生物陶瓷在组织工程中的应用

生物陶瓷材料用于修复人体硬组织历史悠久,近年来已从传统的骨填充替代材料发展到骨组织工程材料,并且逐渐从硬组织修复领域扩展到了软组织再生领域。特别是硅酸盐生物陶瓷,作为一种新型陶瓷材料,因其独特的生物学效应越来越受到研究人员的关注。大量研究表明,通过调控生物陶瓷的化学组成和表面宏微观结构不仅可以促进硬组织再生,还可促进多种软组织再生,为进一步有针对性地设计与开发新型组织工程材料提供了新思路。现结合本课题组近十年的研究,重点介绍磷酸钙及硅酸盐生物陶瓷在多种组织修复及再生中的研究进展,并从材料工程和生物学的角度对生物陶瓷的未来研究方向做了展望。     

多孔β—TCP生物陶瓷骨内植入后的X射线能谱分析

采用两种不同的扫描电镜与Ｘ射线能谱仪测量了多孔磷酸三钙（β－ＴＣＰ）生物陶瓷骨内植入后植入陶瓷,界面和兔股骨的Ｘ射线能谱和元素比,比较了植入后材料以及界面元素比和组成的变化,Ｘ射线能谱结合扫描电镜,拉曼光谱和红外光谱,对植入后磷酸钙生物陶瓷从无生命的材料转为生命骨骼的生物转化作了深入的探讨,为多孔β－ＴＣＰ生物陶瓷的生物降解和骨生成机制提供了更充足的证据。     

生物陶瓷技术的现状与发展趋势

生物陶瓷主要应用于生物硬组织医用材料,其基础研究从1965年开始,临床研究从1975年开始.传统的生物硬组织医用材料有体骨,动物内,后来发展到采用不锈钢和塑料.但这些材料在生物体中使用效果不理想：不锈钢存在溶析、腐蚀和疲劳问题,塑料存在稳定性差和强度低的问题。1990年代初,国际上兴起了人工骨研究,即将生物陶瓷用作医用复合材料,应用于人体生物体的修复,制做人工关节、人工骨、人工牙根、听觉小骨、中耳引流管等。生物陶瓷能模仿人体骨头的成分、强度,不仅具有不锈钢塑料所具有的特性,     

三维重建技术与生物陶瓷相结合在下颌骨连续性缺损个体化修复中的应用

目的探讨三维重建技术与生物陶瓷相结合,制作下颌骨连续性缺损的个体化修复假体的可能性。方法（1）应用三维重建技术获得下颌骨连续性缺损的三维重建模型;（2）完成下颌骨连续性缺损的个体化修复假体的生物陶瓷置换。结果应用三维重建技术,能够准确地获得与下颌骨连续性缺损相匹配的个体化生物陶瓷修复体。结论三维重建技术与生物陶瓷相结合可以完成下颌骨连续性缺损的个体化修复,这种技术可以满足下颌骨连续性缺损的外形和功能重建的需要。     

生物材料与人工器官（一）

人工器官在临床上的应用，挽救了不少垂危的生命，为临床医学的发展开拓了新途径。随着高分子材料、特殊金属材料、生物陶瓷材料在医学领域内应用的不断深入以及外科技术的提高，更为人工器官的研究创造了条件，使之发展更为迅速。人工器官的研究和应用现已基本遍及人体全身，各个部分其内容之丰富，诱人的研究前景，均可写一专著。     

国内外人工脏器发展概况

人工脏器是生物医学工程学的一个重要组成部分,它是生物医学工程学基础研究和应用研究的产物。人工脏器在临床上的应用,挽救了不少垂危的生命,为临床医学的发展开拓了新的途径。随着高分子材料、特殊金属材料和生物陶瓷材料在医学领域内应用的不断深入以及外科技术的提高,更为人工脏器的研制,创造了条件,使之发展更为迅速。目前除了脑(临床置换无实用价值)以外,几乎所有器官都有人工试制的代替装置。     

新型人工骨移植材料

日前,荷兰特文特大学经10年努力开发,研制成功一种生物陶瓷材料,可用于骨移植手术中,促进骨细胞的再生和受损骨组织的愈合。     

多孔β-TCP生物陶瓷骨内植入后的显微红外光谱

磷酸三钙（β－ＴＣＰ）生物陶瓷植入兔股骨后植入生物陶瓷,界面和兔股骨的显微红外光谱,对其红外特征频率作了指认和归属,在植入生物陶瓷和界面的红外光谱中,骨骼矿物相（或磷酸钙）胶原,蛋白质和脂类（或磷奚）的红外特征频率同时出现,它民股骨的红外光谱非常相似,其结果与拉曼光谱相互吻合,相互补充,这些光谱数据为揭示β－ＴＣＰ生物陶瓷的生物降解和新骨生成机理提供了大量分子信息和证据,从而证明生物陶瓷骨内植入后     

多孔β-TCP生物陶瓷骨内植入后的显微红外光谱

磷酸三钙（β－ＴＣＰ）生物陶瓷植入兔股骨后植入生物陶瓷、界面和兔股骨的显微红外光谱,对其红外特征频率作了指认和归属。在植入生物陶瓷和界面的红外光谱中,骨骼矿物相（或磷酸钙）,胶原,蛋白质和脂类（或磷脂）的红外特征频率同时出现,它们与股骨的红外光谱非常相似,其结果与拉曼光谱相互吻合,相互补充。这些光谱数据为揭示β－ＴＣＰ生物陶瓷的生物降解和新骨生成机理提供了大量分子信息和证据,从而证明生物陶瓷骨内植入后不仅陶瓷本身已部分溶解和降解而且在植入陶瓷的表面和孔隙中以及界面处均已生成新生骨组织。     

美国生物材料和工程代表团来沪讲学

我会于1983年10月12日至13日在市科学会堂接待了由美国民间学者组成的生物材料和工程代表团。代表团部分成员分别作了生物材料和工程方面的基础理论研究和临床应用的学术报告。主要内容有:聚合物在医学上的应用、人工心脏和心脏瓣腹、心脏辅助装置、胶原在医学和外科方面的应用、心血管生物材料、一次用弃式医疗器械的进展、电刺激骨细胞生长促进骨折愈合、生物材料的抗凝血措施、人工关节材料的研究、生物陶瓷在骨科的应用等。     

Bone and joint protection ability of ceramic material with biological effects

Ceramic materials with biological effects (bioceramic) have been found to modulate various biological effects, especially those effects involved in antioxidant activity and hydrogen peroxide scavenging. As arthropathy and osteopathy are the major chronic diseases of geriatric medicine, we explored the possible activity of bioceramic on these conditions using animal and cell models. Rabbits received intra-articular injections of lipopolysaccharides (LPS) to induce inflammation that mimic rheumatic arthritis. FDG isotopes were then IV injected for PET scan examinations at 16 hours and 7 days after the LPS injection. We examined and compared the bioceramic and control groups to see if bioceramic was capable of relieving inflammation in the joints by subtracting the final and initial uptake amount of FDG (max SUV). We studied the effects in prostaglandin E2 (PGE2) inhibition on the human chondrosarcoma (SW1353) cell line, and the effects on the murine osteoblast (MC3T3-E1) cell line under oxidative stress. All the subtractions between final and initial uptakes of FDG in the left knee joints of the rabbits after LPS injection indicated larger decreases in the bioceramic group than in the control group. This anti-arthritic or inflammatory effect was also demonstrated by the PGE2 inhibition of the SW1353 cells. We further proved that bioceramic treatment of the MC3T3-E1 cells resulted in increased viability of osteoblast cells challenged with hydrogen peroxide toxicity, and increased alkaline phosphatase activity and the total protein production of MC3T3-E1 cells under oxidative stress. Since LPS-induced arthritis is an experimental model that mimics RA, the potential therapeutic effects of bioceramic on arthropathy merit discussion. Bioceramic may contribute to relieving inflammatory arthritis and maintaining bone health.     

Development and clinical cases of injectable bone void filler used in orthopaedic

This study reports several clinical cases for orthopaedic bone regeneration using an injectable bone substitute (MBCP Gel^®) to demonstrate its safe use and efficiency in clinical applications. The biomaterial is a composite of microporous bioceramic hydroxyapatite granules that are associated with beta tricalcium phosphate (MBCP) and a synthetic hydrosoluble polysaccharide hydrogel (CE mark 123 and FDA dental domain registered). The present exploratory study demonstrated the generative osseous performance of this injectable bioceramic for filling various orthopaedic bone defects. The clinical cases showed bone ingrowth into the cavities created by drilling when removing the aseptic osteonecrosis of the femoral head during biopsy taking. Furthermore, bone reconstruction was seen after filling large cystic defects, at the time of the revision surgery of the hip prosthesis. Resorption and bone ingrowth with trabecular bone architecture were observed in defects created in long bones (femur and tibia). Patients were followed during 5 months to 1 year. The overall results demonstrated the safe use and the clinical performance of this injectable bioceramic in orthopaedics.     

3D Printing Bioceramic Porous Scaffolds with Good Mechanical Property and Cell Affinity

Artificial bone grafting is widely used in current orthopedic surgery for bone defect problems. Unfortunately, surgeons remain unsatisfied with the current commercially available products. One of the major complaints is that these products cannot provide sufficient mechanical strength to support the human skeletal structure. In this study, we aimed to develop a bone scaffold with better mechanical property and good cell affinity by 3D printing (3DP) techniques. A self-developed 3D printer with laser-aided gelling (LAG) process was used to fabricate bioceramic scaffolds with inter-porous structures. To improve the mechanical property of the bioceramic parts after heating, CaCO₃ was added to the silica ceramic slurry. CaCO₃ was blended into a homogenous SiO₂-sol dispersion at weight ratios varying from 0/100 to 5/95 to 9/91 (w/w). Bi-component CaCO₃/SiO₂-sol was prepared as a biocomposite for the 3DP scaffold. The well-mixed biocomposite was used to fabricate the bioceramic green part using the LAG method. The varied scaffolds were sintered at different temperatures ranging from 900 to 1500°C, and the mechanical property was subsequently analyzed. The scaffolds showed good property with the composite ratio of 5:95 CaCO₃:SiO₂ at a sintering temperature of 1300°C. The compressive strength was 47 MPa, and the porosity was 34%. The topography of the sintered 3DP bioceramic scaffold was examined by SEM, EDS and XRD. The silica bioceramic presented no cytotoxicity and good MG-63 osteoblast-like cell affinity, demonstrating good biocompatibility. Therefore, the new silica biocomposite is viable for fabricating 3DP bone bioceramics with improved mechanical property and good cell affinity.     

Apatite formation on nanomaterial calcium phosphate/poly-DL-lactide-co-glycolide in simulated body fluid

Simulated body fluid (SBF) is an artificial fluid which has ionic composition and ionic concentration similar to human blood plasma. Purpose: This paper compares the interaction between the nanomaterial containing calcium phosphate/poly-dl-lactide-co-glycolide (N-CP/PLGA) and SBF, in order to investigate whether and to what extent inorganic ionic composition of human blood plasma leads to the aforementioned changes in the material. Methods: N-CP/PLGA was incubated for 1, 2, 3, and 5 weeks in SBF. The surface of the material was analyzed on SEM-EDS and FTIR spectrometer, while SBF was subjected to pH and electrical conductivity measurement. Results: Our results indicate that dissolution of the polymer component of the material N-CP/PLGA and precipitation of the material similar to hydroxyapatite on its surface are based on the morphologic changes seen in this material. Conclusions: The mechanism of the apatite formation on the bioceramic surface was intensively studied and was considered crucial in designing the new biomaterials. The results obtained in this work indicate that N-CP/PLGA may be a good candidate for application to bone regeneration.     

Comparative proteomics profile of osteoblasts cultured on dissimilar hydroxyapatite biomaterials: an iTRAQ-coupled 2-D LC-MS/MS analysis

Hydroxyapatite (HA) and its derived bioceramic materials have been widely used for skeletal implants and/or bone repair scaffolds. It has been reported that carbon nanotube (CNT) is able to enhance the brittle ceramic matrix without detrimental to the bioactivity. However, interaction between osteoblasts and these bioceramics, as well as the underlying mechanism of osteoblast proliferation on these bioceramic surfaces remain to be determined. Using iTRAQ-coupled 2-D LC-MS/MS analysis, we report the first comparative proteomics profiling of human osteoblast cells cultured on plane HA and CNT reinforced HA, respectively. Cytoskeletal proteins, metabolic enzymes, signaling, and cell growth proteins previous associated with cell adhesion and proliferation were found to be differentially expressed on these two surfaces. The level of these proteins was generally higher in cells adhered to HA surface, indicating a higher level of cellular proliferation in these cells. The significance of these findings was further assessed by Western blot analysis. The differential protein profile in HA and CNT strengthened HA established in our study should be valuable for future design of biocompatible ceramics.     

Nucleation and growth of apatite by a self-assembled polycrystalline bioceramic

The formation aspects of a polycrystalline self-assembled bioceramic leading to the nucleation of hard-tissue mineral from a supersaturated solution are discussed. Scanning electron imaging and surface-sensitive interrogations of the nucleated mineral indicated the presence of an intermediate amorphous layer encompassing a rather crystalline phase that formed on niobium oxide (Nb(2)O(5)) microstructures. The crystalline phase was identified from Raman spectroscopy as hydroxyapatite (HAP), while the phosphorous-rich amorphous layer is suggested to have the chemical form CaO-P(2)O(5). In addition, the mechanism favoring HAP nucleation is discussed in terms of the (0 0 2) and (0 0 1) diffraction planes of HAP and Nb(2)O(5), respectively. The small mismatch along several lattice dimensions strongly suggests epitaxy as a dominant mode in the heterogeneous nucleation of HAP. Furthermore, the effectiveness of this mode was shown to critically depend on the self-organization of the Nb(2)O(5) microstructures. Because nucleation does not appear to depend solely on the integrity of Nb(2)O(5) crystals, the self-organization of Nb(2)O(5) crystals also contributes significantly to HAP nucleation. Based on our results, we propose the organized arrangement of bioceramic crystals as a new mode for the bioinspiration of hydroxyapatite and other hard-tissue mineral.     

3D Bone tissue engineered with bioactive microspheres in simulated microgravity

Three-dimensional (3D) osteoblast cell cultures were obtained in rotating-wall vessels (RWV), simulating microgravity. Three types of bioactive microcarriers, specifically modified bioactive glass particles, bioceramic hollow microspheres, and biodegradable bioactive glass-polymer composite microspheres, were developed and used with osteoblasts. The surfaces of composite microspheres fully transformed into bone apatite after 2-wk immersion in simulated physiological fluid, which demonstrated their bone-bonding ability. The motion of microcarriers in RWVs was photographically recorded and numerically analyzed. The trajectories of hollow microspheres showed that they migrated and eventually stayed around at the central region of the RWV. At their surfaces, shear stresses were low. In contrast, solid glass or polymer particles moved toward and finally bounced off the outer wall of the RWVs. Cell culture studies in the RWV using bone marrow stromal cells showed that the cells attached to and formed 3D aggregates with the hollow microspheres. Extracellular matrix and mineralization were observed in the aggregates. Cell culture studies also confirmed the ability of the composite microspheres to support 3D bone-like tissue formation. These data suggest that the new hollow bioceramic microspheres and degradable composite microspheres can be used as microcarriers for 3D bone tissue engineering in microgravity. They also have potential applications as drug delivery systems.     

Hydroxyapatite-Sheet Parallel Microstructure of Shinbone

Bone is a natural biomaterial. It behaves favorable strength, stiffness and fracture toughness, which are closely related to its eximious microstructure. Scanning Electron Microscope (SEM) observation on a shinbone showed that the bone is a bioceramic composite consisting of laminated hydroxyapatite and collagen matrix. The hydroxyapatite layers are parallel with the surface of the bone and consist of long and thin hydroxyapatite sheets. The observation also showed that the hydroxyapatite sheets in different hydroxyapatite layers also parallel with each other, which composes a hydroxyapatite-sheet parallel microstructure. The maximum pullout energy of the parallel microstructure was investigated based on its representative model. It was shown that the long and thin shape of the hydroxyapatite sheets in the parallel microstructure is profitable to increase the maximum pullout energy and enhance the fracture toughness of the bone.     

Intercrossed Microstructures of Hydroxyapatite Sheets of Tibia Bone

The observation of Scanning Electron Microscope (SEM) shows that a tibia bone is a kind of bioceramic composite consisting of hydroxyapatite layers and collagen protein matrix. All the hydroxyapatite layers are parallel with the surface of the bone and consist of numerous hydroxyapatite sheets. The observation also shows that there is a kind of intercrossed microstructure of the hydroxyapatite sheets. In this kind of microstructure, the hydroxyapatite sheets in an arbitrary hydroxyapatite layer make a large intercrossed angle with the hydroxyapatite sheets in their adjacent hydroxyapatite layers. The maximum pullout force of the intercrossed microstructure, which is closely related to the fracture toughness of the bone, is investigated and compared with that of the parallel microstructure of the sheets through their representative models. The result of the investigation indicates that the maximum pullout force of the intercrossed microstructure is markedly larger than that of the parallel microstructure, which is experimentally verified.