料在纵向维度呈现出明显的生理分层结构和孔径梯度渐进性,可有效模拟真实软骨的天然生理分层结构。比例为9:1:5的Cs/GP/Gel复合梯度支架适于作为骨软骨的支撑材料。对BMSCs-支架复合物Live/Dead染色后发现,细胞在梯度支架材料上存活、分布及伸展良好。该仿生梯度支架为开发新型生物医用材料提供了重要依据。     

钙硅磷基复合生物陶瓷的制备及其性能研究

本研究旨在探究不同比例β-TCP/CS复合生物陶瓷的制备方法及其性能。采用聚乙烯醇和聚乙二醇作为粘结剂和造孔剂,制备出具有良好生物相容性和可降解性能的多孔复合生物陶瓷。通过SEM、XRD、FTIR等测试方法对样品的形貌、相组成和化学结构进行分析,并测定其孔隙率、致密度和降解性能等性能指标。结果表明,质量比为70:30的β-TCP/CS样品具有较好的生物相容性和可降解性,烧结后结晶度高、致密度强,孔隙率稳定,能够促进成骨细胞增殖和分化,28天的体外降解率达到了26.4%。该研究为开发新型骨修复材料提供了一定的理论依据和实验参考,具有一定的应用前景。     

PLA/HA多孔生物支架的制备及性能研究

以聚乳酸(PLA)、羟基磷灰石(HA)为主要原料,氯化钠为致孔剂,采用溶液共混-粒子沥滤法制备了PLA/HA复合多孔生物支架,并测试研究了该PLA/HA多孔支架的孔隙率、孔隙连通率及力学性能。结果表明:PLA/HA(85/15)复合多孔支架的孔隙率略低于纯PLA多孔支架,可达到81.6%,可以满足组织工程对支架材料的要求。另外,PLA/HA支架材料的弯曲强度和压缩强度均在PLA与HA的质量比为85/15时达到最大值,分别为76.1和75.7 MPa。     

用硅烷偶联剂处理生物玻璃表面及其复合支架的制备

为了改善溶胶-凝胶生物活性玻璃与高分子材料的相容性,用硅烷偶联剂氨丙基三乙氧基硅烷对生物活性玻璃进行表面处理,并用X射线光电子能谱对处理后的生物活性玻璃的表面进行元素分析.结果表明:偶联剂通过Si-O-Si键被引入到生物活性玻璃表面.用处理后的生物活性玻璃与壳聚糖-明胶复合制备了多孔支架.扫描电子显微镜观察发现:复合多孔支架的两相相容性好,界面结合紧密;支架的孔隙连通、排列规则.力学测试表明:改性后的溶胶-凝胶生物活性玻璃与壳聚糖-明胶制备的复合支架力学性能得到明显改善.     

Porous chitosan/ZnO-doped bioglass composites as carriers of bioactive peptides

In this study, we aimed to assess whether the composite of chitosan/ZnO-doped bioglass can be applied as a suitable scaffold for the incorporation of bioactive peptides. Material of a porous composite with 1:1 ratio of bioglass:polymer was produced and used as a matrix for delivery of peptide. A peptide with the PEPTIDES sequence (Pro-Glu-Pro-Thr-Ile-Asp-Glu-Ser) was chosen as a model peptide. Microstructure and pore sizes of chitosan/ZnO-doped bioglass were assessed. Open porosity and pore sizes of the composite were suitable for enabling the migration of cells and ensuring the easy delivery of nutrients within the implant. In addition, composite showed bioactivity and bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa strains. Peptide alone did not have any cytotoxic activity on human fibroblasts and keratinocytes. Also it did not show any antibacterial properties and did not cause hemolysis of red blood cells. The peptide incorporated in composite showed a rapid release in the kinetics profile. The obtained results indicate that there is the technological possibility to incorporate peptides in chitosan/ZnO-doped bioglass scaffolds. Such biomaterials have potential application in bone tissue engineering.     

The Tunable Porous Structure of Gelatin–Bioglass Nanocomposite Scaffolds for Bone Tissue Engineering Applications: Physicochemical,Mechanical, and In Vitro Properties

Unidirectional freeze‐casting method is used to fabricate gelatin–bioglass nanoparticles (BGNPs) scaffolds. Transmission electron microscopy (TEM) images show that sol–gel prepared BGNPs are distributed throughout the scaffold with diameters of less than 10 nm. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetric are used to evaluate the physicochemical properties of BGNPs. Scanning electron microscopy (SEM) micrographs present an oriented porous structure and a homogeneous distribution of BGNPs in the gelatin matrix. The lamellar‐type structure indicates an improvement of mechanical strength and absorption capacity of the scaffolds. Increasing the concentration of BGNPs from 0 to 50 wt% have no noticeable effect on pore orientation, but decreases porosity and pore size distribution. Increase in BGNPs content improves the compressive strength. The absorption and biodegradation rate reduces with augmentation in BGNPs concentration. Bioactivity is evaluated through apatite formation after immersion of the nanocomposites in simulated body fluid and is verified by SEM–energy‐dispersive X‐ray spectroscopy (EDS), an element map analysis, X‐ray powder diffractometer, and FTIR spectrum. SEM images and methyl thiazolyl tetrazolium assay confirm the biocompatibility of scaffolds and the supportive behavior of nanocomposites in cellular spreading. The results show that gelatin–(30 wt%)bioglass nanocomposites have incipient physicochemical and biological properties.     

Effect of collagen type I and vitamin D3 functionalization of biomimetic bioglass scaffolds on hydroxyapatite condensation

In previous work, biomimetic nanostructured scaffolds for bone reconstruction, elaborated by sol-gel synthesis coupled to spray drying and template addition, which presented faster bioactivity than the scaffolds obtained by traditional synthesis process [1]. These scaffolds with hierarchical porous structures had an interconnected pore network, a critical parameter in the development of new tissue and biomolecules migration. To enhance their bioactivity, the present work proposes the bioglass scaffold functionalization by using different biomolecules: Collagen type I and Cholecalciferol (vitamin D3) at different concentrations to facilitate the cellular adhesion and stimulate the grown factors. To characterize the functionalized scaffolds and the hydroxyapatite formation by incubation in simulated body fluid, scanning electron microscopy, microanalysis and x-ray diffraction were used to determine changes in the scaffold surface. Different hydroxyapatite morphologies were obtained depending of the biomolecules, such as columns in the collagen-functionalized scaffolds or agglomerated spheres in the cholecalciferol-functionalized scaffolds, covering the entire surface at day two after immersion in SBF.     

Processing of ZrO2 scaffolds coated by glass–ceramic derived from 45S5 bioglass

Three dimensional, highly porous, ZrO₂ scaffolds coated by glass–ceramic derived from 45S5 bioglass were fabricated. The surface reactivity of 45S5 in aqueous solution was investigated as a function of the immersion time. The influence of the solid loading on the rheological behavior of 45S5 aqueous slips with ammonium polyacrylate (NH₄PA) was studied; besides the effect of poly(vinyl)alcohol (PVA) on the relative viscosity was determined. The structure and microstructure of uncoated and coated ZrO₂ scaffolds were characterized. The high ionic exchange capability of 45S5 was demonstrated by the pH rise, the significant weight loss and the amorphous calcium phosphate nucleation, upon its immersion in aqueous solution. The addition of PVA did not affect the dispersion properties of the 45S5 powder, which were basically controlled by its negative surface charge. 30 wt% 45S5 slips with 4 wt% PVA exhibited a yield stress and an adequate viscosity in the low shear rate range, to produce a bioglass coating into the ZrO₂ scaffold. The glass-ceramic coating was distributed along the strut surfaces, forming a thin film without altering the porosity and the strut thickness of the original ZrO₂ scaffold structure.     

Effect of particle size and freezing conditions on freeze-casted scaffold

Freeze casting is one of the emerging and novel manufacturing routes to fabricate porous scaffolds for various applications including orthopedic implants, drug delivery, energy storing devices etc. Thus, it becomes important to understand this process in a deeper sense. Present work was focused to study the effect/influence of basic parameters, particle sizes, and freezing conditions on the mechanical properties and microstructures of porous scaffold fabricated by freeze casting. β-tricalcium phosphate (β-TCP) and hydroxyapatite (HAp) powder with particle sizes of 10?μm and 20?nm were used. Prepared slurries were freeze casted at constant freezing temperature (5?°C) and constant freezing rate (1.86?°C/min) to study the effect of freezing conditions on mechanical and microstructural properties of the porous scaffold. It was observed that porous scaffold fabricated by nanoparticles has given better porosity (63.22–76.16%), than scaffold fabricated by microparticles (13–43.05%) at given solid loading of both freezing conditions. Although, the range of pore size of the scaffold fabricated by nanoparticles (CFR: 2.60–0.84?μm; CFT: 1.66–0.46?μm) was lower than that of scaffold fabricated by microparticles (CFR: 9.45–4.83?μm; CFT: 4.72–2.84?μm). The compressive strength of scaffolds prepared by nanoparticles was in the range of trabecular bone. Moreover, the results of present work will pave the way for the fabrication of porous scaffold with desired pore size and porosity for various implants, energy, and drug delivery applications.     

Silk fibroin/chitosan/heparin scaffold: preparation,antithrombogenicity and culture with hepatocytes

Antithrombogenicity is very important for tissue engineering scaffolds used in situations involving contact with blood. A silk fibroin/chitosan (SFCS) scaffold has been developed for liver tissue engineering with porous structure, suitable mechanical properties and biocompatibility. Because the interaction between silk fibroin and blood coagulation factors can lead to blood coagulation, the anticoagulant property of the SFCS scaffold should be improved. Heparin was added into SFCS scaffold under mild conditions. The effects of heparin on the morphology, swelling properties, structure, porosity, mechanical properties, antithrombogenicity and cytocompatibility of the SFCS scaffold were studied. SFCS scaffold containing heparin maintains the porous structure and good mechanical properties of the fibroin‐based scaffold; moreover, it is not cytotoxic. Addition of heparin leads to the SFCS scaffold being blood‐compatible and an effective heparin‐delivering system. The anticoagulant property of the SFCS scaffold can be improved by the addition of heparin, which may be helpful for scaffolds used in situations involving contact with blood. Copyright © 2009 Society of Chemical Industry     

Ultrasonication‐Induced Modification of Hydroxyapatite Nanoparticles onto a 3D Porous Poly(lactic acid) Scaffold with Improved Mechanical Properties and Biocompatibility

A 3D porous poly(lactic acid) (PLA) scaffold with high porosity and well‐connected pores is fabricated using a vacuum‐assisted solvent casting technique. Its surface is modified with hydroxyapatite (HA) nanoparticles using ultrasonication to prepare an HA‐modified PLA/HA scaffold. For reference, an HA‐blended (b‐PLA‐HA) scaffold is fabricated via the solution blending method. The morphology, porosity, hydrophilicity, swelling ratio, mechanical properties, and cell viability of the PLA, b‐PLA‐HA, and PLA/HA scaffolds are systematically studied. The results show that HA nanoparticles are successfully introduced onto the surface of the PLA/HA scaffold, and strong interactions occur between the HA nanoparticles and the PLA matrix. The PLA/HA scaffold still has a high porosity of more than 85% after ultrasonication. The hydrophilicity and mechanical properties of the PLA/HA scaffold are significantly higher than those of the PLA and b‐PLA‐HA scaffolds. Compared with the PLA and b‐PLA‐HA scaffolds, the attachment and growth of mouse embryonic osteoblasts cells (MC3T3‐E1) cultured on the PLA/HA scaffold significantly improve, due to most HA nanoparticles on the surface, resulting in a good and direct interaction between the cells and the scaffold. Therefore, the PLA/HA scaffold possesses great potential to be used as a tissue engineering scaffold.     

Bioactive and Biocompatible Macroporous Scaffolds with Tunable Performances Prepared Based on 3D Printing of the Pre‐Crosslinked Sodium Alginate/Hydroxyapatite Hydrogel Ink

Bioactive and biocompatible porous scaffold materials with adjustable pore structures and drug delivery capability are one of the key elements in bone tissue engineering. In this work, bioactive and biocompatible sodium alginate (SA)/hydroxyapatite (HAP) macroporous scaffolds are facilely and effectively fabricated based on 3D printing of the pre‐crosslinked SA/HAP hydrogels followed by further crosslinking to improve the mechanical properties of scaffolds. The pore structures and porosity (>80%) of the porous scaffolds can be readily tailored by varying the formation conditions. Furthermore, the in vitro biomineralization tests show that the bioactivity of the porous scaffolds is effectively enhanced by the addition of HAP nanoparticles into the scaffold matrix. Furthermore, the anti‐inflammatory drug curcumin is loaded into the porous scaffolds and the in vitro release study shows the sustainable drug release function of the porous scaffolds. Moreover, mouse bone mesenchymal stem cells (mBMSCs) are cultured on the porous scaffolds, and the results of the in vitro biocompatibility experiment show that the mBMSCs can be adhered well on the porous scaffolds. All of the results suggest that the bioactive and biocompatible SA/HAP porous scaffolds have great application potential in bone tissue engineering.