块状壳聚糖多孔支架内交替浸渍沉积磷灰石层

在聚合物支架内沉积羟基磷灰石涂层有望提高支架的生物活性和骨传导性. 本研究采用交替浸渍沉积法, 以块状壳聚糖(Cs)三维多孔支架为沉积模板, 在氯化钙溶液和磷酸氢二钠溶液中交替浸渍, 沉积了羟基磷灰石(HA)涂层. 应用XRD、FT-IR、SEM、孔隙率测试、焙烧法和压缩实验对沉积前后支架的组成、形貌、孔隙率、无机物沉积量以及压缩强度进行了表征. 研究结果表明, 支架上沉积物为低结晶度的碳酸羟基磷灰石, 沿c轴择优生长, 与天然骨中磷灰石类似. 扫描电镜照片显示, 磷灰石在支架孔壁上的沉积量呈梯度分布, 外部沉积量多于内部, 靠近支架表面孔隙部分堵塞, 但内部仍保持连通的孔隙结构. 经6次交替浸渍处理的支架, 孔隙率为94.0%, 羟基磷灰石沉积量达到总质量的13.5%, 压缩强度则由0.055 MPa提高到0.109 MPa.     

Osteogenesis of Osteoblast Seeded Polyurethane-Hydroxyapatite Scaffolds in Nude Mice

Summary: Biodegradable porous polyurethane (PU) scaffolds were used in a tissue engineering approach to create new bone. Two groups of elastomeric bioresorbable PU disks were seeded with osteoblasts and implanted into nude mice. One group had disks of pure PU while the other group had disks of PU- hydroxyapatite composite (PU-HA). After 5 weeks both groups showed radiographic and histologic evidence of significant bone formation. As the new bone formed it replaced the PU scaffolds. Although not statistically significant, there was a trend toward more bone formation in the PU-HA group. Bioresorbable PU shows promise for use in bone tissue engineering.     

利用溶剂热压方法制备羟基磷灰石多孔纳米固体

利用溶剂热压方法,以羟基磷灰石（HAP）纳米颗粒为原料制备了一种介于纳米粉体和纳米陶瓷体之间的过渡态——体块HAP多孔纳米固体,并用X射线衍射（XRD）、扫描电子显微镜（SEM）、压汞仪和热分析（DSC和TGA）等方法对样品进行了表征,初步研究了溶剂的种类、分布均匀性等因素对HAP多孔纳米固体的孔容和孔径分布的影响,并对HAP多孔纳米固体的热稳定性进行了分析.     

The contribution of rheology for designing hydroxyapatite biomaterials

As a result of aging populations in the industrialized world, the development of biomaterials for bone tissue engineering is becoming increasingly important. Rheology, which is a key parameter in process engineering, plays a decisive role in designing these biomaterials. As a prime example of biomaterials engineering, this review focuses on formulations that are based on hydroxyapatite (HAp). More specifically, we will discuss the contribution of rheology for designing injectable bone replacement materials, composite gel scaffolds, porous scaffolds and scaffolds that can be generated using rapid prototyping or 3D printing techniques.     

造孔剂对电泳沉积制备多孔HA涂层及其生物活性的影响

采用水热法制得的羟基磷灰石(HA)纳米粉体,分别与造孔剂葡萄糖(Glu)、壳聚糖(CS)、炭粉(C)3种微粒(＜38.5 μm)配置成质量比1∶1的悬浮液,电泳沉积 烧结制备钛基多孔HA涂层,并对制得的3种多孔HA涂层在模拟体液浸泡前后的表面形貌、化学组成及物相变化进行表征。 结果表明,经700 ℃烧结处理后制得的3种多孔HA涂层在1.5倍人体模拟体液中浸泡5 d后,多孔HA涂层表面均被层状生长的碳磷灰石颗粒完全覆盖,颗粒直径在5~25 μm,说明这些多孔HA涂层均具有良好的生物活性。 其中以CS为造孔剂制得的多孔HA涂层结合强度最高,达19.5 MPa,有望开发成为新型的人骨植入生物陶瓷材料。     

Spectroscopic characterization of porous nanohydroxyapatite synthesized by a novel amino acid soft solution freezing method

In this paper, we have reported a novel method to synthesize nanoporous hydroxyapatite (HAP) powders by freezing organic–inorganic soft solutions. The formation of porous and crystalline HAP nanopowder was achieved via calcining the samples at 600 °C followed by sintering at temperatures ranging from 900 °C to 1100 °C. The samples were analyzed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopic (SEM) techniques. The results showed the formation of a carbon free nanoporous hydroxyapatite powders due to the decomposition of organic template enclosing the precipitated HAP. It was also observed that the rapid grain growth with retainment of pores while the crystallinity of the HAP nanopowder increased with the increase in sintering temperature which is substantiated from the XRD and SEM results. Such organized porous materials can act as a better biomaterial for bone tissue engineering.     

Porous Calcium Hydroxyapatite as an Efficient Catalyst for Synthesis of Pyrazolines via 1,3‐Dipolar Cycoloaddition Under Solvent‐Free Microwave Irradiation

Adsorbed on porous calcium hydroxyapatite, 1,3‐dipolar cycloaddition of diphenylnitrilimine on olefins is readily catalyzed under solvent‐free microwaves irradiation. The pyrazolines are obtained in few minutes with high yields. Specific surface of porous calcium hydroxyapatite and microwaves effects are discussed.     

Preparation of nanostructure hydroxyapatite scaffold for tissue engineering applications

Hydroxyapatite due to its good biocompatibility and similar chemical composition to the mineral part of bone has found various applications in tissue engineering. Porous hydroxyapatite has high surface area, which leads to excellent osteoconductivity and resorbability, providing fast bone ingrowth. In this study, highly porous body of nanostructure hydroxyapatite was successfully fabricated via gelcasting method. The pure phase of hydroxyapatite was confirmed by X-ray diffraction. The result of scanning electron microscopy analysis showed that the prepared scaffold has highly interconnected spherical pores with a size in the range 100–400 μm. The crystallite size of the hydroxyapatite scaffold was measured in the range 30–42 nm. The mean values of true (total) and apparent (interconnected) porosity were calculated in the range 84–91 and 70–78%, respectively. The maximum values of compressive strength and elastic modulus of the prepared scaffold were found to be about 1.5 MPa and 167 MPa, respectively, which were achieved after sintering at 1,000 °C for 4 h. Transmission electron microscopy analysis showed that the particle sizes are smaller than 80 nm. In vitro test showed good bioactivity of the prepared scaffold. The mentioned properties could make the hydroxyapatite scaffold a good candidate for tissue engineering applications, especially applications that did not need to stand any loading.     

Valorization of Bone Waste of Saudi Arabia by Synthesizing Hydroxyapatite

At present, hydroxyapatite is being frequently used for diverse biomedical applications as it possesses excellent biocompatibility, osteoconductivity, and non-immunogenic characteristics. The aim of the present work was to recycle bone waste for synthesis of hydroxyapatite nanoparticles to be used as bone extracellular matrix. For this reason, we for the first time utilized bio-waste of cow bones of Albaha city. The residual bones were utilized for the extraction of natural bone precursor hydroxyapatite. A facile scientific technique has been used to synthesize hydroxyapatite nanoparticles through calcinations of wasted cow bones without further supplementation of chemicals/compounds. The obtained hydroxyapatite powder was ascertained using physicochemical techniques such as XRD, SEM, FTIR, and EDX. These analyses clearly show that hydroxyapatite from native cow bone wastes is biologically and physicochemically comparable to standard hydroxyapatite, commonly used for biomedical functions. The cell viability and proliferation over the prepared hydroxyapatite was confirmed with CCk-8 colorimetric assay. The morphology of the cells growing over the nano-hydroxyapatite shows that natural hydroxyapatite promotes cellular attachment and proliferation. Hence, the as-prepared nano-hydroxyapatite can be considered as cost-effective source of bone precursor hydroxyapatite for bone tissue engineering. Taking into account the projected demand for reliable bone implants, the present research work suggested using environment friendly methods to convert waste of Albaha city into nano-hydroxyapatite scaffolds. Therefore, besides being an initial step towards accomplishment of projected demands of bone implants in Saudi Arabia, our study will also help in reducing the environmental burden by recycling of bone wastes of Albaha city.     

Evaluation of a novel nanocrystalline hydroxyapatite powder and a solid hydroxyapatite/Chitosan-Gelatin bioceramic for scaffold preparation used as a bone substitute material

Artificially fabricated hydroxyapatite (HAP) shows excellent biocompatibility with various kinds of cells and tissues which makes it an ideal candidate for a bone substitute material. In this study, hydroxyapatite nanoparticles have been prepared by using the wet chemical precipitation method using calcium nitrate tetra-hydrate [Ca(NO₃)₂.4H₂O] and di-ammonium hydrogen phosphate [(NH₄)₂ HPO₄] as precursors. The composite scaffolds have been prepared by a freeze-drying method with hydroxyapatite, chitosan, and gelatin which form a 3D network of interconnected pores. Glutaraldehyde solution has been used in the scaffolds to crosslink the amino groups (|NH₂) of gelatin with the aldehyde groups (|CHO) of chitosan. The X-ray diffraction (XRD) performed on different scaffolds indicates that the incorporation of a certain amount of hydroxyapatite has no influence on the chitosan/gelatin network and at the same time, the organic matrix does not affect the crystallinity of hydroxyapatite. Transmission electron microscope (TEM) images show the needle-like crystal structure of hydroxyapatite nanoparticle. Scanning Electron Microscope (SEM) analysis shows an interconnected porous network in the scaffold where HAP nanoparticles are found to be dispersed in the biopolymer matrix. Fourier transforms infrared spectroscopy (FTIR) confirms the presence of hydroxyl group (OH^-) , phosphate group (PO^3-₄) , carbonate group (CO^2-₃) , imine group (C=N), etc. TGA reveals the thermal stability of the scaffolds. The cytotoxicity of the scaffolds is examined qualitatively by VERO (animal cell) cell and quantitatively by MTTassay. The MTT-assay suggests keeping the weight percentage of glutaraldehyde solution lower than 0.2%. The result found from this study demonstrated that a proper bone replacing scaffold can be made up by controlling the amount of hydroxyapatite, gelatin, and chitosan which will be biocompatible, biodegradable, and biofriendly for any living organism.     

Improving mechanical and biological properties of macroporous HA scaffolds through composite coatings

Interconnected porous hydroxyapatite (HA) scaffolds are widely used for bone repair and replacement, owing to their ability to support the adhesion, transfer, proliferation and differentiation of cells. In the present study, the polymer impregnation approach was adopted to produce porous HA scaffolds with three-dimensional (3D) porous structures. These scaffolds have an advantage of highly interconnected porosity (≈85%) but a drawback of poor mechanical strength. Therefore, the as-prepared HA scaffolds were lined with composite polymer coatings in order to improve the mechanical properties and retain its good bioactivity and biocompatibility at the same time. The composite coatings were based on poly(d,l-lactide) (PDLLA) polymer solutions, and contained single component or combination of HA, calcium sulfate (CS) and chondroitin sulfate (ChS) powders. The effects of composite coatings on scaffold porosity, microstructure, mechanical property, in vitro mineralizing behavior, and cell attachment of the resultant scaffolds were investigated. The results showed that the scaffolds with composite coatings resulted in significant improvement in both mechanical and biological properties while retaining the 3D interconnected porous structure. The in vitro mineralizing behaviors were mainly related to the compositions of CS and ChS powders in the composite coatings. Excellent cell attachments were observed on the pure HA scaffold as well as the three types of composite scaffolds. These composite scaffolds with improved mechanical properties and bioactivities are promising bone substitutes in tissue engineering fields.     

不同钙源的羟基磷灰石的合成及表征

通过比较法研究了不同钙源在水热条件下合成羟基磷灰石的方法。SEM,XRD和FT-IR的测试结果表明,蛋壳不仅可以成为有效钙源,而且多孔结构还可充当硬模板,在磷酸二氢钠缓慢腐蚀CaCO_3的同时提供PO_4~(3-)诱导生成花状羟基磷灰石。研究表明,磷酸肌酸钠水热缓慢分解释放磷酸根在合成高纯度羟基磷灰石方面有着广阔的应用前景。     

非化学计量羟基磷灰石骨水泥的制备及性能研究

采用磷酸四钙和磷酸氢钙混合粉末制备了nCa/nP比为1.58的非化学计量羟基磷灰石骨水泥(n-HAC)及其多孔支架材料。结果表明:与nCa/nP=1.67的化学计量羟基磷灰石骨水泥(HAC)相比,n-HAC的凝结时间和抗压强度没有明显的区别。XRD和IR显示:n-HAC与HAC都为羟基磷灰石结构,但n-HAC在Tris-HCl缓冲溶液的降解性明显大于HAC。细胞培养结果表明:成骨细胞在n-HAC和HAC两种材料上的粘附和细胞形态没有明显的区别,但细胞在n-HAC上的增殖率明显高于HAC。将多孔n-HAC支架材料植入兔股骨缺损处,观察其修复骨缺损情况,组织学分析结果表明:新生骨在多孔支架的表面形成,并长入其内部;n-HAC在体内的降解比HAC快,能明显地促进新骨生成。     

Fabrication and In vitro Bioactivity of Robust Hydroxyapatite Coating on Porous Titanium Implant

Compared witli the traditional dental implant, TixOs■ manufactured by direct laser metal forming(DLMF) technology exhibits improved capability for bone osteointegration due to its porous surface structure, and has achieved remarkable clinical effect. However, like the traditional titanium and other alloyed implants, the porous titanium implant TixOsR also has relatively weak bioactivity. To address this issue, a proper surface modification method may be needed. Hydroxyapatite(HA) has been widely used in implant surface coating for its similar chemical composition to bone tissue and its osteoconductive properties. Thus, combining TixOs■ implants with hydroxyapatite can be an efficient way to enhance their bioactivity. We herewith reported a competent pulsed laser deposition(PLD) method of coating nano-sized HA thin film onto the porous TixOs■ implant. The HA coatings were characterized by means of scanning electron microscopy(SEM), energy dispersive X-ray spectroscopy(EDS), X-ray photoelectron spectroscopy(XPS) and focused ion beam(FIB) method, and nanocrystal sized thin HA films were identified on the surface of TixOs■ implants. The low cytotoxicity and improved cell proliferation ability of HA coated implants were further tested and verified using MC 3T3 E1 cells with the consideration of the controlling group. Our results show that a stable and bioactive HA tliin film is able to form on the surtace of the porous titanium implant by PLD method.This may benefit the fiirther clinical application of TixOs■ implants.     

A New Spherical Hydroxyapatite for High Performance Liquid Chromatography of Proteins

Abstract

Basic properties of a newly developed hydroxyapatite column and results of its application to the separation of proteins are described. The hydroxyapatite was completely spherical and porous beads in appearance by scanning electron microscopy, and showed superior properties to other types of hydroxyapatite column. The column was mechanically strong enough to show the pressure limit of 140–150 kg/cm². The hydroxyapatite column showed excellent mechanical and chemical stability, and was applicable to high speed and high resolution separation of proteins. Proteins are recovered in high yield after the chromatography.     

Effects of PCL,PEG and PLGA polymers on curcumin release from calcium phosphate matrix for in vitro and in vivo bone regeneration

Calcium phosphate materials are widely used as bone-like scaffolds or coating for metallic hip and knee implants due to their excellent biocompatibility, compositional similarity to natural bone and controllable bioresorbability. Local delivery of drugs or osteogenic factors from scaffolds and implants are required over a desired period of time for an effectual treatment of various musculoskeletal disorders. Curcumin, an antioxidant and anti-inflammatory molecule, enhances osteoblastic activity in addition to its anti-osteoclastic activity. However, due to its poor solubility and high intestinal liver metabolism, it showed limited oral efficacy in various preclinical and clinical studies. To enhance its bioavailability and to provide higher release, we have used poly (ε-caprolactone) (PCL), poly ethylene glycol (PEG) and poly lactide co glycolide (PLGA) as the polymeric system to enable continuous release of curcumin from the hydroxyapatite matrix for 22 days. Additionally, curcumin was incorporated in plasma sprayed hydroxyapatite coated Ti6Al4V substrate to study in vitro cell material interaction using human fetal osteoblast (hFOB) cells for load bearing implants. MTT cell viability assay and morphological characterization by FESEM showed highest cell viability with samples coated with curcumin-PCL-PEG. Finally, 3D printed interconnected macro porous β-TCP scaffolds were prepared and curcumin-PCL-PEG was loaded to assess the effects of curcumin on in vivo bone regeneration. The presence of curcumin in TCP results in enhanced bone formation after 6 weeks. Complete mineralized bone formation increased from 29.6% to 44.9% in curcumin-coated scaffolds compared to pure TCP. Results show that local release of curcumin can be designed for both load bearing or non-load bearing implants with the aid of polymers, which can be considered an excellent candidate for wound healing and tissue regeneration applications in bone tissue engineering.     

Low-temperature synthesis of porous hydroxyapatite scaffolds using polyaphron templates

A method to synthesize porous hydroxyapatite (HA) structures at a low temperature was investigated in this study. Polyaphrons, a class of high-internal-phase-ratio emulsions were used as the shape-directing template for the sol-gel reactions that facilitated the formation of the structures. Electron micrographs revealed a three dimensional porous structure with pore sizes in the range of 1–5 microns. X-ray diffraction images showed that the hydroxyapatite structure formed after treatment at 400°C matched exactly with commercial HA spectra indicating that the phase transformation was complete. IR spectra of the samples confirm the formation of the structural components characteristic of commercial HA.     

Evaluation of the interaction between hydroxyapatite and bisphosphonate by nonlinear capillary electrochromatography

Bisphosphonates are a class of chemical compounds used to treat diseases caused by increased bone resorption. Zoledronate is a third‐generation bisphosphonate drug. Hydroxyapatite is main mineral constituent of bones, which can be bound by bisphosphonates in vivo. In this work, we report a method of nonlinear capillary electrochromatography for study on the interaction between hydroxyapatite and bisphosphonate. Hydroxyapatite was modified on the inner wall of capillary by a biomimetic‐mineralization method. Then nonlinear chromatography was used to fit and analyze the interaction between zoledronate and hydroxyapatite. The association rate constants of zoledronate in hydroxyapatite‐modified capillary and bare capillary are 642.3 and 195/M/min, respectively. This indicates that there is strong binding interactions and affinity between zoledronate and hydroxyapatite. Besides, the interaction between zoledronate and hydroxyapatite was confirmed further by ultraviolet spectroscopy. The method of nonlinear capillary electrochromatography provides a fast and effect approach for studying of bone metabolism disease by evaluation of interaction between hydroxyapatite and bisphosphonates.     

Iodine measurement in porous matrices based on calcium phosphate compounds

Porous ceramic materials based on calcium phosphate compounds (CFC) have been studied and developed for several biomedical applications such as implants, controlled drug delivery, and radioactive sources for brachytherapy. Two kinds of hydroxyapatite (HAp) powders and their ceramic bodies were characterized. In this study, non-radioactive iodine was incorporated in two types of biodegradable hydroxyapatite-based porous matrices (HA and HACL). The results reveal that both systems present a high capacity of incorporating iodine. The quantity of incorporated iodine was measured by neutron activation analysis (NAA). The porous ceramic matrices based on hydroxyapatite demonstrated a great potential for uses in low dose rate (LDR) brachytherapy.     

Biomimetic Mineralized Fiber Bundle-Inspired Scaffolding Surface on Polyetheretherketone Implants Promotes Osseointegration

The stress shielding effect caused by traditional metal implants is circumvented by using polyetheretherketone (PEEK), due to its excellent mechanical properties; however, the biologically inert nature of PEEK limits its application. Endowing PEEK with biological activity to promote osseointegration would increase its applicability for bone replacement implants. A biomimetic study is performed, inspired by mineralized collagen fiber bundles that contact bone marrow mesenchymal stem cells (BMMSCs) on the native trabecular bone surface. The PEEK surface (P) is first sulfonated with sulfuric acid to form a porous network structure (sP). The surface is then encapsulated with amorphous hydroxyapatite (HA) by magnetron sputtering to form a biomimetic scaffold that resembles mineralized collagen fiber bundles (sPHA). Amorphous HA simulates the composition of osteogenic regions in vivo and exhibits strong biological activity. In vitro results show that more favorable cell adhesion and osteogenic differentiation can be attained with the novelsurface of sPHA than with SP. The results of in vivo experiments show that sPHA exhibits osteoinductive and osteoconductive activity and facilitates bone formation and osseointegration. Therefore, the surface modification strategy can significantly improve the biological activity of PEEK, facilitate effective osseointegration, and inspire further bionic modification of other inert polymers similar to PEEK.