纳米相羟基磷灰石/胶原复合材料研究进展

综述羟基磷灰石（hydroxyapatite,HA）/胶原复合材料的研究进展,着重阐述自组装纳米相羟基磷灰石/胶原复合材料的制作方法、结构特点、体内植入后修复骨缺损的效果及降解过程.基于仿生学设计的纳米相羟基磷灰石/胶原复合材料,其HA纳米晶体约50～100nm,HA的C-轴沿胶原纤维排列,形成片状包绕胶原纤维束,HA和胶原分子之间为牢固的化学键性结合,为自组装的纳米结构,和自然骨中钙化的胶原相同.复合材料体内植入后降解和骨替代的过程与骨的改建过程相似.纳米相羟基磷灰石/胶原复合材料具有生物降解性高、表面能大、生物活性好、生物相容性好等特点,作为骨修复和重建材料具有更好的前景.     

纳米相羟基磷灰石/胶原复合材料研究进展

综述羟基磷灰石(hydroxyapatite,HA)/胶原复合材料的研究进展,着重阐述自组装纳米相羟基磷灰石/胶原复合材料的制作方法、结构特点、体内植入后修复骨缺损的效果及降解过程。基于仿生学设计的纳米相羟基磷灰石/胶原复合材料,其HA纳米晶体约50～100nm,HA的C-轴沿胶原纤维排列,形成片状包绕胶原纤维束,HA和胶原分子之间为牢固的化学键性结合,为自组装的纳米结构,和自然骨中钙化的胶原相同。复合材料体内植入后降解和骨替代的过程与骨的改建过程相似。纳米相羟基磷灰石/胶原复合材料具有生物降解性高、表面能大、生物活性好、生物相容性好等特点,作为骨修复和重建材料具有更好的前景。     

纳米羟基磷灰石在基因药物载体中的应用

目的讨论HAP纳米粒子作为药物或基因载体的进展。方法本文主要对HAP纳米粒子作为药物或基因载体的研究现状及他的生物相容性评价作了综述。结果指出了HAP纳米粒子作为药物或基因载体的主要发展趋势及存在的问题。结论药物或基因载体的研究较多,但是尚未找到一种理想的载体材料。作为一种新的药物基因载体,HAP纳米粒子有高的药物吸附量及良好的生物相容性,他有望作为一种新的基因药物载体。     

纳米含氟羟基磷灰石牙种植体的生物相容性

背景：有关纳米含氟羟基磷灰石牙种植体材料生物相容性的报道较少。 目的：检测纳米含氟羟基磷灰石牙种植体材料的体外生物相容性。 方法：采用溶胶凝胶技术分别制备羟基磷灰石与纳米含氟羟基磷灰石。①溶血性实验：在0.2 mL稀释兔抗凝血中分别加入0.01,0.15,0.2 g/L纳米含氟羟基磷灰石溶液、生理盐水及蒸馏水各10 mL,检测各组上清液吸光度值。②体外细胞毒性实验：分别以100%,50%纳米含氟羟基磷灰石浸提液、100%羟基磷灰石浸提液、苯酚溶液及RPMI1640培养液培养传至第2代的L929细胞,MTT法检测培养2,4,7 d的吸光度值。 结果与结论：体外溶血性实验显示,各浓度梯度纳米含氟羟基磷灰石的溶血率均在5%以内,符合医用材料的溶血要求。体外细胞毒性实验显示,随着培养时间的增加,100%,50%纳米含氟羟基磷灰石浸提液组细胞贴壁覆盖率增加,细胞密度增高,细胞为长梭形或多角形,细胞增殖及形态与RPMI1640培养液组、羟基磷灰石组无明显差别,细胞毒性为0级。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

羟基磷灰石/胶原-聚乳酸三维多孔框架材料的制备成形及分析

目的：合成新型的复合生物材料框架作为骨组织工程研究的细胞外基质材料。方法：本研究采用材料学自组装技术的原理，以Ⅰ型胶原蛋白为分子模板，引导钙磷盐在液相中的矿化，制备具有天然骨基质层状结构的羟基磷灰石／胶原复合材料，并以热致分相法制备了羟基磷灰石／胶原-聚乳酸复合三维多孔框架。结果：羟基磷灰石／胶原复合材料具有与天然骨基质相似的成分与结构，加入聚乳酸制备成三维多孔框架，孔隙直径界于50um-300um。结论：羟基磷灰石／胶原-聚乳酸复合三维多孔框架可能作为骨组织工程良好的细胞外基质材料。     

纳米羟基磷灰石/Ⅰ型胶原/壳聚糖复合支架材料的制备与优化

目的制备适合于骨组织工程的高强度纳米羟基磷灰石/Ⅰ型胶原/壳聚糖复合支架材料。方法用原位合成法代替传统的直接分散法,以胶原和壳聚糖为模板原位合成羟基磷灰石,再用冷冻干燥法使材料成型,制成可用于骨组织工程的多孔支架材料。结果制备的材料孔隙率高,孔的连通性好,材料中羟基磷灰石结晶度更小,表面能大,与有机物基底结合紧密,也能为成骨细胞的粘附提供更多的活性位点。结论用紫外辐照对材料进行处理,能使其抗压性能得到提高。制备的支架材料适用于骨组织工程。     

胶原羟基磷灰石（C／HA）组织埋藏

我们采用自制的Ｉ型胶原和羟基磷灰石做家兔皮下组织埋藏，分别在一个月和一个半月取出，组织切片证明应用胶原组比对照组的羟基磷灰石间的纤维结缔组织多，成纤维细胞浸润多，微血管丰富。炎症反应消失，无脱粒现象，结果证明胶原和羟基磷灰石联合植入组织比单用羟基磷灰石好。     

胶原/羟基磷灰石复合材料的制备及用于骨缺损修复的研究现状

通过模拟天然骨的结构,制备胶原/羟基磷灰石复合材料,与天然骨具有相似的组成、结构和性能,并具有良好的生物活性和生物降解性。本文就胶原/羟基磷灰石复合材料的制备方法、仿生形成机制、表征手段及骨缺损修复的应用等进行综述,并展望其未来发展方向。     

壳聚糖/纳米羟基磷灰石分层复合支架的生物相容性研究

制备壳聚糖/纳米羟基磷灰石(CS/nHA)分层复合支架,对其进行细胞毒性评价.分离培养大鼠软骨细胞接种于支架,相差显微镜和扫描电镜观察细胞的黏附及生长情况.动物皮下埋植试验观察其组织相容性.实验结果证实壳聚糖/纳米羟基磷灰石分层复合支架具有良好的生物相容性,有望成为较好的骨软骨组织工程支架.     

胶原-纳米羟基磷灰石复合支架的细胞相容性

背景：观察成骨细胞在生物材料上的形态、增殖和分化等项目,可评估生物支架材料的生物相容性。 目的：观察复合支架材料纳米羟基磷灰石/胶原对成骨细胞增殖、分化的影响。 方法：取新生24 h内Wistar大鼠的颅盖骨,采用改良胶原酶消化法进行成骨细胞原代培养,取第3代细胞与纳米羟基磷灰石/胶原支架或普通羟基磷灰石材料体外复合培养。培养3,6,9 d后,观察材料周边的细胞形态及支架材料对细胞分化、增殖的影响。 结果与结论：纳米羟基磷灰石/胶原材料较普通的羟基磷灰石材料更有利于成骨细胞的黏附、生长、分化、增殖,证实其生物相容性更好,有望成为一种新型的骨组织工程支架材料。     

纳米羟基磷灰石急性毒性试验研究

对纳米羟幕磷灰石(nano-HAP)进行急性毒性试验研究,为长期毒性试验和其他毒理学试验提供参考依据,并初步了解nano-HAP进入血液循环系统后,是否会迁移到其它器官和组织.实验选用清洁级的110～130g Wistar大鼠70只,分为7组,实验组各组剂量分别为21.66mg/kg、29.97 mg/kg、41.49 mg/kg、57.42 mg/kg、79.48 mg/kg、110.39 mg/kg,以生理盐水为对照组.单次尾静脉注射,14d内观察动物的毒性症状,记录动物死亡情况.将死亡动物解剖,对动物主要脏器进行病理组织学检查.结果显示nano-HAP在Wistar大鼠身上尾静脉注射时LD50为51.79 mg/kg,由病理结果推测实验动物的死亡原因是由血管栓塞所致.在一只最低剂量组死亡动物肝的汇管区及附近肝内有占位性蓝染无定型物,肝内灶性炎细胞浸润.说明nano-HAP颗粒在充分分散的情况下会通过血液循环进入到身体其它器官,因此有必要对nano-HAP的生物安全性进行进一步研究.     

Preparation and characterization of electrospun PLGA/gelatin nanofibers as a drug delivery system by emulsion electrospinning

Novel biocompatible poly(lactide-co-glycolide) (PLGA) nanofiber mats with favorable biocompatibility and good mechanical strength were prepared, which could serve as an innovative type of tissue engineering scaffold or an ideal controllable drug delivery system. Both hydrophobic and hydrophilic drugs, Cefradine and 5-fluorouracil were successfully loaded into PLGA nanofiber mats by emulsion electrospinning. The natural bioactive protein gelatin (GE) was incorporated into the nanofiber mats to improve the surface properties of the materials for cell adhesion. Nanofibrous scaffolds were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, contact angle and tensile measurements. Emulsion electrospun fibers with GE had perfect hydrophilic and good mechanical property. The in vitro release test showed thedrugs released from emulsion electrospun fibers, which achieved lower burst release. The cells cytotoxicity experiment indicated that emulsion electrospun fibers were less toxic and tended to promote fibroblasts cells attachment and proliferation, which implied that the electrospun fibers had promising potential application in tissue engineering or drug delivery.     

纳米羟基磷灰石前体与胶原自组装成类骨质复合材料的表征

文题释义： 纳米羟基磷灰石前体：纳米羟基磷灰石的悬浮液,制备方程为10Ca(NO₃)₂+6(NH₄)₂HPO₄+8NH₃•H₂O=Ca₁₀(PO₄)₆(OH)₂+ 20NH₄NO₃+6H₂O,反应时pH值10左右,反应完成后静置、洗涤,得到pH值8.0-9.0的纳米羟基磷灰石悬浮液。 自组装：是指基本的结构单元(分子、纳米材料、微米或更大尺度的物质)自发形成有序结构的一种技术。自组装过程中,基本结构单元在非共价键的相互作用下自发的成为一个稳定、外观具有一定规则的结构。 背景：制作类似于天然骨的材料来修复骨缺损,或者作为组织工程支架材料是研究的热点。 目的：探讨以纳米羟基磷灰石的前体及胶原为材料自组装成类骨质复合材料的可行性。 方法：将胶原材料分别浸泡于0.25%戊二醛溶液中0.5 h(A组),24 h(B组),72 h(C组)进行交联反应,D组将胶原浸泡于碳化二亚胺中交联4 h,将交联后的各组胶原浸泡于纳米羟基磷灰石前体溶液中7 d,制备类骨质复合材料。分析各组复合材料与天然骨的矿化物物相分析、组成成分及微观结构。 结果与结论：①X射线衍射分析：复合材料的非晶象衍射峰稍高于天然骨,各组复合物中非晶象变化不明显;随戊二醛交联时间的延长,材料晶体峰值有增高趋势;碳化二亚胺交联后材料的晶体衍射峰值较戊二醛交联材料稍低;②傅里叶转换红外光谱分析：复合材料的化学组成与天然骨的组成相似,都是由胶原和羟基磷灰石组成,其中羟基磷灰石中部分PO₄^3-被CO₃^2-离子取代;不同交联方法对材料无机相改变的影响差别不明显;③扫描电镜：胶原的不同交联方法对所形成晶体的形貌影响不明显：胶原纤维互相缠绕,其上有大量的细针样晶体沉积,聚成团,晶体分布均匀,晶体尺寸是纳米量级;④结果表明,以纳米羟基磷灰石前体及胶原为材料可制作自组装成类骨质复合材料。 ORCID: 0000-0003-1620-3673(张雪梅) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

A three-layered nano-carbonated hydroxyapatite/collagen/PLGA composite membrane for guided tissue regeneration

Functional graded materials (FGM) provided us one new concept for guided tissue regeneration (GTR) membrane design with graded component and graded structure where one face of the membrane is porous thereby allowing cell growth thereon and the opposite face of the membrane is smooth, thereby inhibiting cell adhesion in periodontal therapy. The goal of the present study was to develop a three-layered graded membrane, with one face of 8% nano-carbonated hydroxyapatite/collagen/poly(lactic-co-glycolic acid) (nCHAC/PLGA) porous membrane, the opposite face of pure PLGA non-porous membrane, the middle layer of 4% nCHAC/PLGA as the transition through layer-by-layer casting method. Then the three layers were combined well with each other with flexibility and enough high mechanical strength as membrane because the three layers all contained PLGA polymer that can be easily used for practical medical application. This high biocompatibility and osteoconductivity of this biodegraded composite membrane was enhanced by the nCHAC addition, for the same component and nano-level crystal size with natural bone tissue. The osteoblastic MC3T3-E1 cells were cultured on the three-layered composite membrane, the primary result shows the positive response compared with pure PLGA membrane.     

纳米晶胶原基骨复合骨髓单个核细胞修复下颌骨缺损

背景：纳米晶胶原基骨复合骨髓单个核细胞可促进各种干细胞生长,诱导新骨形成和成血管化,促进最终成骨。 目的：探讨骨髓单个核细胞复合纳米晶胶原基骨支架材料修复兔下颌骨缺损的可行性。 方法：选择健康新西兰大白兔27只,制备新西兰大白兔双侧下颌骨人工制备骨缺损模型,分为3组,实验组骨缺损处植入自体骨髓单个核细胞复合纳米晶胶原基骨支架材料,对照组骨缺损处植入纳米晶胶原基骨支架材料,空白组骨缺损处不植入任何材料。术后4,8,12周制备组织标本,行大体观察、影像学分析、苏木       精-伊红染色、扫描电镜检测。 结果与结论：影像学检查及组织学染色显示,实验组骨缺损处愈合程度、成骨速度及质量明显优于其他组;扫描电镜显示实验组材料与骨接触紧密,组织相容性好,无炎症刺激反应;分析牙CT数据及新骨形成检测结果表明,实验组骨修复情况优于其他组(P < 0.05)。表明骨髓单个核细胞复合纳米晶胶原基骨支架材料具有骨诱导和骨形成作用,可用于修复颌骨缺损。     

Near-infrared light for on-demand drug delivery

Abstract

There are currently many basic technologies for the controlled release of therapeutic molecules for the treatment of chronic pathologies such as arthritis, asthma, and diabetes. Examples of such technologies include selectively dissolvable capsules and tablets that are designed to respond to specific stimuli – such as pH, temperature, or specific enzymes – in a time-specific fashion. However, because of the biological variations between different individuals, which contribute to differences in the environments of therapeutic target locations, these technologies are not fully controllable. In the pursuit of drug-release technologies that are fully controllable, many approaches have been examined. One such approach involves the utilization of various light-sensitive molecules that are designed to release therapeutic agents when stimulated by light of specific wavelengths. Potential light sources that have been explored for this approach include ultraviolet (UV) and near-infrared (NIR) light. UV light, which exists in the range of 10–400 nm, is easily to utilize, and many chemicals and particles can be stimulated with light in this spectrum. Unfortunately, when used extensively – as would be the case for chronic pathologies – UV light can cause cellular damage at the molecular level, potentially leading to skin cancer. A viable alternative to UV light is NIR light, which offers deeper transdermal penetration and does not have many known adverse long-term side effects. Therefore, the purpose of this review is to investigate the use of NIR light and the associated therapeutic molecules for the controlled release of therapeutic agents in the potential treatment of chronic pathologies.     

羟基磷灰石／胶原人工骨在创伤后骨缺损修复中的初步研究

目的评估羟基磷灰石，胶原（hydroxyapatite/collagen，HAC）人工骨在创伤后骨缺损修复中的临床效果。方法48例创伤后四肢骨骨折患者，无其他病史，分为2组。试验组25例，其中男性15例，女性10例，年龄22～82岁，平均年龄45.3岁。对照组患者23例，其中男性13例，女性10例，年龄21～81岁，平均年龄46岁。对所有患者进行骨折切开复位，选择合适的内固定。试验组于固定后，在骨缺损处、骨髓腔、骨折线周围直接植骨，羟基磷灰石，胶原人工骨修复材料植入量0.4～4.0g不等。对照组不植入羟基磷灰石，胶原人工骨。结果两组46例病例获随访。试验组中2例失随访，余23例患者无局部或全身不良反应，骨折均达临床愈合。X线片显示,术后1～3个月材料植入区与缺损周围的骨组织间界限模糊，有新骨形成，3～6个月材料植入区内有明显的新骨长入，人工骨与骨组织融合，骨缺损基本修复。对照组3例延迟愈合和1例骨折不愈合患者在功能上恢复较差；试验组与对照组比较具有统计学意义，P〈0．05。结论胶原，羟基磷灰石人工骨具有良好的材料，细胞界面，使材料本身更具备与骨键合的能力。其三维多孔结构便于骨组织的长入，生物降解性有利于骨组织的改建和塑形，具有良好的临床应用前景。     

人骨髓间充质干细胞接种纳米晶胶原骨构建组织工程骨

目的观察体外培养的人骨髓间充质干细胞（mesenchymal stem cells,MSCs）与纳米晶羟基磷灰石/胶原骨（nano-hydroxyapatite/collagen,nHAC）的生物相容性及细胞在nHAC上的生长情况。方法全骨髓法体外培养骨髓间充质干细胞,应用成骨诱导剂诱导向成骨细胞表型转化,通过细胞活性、免疫组化鉴定诱导培养的成骨细胞的细胞学特性。通过倒置显微镜、扫描电镜观察细胞生长及其在nHAC上的生长情况。结果原代培养的骨髓细胞增殖迅速,10～12d左右即可稳定传代,传代细胞7～9d即可传代。经诱导培养的细胞的ALP染色阳性,Von Kossa染色阳性,可见钙化的基质沉积,呈现典型的成骨细胞形态和生物学特征。构建的MSCs与nHAC共培养的模型中,细胞可在nHAC表面良好贴壁。复合培养8天,分布于支架材料上的细胞大量增殖、分泌细胞外基质。第14天,大量细胞在材料表面和孔隙中生长。细胞之间广泛存在突起连接。结论nHAC适合种子细胞的贴附、生长和增殖,是组织工程良好的载体材料。     

Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery

This paper presents fabrication and testing of membrane-sealed hollow microneedles. This novel concept offers the possibility of a sealed microneedle-based transdermal drug delivery system in which the drug is stored and protected from the environment. Sealed microneedles were fabricated by covering the tip openings of out-of-plane silicon microneedles with thin gold membranes. In this way a leak-tight seal was established which hinders both contamination and evaporation. To allow drug release from the microneedles, three different methods of opening the seals were investigated: burst opening by means of pressure; opening by applying a small voltage in the presence of physiological saline; and opening as a result of microneedle insertion into the skin. It was found that a 170 nm thick gold membrane can withstand a pressure of approximately 120 kPa. At higher pressures the membranes burst and the microneedles are opened up. The membranes can also be electrochemically dissolved within 2 min in saline conditions similar to interstitial fluid present in the skin. Moreover, through in vivo tests, it was demonstrated that 170 nm thick membranes break when the microneedles were inserted into skin tissue. The proposed concept was demonstrated as a feasible option for sealing hollow microneedles. This enables the realization of a closed-package transdermal drug delivery system based on microneedles.