可缓释药物的明胶/磷酸钙骨水泥复合组织工程支架材料

采用向孔隙中灌注含聚乳酸聚乙醇酸共聚物（PLGA）载药微球的明胶溶液的方法制备了具有药物缓释功能的明胶/磷酸钙骨水泥复合组织工程支架。用扫描电子显微镜观察了微球和支架的形貌特征,用万能材料试验机测定了支架材料的抗压强度,用紫外-可见分光光度计分析了复合支架的释药率。结果表明,灌注明胶对多孔磷酸钙骨水泥支架起到显著的增强作用,抗压强度达2.42 MPa。复合支架携载硫酸庆大霉素, 具有良好的药物缓释功能,缓释时间可达30天以上,使支架在修复骨缺损的同时能消除炎症反应,成为一种集骨修复和治疗于一体的新型组织工程支架材料,具有良好的应用前景。      

天然高分子基复合骨支架研究进展

在生物医用材料中,天然高分子因具有良好的生物相容性和生物识别性而受到极大的关注。天然高分子与羟基磷灰石(HA)、生物活性玻璃(BG)、双相磷酸钙(BCP)等陶瓷材料复合形成的骨支架成为了骨组织再生领域的研究重点。综述了近年来天然高分子基复合骨支架的研究进展及其发展方向,并详细介绍了胶原、明胶、壳聚糖与不同陶瓷材料复合形成的骨支架在骨组织再生中的成效。     

多孔磷酸钙骨水泥组织工程支架的高分子灌注增强

利用棒状谷氨酸钠晶体作为造孔粒子,采用可溶盐造孔法,制备了三维连通的大孔径多孔磷酸钙骨水泥支架,分别将明胶(Gelatin) 、聚乳酸2羟基乙酸共聚物(PLGA) 、聚乳酸(PLA) 、聚己内酯(PCL) 、聚羟基丁酸戊酸酯(PHBV)灌注到多孔磷酸钙骨水泥(CPC)支架的孔隙中以改善支架材料的力学性能。结果表明,5 种高分子材料与水的接触角大小顺序为PHBV > PCL > PLA > PL GA > Gelatin , 复合支架材料的强度随高分子材料与水接触角的减小而增大;除PHBV外,其余4种均有明显的增强效果,其中Gelatin/CPC复合支架增强效果最好,强度达到2. 25 MPa±0. 02 MPa ,是CPC支架强度的25倍。经过增强的大孔径多孔磷酸钙骨水泥复合支架可用作骨组织工程支架材料。      

磷酸钙/纤维蛋白胶复合支架材料的结构及力学性能分析

用可吸收磷酸钙骨水泥和纤维蛋白胶按一定比例体外构建复合支架材料,通过XRD、SEM、抗压实验和空隙率测试等方法对其结构及力学性能进行分析.结果发现:由于加入纤维蛋白胶,复合支架材料在一定程度上延长了磷酸钙骨水泥的初凝时间,但并不影响磷酸钙骨水泥的终凝时间;同时,加入纤维蛋白胶改变了骨水泥固化体的微观结构,提高了骨水泥的抗压强度,其最大抗压强度达到14MPa,弹性模量在96.64～269.39MPa之间,空隙率为38.8%.与在同样条件下制备的磷酸钙骨水泥比较,复合支架材料的抗压强度增强了55.6%,而空隙率仅仅下降了6.9%;XRD分析显示,复合支架材料并不影响磷酸钙骨水泥的最终的转化,其结晶结构仍是羟基磷灰石结构,是更好的骨组织工程支架材料.     

溶胶-凝胶生物活性玻璃与胶原复合多孔支架的生物相容性研究

实验前期用冷冻干燥法合成一种溶胶?凝胶生物活性玻璃(BG/COL)与粗胶原纤维复合的组织工程支架. 本实验将支架与鼠骨髓间充质干细胞(rMSCs)共同培养, 评价支架材料的细胞相容性. 并将复合了成骨细胞的支架材料植入裸鼠皮下, 探讨其异位成骨的性能. 研究结果显示rMSCs可以在BG/COL多孔支架材料表面成功粘附、铺展、并向多孔支架内部迁移, 随着培养时间的延长, 双链DNA(ds DNA)数量增多, 细胞增殖情况与对照组差异明显. 将种在复合材料上的骨髓间充质干细胞诱导培养14d后切片染色, 其碱性磷酸酶(ALP)和钙素表达均呈强阳性. 体内植入实验的裸鼠健康状况良好, 伤口完全愈合, 6w后BG/COL周边及内部有骨组织和血管生成. 由此证明, 这种新型的复合多孔支架材料具有良好的生物相容性, 其复合了成骨细胞的组织工程骨具有良好的诱导成骨的性能, 因此这种材料是理想的应用于骨组织修复和再生的组织工程支架材料.     

壳聚糖类复合材料应用于骨修复的研究进展

壳聚糖是天然多糖类高分子化合物甲壳素的脱乙酰产物,具有良好的生物相容性、可降解性和生物活性,可作为骨修复材料,并可应用于骨组织工程材料中的三维生长支架,作为种子细胞或活性生长因子的生物载体材料.综述了壳聚糖类复合材料在骨填充修复材料、骨组织工程和软骨组织工程方面应用的状况及前景.     

聚乳酸-羟基乙酸共聚物/磷酸钙骨水泥多孔复合支架的制备

利用定向冰晶-冷冻干燥法制备了具有定向孔隙结构的磷酸钙骨水泥支架材料, 将两种具有不同降解速率的聚乳酸-羟基乙酸共聚物(PLGA) 与磷酸钙骨水泥多孔支架进行多次浸润复合, 以改善支架的力学性能。结果表明: PLGA 与支架材料复合可大大提高复合支架材料的抗压强度, 经过PLGA 二次复合后, 复合支架抗压强度可达6. 37 MPa ±0. 54 MPa 。经过PLGA 复合的支架材料保持了复合前的孔隙结构, 在孔的轴向方向上具有定向排列的开口孔隙, 这些开口孔隙的存在有利于植入初期新生组织的长入。覆盖在骨水泥基体表面的PLGA 膜可以增强基体的强度并弥补基体表面的缺陷, 充填在孔隙内部的PLGA 泡沫体可以很好地承受外加载荷, 使复合支架材料具有较好的强度和韧性。      

磷酸钙骨水泥大孔径多孔组织工程支架的制备及其纤维增强

采用粒子溶出造孔法, 用棒状谷氨酸钠晶体作为造孔粒子, 制备磷酸钙骨水泥多孔支架, 研究了造孔粒子含量和多孔支架孔隙率之间的关系, 并加入甲壳素纤维来改善支架材料的力学性能. 结果表明, 支架材料的孔隙率可达(79.8±2.3)%,孔隙直径100～600μm; 复合纤维后支架的强度提高了3～4倍, 断裂应变显著提高, 可作为非承重部位骨缺损修复的骨组织工程支架材料.     

磷酸钙骨水泥的生物学性能

寻求修复各种原因引起的骨组织缺损、畸形的新型材料和技术一直是生命科学和生物材料科学领域的一个重要课题.磷酸钙骨水泥具有良好的生物相容性、骨引导活性和生物降解性,具有一定的抗压强度,是一种较理想的骨移植替代材料.     

可注射磷酸钙骨水泥复合材料研究进展

研制既具有多孔结构又具有足够力学强度的磷酸钙骨水泥材料是当前骨修复材料研究的热点之一。报道了研制的磷酸钙骨水泥复合材料,在植入初期具有较高的力学强度,植入后可渐渐降解成孔,为骨修复材料的研究提供了新的方法和途径。磷酸钙骨水泥复合材料以磷酸钙骨水泥为基体,在基体中加入具有生物降解性的微球形成复合材料,保证了复合材料植入初期有足够力学强度为新生组织提供支撑,防止自身的坍塌,而具有生物降解性微球的降解速度比磷酸钙骨水泥的固化体快,随着微球的降解在磷酸钙骨水泥基体中就会产生很多三维孔隙,利于细胞粘附生长,血管和神经长入,以及营养成分的渗入和代谢产物排出。这种结构设计使可体内降解成孔的磷酸钙骨水泥既具有足够力学强度又具有多孔结构,还可以通过改变不同材料的比例来调节复合材料的初始力学强度和降解速度。目前已研制成功了壳聚糖微球/磷酸钙骨水泥复合材料、聚羟基丁酸—戊酸酯(PHBV)/磷酸钙骨水泥复合材料,其凝固时间为10～15min,抗压强度达到30～40MPa,孔隙率70%～80%,孔径分布为100～300μm,并对复合材料的降解性、细胞相容性和动物体内植入试验进行了研究,表明所研制的材料具有良好的生物相容性,可降解性和成...     

Bi-layered calcium phosphate cement-based composite scaffold mimicking natural bone structure

Abstract

In this study, a core/shell bi-layered calcium phosphate cement (CPC)-based composite scaffold with adjustable compressive strength, which mimicked the structure of natural cortical/cancellous bone, was fabricated. The dense tubular CPC shell was prepared by isostatic pressing CPC powder with a specially designed mould. A porous CPC core with unidirectional lamellar pore structure was fabricated inside the cavity of dense tubular CPC shell by unidirectional freeze casting, followed by infiltration of poly(lactic-co-glycolic acid) and immobilization of collagen. The compressive strength of bi-layered CPC-based composite scaffold can be controlled by varying thickness ratio of dense layer to porous layer. Compared to the scaffold without dense shell, the pore interconnection of bi-layered scaffold was not obviously compromised because of its high unidirectional interconnectivity but poor three dimensional interconnectivity. The in vitro results showed that the rat bone marrow stromal cells attached and proliferated well on the bi-layered CPC-based composite scaffold. This novel bi-layered CPC-based composite scaffold is promising for bone repair.     

In Vitro Characterizations of PLLA/β-TCP Porous Matrix Materials and RMSC-PLLA-β-TCP Composite Scaffolds

To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissueengineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, i.e. solventcasting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behaviorof the porous scaffold, e.g. weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP,the particle size of β-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporatedinto the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold weredetermined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Resultsshow that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strengthneeded for surgery. RMSCs seeding on porous PLLA/     

In vivo study of a bioactive nanoparticle-gelatin composite scaffold for bone defect repair in rabbits

The purpose is to study the in vivo bioactivity of this scaffold and verify its ability to simulate the characteristics of cancellous bone. Twenty-four adult New Zealand white rabbits were divided into three groups. Bone defects above the femoral condylar of both sides were created. A newly designed bioactive nanoparticle–gelatin composite scaffold was implanted to the experimental side, while the control side was left without implantation. The repair of bone defect was monitored by X-ray examination, gross observation, Micro-CT examination and histological observation of the area of bone defect 4, 8 and 12 weeks after surgery. There was void of new bone tissue in medullary cavity in the bone defect area of the control side. In the experimental side, the composite scaffold displayed excellent biodegradability, bioactivity and cyto-compatibility. With the time laps, new bone tissue grew from the edge to center as revealed by both Micro-CT image and staining biopsy, which complies with the “creeping substitution” process. The mechanical properties of the newly designed bioactive nanoparticle–gelatin composite scaffold and the 3-D structure of new bone tissue are comparable to the surrounding cancellous bones. This newly developed bioactive nanoparticle–gelatin composite scaffold possesses good biocompatibility and in vivo osteogenic capability for bone defect repair. It may be a promising artificial bone grafts.     

Feasibility of three-dimensional macroporous scaffold using calcium phosphate glass and polyurethane sponge

Tissue engineering presents an alternative approach to the repair of a damaged tissue by avoiding the need for a permanent implant made of an engineered artificial material. A suitable temporary scaffold material that exhibits adequate mechanical and biological properties is required to enable tissue regeneration by exploiting the body’s inherent repair mechanism, i.e. a regenerative allograft. Synthetic bioresorbable polymers have been attracting attention as tissue engineering scaffolds. However, a number of problems have been encountered such as inflammatory responses and lack of bioactivity. Another good candidate for a tissue engineering scaffold is the calcium phosphates because of their good biocompatibility and osteointegrative properties. Their slow biodegradation is still remains problem, especially for the filling of large bony defects. In this study, we investigated the fabrication method of a three-dimensional reticulated scaffold with interconnected pores of several hundred micrometers using calcium phosphate glass in the system of CaO-CaF₂-P₂O₅-MgO-ZnO and a polyurethane sponge as a template. Calcium phosphate glass slurry was homogenously thick coated when the weight percentage of the calcium phosphate glass powder was 40% with 8 wt% of polyvinyl alcohol as a binder. Addition of 10 wt% dimethyl formamide as a drying control chemical additive into a slurry almost prevented the crack formation during drying. Sintering of the dried porous block at 850°C exhibited the densest microstructure as well as the entire elimination of the organic additives. Repeating the process significantly increased compressive strength of sintered porous body due to the thickening of the struts. To summarize, macroporous calcium phosphate glass can be fabricated with 500∼800 μm of pore size and a three-dimensionally interconnected open pore system. It is thought that this kind of biodegradable glass scaffold combined with osteogenic cells has potential to be studied further as a tissue-engineered bone substitute.     

Preparation of a biphasic scaffold for osteochondral tissue engineering

Tissue engineering has been developed as a prospective approach for the repair of articular cartilage defects. Engineered osteochondral implants can facilitate the fixation and integration with host tissue, and therefore promote the regeneration of osteochondral defects. A biphasic scaffold with a stratified two-layer structure for osteochondral tissue engineering was developed from biodegradable synthetic and naturally derived polymers. The upper layer of the scaffold for cartilage engineering was collagen sponge; the lower layer for bone engineering was a composite sponge of poly(DL-lactic-co-glycolic acid) (PLGA) and naturally derived collagen. The PLGA–collagen composite sponge layer had a composite structure with collagen microsponge formed in the pores of a skeleton PLGA sponge. The collagen sponge in the two respective layers was connected. Observation of the collagen/PLGA–collagen biphasic scaffold by scanning electron microscopy (SEM) demonstrated the connected stratified structure. The biphasic scaffold was used for culture of canine bone-marrow-derived mesenchymal stem cells. The cell/scaffold construct was implanted in an osteochondral defect in the knee of a one-year old beagle. Osteochondral tissue was regenerated four months after implantation. Cartilage- and bone-like tissues were formed in the respective layers. The collagen/PLGA–collagen biphasic scaffold will be useful for osteochondral tissue engineering.