A novel composite membrane of chitosan-carboxymethyl cellulose polyelectrolyte complex membrane filled with nano-hydroxyapatite I. Preparation and properties

A novel tri-component composite membranes of chitosan/carboxymethyl cellulose (CS/CMC) polyelectrolyte complex membranes filled with different weight ratios of nano-hydroxyapatite (n-HA)(0, 20, 40 and 60 wt%), namely, n-HA/CS/CMC composite membrane, were prepared by self-assembly of static electricity. The structure and the properties of the composite membranes were investigated by Fourier transformed infrared spectroscopy(IR), X-ray diffraction(XRD), Scanning electron microscopy(SEM), mechanical performance measurement, swelling behavior test, and soaking behavior study in phosphate buffered saline (PBS) and simulate body fluid (SBF). The results showed that the n-HA/CS/CMC composite membrane was formed though superficial static electricity interaction among n-HA, CS and CMC. For the n-HA/CS/CMC composite membrane, the microstructure compatibility, mechanical property, swelling behavior, the degradation and bioactivity in vitro of the composite membrane were improved by the addition of n-HA, compared with CS/CMC polyelectrolyte complex membrane. Moreover, the n-HA/CS/CMC composite membrane with 40 wt% n-HA had the most highest mechanical property, which suggested that the novel n-HA/CS/CMC composite membrane with 40 wt% n-HA was more suitable to be used as guided bone tissue regeneration membrane than CS/CMC polyelectrolyte complex membrane.     

Preparation and properties of a novel bone repair composite: nano-hydroxyapatite/chitosan/carboxymethyl cellulose

Nano-hydroxyapatite/chitosan/carboxymethyl cellulose (n-HA/CS/CMC) composites with weight ratios of 70/10/20, 70/15/15 and 70/20/10 were prepared through a co-solution method. The properties of the composites were characterized by means of burn-out test, IR, XRD, TEM and universal material testing machine. The degradation and bioactivity were also investigated by in vitro test in a simulated body fluid (SBF) for 8 weeks. The results showed that n-HA particles were dispersed uniformly in organic phase, and strong chemical interactions formed among the three phases. Moreover, the composites were similar to natural bone in morphology and size. In addition, the compressive strength was improved compared with n-HA/CS composite. The biodegradation rate was controllable by altering weight ratio of the CS/CMC. Meanwhile, the composites could induce apatite particles to deposit in SBF. All the above results indicate that the novel composites of n-HA/CS/CMC have a promising prospect used for bone repair materials in view of the good mechanical property, adjustable biodegradation rate and bioactivity in SBF. Additionally, the study would provide a good guide to exploit clinical application of natural cellulose.     

纳米羟基磷灰石/壳聚糖-羧甲基纤维素复合支架材料的研究

用冷冻干燥法制备了不同比例的纳米羟基磷灰石/壳聚糖-羧甲基纤维素(n-HA/CS-CMC)无机/有机复合多孔支架材料, 并探讨了其复合机理及无机组分n-HA对复合支架的结构形貌、力学性能、体外降解性能的影响. 结果表明, 其复合支架主要是通过无机组分n-HA均匀分散充填在CS-CMC聚电解质有机网络结构中形成的, 且三组分间有较强的化学键合. 无机组分n-HA的加入使孔结构变得不规则, 孔隙率略有减小, 使复合支架的抗压缩强度提高, 并且可使其体外降解速度减慢. 无机组分n-HA含量为40\%复合支架材料的性能最佳, 有望用作骨组织工程支架材料.     

分级多孔壳聚糖/聚乳酸复合支架的制备及骨修复性能

为了仿生莲藕内部的贯穿大孔结构,以生物相容性好的壳聚糖(CS)作为基质材料,利用冰粒致孔、石蜡模具和冰模具成型3种成型方法制备了分级多孔CS支架材料,然后与力学强度较高的聚乳酸(PLLA)复合,制备网络互穿CS/PLLA复合支架。通过SEM、压缩强度测试和兔股骨髁骨缺损模型对CS/PLLA复合材料的形貌、力学强度和骨修复性能进行了表征。结果表明:利用冰模具制备的CS/PLLA复合支架能可控、批量制备,具有微米-毫米分级多孔结构,大孔孔径约为2mm,内部均匀分布着孔径约为60μm的贯穿微孔,并在微孔内形成密集的PLLA絮状网络结构。干态复合材料的压缩强度和模量分别比纯CS支架的提高了6倍和15倍。体内植入实验结果表明,CS/PLLA复合材料能够促进骨缺损的愈合,并随着新骨的形成,复合材料逐渐被降解吸收。     

壳聚糖/磷灰石-硅灰石复合多孔支架材料的制备与性能

以磷灰石-硅灰石(AW)生物活性多孔玻璃陶瓷支架材料为基体,采用物理包被法制备了壳聚糖(CS)/AW复合多孔支架材料,通过红外图谱分析、扫描电镜、光学显微镜、强度检测等分析测试方法,研究了复合材料的组成、微观结构、力学和矿化性能。结果发现：复合材料与AW多孔支架材料基体相比,仍具有三维贯通且分布均匀的孔隙结构,孔径尺寸约 100～500μm,孔隙率为80%左右,且力学性能明显增强,平均抗压强度可达3.11 MPa,比多孔AW支架材料基体的平均抗压强度提高了8.3倍。体外模拟体液浸泡实验表明,复合材料具有较高的矿化功能,预示材料具有较好的生物活性。这种复合材料可望作为人体非承重部位的植入骨修复体和组织工程支架使用。     

三维打印羟基磷灰石晶须增强复合骨修复支架

利用三维打印技术成功制备羟基磷灰石晶须(HAPw)增强的聚己内酯(PCL)复合骨修复支架。通过改变三维打印的挤出速度和挤出气压, 使不同含量HAPw均能在PCL基材中一致排列并均匀分布。PCL支架的机械强度随HAPw含量增加显著提高, 添加33wt%HAPw使PCL支架强度提升了高达3倍。此外, HAPw使PCL支架表面与水的接触角从近100º降低至约50º, 有效改善了细胞表面粘附。经过体外人类骨髓间充质干细胞(hBMSC)在支架上的培养实验, 发现添加HAPw的复合支架具有更好的生物相容性, 能够有效促进hBMSC的增殖生长, 且HAPw-PCL复合支架上细胞具有更高的碱性磷酸酶(ALP)活性和OCN、RUNX2等相关成骨基因表达, 显示出hBMSCs向成骨方向更好的分化及成骨活性。     

Changes in physicochemical and biological properties of porcine bone derived hydroxyapatite induced by the incorporation of fluoride

Abstract

As the main inorganic component of xenogenic bone graft material, bone-derived biological apatite (BAp) has been widely used in implant dentistry, oral and maxillofacial surgery and orthopedics. However, BAp produced via calcination of animal bones still suffers from some drawbacks, such as insufficient mechanical strength and inadequate degradation rate, which impede its application. Fluoride is known to play important roles in both physiological and pathological processes of human hard tissues for its double effects on bones and teeth. In order to understand the effects of fluoride on the properties of BAp, as well as the mechanism behind them, porcine bone derived hydroxyapatite (PHAp) was prepared via thermal treatment, which was then fluoride incorporated at a series concentrations of sodium fluoride, and noted as 0.25-FPHAp, 0.50-FPHAp, and 0.75-FPHAp respectively. The physicochemical characteristics of the materials, including crystal morphology, crystallinity, functional groups, elemental composition, compressive strength, porosity and solubility, were then determined. The biological properties, such as protein adsorption and cell attachment, were also evaluated. It was found that the spheroid-like crystals of PHAp were changed into rod-like after fluoride substitution, resulting in a fluoride concentration-dependent increase in compressive strength, as well as a decreased porosity and solubility of the apatite. However, even though the addition of fluoride was demonstrated to enhance protein adsorption and cell attachment of the materials, the most favorable results were intriguingly achieved in FPHAp with the least fluoride content. Collectively, low level of fluoride incorporation is proposed promising for the modification of clinically used BAp based bone substitute materials, because of its being able to maintain a good balance between physicochemical and biological properties of the apatite.     

纳米羟基磷灰石/聚合物多孔复合支架材料

为提高骨组织工程支架材料的力学性能,改善其生物活性,综合天然与合成高分子的优点,采用溶液共混相分离法制备出聚己内酯(PCL)-壳聚糖(CS)多孔支架材料, 并进一步采用离心注浆法填充具有生物活性的纳米羟基磷灰石(HA)-聚乙烯醇(PVA)复合浆料, 制备了n-HA-PVA/PCL-CS复合多孔支架材料, 改善了PCL-CS支架材料力学性能。采用扫描电子显微镜、红外光谱、元素分析、孔隙率和抗压强度试验对材料进行了表征。结果表明, PCL-CS支架材料的内部具有蜂窝状的相互贯通的孔隙结构,孔隙率可以达到60%～80%。CS含量越大,孔隙率越大,而抗压强度越小。填充后的n-HA-PVA/PCL-CS复合多孔支架材料,孔隙率有所下降,但仍大于60%,而其弹性模量可提高至25.71 MPa。      

In vitro degradation of porous nano-hydroxyapatite/collagen/PLLA scaffold reinforced by chitin fibres

In this paper, a novel porous scaffold for bone tissue engineering was prepared with nano-hydroxyapatite/collagen/Poly-l-lactic acid (PLLA) composite reinforced by chitin fibres. To enhance the strength of the scaffold further, PLLA was linked with chitin fibres by Dicyclohexylcarbodimide (DCC). The structures of the reinforced scaffold with and without linking were characterized by Scanning Electron Microscopy (SEM). The chemical characteristics of the chitin fibres with and without linking were evaluated by Fourier-transformed infrared (FTIR) spectroscopy. The mechanical performance during degradation in vitro was investigated. The results indicated that the nano-hydroxyapatite/collagen/PLLA composite reinforced by chitin fibres with linking kept better mechanical properties than that of the composite without linking. These results denoted that the stronger interfacial bonding strength of the scaffold with linking could decrease the degradation rate in vitro. The reinforced composite with the link-treatment can be severed as a scaffold for bone tissue engineering.     

多孔ZnO/羟基磷灰石生物复合材料的制备与性能

利用放电等离子烧结技术制备多孔ZnO/羟基磷灰石（HA）生物复合材料,研究不同纳米ZnO含量对ZnO/HA复合材料微观结构、孔隙特征、力学性能、矿化和降解性能的影响。结果表明:烧结后ZnO/HA复合材料主要由HA相和ZnO相组成;随着ZnO含量提高,多孔ZnO/HA复合材料孔隙率缓慢增大,抗压强度略有减小,弹性模量变化不大;多孔ZnO/HA复合材料的孔隙率>40%,孔径在50～500 μm之间,抗压强度>148 MPa,弹性模量为6.5 GPa左右,能够满足骨修复材料的要求;模拟人工体液中矿化和降解实验表明,多孔ZnO/HA复合材料浸泡7天后表面开始形成大量类骨磷灰石层,且随着ZnO含量增加,磷灰石形成能力明显增强而降解速率加快。      

类生理环境下可降解纤维/磷酸钙复合骨水泥的性能与结构变化

采用生理盐水浸泡与肌肉埋植的方法分别研究了可降解纤维/磷酸钙复合骨水泥的体外力学性能、体内降解性能以及相组成、微结构随浸泡（或植入）时间的变化规律。浸泡结果表明:浸泡初期,纤维的加入一定程度上降低了复合骨水泥的抗压强度,但大大改善了其断裂韧性,而且抗弯强度略有增加;浸泡后期,复合骨水泥的抗压强度、抗弯强度、断裂功均明显下降。体内降解结果表明,随着植入时间延长,含纤维复合骨水泥的降解速率及其增加幅度均高于未掺纤维骨水泥。类生理环境下含纤维复合骨水泥力学性能、降解性能的变化与纤维的降解、材料微观结构的变化密切相关。      

Preparation and properties of calcium phosphate cements incorporated gelatin microspheres and calcium sulfate dihydrate as controlled local drug delivery system

To develop high macroporous and degradable bone cements which can be used as the substitute of bone repairing and drug carriers, cross-linked gelatin microspheres (GMs) and calcium sulfate dihydrate (CSD) powder were incorporated into calcium phosphate bone cement (CPC) to induce macropores, adjust drug release and control setting time of α-TCP–liquid mixtures after degradation of GMs and dissolution of CSD. In this study, CSD was introduced into CPC/10GMs composites to offset the prolonged setting time caused by the incorporation of GMs, and gentamicin sulphate (GS) was chosen as the model drug entrapped within the GMs. The effects of CSD amount on the cement properties, drug release ability and final macroporosity after GMs degradation were studied in comparison with CPC/GMs cements. The resulting cements presented reduced setting time and increased compressive strength as the content of CSD below 5 wt%. Sustained release of GS was obtained on at least 21 days, and release rates were found to be chiefly controlled by the GMs degradation rate. After 4 weeks of degradation study, the resulting composite cements appeared macroporous, degradable and suitable compressive strength, suggesting that they have potential as controlled local drug delivery system and for cancellous bone applications.     

纳米羟基磷灰石/聚酰胺6医用复合材料的制备及性能表征

为防止纳米羟基磷灰石(nano HAP)粉末的团聚,采用溶剂沉淀法制备了nano HAP/聚酰胺6(PA6)复合粉末,并对粉末进行热压成型制得nano HAP/PA6复合材料。然后,通过FTIR、XRD和SEM对nano HAP/PA6复合材料的成分、结构和形貌进行了表征,并对复合材料的热稳定性、力学性能和细胞相容性进行了检测。结果表明:所制备的nano HAP/PA6复合材料结晶体大小均匀,且PA6只存在α型结晶;由于nano HAP与PA6界面上形成新的氢键和COO—Ca,复合材料具有良好的综合性能;在低于350℃时,nano HAP/PA6复合材料不会发生裂解,力学性能与人骨匹配,50wt%nano HAP/PA6复合材料的弯曲强度、压缩强度和弹性模量分别为146.87MPa、98.44MPa和5.44GPa。MG-63骨瘤细胞在nano HAP/PA6复合材料表面粘附和生长状况良好,说明nano HAP/PA6复合材料具有良好的细胞相容性。所得结论表明nano HAP/PA6复合材料在骨修复方面具有应用价值。     

氧化石墨烯/丝素蛋白凝胶结构及其性能研究

目前医用凝胶材料普遍存在力学强度较差及生物降解速度过快等问题。以蚕丝丝素蛋白(SF)凝胶为基础材料,加入氧化石墨烯(GO),并将1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)及N-羟基琥珀酰亚胺(NHS)作为交联剂制备SF/GO复合凝胶,旨在改善凝胶材料的力学性能,使其在保证复合凝胶材料应有的力学强度的同时,发挥丝素蛋白、氧化石墨烯的生物学效应及凝胶材料的多孔支架作用。实验结果显示,EDC的加入可以使得SF、GO共混形成稳定、均匀的无规卷曲结构,扫描电镜(SEM)显示SF/GO凝胶具有典型的多孔结构。GO的加入可以有效缩短复合材料的凝胶时间,同时复合凝胶材料的力学性能得到明显改善,其压缩强度提高40%以上。GO的加入还可明显延长材料的降解时间。基于SF/GO的复合凝胶在组织修复及再生领域具有较好的应用前景。     

用于骨缺损修复的新型可注射自固化复合材料

硫酸钙骨水泥具有良好的骨传导性,但降解速率快、生物活性差的缺点限制了其临床应用.本文将β-磷酸三钙纳米颗粒(粒径43.8±9.0 nm)和半水硫酸钙颗粒(粒径5–21μm)混合作为固相,与液相聚乙烯醇溶液(5 wt.%)按优化重量比混匀,制备了可注射自固化复合材料.该材料具有合理的自固化时间(11.7–19.2 min)及适宜的压缩强度(2.28–6.33 MPa).同时,利用镁颗粒作为成孔剂,制备出大孔径(大于100μm)的多孔支架.体外细胞实验显示,MC3T3-E1细胞伸展良好,表现出大量的板状伪足和伸展的丝状伪足,表明该复合材料无细胞毒性.将可注射复合材料植入比格犬股骨髁缺损区,10个月后骨缺损愈合良好,表明该材料具有良好的骨缺损修复潜力.     

Shape memory and mechanical characterization of polylactic acid wood composite fabricated by fused filament fabrication 4D printing technology

The present study focuses on fabrication and characterization of polylactic acid wood composite fabricated using fused filament fabrication 4D printing technology. The major tests performed to investigate the effect of nanosilica and nanoalumina included shape recovery rate, hardness, compressive strength, dynamic mechanical properties and Thermo-gravimetric analysis. The result of mechanical test indicated that the addition of 2 wt.% nanoalumina improved the hardness, compressive strength and flexural strength by 40 %, 25 % and 3.3 % respectively. On the other hand, the addition of 2 wt.% nanosilica improved the hardness, compressive strength and flexural strength by 60 %, 55 % and 10 % respectively. Further, the addition of nanosilica and nanoalumina improved the thermal stability and decreased the maximum shape recovery rate of wood polylactic acid composite. Nanosilica reinforced wood polylactic acid composite indicated a better choice as compared to nanoalumina reinforced wood polylactic acid composite in terms of mechanical properties, thermal properties and maximum shape recovery rate.     

Direct scaffolding of biomimetic hydroxyapatite-gelatin nanocomposites using aminosilane cross-linker for bone regeneration

Hydroxyapatite-gelatin modified siloxane (GEMOSIL) nanocomposite was developed by coating, kneading and hardening processes to provide formable scaffolding for alloplastic graft applications. The present study aims to characterize scaffolding formability and mechanical properties of GEMOSIL, and to test the in vitro and in vivo biocompatibility of GEMOSIL. Buffer Solution initiated formable paste followed by the sol-gel reaction led to a final hardened composite. Results showed the adequate coating of aminosilane, 11-19?wt%, affected the cohesiveness of the powders and the final compressive strength (69?MPa) of the composite. TGA and TEM results showed the effective aminosilane coating that preserves hydroxyapatite-gelatin nanocrystals from damage. Both GEMOSIL with and without titania increased the mineralization of preosteoblasts in vitro. Only did titania additives revealed good in vivo bone formation in rat calvarium defects. The scaffolding formability, due to cohesive bonding among GEMOSIL particles, could be further refined to fulfill the complicated scaffold processes.     

Biodegradation and compressive strength of phosphorylated chitosan/chitosan/hydroxyapatite bio-composites

The research about how to obtain an organic/inorganic bio-composite with excellent comprehensive properties is an active research field. Nowadays, very few of the achievements were applied to the clinical use due to many reasons. In this work, the purpose was to get a three-phase composite with good compressive strength by using phosphorylated chitosan. Phosphorylated modification of chitosan would bring new properties such as metal chelating. Four phosphorylated chitosan/chitosan/hydroxyapatite (PCS/CS/HA) composites with the weight ratios of 40/40/20, 30/30/40, 20/20/60, 10/10/80 were prepared through the coprecipitation method. The maximum value of compressive strength was measured about 70.25 MPa corresponding to the PCS/CS/HA composite rod with a weight ratio of 30/30/40. The composite rod maintained 64% of original compressive strength after soaking in simulated body fluid for 20 days. All the results showed that the PCS/CS/HA composite (30/30/40), had a good compressive strength, was appropriate to be used as a novel bio-composite for bone tissue engineering.     

Elaboration of self-coating alumina-based porous ceramics

Materials used for bone substitution (i.e. hydroxyapatite and calcium phosphate) are highly successful, since when implanted they provide an efficient scaffold that can be colonized by the patient’s bone. However, their poor mechanical properties impede their use for load-bearing applications. In contrast, no material with high mechanical properties also presents a high bioactivity. A possible way of finding a material both strong and bioactive is to use a composite. We propose here a composite deriving its strength from its alumina core and its bioactivity from a calcium phosphate surface. Ceramic scaffolds have been produced by infiltration of polymer open-celled foams. Several compositions of the slurries have been tested, leading to the realization of porous pieces with a biocompatibility gradient at a micrometric scale. The mechanical properties of several new materials are presented and correlated to their microstructure.     

钛酸酯偶联剂对磷灰石/壳聚糖多孔生物材料性能的影响

以螯合型焦磷酸钛酸酯偶联剂(NDZ-311)为改性剂对壳聚糖(CS)进行改性,采用真空冷冻干燥法制备了HA-TCP/CS多孔生物材料,研究了NDZ-311的用量与多孔生物材料抗压强度和孔隙率的关系,并采用SEM、XRD、IR等对材料进行了分析测试.结果表明,NDZ-311中-O-链状醚键官能团能发生各种类型的酯基转化反应,与CS填料产生交联,材料的抗压强度得到提高,CS填料添加量可达50%以上,且不会发生相分离.随着NDZ-311含量的增加,多孔生物材料的抗压强度先逐渐降低然后升高,孔隙率先逐渐升高然后降低.当m(HA-TCP):m(CS)=7:3时,NDZ-311质量分数为1%时抗压强度为2.3MPa,孔隙率升至最高84.8%,此时多孔生物材料的抗压强度和孔隙率匹配较好,孔隙呈层错板条搭接,且分布均匀,HA-TCP颗粒均匀分散在CS模板上,材料的相结构变化不大,只是材料中各相对应的特征衍射峰的强度略有增强.