磷酸钙生物陶瓷的孔性、内部连通性及表面形态对骨质再生的影响

磷酸钙生物陶瓷是一类具有良好生物相容性和骨传导性的生物活性材料，由于其成分与骨的无机组分基本相当，是目前公认的最具前途的硬组织修复材料，将该材料制成多也结构，更有利于新生骨组织生长所需的物质交流，促进新生骨形成，因而成为近年来生物材料的研究热点之一。本从多孔磷酸钙生物陶瓷与组织的响应关系角度出发，评述了近年来磷酸钙生物陶瓷的孔性、孔和孔间的内部连通性及孔的表向形态对骨质再生影响的研究进展。     

壳聚糖抗菌生物陶瓷的制备及其体内外实验研究*

目的利用壳聚糖固化液和磷酸钙骨水泥（CPC）复合头孢曲松钠,研制一种新型的抗菌生物陶瓷。方法使用壳聚糖固化液将磷酸钙骨水泥与头孢曲松钠共混制备抗菌生物陶瓷,根据头孢曲松钠的紫外吸光度-浓度标准直线研究生物陶瓷中头孢曲松钠的体外释放。微生物法测定生物陶瓷体外抑菌效果。利用大鼠污染骨缺损模型,研究其体内抗感染作用。结果2.4ml壳聚糖固化液与0.1g磷酸钙骨水泥固体及10.4mg头孢曲松钠混合,在60摄氏度100%湿度下固化24h得到的抗菌生物陶瓷体外头孢曲松钠体外持续释放1W均高于金黄色葡萄球菌的最小抑菌浓度,大鼠白细胞计数和组织切片证实污染缺损实验组较对照组的炎症反应轻微。结论复合头孢曲松钠和壳聚糖的磷酸钙骨水泥陶瓷具有良好的抑菌抗感染作用。     

多孔复合掺杂聚磷酸钙支架骨修复材料的制备及其性能

背景：离子掺杂是生物陶瓷改性的一种重要方法。 目的：评估复合掺杂生物陶瓷作为骨修复材料的可行性。 方法：将钾离子和锶离子复合掺入聚磷酸钙中,制得一种新型骨修复材料—KSCPP。采用扫描电镜和X射线衍射检测分析聚磷酸钙和KSCPP的微观结构和结晶情况;采用抗压强度测试实验、体外降解实验、体外细胞培养实验表征KSCPP的性能,并且进行短期兔肌肉植入实验观察KSCPP的组织相容性。 结果与结论：与羟基磷灰石和聚磷酸钙相比较,KSCPP支架材料拥有更高的抗压强度和更快的降解速度及更低的细胞毒性和更好的组织相容性。     

骨组织工程支架材料聚磷酸钙生物陶瓷研究进展

为修复创伤及病理因素导致的骨缺损,骨组织工程是一项迅速发展、不断革新的课题。多孔聚磷酸钙生物陶瓷是可吸收生物陶瓷的一种,具有良好的生物相容性以及可降解性,在骨组织工程中日益被人们所认识。骨组织工程中细胞生长速率与材料的降解速率相匹配一直是有待解决的问题,聚磷酸钙由于具有独特的结构及降解性能,因此有望解决这个问题。本文对作为骨组织工程支架材料之一的聚磷酸钙生物陶瓷的理化性质、制备方法、研究进展、骨结合机理等进行了综述,并对其研究和发展作出了展望。     

一种可注射体内成孔的磷酸钙骨水泥

背景：磷酸钙骨水泥存在脆性大、抗水溶性(血溶性)差、力学性能不足、降解缓慢等缺点,其临床应用受到一定限制,故需要对其进行改性研究。 目的：制备一种具有一定强度、孔隙率、适合骨生长的多孔磷酸钙骨水泥生物支架材料。 方法：以磷酸钙骨水泥为基本体系,液相采用壳聚糖的弱酸溶液,以提高磷酸钙骨水泥的可塑性和黏弹性,使骨水泥具有可注射性,显著提升骨水泥的应用范围及应用舒适度。固相为双相磷酸钙(磷酸四钙+磷酸氢钙)粉体,并在固相中添加一定量的甘露醇及聚乳酸-乙醇酸共聚物作为造孔剂,制备磷酸钙支架材料。 结果与结论：此材料孔径可达到10~300 μm。添加60%致孔剂时,磷酸钙骨水泥固化体孔隙率可达到(68.3±1.5)%。磷酸钙骨水泥孔隙率的增加使材料的力学性能下降,其抗压强度从最初不含致孔剂时的(53.0±1.4) MPa下降到含60%致孔剂的(2.5±0.2) MPa。实验制备的此种多孔磷酸钙骨水泥材料,是具有一定抗压强度、较好的孔隙率,并能体内降解的可注射生物支架材料。     

磷酸钙骨水泥与骨形态蛋白复合材料修复下颌骨缺损的研究

为提高磷酸钙骨水泥的成骨活性，将自制的磷酸钙骨水泥作为骨形态蛋白．2的载体予以复合，对复合载体材料进行物性研究和异位成骨试验。并以该复合材料修复兔下颌骨缺损，通过生物力学检测和骨界面新生骨计量，观察其修复下颌骨缺损的效果。结果表明，以该复合材料修复兔下颌骨缺损，其材料与宿主骨界面的结合强度以及新生骨量均明显高于单纯材料的修复。     

磷酸钙骨水泥复合骨形态发生蛋白6和血管内皮生长因子修复骨缺损

背景：单独将骨形态发生蛋白或血管内皮生长因子植入体内易被血液冲刷掉而不能最大限度发挥诱导成骨和血管生成作用,同时缺少载体的支撑作用。 目的：观察骨形态发生蛋白6、血管内皮生长因子及磷酸钙骨水泥联合应用在骨缺损修复过程中的作用。 方法：制作新西兰兔双侧股骨内侧髁骨缺损模型,左侧分别植入磷酸钙骨水泥/骨形态发生蛋白6/血管内皮生长因子、磷酸钙骨水泥/骨形态发生蛋白6及磷酸钙骨水泥,右侧不植入任何物质作为空白对照。植入8,16周通过硬组织切片组织学观察、电镜扫描等手段观察新骨形成情况。 结果与结论：各组材料的组织相容性良好,未见明显炎症组织反应。植入8周时,磷酸钙骨水泥/骨形态发生蛋白6/血管内皮生长因子组骨水泥-骨组织交界处基本上被新生骨小梁包绕,材料进一步降解,新生骨小梁表面可见大量活跃的成骨细胞;16周时,新生骨小梁继续长入,进一步增长、增粗、增多,有大量新生编织骨成网格状长入材料中,骨水泥材料降解明显,与周围组织结合紧密,降解与骨长入同步,此组不同时间点成骨速度及成骨效果均明显优于其他两组材料(P < 0.05)。表明3种材料联合应用可协同促进骨缺损修复。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：     

β-TCP的制备及研究进展

前言 目前生物陶瓷的研究日益受到人们的重视，其作为骨替代材料已经得到广泛应用。生物陶瓷按照其生物学特性可以分为生物惰性陶瓷、生物降解陶瓷、生物活性陶瓷、生物活性玻璃陶瓷以及双相钙磷陶瓷等。β-TCP（β-磷酸钙）作为良好的生物降解陶瓷，尤其受到研究者的关注。[第一段]     

磷酸钙骨水泥作为药物缓释载体的研究进展

目的：探讨磷酸钙骨水泥的优良性质,以作为骨骼系统理想药物载体的应用。方法：检索万方数据库,CNKI,PUBMED1998年1月-2008年12月期间的相关文章,检索词为“药物载体,药物缓释,磷酸钙骨水泥”,并对资料进行提炼与分析。结果：磷酸钙骨水泥是一种自固化、生物陶瓷型骨水泥,与周围组织相容性高,具有大量的微孔结构,不改变药物的特性。结论：磷酸钙骨水泥所载药物释药稳定,具有可注射性、低温自固化,以及良好的生物相容性和骨传导性,有望成为治疗多种骨骼系统疾病理想的药物载体。     

磷酸钙骨水泥结合自体带血运骨膜修复节段性骨缺损

背景：磷酸钙骨水泥是一种新型骨替代材料,但具有降解慢、力学性能差等缺点。 目的：探讨磷酸钙骨水泥结合自体带血运骨膜修复节段性骨缺损的可行性。 方法：将72只新西兰大白兔随机数字法均分为4组：保留/不保留骨膜的不用磷酸钙骨水泥修复组、保留/不保留骨膜的磷酸钙骨水泥修复组。修复后4,12,24周取标本进行大体、放射学、组织学及生物力学测试。 结果与结论：不用磷酸钙骨水泥修复组：不保留骨膜12周时才开始出现骨痂,24周时骨端硬化,髓腔闭合;保留骨膜后4周时出现少量的骨痂,12周时骨痂增多,24周时形成新生骨。磷酸钙骨水泥修复组：不保留骨膜时4周材料与骨端分界明显,12周时分解模糊,24周时材料与骨端形成骨性连接;保留骨膜4周材料未见降解,12周时材料有降解,24周时材料吸收更多,髓腔再通。24周时磷酸钙骨水泥修复组行三点弯曲生物力学测试,不保留骨膜组最大负荷低于保留骨膜组(P < 0.05)。说明磷酸钙骨水泥较好促进骨的生长,自体带血运骨膜的存在有利于磷酸钙的吸收,促进骨的形成。     

双相钙磷生物陶瓷/硫酸钙骨水泥多孔三维支架的生物性能

背景：随着组织工程技术的发展,多孔生物陶瓷被越来越多的运用到骨缺损的修复中,当前的研究主要集中在这种生物陶瓷的合成及其各项性能的评价。 目的：研究一种新型骨水泥的制备方法并测定其理化性能及与成骨细胞的生物相容性。 方法：共沉淀法制备双相钙磷生物陶瓷粉体,利用胶体团聚成颗粒,烧结后得到颗粒状、多孔羟基磷灰石/磷酸三钙生物陶瓷,并按不同比例与高纯度医用半水硫酸钙混合制备钙磷陶瓷/硫酸钙骨水泥。 结果与结论：X射线衍射证实合成物质为双相钙磷陶瓷,颗粒状双相钙磷陶瓷具有多孔网状结构,骨水泥在   3 min内保持可塑状态,固化时间为15 min,固化温度为36.5 ℃,压缩强度最高为5.82 MPa,MTT毒性级为0级,成骨细胞在材料表面生长良好。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：     

Effect of nanostructure on osteoinduction of porous biphasic calcium phosphate ceramics

In order to evaluate the effect of the nanostructure of calcium phosphate ceramics on osteoinductive potential, porous biphasic calcium phosphate (BCP) ceramics with a nano- or submicron structure were prepared via microwave sintering and compared to conventional BCP ceramics. The selective protein adsorption of bovine serum albumin and lysozyme (LSZ) and the osteogenic differentiation of human mesenchymal stem cells in vitro was investigated. Porous BCP nanoceramics showed higher ability to adsorb proteins, especially low molecular weight protein of LSZ, than conventional BCP ceramics, and the BCP nanoceramics promoted bone sialoprotein expression more than conventional BCP did. Further in vivo study to investigate ectopic bone formation and bone repair efficiency proved the highly osteoinductive potential of nanostructured BCP ceramics. The results suggest that nanostructured BCP ceramics have the potential to become a new generation of bioceramics for bone tissue engineering grafts.     

Macroporous bioceramics: a remarkable material for bone regeneration

This review summarises the major developments of macroporous bioceramics used mainly for repairing bone defects. Porous bioceramics have been receiving attention ever since their larger surface area was reported to be beneficial for the formation of more rigid bonds with host tissues. The study of porous bioceramics is important to overcome the less favourable bonds formed between dense bioceramics and host tissues, especially in healing bone defects. Macroporous bioceramics, which have been studied extensively, include hydroxyapatite, tricalcium phosphate, alumina, and zirconia. The pore size and interconnections both have significant effects on the growth rate of bone tissues. The optimum pore size of hydroxyapatite scaffolds for bone growth was found to be 300?μm. The existence of interconnections between pores is critical during the initial stage of tissue ingrowth on porous hydroxyapatite scaffolds. Furthermore, pore formation on β-tricalcium phosphate scaffolds also allowed the impregnation of growth factors and cells to improve bone tissues growth significantly. The formation of vascularised tissues was observed on macroporous alumina but did not take place in the case of dense alumina due to its bioinert nature. A macroporous alumina coating on scaffolds was able to improve the overall mechanical properties, and it enabled the impregnation of bioactive materials that could increase the bone growth rate. Despite the bioinertness of zirconia, porous zirconia was useful in designing scaffolds with superior mechanical properties after being coated with bioactive materials. The pores in zirconia were believed to improve the bone growth on the coated system. In summary, although the formation of pores in bioceramics may adversely affect mechanical properties, the advantages provided by the pores are crucial in repairing bone defects.     

Bioinspired structure of bioceramics for bone regeneration in load-bearing sites

The major problem with the use of porous bioceramics as bone regeneration grafts is their weak mechanical strength, which has not been overcome to date. Here we described a novel way to solve this problem. Beta-tricalcium phosphate (β-TCP) bioceramics with a bioinspired structure were designed and prepared with a porous cancellous core (porosity: 70–90%) inside and a dense compact shell (porosity: 5–10%) outside that mimics the characteristics of natural bone. They showed excellent mechanical properties, with a compressive strength of 10–80 MPa and an elastic modulus of 180 MPa–1.0 GPa, which could be tailored by the dense/porous cross-sectional area ratio obeying the rule of exponential growth. The in vitro degradation of the bioinspired bioceramics was faster than that of dense bioceramics but slower than that of porous counterparts. The changes in mechanical properties of the bioinspired ceramics during in vitro degradation were also investigated. A concept of the bioinspired macrostructure design of natural bone was proposed which provided a simple but effective way to increase the mechanical properties of porous bioceramics for load-bearing bone regeneration applications. It should be readily applicable to other porous materials.     

Three-dimensional macroporous calcium phosphate bioceramics with nested chitosan sponges for load-bearing bone implants

Three-dimensional macroporous calcium phosphate bioceramics embedded with porous chitosan sponges were synthesized to produce composite scaffolds with high mechanical strength and a large surface/volume ratio for load-bearing bone repairing and substitutes. The macroporous calcium phosphate bioceramics with pore diameters of 300 microm to 600 microm were developed using a porogen burnout technique, and the chitosan sponges were formed inside the pores of the bioceramics by first introducing chiosan solution into the pores followed by a freeze-drying process. Our scanning electron microscopy results showed that the pore size of chitosan sponges formed inside the macroporous structure of bioceramics was approximately 100 microm, a structure favorable for bone tissue in-growth. The compressive modulus and yield stress of the composite scaffolds were both greatly improved in comparison with that of HA/beta-TCP scaffolds. The simulated body fluid (SBF) and cell culture experiments were conducted to assess the bioactivity and biocompatibility of the scaffolds. In the SBF tests, a layer of randomly oriented needle-like apatite crystals formed on the scaffold surface after sample immersion in SBF, which suggested that the composite material has good bioactivity. The cell culture experiments showed that MG63 osteoblast cells attached to the composite scaffolds, proliferated on the scaffold surface, and migrated onto the pore walls, indicating good cell biocompatibility of the scaffold. The cell differentiation on the composite scaffolds was evaluated by alkaline phosphatase (ALP) assay. Compared with the control in tissue culture dishes, the cells had almost the same ALP activity on the composite scaffolds during the first 11 days of culture.     

Hybrid composites of calcium phosphate granules, fibrin glue, and bone marrow for skeletal repair

Synthetic bone substitutes, such as calcium phosphate ceramics, give good results in clinical applications. In order to adapt to surgical sites, bioceramics come in the form of blocks or granules, and are either dense or porous. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial with the biochemical properties of each component. Critical-sized defects in the femoral condyle of rabbits were filled with TricOs/fibrin glue/bone marrow hybrid/composite material. The TricOs granules (1-2 mm) were composed of hydroxyapatite and beta tricalcium phosphate (60/40 in weight). The fibrin glue was composed of fibrinogen, thrombin and other biological factors and mixed with MBCP granules either simultaneously or sequentially. Bone marrow was also added to the MBCP/fibrin composite prior to filling the defects. After 3, 6, 12, and 24 weeks of implantation, the newly-formed bone was analysed with histology, histomorphometry and mechanical tests. The newly-formed bone had grown centripetally. Simultaneous application of fibrin glue showed better results for mechanical properties than sequential application after 6 weeks. Around 40% of bone had formed after 24 weeks in the three groups. Although the addition of bone marrow did not improve bone formation, the MBCP/fibrin material could be used in clinical bone filling applications.     

A comparative study of calcium phosphate formation on bioceramics in vitro and in vivo

Formation of calcium phosphate (Ca-P) on various bioceramic surfaces in simulated body fluid (SBF) and in rabbit muscle sites was investigated. The bioceramics were sintered porous solids, including bioglass, glass-ceramics, hydroxyapatite, alpha-tricalcium phosphate and beta-tricalcium phosphate. The ability of inducing Ca-P formation was compared among the bioceramics. The Ca-P crystal structures were identified using single-crystal diffraction patterns in transmission electron microscopy. The examination results show that ability of inducing Ca-P formation in SBF was similar among bioceramics, but considerably varied among bioceramics in vivo. Sintered beta-tricalcium phosphate exhibited a poor ability of inducing Ca-P formation both in vitro and in vivo. Octacalcium phosphate (OCP) formed on the surfaces of bioglass, A-W, hydroxyapatite and alpha-tricalcium phosphate in vitro and in vivo. Apatite formation in physiological environments cannot be confirmed as a common feature of bioceramics.     

Osteoinduction of hydroxyapatite/β-tricalcium phosphate bioceramics in mice with a fractured fibula

Many studies have shown that calcium phosphate ceramics can induce bone formation in non-osseous sites without the application of any osteoinductive biomolecules, but the mechanisms of this phenomenon (intrinsic osteoinduction of bioceramics) remain unclear. In this study, we compared the intrinsic osteoinduction of porous hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) implanted in mice at different sites. In 30 mice the left fibula was fractured and the right fibula was kept intact. A porous HA/β-TCP cylinder was implanted into both the left (group 1) and right (group 2) leg muscles of each animal. In addition, two HA/β-TCP cylinders were bilaterally implanted into leg subcutaneous pockets (group 3) in each of the remaining 15 mice. New bone formation was studied in the three groups by histology, histomorphometry and immunostaining. In group 1 new bone was observed at week 6 and bone marrow appeared at week 12. In group 2 new bone was observed at week 8 and bone marrow appeared at week 12. The new bone area percentage in group 1 was significantly higher than in group 2 at both weeks 8 and 12. In contrast, group 3 did not show any new bone within the period studied. These differences were explained based on the location of the implants and thus their proximity to the osteogenic environment of fracture healing. The results support the hypothesis that intrinsic osteoinduction by calcium phosphate ceramics is the result of adsorption of osteoinductive substances on the surface.     

Macroporous calcium phosphate ceramics for bone substitution: a tracer study on biodegradation with 45Ca tracer.

The value of artificial materials in bone replacement depends highly on their biocompatibility and biostability. Porous calcium phosphate ceramics have a good compatibility with natural bone. To study the biodegradation process of calcium phosphate bioceramics, labelled [45Ca]-beta-whitlockite and [45Ca]-hydroxyapatite were implanted in the femurs of dogs. The effects accompanying the ingrowth of new bone into the pores of these bioceramics and its replacement by natural bone were investigated. In vivo degradation of the implant material by biochemical dissolution processes was observed. The beta-whitlockite implants showed a conspicuous decrease in radioactive calcium, in contrast to the hydroxyapatite implants. 45Ca was absent in adjacent bones and locally newly formed bone in both beta-whitlockite and hydroxyapatite suggesting a restricted availability of the 45Ca liberated in these processes. Indications of minor mechanical degradation of the materials were also found; in the lymph nodes a very small amount of 45Ca with a high specific activity was detectable. Urine, blood or faeces contained no detectable amounts of 45Ca activity.     

TEM study of calcium phosphate precipitation on HA/TCP ceramics

This study focuses on phase identification of precipitation on bioactive calcium phosphate (BCP) surfaces in vitro and in vivo. The BCP used in this study consisted of 70 wt% hydroxyapatite (HA) and 30 wt% beta-tricalcium phosphate. Single crystalline precipitates of calcium phosphates on porous BCP bioceramics obtained after immersion in dynamic simulated body fluid (SBF) and after implantation in pig muscle were examined using electron diffraction in transmission electron microscope. The crystals formed in vitro in dynamic SBF were identified as octacalcium phosphate (OCP), instead of apatite. Most of the precipitated crystals in vivo samples had an HA structure; while OCP and dicalcium phosphate dihydrate were also identified. The evidence from single diffraction patterns indicates that apatite formation on bioactive ceramics is a complicated process, particularly in physiological environments where formation might include a transient stage of intermediate phases.