Startseite Synthesis and application of nanometer hydroxyapatite in biomedicine
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Synthesis and application of nanometer hydroxyapatite in biomedicine

  • Xingyu Gui , Wei Peng , Xiujuan Xu EMAIL logo , Zixuan Su , Gang Liu , Zhigang Zhou , Ming Liu , Zhao Li , Geyang Song EMAIL logo , Changchun Zhou und Qingquan Kong
Veröffentlicht/Copyright: 15. Juni 2022
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Nanotechnology Reviews
Aus der Zeitschrift Nanotechnology Reviews Band 11 Heft 1

Abstract

Nano-hydroxyapatite (nano-HA) has been widely studied as a promising biomaterial because of its potential mechanical and biological properties. In this article, different synthesis methods for nano-HA were summarized. Key factors for the synthesis of nano-HA, including reactant concentration, effects of temperature, PH, additives, aging time, and sintering, were separately investigated. The biological performances of the nano-HA depend strongly on its structures, morphology, and crystallite sizes. Nano-HA with different morphologies may cause different biological effects, such as protein adsorption, cell viability and proliferation, angiogenesis, and vascularization. Recent research progress with respect to the biological functions of the nano-HA in some specific biological applications are summarized and the future development of nano-sized hydroxyapatite is prospected.

Keywords: nano-HA; synthesis methods; drug carrier

1 Introduction

Calcium phosphate is a kind of bioactive ceramic composed of calcium and phosphorus ions. Because its chemical composition is similar to natural bone tissue, it is widely used in clinical practice. Among them, calcium phosphate also contains hydroxyapatite (HA), tricalcium phosphate, bipolar calcium phosphate, and other applications of the most common component materials. Calcium phosphate not only has good biocompatibility, but also can form chemical bonds with new bone. It can induce bone tissue regeneration, so it is widely used in bone tissue repair. Among calcium phosphate, HA is the thermodynamically most stable crystalline phase of calcium phosphate in body fluids, most similar to the mineral parts of human bones and teeth. Calcium phosphate in natural bone tissue is mainly deposited in the collagen matrix in the form of nano-crystallites in an orderly manner [1]. Nanoscale HA has certain similarities with natural bone apatite in chemical composition, structure, and scale. In the microstructure of nano-bioceramics, the grains, grain boundaries, and their combination are all at the nanoscale level. The refined grains and the increase of the grain boundary numbers can make its mechanical properties (especially fracture toughness) and biological activity increase. This makes nano-hydroxyapatite (nano-HA) to be an ideal bone repair material. Among the calcium phosphate-based bioceramics, the bioactive ceramics represented by HA ceramics are the most widely used in bone tissue repair [2,3,4]. From the point of view of the process itself, the preparation process of nano-ceramics is not much different from that of ordinary ceramics (generally follows the process of “powder-forming-sintering”), but from a technical point of view, the preparation process of nano-ceramics is extremely harsh.

The successful preparation of nano-HA ceramics should first synthesize nanoscale HA powder. Nano-HA powder has high surface activity and is easy to agglomerate. So, it is difficult to obtain nanoscale solid powder under normal conditions. During the molding process, whether the particles can be stabilized at the nanoscale relies on extremely strict control of the sintering process of ceramics [5,6]. During the sintering process, with the increase of temperature and the extension of time, the nano solid particles are fused with each other, and the pores and grain boundaries are gradually reduced, which lead to a high probability to cause the growth of HA grains. So, how to effectively inhibit the growth of nano-grains during the sintering process is a difficult problem in the preparation process of nano-HA ceramics. In short, the two major difficulties in the preparation of nano-HA ceramics lie in the synthesis of nano-powder and the sintering of nano-ceramics. To this end, this article comprehensively summarizes and analyzes the current progress of nano-HA powder synthesis and nano-ceramic sintering technology, and prospects for future research.

2 Synthesis and preparation of nanometer HA

2.1 Different synthesis methods for nano-HA

The synthesis methods of HA ceramic powder, represented by HA powder, mainly include dry synthesis and wet synthesis. Dry preparation of HA is a preparation method of selecting finely ground precursor and mixing it, and then heat treating the precursor. This method has strict requirements on the purity and dosage of reactants and has the advantage of better crystallinity of the products. However, dry synthesis requires a relatively high temperature, which affects the porosity of the products. Wet preparation of HA consists of sol–gel method, chemical precipitation method, hydrothermal reaction method, and so on, which is carried out in water or organic solvents and can be applied to a variety of equipment with the addition of various catalysts. The advantages are that the structure and morphology of HA can be well controlled and the yield can be improved. The disadvantage is that the purity and crystallinity of the product are not enough, and there may be other phosphate crystals in the product. According to the various synthesis methods, the synthesized calcium apatite powders have certain differences in structure, morphology, and size. In addition, under the same synthesis method, different synthesis conditions will also affect the final powder morphology. Figure 1 shows the morphology of nano-HA prepared under different synthesis conditions [7,8,9]. This article summarizes the synthesis process of nano-powder in the following aspects.

Figure 1 (a) Spherical nano-HA particles, particle size is about 80 nm; (b) rod-like nano-HA particles, particle diameter is about 60 nm; (c) needle-like nano-HA particles, particle diameter ranged from 50 to 70 nm [7,9].
Figure 1

(a) Spherical nano-HA particles, particle size is about 80 nm; (b) rod-like nano-HA particles, particle diameter is about 60 nm; (c) needle-like nano-HA particles, particle diameter ranged from 50 to 70 nm [7,9].

2.2 Key factors for synthesis of nano-HA

2.2.1 Effects of reactant concentration

The concentration of reactants is the key factor affecting HA synthesis [10]. The Ca/P ratio of HA is 1.6, so the concentration of reactants determines the purity of HA and also affects the grain size of HA under certain conditions. For example, when Ca/P ratio is within the range of 1.5–1.67, the synthesized product is the mixed phase of HA and beta-TCP; when Ca/P ratio is within the range of 1.68–1.7, the synthesized product is HA; when Ca/P molar ratio is greater than or equal to 1.7, the synthesized product is HA + CaO [11]. From the perspective of crystal chemistry, crystal nuclei are formed first in the solution, and then they migrate and adhere to the particles under the action of thermal dynamics, grow up and form crystals. There are many nucleate particles in the high-concentration reactant solution, and HA with small grain size is easy to be formed [12,13].

2.2.2 Effects of temperature

Temperature affects not only the grain size of HA, but also the morphology of HA. Every chemical reaction involves heat, and temperature affects the speed of chemical reaction. In the synthesis reaction of HA, the higher the temperature, the faster the reaction speed, and the easier it is to nucleate and crystallize. However, at high temperature, the grain growth rate is accelerated, and the synthesized nanometer powder has high activity and is easy to aggregate. Yunjing et al. [14] prepared HA powder by precipitation in heat treatment at 200, 500, 700, and 900°C, respectively. They found that HA crystallized at 200°C was not high and its morphology was in the shape of needles or stripes. Lianfeng et al. [15] prepared nano-HA by chemical precipitation and studied the influence of temperature on the final particle size and phase structure. They studied particle size changes at 25, 40, 60, and 90°C, respectively (as shown in Table 1). With the increase of temperature, the crystallinity of nano-HA increased, and the particle size was within the range of 25–60°C. With the increase of temperature, the particle size increased, and needle-like nanoparticles were synthesized. At 90°C, the particle size tends to decrease, but the synthesized nanoparticles have rod structure. Rodriguez-Lorenzo and Vallet-Regi [16] prepared nano-HA by precipitation method. They also found that the grain size increased between 25–90°C and 20–80 nm as the temperature increased. The surface area of the synthesized HA particles decreased as the temperature increased, meaning that the reaction temperature directly affected the size of the particles, with the higher the reaction temperature, the larger the particles. The grain size of nanoparticles synthesized at 25°C was comparable to that of human bone, and the grain size of nanoparticles synthesized at 90°C was comparable to that of tooth enamel.

Table 1

Influence of temperature on the synthesis of nano-HA [15]

Temperature (°C) 25 40 60 90
Particle size (nm) 68.5 84.8 118.1 87.6
Morphology of nanoparticles Needle-like Needle-like Needle-like Rod-like

2.2.3 Effects of stress

The influence of pressure only works in dry synthesis and has no effect on general wet synthesis. Dry synthesis is mainly based on ball milling. The grinding balls in the ball mill directly extrude the material to convert mechanical energy into chemical energy. Therefore, the mass of the grinding balls is converted into the pressure of the reaction environment, which in turn affects the particle size of the synthesized HA. Toriyama et al. [17] used CaCO3 and CaHPO4·2H2O as raw materials to grind and synthesize nano-HA by dry method. In this process, grinding pressure is an important factor affecting powder synthesis. When the grinding pressure reaches the critical value and above, the reaction starts, and the higher the pressure, the faster the reaction rate, which in turn increases the crystallization rate of HA, and reduces its crystallinity and grain size.

2.2.4 Effects of pH

pH is a key factor in HA synthesis. When HA is alkaline, the alkaline environment provides the necessary OH root ions for HA synthesis and precipitates HA. Increasing pH value is conducive to the synthesis of a single HA phase with fewer impurities and smaller grain size [13]. If the pH value is too small, HA will decompose into impurity phases, such as preparing HA with Ca (NO3)2·4H2O, and (NH4)2HPO4 as the precursor system. When the pH value is equal to 4.5, 9, and 12.4, the prepared powders are, respectively, β-Ca2P2O7, HA + β-TCP, and HA [14]. Increasing pH will increase Ca/P ratio, so if you want to synthesize pure HA, you must strictly control the pH value. Generally, the pH value of wet synthesis is between 10 and 10.5 [18].

2.2.5 Effects of additives

Admixtures include organic matter, inorganic matter, and doped ions. Admixtures can affect not only grain size but also grain morphology. For example, Sr2+ can enter HA lattice to replace Ca2+, reduce the crystallization rate of HA, and reduce the grain size [19]. Additives affect the surface energy of the reactants. The higher the surface energy is, the faster the reaction speed is and the easier it is to crystallize and nucleate. The nucleation energy of HA is relatively large, and the addition of nucleating agent can accelerate the nucleation formation and synthesize HA with smaller grains [20]. Xinlong et al. [21] added 3–5 wt% citric acid in the synthesis process and effectively inhibited the growth of HA grains through competitive adsorption between ions. Adding ethanol can improve the dispersibility of nano powder. Adding cerium salt can refine the grain and improve the dispersibility [22].

2.2.6 Effects of stirring

The influence of stirring is mainly reflected in the time and speed of stirring. The longer the stirring time is, the more beneficial it is to the full contact of the reaction materials and improve the conversion efficiency. The speed of mixing also plays a role. Martins et al. [23] suggested that the faster the mixing speed, the better the nucleation formation and the easier the formation of HA with smaller grains. It has been reported that the higher stirring speed and longer stirring time affect the crystal morphology, making the morphology of HA similar to that of rod or rice shape [24].

2.2.7 Effects of aging time

Aging time determines the integrity of HA crystal growth and grain size. In the aging stage, the longer the aging time is, the better the formation of HA and the perfection of grain [24]. With the further extension of aging time, the grain size became larger and agglomerated, mainly due to the dissolution of small-size particles and the regrowth of secondary grains [25].

2.3 Sintering process

For nanostructured HA ceramics, sintering process is an independent step. Nanometer powders have large specific surface area and high activity. During sintering, the sintering temperature is lower than that of embryos with conventional particle size, and the grains are easy to grow and difficult to control [26]. In order to sinter nano-HA ceramics, it is necessary to prevent the grain growth during densification. Zhou et al. [27] studied the sintering properties of nano-HA; according to the DSC and TG curves of the nano-HA powder curve, the sintering temperature of the DSC curve is 761°C, and the material has an obvious endothermic peak. The concave surface indicates that the material corresponding to the sintering temperature is a violent crystal fusion and phase transformation, and the rapid fusion of nano-grains. After a short exothermic, from 761.6 to 1158.3°C, the material absorbs heat rapidly and the nanocrystals rapidly grow into ceramics.

When the nano powder of HA is over 900°C, the material grain grows rapidly, and most of the ceramic grains sintered above 1,000°C are above 1 µm. Therefore, it is difficult to obtain the final nano-ceramics by conventional sintering technology. Further study found that nano-HA ceramics grain in different sintering stages have different state changes. The initial nanoparticles in the green body of ceramic would undergoing size change during the process of continuous sintering. With the increase of the sintering temperature and time, the nanoparticles would undergo fusion, grains grow up and density in different stages of sintering. By controlling of the sintering process, such as rapid cooling would affect the finial grain size and obtain nano-structured ceramic. Therefore, nano-HA ceramic sintering process should be rigorous. Current sintering process mainly through the high efficiency of energy conversion and sintering for a short period of time makes grain to grow up. The concrete method consists of two sections of pressureless sintering, the discharge plasma sintering, hot-pressing sintering, hot isostatic pressing sintering, microwave sintering, etc. [28,29]. In this article, the several kinds of sintering methods of nano-HA ceramics sintering process were analyzed.

In order to overcome excessive grain growth in the later stage, Chen and Wang [30] invented a two-step sintering method. The principle is to raise the temperature to the critical point where the ceramic-sintered grain grows, so that the surface atom has a certain diffusion energy. Then, hold the temperature below the critical point to densify it. Mazaheri et al. [31] sintered HA by conventional sintering method and two-step sintering method, and found that the grain size of ceramics with the same densification degree was 1.7 μm in conventional sintering at 1,100°C. The grain size in the two-stage sintering of T1 = 900 and T2 = 800 was 0.19 μm. Compared with other sintering methods, the two-step nonpressure sintering method has the characteristics of simplicity, low cost, and remarkable effect.

Plasma discharge sintering is a new sintering method, which has the characteristics of fast heating rate, short sintering time, even grain size, and good control of sintering structure. Gu et al. [32] sintered the compact HA block in the plasma at 950°C for 5 min to obtain HA ceramics with density greater than 99.5%.

Microwave sintering is a new sintering technology in recent years. It used the coupling of the microstructure of the powder with the special wave band of the microwave to generate heat for sintering ceramic embryos. It has the advantages of fast heating rate, short sintering time, overall heating, and easy to obtain fine sintered materials with even grain size [33,34]. Wang et al. [35] found that even though the heating rate of microwave sintering was very high, the HA/β-TCP ceramics were not cracked or deformed. Due to the overall heating of microwave heating, there is no temperature gradient in the material, reducing the internal stress. To a certain extent, it can improve the mechanical strength of ceramic materials. Compared with the conventional sintering method, the ceramic grain size prepared by microwave sintering at the same temperature of 1,100°C is 200–400 nm, while the ceramic grain size prepared by conventional sintering is 1.0–1.5 μm.

3 Application of nanometer HA in biomedicine

Nano-HA has the advantages of good biocompatibility, large specific surface area, high biological activity, and stable chemical properties [36,37]. In recent years, researchers have probed and utilized the regeneration ability of nano-HA in numerous application fields. Here, we summarize and discuss the application of drug carrier, surface coating, antineoplastic, and composite materials [38,39,40,41,42,43,44].

3.1 Drug carrier

Nano-HA has high specific surface area and strong plasticity. Through surface receptor modification or modification to improve in vivo targeting, nano-HA can absorb different drugs and can be adapted to different site delivery needs [40,41]. The adsorption of drugs on nano-HA is mainly determined by its own properties and microscopic morphology [42,43].

The adsorption sites of nano-HA for drugs mainly include carboxyl group, hydroxyl group, phosphate group, and amino group [45,46]. Nano-HA has different adsorption effects on drugs with different groups. Zhao et al. [47] studied the molecular simulation of HA on doxorubicin and tinidazole. According to the results of molecular dynamics simulation, for doxorubicin, the binding energy to HA is much higher than that of tinidazole. Then they, respectively, prepared hollow HA microspheres and nano-HA (Figure 2), and used them to carry out adsorption experiments on two drugs, doxorubicin and tinidazole. The results show that the adsorption efficiency of HA is affected by the group in the drug molecule. The adsorption of drugs on HA is mainly through the formation of Ca–O bonds between Ca ions on the surface of HA and “O” atoms in the drug molecule. The number and activity of oxygen atoms are the main factors affecting the binding ability of drugs on HA.

Figure 2 (a and b) TEM micrographs of the as-prepared HA. (a) HA nanoparticle, (b) HA hollow microsphere. (c and d) Adsorption configurations of DOX (c) and tinidazole (d) on the (110) plane of HA. The colors are as follows: calcium (green), phosphorus (purple), oxygen (red), hydrogen (white), carbon (gray), nitrogen (blue), and sulfur (yellow) [47].
Figure 2

(a and b) TEM micrographs of the as-prepared HA. (a) HA nanoparticle, (b) HA hollow microsphere. (c and d) Adsorption configurations of DOX (c) and tinidazole (d) on the (110) plane of HA. The colors are as follows: calcium (green), phosphorus (purple), oxygen (red), hydrogen (white), carbon (gray), nitrogen (blue), and sulfur (yellow) [47].

In addition to the adsorption of drugs by HA itself, nano-HA is often combined with various substances to form nanoparticles with hollow or mesoporous shell structures to increase drug loading and sustained drug release. Li et al. [48] successfully prepared a hollow nano-HA structure by adding a pore-enlarging agent, and used LA–BSA to encapsulate the pores to obtain pH-responsive nanoparticles while increasing the drug loading. Zhang et al. [49] introduced Sr ions to form luminescent rod-like HA with mesoporous structure when preparing nano-HA particles by hydrothermal reaction. Nano-HA was loaded with ibuprofen. The luminescence intensity of Sr-HA was positively correlated with drug release, realizing the tracking of the drug release process. Yang et al. [50] successfully synthesized nanoparticles with a mesoporous nano-HA shell and a hollow calcium carbonate core by adjusting the oppositely charged ions between the shell and the core (Figure 3), and loaded the antitumor drug doxorubicin. The outer shell of nano-HA can achieve sustained release of drugs and pH-responsive release against tumor tissue, and the hollow calcium carbonate in the inner layer greatly increases the drug load.

Figure 3 (a) An illustration indicating the synthetic process of hmHANP. SEM images of (b) CaCO3 nanoparticles, (c) CaCO3/HA core/shell nanocomposites, (d) hmHANP; TEM images of (e) CaCO3 nanoparticles, (f) CaCO3/HA core/shell nanocomposites, (g) hmHANP (inset: dark-field STEM image) [50].
Figure 3

(a) An illustration indicating the synthetic process of hmHANP. SEM images of (b) CaCO3 nanoparticles, (c) CaCO3/HA core/shell nanocomposites, (d) hmHANP; TEM images of (e) CaCO3 nanoparticles, (f) CaCO3/HA core/shell nanocomposites, (g) hmHANP (inset: dark-field STEM image) [50].

Not only drugs, nano-HA can also adsorb DNA and proteins. Nano-HA can be used as an ideal drug, protein, and gene carrier. HA nanoparticles have been used as carriers due to their affinity with DNA, proteins, several drugs, and appropriate release activity [51,52]. Ko et al. [53] modified HA with calcium chloride and carried the si-Stat3 plasmid that could inhibit the expression of Stat3. After injecting HA into the tumor, it was found that the growth in the tumor was significantly inhibited, and the inhibition rate was as high as 74%. The expression of Stat3 was significantly downregulated in the tumor. The use of nano-HA carrying RNA plasmids for tumor treatment is a reliable choice. Wan et al. [54] prepared layered HA nanoplates with different structures and morphologies by adjusting the content of the template agent and the concentration of the precursor, and embedded DNA molecules into the L-HA nanoplates (Figure 4). Under high SDS loading and low precursor concentration, L-HA nanoplates with higher order degree and larger size were obtained, which improved the DNA loading efficiency and transfection efficiency.

Figure 4 Schematic illustration of the loading process of DNA molecules to L-HA nanoplates [54].
Figure 4

Schematic illustration of the loading process of DNA molecules to L-HA nanoplates [54].

3.2 Antitumor effects

Nano-HA has an inhibitory effect on the growth of various tumor cells, but has no effect on the growth of normal cells [55,56,57,58]. Judging from the existing inferred mechanism, nano-HA degrades fast, increasing the concentration of Ca2+ in tumor cell fluid leads to disorder of tumor cell function, degrades its DNA and inhibits telomerase gene expression, and so on, thereby inhibiting the growth and proliferation of tumor cells [59,60,61,62,63]. Ezhaveni et al. [64] explored the effect of nano-HA with different particle sizes prepared under different hydrothermal conditions on liver cancer cells, and found that the HA with an average particle size of 19 nm prepared by treating at 100°C for 5 h provides the most obvious inhibitory effect on tumor. Zhang et al. [65] prepared porous titanium scaffolds with nano-HA coating and cocultured with VX2 tumor cells in vitro and repaired the truncated bone defect of a critical defect size in a rabbit bone tumor model, and found that nano-HA-loaded scaffold not only has a significant effect of inhibiting tumor growth, but also has the effect of promoting bone regeneration. At the same time, they also conducted experiments on the effects of n-HA regulation on tumor suppression, calcium homeostasis, and immune response-related gene expression (Figure 5). Combined with its own antitumor properties, nano-HA loaded with drugs, DNA or protein is used as a more choice in tumor treatment.

Figure 5 Nano-HA regulates gene expressions related to tumor suppression, calcium homeostasis, and immune response. (a) Volcano plot showing differentially regulated genes in the n-HA-treated tumor tissue as compared to the nontreated control. (b) Gene set enrichment analysis of the regulated gene pathways with the Kyoto Encyclopedia of Genes and Genomes database. (c) Circular visualization of the results of gene-annotation enrichment analysis. (d) Heat map of genes that were differentially expressed in n-HA versus control tumor tissues. (e) Enzyme-linked immunosorbent assay of inflammatory cytokines. (f) Wound healing assay of mouse 4T1 tumor cells treated for 24 h. (g) Transwell assay after crystal violet staining showing serum-induced migration of 4T1 tumor cells treated for 24 h [65].
Figure 5

Nano-HA regulates gene expressions related to tumor suppression, calcium homeostasis, and immune response. (a) Volcano plot showing differentially regulated genes in the n-HA-treated tumor tissue as compared to the nontreated control. (b) Gene set enrichment analysis of the regulated gene pathways with the Kyoto Encyclopedia of Genes and Genomes database. (c) Circular visualization of the results of gene-annotation enrichment analysis. (d) Heat map of genes that were differentially expressed in n-HA versus control tumor tissues. (e) Enzyme-linked immunosorbent assay of inflammatory cytokines. (f) Wound healing assay of mouse 4T1 tumor cells treated for 24 h. (g) Transwell assay after crystal violet staining showing serum-induced migration of 4T1 tumor cells treated for 24 h [65].

3.3 Surface coating

Many components in cells are affected by nanoscale factors. According to reports, the adhesion sites of cells, proteins, etc., are generally 5–200 nm [66,67,68]. Thus, nano-grain-sized ceramics, metals, polymers, and composites stimulate cellular activity compared to micro-grain sizes. Nano-HA crystals can increase cell adhesion and proliferation, create a biocompatible surface that combines well with bone tissue [69,70,71]. As a HA ceramic material, nano-HA can promote the development of stem cells toward osteogenesis by degrading calcium and phosphate ions [72,73]. Bryington et al. [74] studied the long-term repair of titanium alloy stents with nano-HA coating and without nano-HA coating in vivo, and found that nano-HA coating has a greater impact in the early stage of bone healing.

Different structure of nanometer HA has different effect on cell behavior. He et al. [75] deposited two types of amorphous CaP nanoparticle nano-HA coating on the surface of titanium alloy and simulated the adhesion of osteoblasts on the scaffold (Figure 6). The results showed that the coating prepared by different forms of nano-HA particles had different upregulation of gene expression during bone tissue reconstruction. Xiao et al. [76] used a hydrothermal method to prepare nano-HA coating with different shapes and length on HA scaffolds by adjusting the concentration of 1,2,3,4,5,6-cycloadipic acid. In vitro studies have shown that the differentiation of cells cultured on spherical nanostructure coatings is significantly enhanced compared to plate-like or wire-like nanostructures. The results showed that the surface nanotopography of the scaffolds had a greater effect on cell differentiation than on cell proliferation.

Figure 6 Schematic of biological response of nano-HA-coated titanium implant (Ti implant). (a) Ti implant coated with ACP nanoparticles; (b) release of Ca2+ and PO4 3+ ions from ACP hydrolysis after implantation; (c) cell binding on the implant surface with the help of serum proteins and integrin receptors; (d) cell proliferation on the implant surface; (e) formation of apatite on the implant surface [75].
Figure 6

Schematic of biological response of nano-HA-coated titanium implant (Ti implant). (a) Ti implant coated with ACP nanoparticles; (b) release of Ca2+ and PO4 3+ ions from ACP hydrolysis after implantation; (c) cell binding on the implant surface with the help of serum proteins and integrin receptors; (d) cell proliferation on the implant surface; (e) formation of apatite on the implant surface [75].

In addition, nano-HA has strong plasticity. It is often multifunctional nano-HA by compounding other particles. Zhang et al. [77] mixed Ag and ZnO into nano-HA powder to form a coating on the surface of titanium alloy by laser cladding technology. Ag+ released antibacterial, Zn2+ released to enhance bone formation. On the basis of nano-HA coating, the antibacterial and osteogenic functions are enhanced. The experimental results showed that the coated scaffolds achieved good osteogenesis and rapid osseointegration under the condition of S. aureus injection. Rios-Pimentel et al. [78] prepared amphiphilic peptide nanoparticles (APNPs), and APNPs can promote the attachment and proliferation of osteoblasts. Nanocrystalline HA and APNP coatings were prepared on poly-2-hydroxyethyl methacrylate, respectively, and the experimental surface osteoblast density of the group with APNPs coating increased by 3 times after 3 days.

Therefore, nano-HA plays a significant role in improving the surface roughness of the material, increasing cell adhesion and enhancing the biological activity of the material. In addition, coating the nano-HA coating on the bone repair material can better improve the bone formation of the material. In addition, nano-HA coating can better improve osteogenic activity for bone repair materials.

3.4 Nano-HA composited materials

The natural bone tissue in the human body is a nanocomposite material, which is composed of crystals and collagen at the microscopic level [79,80,81,82]. Bone tissue is the compound tissue of nanometer HA and collagen. Using nano-HA as composite material can effectively improve biological activity and enhance cell survival. At the same time, nano-HA can effectively increase the surface roughness and mechanical properties of composites, and has a positive effect on the adhesion and proliferation of proteins and cells. In addition, the composite materials of nano-HA release calcium and phosphorus ions in the body, which has a positive effect on osteogenesis. The composite of nano-HA with polymer materials and hydrogel materials can improve the biological activity, surface roughness (Figure 7), and osteogenic activity of the materials [39,83–89]. By adding nano-HA to the cell-loaded hydrogel material, cell survival and regulation of cell differentiation can be enhanced [84,90]. Deng et al. [91] prepared nano-HA hybrid methyl cellulose (MC) hydrogel. The nano-HA-MC hydrogel loading bone marrow mesenchymal stem cells was used for rat skull defect experiments. The addition of nano-HA improved the gelling temperature of MC and enhanced the survival of marrow mesenchymal stem cells. Nabavinia et al. [92] prepared nano-HA/alginate/gelatin microcapsules as osteogenic building blocks in modular bone tissue engineering. By regulating the proportion of nano-HA and gelatin, the interaction between nano-HA and gelatin can enhance cell proliferation and differentiation.

Figure 7 SEM of cell morphology on scaffolds. (a) PLA/nano-HA scaffolds; (b) nano-HA/CM/B9 scaffolds; (c) CS/nano-HA/Zol scaffolds; (d) gel:nano-HA = 1:1 scaffolds [83,88].
Figure 7

SEM of cell morphology on scaffolds. (a) PLA/nano-HA scaffolds; (b) nano-HA/CM/B9 scaffolds; (c) CS/nano-HA/Zol scaffolds; (d) gel:nano-HA = 1:1 scaffolds [83,88].

For natural bone tissue, cells are micron-sized entities embedded in the natural extracellular matrix (ECM). This ECM is highly organized at macroscopic, microscopic, and nanoscale [93,94]. Cells interact with topographic features at all scales, from macroscale (such as the shape of bone, ligament, or blood vessels) to nanoscale features (such as collagen ribbon shape, protein conformation, and ligand presentation). These topographic features strongly influence cell morphology, adhesion, attachment, movement, proliferation, endocytic activity, protein abundance and gene regulation, and other phenomena [95]. Inspired by the nano-layered structure and composition of bone, nanofibers and nanocomposite scaffolds doped with nanostructured HA that mimic the ECM of bone are increasingly used in bone tissue engineering [96,97]. Zhang et al. [94] used polylactic acid combined with nano-HA to simulate natural bone tissue structure and 3D printed it (Figures 8 and 9). According to the amount of nano-HA, the surface morphology of the printed scaffold is significantly different, and the hydrophilicity of the material will increase with the increase of the content of HA. The composite of nanometer HA can improve the surface roughness and hydrophilicity of materials. Zhang et al. [98] introduced an ECM-like self-assembly peptide (SAP) to nano-HA/chitosan (CTS) composite scaffolds. The SAP/nano-HA/CTS scaffolds enhanced the cell adhesion and overall mechanical properties of scaffolds. Chen et al. [99] used electrospinning technology to prepare multilayer nano-HA/polyhydroxybutyrate (PHB) film laminate scaffolds, and seeded cells on the scaffolds for bone defect repair experiments. The experimental results show that the scaffold with nanoscale simulated ECM enhances the adhesion and proliferation of osteoblasts and promotes the repair of bone defects. Yin et al. [100] perfused GelMA loaded with nano-HA into porous titanium alloy scaffolds, which enhanced the characteristics of low bioactivity and poor bone repair ability of traditional titanium alloy scaffolds.

Figure 8 The morphology of composite scaffolds with different nHA contents, (a) PLLA scaffolds, (b) 30% nHA composite scaffolds, (c) 50% nHA composite scaffolds, (d) the water contact angle of the different composite.
Figure 8

The morphology of composite scaffolds with different nHA contents, (a) PLLA scaffolds, (b) 30% nHA composite scaffolds, (c) 50% nHA composite scaffolds, (d) the water contact angle of the different composite.

Figure 9 (a) Schematic of 3D multi-nozzle pneumatic printing system. 30/3% GelMA/nano-HA (red) for subchondral bone layer, 20/3% GelMA/nano-HA (yellow) for interfacial layer, 15% GelMA/nano-HA (blue) for cartilage layer; (b) cartilage layer; (c) interfacial layer; (d) subchondral bone layer [102].
Figure 9

(a) Schematic of 3D multi-nozzle pneumatic printing system. 30/3% GelMA/nano-HA (red) for subchondral bone layer, 20/3% GelMA/nano-HA (yellow) for interfacial layer, 15% GelMA/nano-HA (blue) for cartilage layer; (b) cartilage layer; (c) interfacial layer; (d) subchondral bone layer [102].

In addition, with the development of 3D printing technology, the polymer materials of composite nano-HA are prepared by melt extrusion (FDM), photocuring printing (DLP), or ink jet extrusion (IJD) to obtain porous scaffolds in bone tissue repair. Chen et al. [101] used FDM printing technology to prepare porous PLA/nano-HA composite scaffolds for the repair of large-segment bone defects. The composite of nano-HA enhanced the osteogenesis and angiogenesis ability of the scaffolds. Liu et al. [102] used GelMA hydrogels with different concentrations of ECM, mixed with different proportions of nano-HA to improve the electrical conductivity of the scaffold, and prepared a multilevel composite cartilage repair scaffold by 3D printing (Figure 9). The three-layer gradient scaffold can better simulate the complex layered structure of natural osteochondral tissue, and can repair osteochondral and lower bone at the same time.

4 Conclusions

Due to its good mechanical properties and high biological activity, nano-HA ceramics have attracted the attention of many researchers. However, there are still many problems in the preparation of nano-ceramics, including the synthesis of nano-powders and ceramic sintering, which still need to be further studied. In order to ideally control the particle size of nano-powders synthesized by HA materials, and to effectively suppress the growth of ceramic grains in the sintering process, it is still necessary to further optimize the process technology. The various powder synthesis methods and sintering processes reported so far have their own advantages and disadvantages. How to choose the appropriate nano-powder and sintering process according to the needs of the final application of nano-ceramics needs to be further explored.

# These authors contributed equally to this work.

tel: +86-28-85412757; fax: +86-28-85410246

  1. Funding information: This work was partially supported by the National Natural Science Foundation of China (31971251, 81171731), Sichuan Province Science & Technology Department Projects (2019FYQ0003), Project of Chengdu Science and Technology Bureau (2021-YF05-01619-SN), Sichuan University Panzhihua Science and Technology cooperation project (2021CDPZH–4), Science and Technology Project of Tibet Autonomous Region (XZ201901-GB-08) and the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21026, ZYGD21001, ZYJC21077).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Conflict of interest: The authors state no conflict of interest.

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Received: 2022-03-04
Revised: 2022-05-10
Accepted: 2022-05-11
Published Online: 2022-06-15

© 2022 Xingyu Gui et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Research Articles
  2. Theoretical and experimental investigation of MWCNT dispersion effect on the elastic modulus of flexible PDMS/MWCNT nanocomposites
  3. Mechanical, morphological, and fracture-deformation behavior of MWCNTs-reinforced (Al–Cu–Mg–T351) alloy cast nanocomposites fabricated by optimized mechanical milling and powder metallurgy techniques
  4. Flammability and physical stability of sugar palm crystalline nanocellulose reinforced thermoplastic sugar palm starch/poly(lactic acid) blend bionanocomposites
  5. Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione
  6. Relationship between mechano-bactericidal activity and nanoblades density on chemically strengthened glass
  7. In situ regulation of microstructure and microwave-absorbing properties of FeSiAl through HNO3 oxidation
  8. Research on a mechanical model of magnetorheological fluid different diameter particles
  9. Nanomechanical and dynamic mechanical properties of rubber–wood–plastic composites
  10. Investigative properties of CeO2 doped with niobium: A combined characterization and DFT studies
  11. Miniaturized peptidomimetics and nano-vesiculation in endothelin types through probable nano-disk formation and structure property relationships of endothelins’ fragments
  12. N/S co-doped CoSe/C nanocubes as anode materials for Li-ion batteries
  13. Synergistic effects of halloysite nanotubes with metal and phosphorus additives on the optimal design of eco-friendly sandwich panels with maximum flame resistance and minimum weight
  14. Octreotide-conjugated silver nanoparticles for active targeting of somatostatin receptors and their application in a nebulized rat model
  15. Controllable morphology of Bi2S3 nanostructures formed via hydrothermal vulcanization of Bi2O3 thin-film layer and their photoelectrocatalytic performances
  16. Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment
  17. Enhancement of the mechanical properties of HDPE mineral nanocomposites by filler particles modulation of the matrix plastic/elastic behavior
  18. Effect of plasticizers on the properties of sugar palm nanocellulose/cinnamon essential oil reinforced starch bionanocomposite films
  19. Optimization of nano coating to reduce the thermal deformation of ball screws
  20. Preparation of efficient piezoelectric PVDF–HFP/Ni composite films by high electric field poling
  21. MHD dissipative Casson nanofluid liquid film flow due to an unsteady stretching sheet with radiation influence and slip velocity phenomenon
  22. Effects of nano-SiO2 modification on rubberised mortar and concrete with recycled coarse aggregates
  23. Mechanical and microscopic properties of fiber-reinforced coal gangue-based geopolymer concrete
  24. Effect of morphology and size on the thermodynamic stability of cerium oxide nanoparticles: Experiment and molecular dynamics calculation
  25. Mechanical performance of a CFRP composite reinforced via gelatin-CNTs: A study on fiber interfacial enhancement and matrix enhancement
  26. A practical review over surface modification, nanopatterns, emerging materials, drug delivery systems, and their biophysiochemical properties for dental implants: Recent progresses and advances
  27. HTR: An ultra-high speed algorithm for cage recognition of clathrate hydrates
  28. Effects of microalloying elements added by in situ synthesis on the microstructure of WCu composites
  29. A highly sensitive nanobiosensor based on aptamer-conjugated graphene-decorated rhodium nanoparticles for detection of HER2-positive circulating tumor cells
  30. Progressive collapse performance of shear strengthened RC frames by nano CFRP
  31. Core–shell heterostructured composites of carbon nanotubes and imine-linked hyperbranched polymers as metal-free Li-ion anodes
  32. A Galerkin strategy for tri-hybridized mixture in ethylene glycol comprising variable diffusion and thermal conductivity using non-Fourier’s theory
  33. Simple models for tensile modulus of shape memory polymer nanocomposites at ambient temperature
  34. Preparation and morphological studies of tin sulfide nanoparticles and use as efficient photocatalysts for the degradation of rhodamine B and phenol
  35. Polyethyleneimine-impregnated activated carbon nanofiber composited graphene-derived rice husk char for efficient post-combustion CO2 capture
  36. Electrospun nanofibers of Co3O4 nanocrystals encapsulated in cyclized-polyacrylonitrile for lithium storage
  37. Pitting corrosion induced on high-strength high carbon steel wire in high alkaline deaerated chloride electrolyte
  38. Formulation of polymeric nanoparticles loaded sorafenib; evaluation of cytotoxicity, molecular evaluation, and gene expression studies in lung and breast cancer cell lines
  39. Engineered nanocomposites in asphalt binders
  40. Influence of loading voltage, domain ratio, and additional load on the actuation of dielectric elastomer
  41. Thermally induced hex-graphene transitions in 2D carbon crystals
  42. The surface modification effect on the interfacial properties of glass fiber-reinforced epoxy: A molecular dynamics study
  43. Molecular dynamics study of deformation mechanism of interfacial microzone of Cu/Al2Cu/Al composites under tension
  44. Nanocolloid simulators of luminescent solar concentrator photovoltaic windows
  45. Compressive strength and anti-chloride ion penetration assessment of geopolymer mortar merging PVA fiber and nano-SiO2 using RBF–BP composite neural network
  46. Effect of 3-mercapto-1-propane sulfonate sulfonic acid and polyvinylpyrrolidone on the growth of cobalt pillar by electrodeposition
  47. Dynamics of convective slippery constraints on hybrid radiative Sutterby nanofluid flow by Galerkin finite element simulation
  48. Preparation of vanadium by the magnesiothermic self-propagating reduction and process control
  49. Microstructure-dependent photoelectrocatalytic activity of heterogeneous ZnO–ZnS nanosheets
  50. Cytotoxic and pro-inflammatory effects of molybdenum and tungsten disulphide on human bronchial cells
  51. Improving recycled aggregate concrete by compression casting and nano-silica
  52. Chemically reactive Maxwell nanoliquid flow by a stretching surface in the frames of Newtonian heating, nonlinear convection and radiative flux: Nanopolymer flow processing simulation
  53. Nonlinear dynamic and crack behaviors of carbon nanotubes-reinforced composites with various geometries
  54. Biosynthesis of copper oxide nanoparticles and its therapeutic efficacy against colon cancer
  55. Synthesis and characterization of smart stimuli-responsive herbal drug-encapsulated nanoniosome particles for efficient treatment of breast cancer
  56. Homotopic simulation for heat transport phenomenon of the Burgers nanofluids flow over a stretching cylinder with thermal convective and zero mass flux conditions
  57. Incorporation of copper and strontium ions in TiO2 nanotubes via dopamine to enhance hemocompatibility and cytocompatibility
  58. Mechanical, thermal, and barrier properties of starch films incorporated with chitosan nanoparticles
  59. Mechanical properties and microstructure of nano-strengthened recycled aggregate concrete
  60. Glucose-responsive nanogels efficiently maintain the stability and activity of therapeutic enzymes
  61. Tunning matrix rheology and mechanical performance of ultra-high performance concrete using cellulose nanofibers
  62. Flexible MXene/copper/cellulose nanofiber heat spreader films with enhanced thermal conductivity
  63. Promoted charge separation and specific surface area via interlacing of N-doped titanium dioxide nanotubes on carbon nitride nanosheets for photocatalytic degradation of Rhodamine B
  64. Elucidating the role of silicon dioxide and titanium dioxide nanoparticles in mitigating the disease of the eggplant caused by Phomopsis vexans, Ralstonia solanacearum, and root-knot nematode Meloidogyne incognita
  65. An implication of magnetic dipole in Carreau Yasuda liquid influenced by engine oil using ternary hybrid nanomaterial
  66. Robust synthesis of a composite phase of copper vanadium oxide with enhanced performance for durable aqueous Zn-ion batteries
  67. Tunning self-assembled phases of bovine serum albumin via hydrothermal process to synthesize novel functional hydrogel for skin protection against UVB
  68. A comparative experimental study on damping properties of epoxy nanocomposite beams reinforced with carbon nanotubes and graphene nanoplatelets
  69. Lightweight and hydrophobic Ni/GO/PVA composite aerogels for ultrahigh performance electromagnetic interference shielding
  70. Research on the auxetic behavior and mechanical properties of periodically rotating graphene nanostructures
  71. Repairing performances of novel cement mortar modified with graphene oxide and polyacrylate polymer
  72. Closed-loop recycling and fabrication of hydrophilic CNT films with high performance
  73. Design of thin-film configuration of SnO2–Ag2O composites for NO2 gas-sensing applications
  74. Study on stress distribution of SiC/Al composites based on microstructure models with microns and nanoparticles
  75. PVDF green nanofibers as potential carriers for improving self-healing and mechanical properties of carbon fiber/epoxy prepregs
  76. Osteogenesis capability of three-dimensionally printed poly(lactic acid)-halloysite nanotube scaffolds containing strontium ranelate
  77. Silver nanoparticles induce mitochondria-dependent apoptosis and late non-canonical autophagy in HT-29 colon cancer cells
  78. Preparation and bonding mechanisms of polymer/metal hybrid composite by nano molding technology
  79. Damage self-sensing and strain monitoring of glass-reinforced epoxy composite impregnated with graphene nanoplatelet and multiwalled carbon nanotubes
  80. Thermal analysis characterisation of solar-powered ship using Oldroyd hybrid nanofluids in parabolic trough solar collector: An optimal thermal application
  81. Pyrene-functionalized halloysite nanotubes for simultaneously detecting and separating Hg(ii) in aqueous media: A comprehensive comparison on interparticle and intraparticle excimers
  82. Fabrication of self-assembly CNT flexible film and its piezoresistive sensing behaviors
  83. Thermal valuation and entropy inspection of second-grade nanoscale fluid flow over a stretching surface by applying Koo–Kleinstreuer–Li relation
  84. Mechanical properties and microstructure of nano-SiO2 and basalt-fiber-reinforced recycled aggregate concrete
  85. Characterization and tribology performance of polyaniline-coated nanodiamond lubricant additives
  86. Combined impact of Marangoni convection and thermophoretic particle deposition on chemically reactive transport of nanofluid flow over a stretching surface
  87. Spark plasma extrusion of binder free hydroxyapatite powder
  88. An investigation on thermo-mechanical performance of graphene-oxide-reinforced shape memory polymer
  89. Effect of nanoadditives on the novel leather fiber/recycled poly(ethylene-vinyl-acetate) polymer composites for multifunctional applications: Fabrication, characterizations, and multiobjective optimization using central composite design
  90. Design selection for a hemispherical dimple core sandwich panel using hybrid multi-criteria decision-making methods
  91. Improving tensile strength and impact toughness of plasticized poly(lactic acid) biocomposites by incorporating nanofibrillated cellulose
  92. Green synthesis of spinel copper ferrite (CuFe2O4) nanoparticles and their toxicity
  93. The effect of TaC and NbC hybrid and mono-nanoparticles on AA2024 nanocomposites: Microstructure, strengthening, and artificial aging
  94. Excited-state geometry relaxation of pyrene-modified cellulose nanocrystals under UV-light excitation for detecting Fe3+
  95. Effect of CNTs and MEA on the creep of face-slab concrete at an early age
  96. Effect of deformation conditions on compression phase transformation of AZ31
  97. Application of MXene as a new generation of highly conductive coating materials for electromembrane-surrounded solid-phase microextraction
  98. A comparative study of the elasto-plastic properties for ceramic nanocomposites filled by graphene or graphene oxide nanoplates
  99. Encapsulation strategies for improving the biological behavior of CdS@ZIF-8 nanocomposites
  100. Biosynthesis of ZnO NPs from pumpkin seeds’ extract and elucidation of its anticancer potential against breast cancer
  101. Preliminary trials of the gold nanoparticles conjugated chrysin: An assessment of anti-oxidant, anti-microbial, and in vitro cytotoxic activities of a nanoformulated flavonoid
  102. Effect of micron-scale pores increased by nano-SiO2 sol modification on the strength of cement mortar
  103. Fractional simulations for thermal flow of hybrid nanofluid with aluminum oxide and titanium oxide nanoparticles with water and blood base fluids
  104. The effect of graphene nano-powder on the viscosity of water: An experimental study and artificial neural network modeling
  105. Development of a novel heat- and shear-resistant nano-silica gelling agent
  106. Characterization, biocompatibility and in vivo of nominal MnO2-containing wollastonite glass-ceramic
  107. Entropy production simulation of second-grade magnetic nanomaterials flowing across an expanding surface with viscidness dissipative flux
  108. Enhancement in structural, morphological, and optical properties of copper oxide for optoelectronic device applications
  109. Aptamer-functionalized chitosan-coated gold nanoparticle complex as a suitable targeted drug carrier for improved breast cancer treatment
  110. Performance and overall evaluation of nano-alumina-modified asphalt mixture
  111. Analysis of pure nanofluid (GO/engine oil) and hybrid nanofluid (GO–Fe3O4/engine oil): Novel thermal and magnetic features
  112. Synthesis of Ag@AgCl modified anatase/rutile/brookite mixed phase TiO2 and their photocatalytic property
  113. Mechanisms and influential variables on the abrasion resistance hydraulic concrete
  114. Synergistic reinforcement mechanism of basalt fiber/cellulose nanocrystals/polypropylene composites
  115. Achieving excellent oxidation resistance and mechanical properties of TiB2–B4C/carbon aerogel composites by quick-gelation and mechanical mixing
  116. Microwave-assisted sol–gel template-free synthesis and characterization of silica nanoparticles obtained from South African coal fly ash
  117. Pulsed laser-assisted synthesis of nano nickel(ii) oxide-anchored graphitic carbon nitride: Characterizations and their potential antibacterial/anti-biofilm applications
  118. Effects of nano-ZrSi2 on thermal stability of phenolic resin and thermal reusability of quartz–phenolic composites
  119. Benzaldehyde derivatives on tin electroplating as corrosion resistance for fabricating copper circuit
  120. Mechanical and heat transfer properties of 4D-printed shape memory graphene oxide/epoxy acrylate composites
  121. Coupling the vanadium-induced amorphous/crystalline NiFe2O4 with phosphide heterojunction toward active oxygen evolution reaction catalysts
  122. Graphene-oxide-reinforced cement composites mechanical and microstructural characteristics at elevated temperatures
  123. Gray correlation analysis of factors influencing compressive strength and durability of nano-SiO2 and PVA fiber reinforced geopolymer mortar
  124. Preparation of layered gradient Cu–Cr–Ti alloy with excellent mechanical properties, thermal stability, and electrical conductivity
  125. Recovery of Cr from chrome-containing leather wastes to develop aluminum-based composite material along with Al2O3 ceramic particles: An ingenious approach
  126. Mechanisms of the improved stiffness of flexible polymers under impact loading
  127. Anticancer potential of gold nanoparticles (AuNPs) using a battery of in vitro tests
  128. Review Articles
  129. Proposed approaches for coronaviruses elimination from wastewater: Membrane techniques and nanotechnology solutions
  130. Application of Pickering emulsion in oil drilling and production
  131. The contribution of microfluidics to the fight against tuberculosis
  132. Graphene-based biosensors for disease theranostics: Development, applications, and recent advancements
  133. Synthesis and encapsulation of iron oxide nanorods for application in magnetic hyperthermia and photothermal therapy
  134. Contemporary nano-architectured drugs and leads for ανβ3 integrin-based chemotherapy: Rationale and retrospect
  135. State-of-the-art review of fabrication, application, and mechanical properties of functionally graded porous nanocomposite materials
  136. Insights on magnetic spinel ferrites for targeted drug delivery and hyperthermia applications
  137. A review on heterogeneous oxidation of acetaminophen based on micro and nanoparticles catalyzed by different activators
  138. Early diagnosis of lung cancer using magnetic nanoparticles-integrated systems
  139. Advances in ZnO: Manipulation of defects for enhancing their technological potentials
  140. Efficacious nanomedicine track toward combating COVID-19
  141. A review of the design, processes, and properties of Mg-based composites
  142. Green synthesis of nanoparticles for varied applications: Green renewable resources and energy-efficient synthetic routes
  143. Two-dimensional nanomaterial-based polymer composites: Fundamentals and applications
  144. Recent progress and challenges in plasmonic nanomaterials
  145. Apoptotic cell-derived micro/nanosized extracellular vesicles in tissue regeneration
  146. Electronic noses based on metal oxide nanowires: A review
  147. Framework materials for supercapacitors
  148. An overview on the reproductive toxicity of graphene derivatives: Highlighting the importance
  149. Antibacterial nanomaterials: Upcoming hope to overcome antibiotic resistance crisis
  150. Research progress of carbon materials in the field of three-dimensional printing polymer nanocomposites
  151. A review of atomic layer deposition modelling and simulation methodologies: Density functional theory and molecular dynamics
  152. Recent advances in the preparation of PVDF-based piezoelectric materials
  153. Recent developments in tensile properties of friction welding of carbon fiber-reinforced composite: A review
  154. Comprehensive review of the properties of fly ash-based geopolymer with additive of nano-SiO2
  155. Perspectives in biopolymer/graphene-based composite application: Advances, challenges, and recommendations
  156. Graphene-based nanocomposite using new modeling molecular dynamic simulations for proposed neutralizing mechanism and real-time sensing of COVID-19
  157. Nanotechnology application on bamboo materials: A review
  158. Recent developments and future perspectives of biorenewable nanocomposites for advanced applications
  159. Nanostructured lipid carrier system: A compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery
  160. 3D printing customized design of human bone tissue implant and its application
  161. Design, preparation, and functionalization of nanobiomaterials for enhanced efficacy in current and future biomedical applications
  162. A brief review of nanoparticles-doped PEDOT:PSS nanocomposite for OLED and OPV
  163. Nanotechnology interventions as a putative tool for the treatment of dental afflictions
  164. Recent advancements in metal–organic frameworks integrating quantum dots (QDs@MOF) and their potential applications
  165. A focused review of short electrospun nanofiber preparation techniques for composite reinforcement
  166. Microstructural characteristics and nano-modification of interfacial transition zone in concrete: A review
  167. Latest developments in the upconversion nanotechnology for the rapid detection of food safety: A review
  168. Strategic applications of nano-fertilizers for sustainable agriculture: Benefits and bottlenecks
  169. Molecular dynamics application of cocrystal energetic materials: A review
  170. Synthesis and application of nanometer hydroxyapatite in biomedicine
  171. Cutting-edge development in waste-recycled nanomaterials for energy storage and conversion applications
  172. Biological applications of ternary quantum dots: A review
  173. Nanotherapeutics for hydrogen sulfide-involved treatment: An emerging approach for cancer therapy
  174. Application of antibacterial nanoparticles in orthodontic materials
  175. Effect of natural-based biological hydrogels combined with growth factors on skin wound healing
  176. Nanozymes – A route to overcome microbial resistance: A viewpoint
  177. Recent developments and applications of smart nanoparticles in biomedicine
  178. Contemporary review on carbon nanotube (CNT) composites and their impact on multifarious applications
  179. Interfacial interactions and reinforcing mechanisms of cellulose and chitin nanomaterials and starch derivatives for cement and concrete strength and durability enhancement: A review
  180. Diamond-like carbon films for tribological modification of rubber
  181. Layered double hydroxides (LDHs) modified cement-based materials: A systematic review
  182. Recent research progress and advanced applications of silica/polymer nanocomposites
  183. Modeling of supramolecular biopolymers: Leading the in silico revolution of tissue engineering and nanomedicine
  184. Recent advances in perovskites-based optoelectronics
  185. Biogenic synthesis of palladium nanoparticles: New production methods and applications
  186. A comprehensive review of nanofluids with fractional derivatives: Modeling and application
  187. Electrospinning of marine polysaccharides: Processing and chemical aspects, challenges, and future prospects
  188. Electrohydrodynamic printing for demanding devices: A review of processing and applications
  189. Rapid Communications
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https://doi.org/10.1515/ntrev-2022-0127
Schlagwörter für diesen Artikel
nano-HA; synthesis methods; drug carrier
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Theoretical and experimental investigation of MWCNT dispersion effect on the elastic modulus of flexible PDMS/MWCNT nanocomposites
  3. Mechanical, morphological, and fracture-deformation behavior of MWCNTs-reinforced (Al–Cu–Mg–T351) alloy cast nanocomposites fabricated by optimized mechanical milling and powder metallurgy techniques
  4. Flammability and physical stability of sugar palm crystalline nanocellulose reinforced thermoplastic sugar palm starch/poly(lactic acid) blend bionanocomposites
  5. Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione
  6. Relationship between mechano-bactericidal activity and nanoblades density on chemically strengthened glass
  7. In situ regulation of microstructure and microwave-absorbing properties of FeSiAl through HNO3 oxidation
  8. Research on a mechanical model of magnetorheological fluid different diameter particles
  9. Nanomechanical and dynamic mechanical properties of rubber–wood–plastic composites
  10. Investigative properties of CeO2 doped with niobium: A combined characterization and DFT studies
  11. Miniaturized peptidomimetics and nano-vesiculation in endothelin types through probable nano-disk formation and structure property relationships of endothelins’ fragments
  12. N/S co-doped CoSe/C nanocubes as anode materials for Li-ion batteries
  13. Synergistic effects of halloysite nanotubes with metal and phosphorus additives on the optimal design of eco-friendly sandwich panels with maximum flame resistance and minimum weight
  14. Octreotide-conjugated silver nanoparticles for active targeting of somatostatin receptors and their application in a nebulized rat model
  15. Controllable morphology of Bi2S3 nanostructures formed via hydrothermal vulcanization of Bi2O3 thin-film layer and their photoelectrocatalytic performances
  16. Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment
  17. Enhancement of the mechanical properties of HDPE mineral nanocomposites by filler particles modulation of the matrix plastic/elastic behavior
  18. Effect of plasticizers on the properties of sugar palm nanocellulose/cinnamon essential oil reinforced starch bionanocomposite films
  19. Optimization of nano coating to reduce the thermal deformation of ball screws
  20. Preparation of efficient piezoelectric PVDF–HFP/Ni composite films by high electric field poling
  21. MHD dissipative Casson nanofluid liquid film flow due to an unsteady stretching sheet with radiation influence and slip velocity phenomenon
  22. Effects of nano-SiO2 modification on rubberised mortar and concrete with recycled coarse aggregates
  23. Mechanical and microscopic properties of fiber-reinforced coal gangue-based geopolymer concrete
  24. Effect of morphology and size on the thermodynamic stability of cerium oxide nanoparticles: Experiment and molecular dynamics calculation
  25. Mechanical performance of a CFRP composite reinforced via gelatin-CNTs: A study on fiber interfacial enhancement and matrix enhancement
  26. A practical review over surface modification, nanopatterns, emerging materials, drug delivery systems, and their biophysiochemical properties for dental implants: Recent progresses and advances
  27. HTR: An ultra-high speed algorithm for cage recognition of clathrate hydrates
  28. Effects of microalloying elements added by in situ synthesis on the microstructure of WCu composites
  29. A highly sensitive nanobiosensor based on aptamer-conjugated graphene-decorated rhodium nanoparticles for detection of HER2-positive circulating tumor cells
  30. Progressive collapse performance of shear strengthened RC frames by nano CFRP
  31. Core–shell heterostructured composites of carbon nanotubes and imine-linked hyperbranched polymers as metal-free Li-ion anodes
  32. A Galerkin strategy for tri-hybridized mixture in ethylene glycol comprising variable diffusion and thermal conductivity using non-Fourier’s theory
  33. Simple models for tensile modulus of shape memory polymer nanocomposites at ambient temperature
  34. Preparation and morphological studies of tin sulfide nanoparticles and use as efficient photocatalysts for the degradation of rhodamine B and phenol
  35. Polyethyleneimine-impregnated activated carbon nanofiber composited graphene-derived rice husk char for efficient post-combustion CO2 capture
  36. Electrospun nanofibers of Co3O4 nanocrystals encapsulated in cyclized-polyacrylonitrile for lithium storage
  37. Pitting corrosion induced on high-strength high carbon steel wire in high alkaline deaerated chloride electrolyte
  38. Formulation of polymeric nanoparticles loaded sorafenib; evaluation of cytotoxicity, molecular evaluation, and gene expression studies in lung and breast cancer cell lines
  39. Engineered nanocomposites in asphalt binders
  40. Influence of loading voltage, domain ratio, and additional load on the actuation of dielectric elastomer
  41. Thermally induced hex-graphene transitions in 2D carbon crystals
  42. The surface modification effect on the interfacial properties of glass fiber-reinforced epoxy: A molecular dynamics study
  43. Molecular dynamics study of deformation mechanism of interfacial microzone of Cu/Al2Cu/Al composites under tension
  44. Nanocolloid simulators of luminescent solar concentrator photovoltaic windows
  45. Compressive strength and anti-chloride ion penetration assessment of geopolymer mortar merging PVA fiber and nano-SiO2 using RBF–BP composite neural network
  46. Effect of 3-mercapto-1-propane sulfonate sulfonic acid and polyvinylpyrrolidone on the growth of cobalt pillar by electrodeposition
  47. Dynamics of convective slippery constraints on hybrid radiative Sutterby nanofluid flow by Galerkin finite element simulation
  48. Preparation of vanadium by the magnesiothermic self-propagating reduction and process control
  49. Microstructure-dependent photoelectrocatalytic activity of heterogeneous ZnO–ZnS nanosheets
  50. Cytotoxic and pro-inflammatory effects of molybdenum and tungsten disulphide on human bronchial cells
  51. Improving recycled aggregate concrete by compression casting and nano-silica
  52. Chemically reactive Maxwell nanoliquid flow by a stretching surface in the frames of Newtonian heating, nonlinear convection and radiative flux: Nanopolymer flow processing simulation
  53. Nonlinear dynamic and crack behaviors of carbon nanotubes-reinforced composites with various geometries
  54. Biosynthesis of copper oxide nanoparticles and its therapeutic efficacy against colon cancer
  55. Synthesis and characterization of smart stimuli-responsive herbal drug-encapsulated nanoniosome particles for efficient treatment of breast cancer
  56. Homotopic simulation for heat transport phenomenon of the Burgers nanofluids flow over a stretching cylinder with thermal convective and zero mass flux conditions
  57. Incorporation of copper and strontium ions in TiO2 nanotubes via dopamine to enhance hemocompatibility and cytocompatibility
  58. Mechanical, thermal, and barrier properties of starch films incorporated with chitosan nanoparticles
  59. Mechanical properties and microstructure of nano-strengthened recycled aggregate concrete
  60. Glucose-responsive nanogels efficiently maintain the stability and activity of therapeutic enzymes
  61. Tunning matrix rheology and mechanical performance of ultra-high performance concrete using cellulose nanofibers
  62. Flexible MXene/copper/cellulose nanofiber heat spreader films with enhanced thermal conductivity
  63. Promoted charge separation and specific surface area via interlacing of N-doped titanium dioxide nanotubes on carbon nitride nanosheets for photocatalytic degradation of Rhodamine B
  64. Elucidating the role of silicon dioxide and titanium dioxide nanoparticles in mitigating the disease of the eggplant caused by Phomopsis vexans, Ralstonia solanacearum, and root-knot nematode Meloidogyne incognita
  65. An implication of magnetic dipole in Carreau Yasuda liquid influenced by engine oil using ternary hybrid nanomaterial
  66. Robust synthesis of a composite phase of copper vanadium oxide with enhanced performance for durable aqueous Zn-ion batteries
  67. Tunning self-assembled phases of bovine serum albumin via hydrothermal process to synthesize novel functional hydrogel for skin protection against UVB
  68. A comparative experimental study on damping properties of epoxy nanocomposite beams reinforced with carbon nanotubes and graphene nanoplatelets
  69. Lightweight and hydrophobic Ni/GO/PVA composite aerogels for ultrahigh performance electromagnetic interference shielding
  70. Research on the auxetic behavior and mechanical properties of periodically rotating graphene nanostructures
  71. Repairing performances of novel cement mortar modified with graphene oxide and polyacrylate polymer
  72. Closed-loop recycling and fabrication of hydrophilic CNT films with high performance
  73. Design of thin-film configuration of SnO2–Ag2O composites for NO2 gas-sensing applications
  74. Study on stress distribution of SiC/Al composites based on microstructure models with microns and nanoparticles
  75. PVDF green nanofibers as potential carriers for improving self-healing and mechanical properties of carbon fiber/epoxy prepregs
  76. Osteogenesis capability of three-dimensionally printed poly(lactic acid)-halloysite nanotube scaffolds containing strontium ranelate
  77. Silver nanoparticles induce mitochondria-dependent apoptosis and late non-canonical autophagy in HT-29 colon cancer cells
  78. Preparation and bonding mechanisms of polymer/metal hybrid composite by nano molding technology
  79. Damage self-sensing and strain monitoring of glass-reinforced epoxy composite impregnated with graphene nanoplatelet and multiwalled carbon nanotubes
  80. Thermal analysis characterisation of solar-powered ship using Oldroyd hybrid nanofluids in parabolic trough solar collector: An optimal thermal application
  81. Pyrene-functionalized halloysite nanotubes for simultaneously detecting and separating Hg(ii) in aqueous media: A comprehensive comparison on interparticle and intraparticle excimers
  82. Fabrication of self-assembly CNT flexible film and its piezoresistive sensing behaviors
  83. Thermal valuation and entropy inspection of second-grade nanoscale fluid flow over a stretching surface by applying Koo–Kleinstreuer–Li relation
  84. Mechanical properties and microstructure of nano-SiO2 and basalt-fiber-reinforced recycled aggregate concrete
  85. Characterization and tribology performance of polyaniline-coated nanodiamond lubricant additives
  86. Combined impact of Marangoni convection and thermophoretic particle deposition on chemically reactive transport of nanofluid flow over a stretching surface
  87. Spark plasma extrusion of binder free hydroxyapatite powder
  88. An investigation on thermo-mechanical performance of graphene-oxide-reinforced shape memory polymer
  89. Effect of nanoadditives on the novel leather fiber/recycled poly(ethylene-vinyl-acetate) polymer composites for multifunctional applications: Fabrication, characterizations, and multiobjective optimization using central composite design
  90. Design selection for a hemispherical dimple core sandwich panel using hybrid multi-criteria decision-making methods
  91. Improving tensile strength and impact toughness of plasticized poly(lactic acid) biocomposites by incorporating nanofibrillated cellulose
  92. Green synthesis of spinel copper ferrite (CuFe2O4) nanoparticles and their toxicity
  93. The effect of TaC and NbC hybrid and mono-nanoparticles on AA2024 nanocomposites: Microstructure, strengthening, and artificial aging
  94. Excited-state geometry relaxation of pyrene-modified cellulose nanocrystals under UV-light excitation for detecting Fe3+
  95. Effect of CNTs and MEA on the creep of face-slab concrete at an early age
  96. Effect of deformation conditions on compression phase transformation of AZ31
  97. Application of MXene as a new generation of highly conductive coating materials for electromembrane-surrounded solid-phase microextraction
  98. A comparative study of the elasto-plastic properties for ceramic nanocomposites filled by graphene or graphene oxide nanoplates
  99. Encapsulation strategies for improving the biological behavior of CdS@ZIF-8 nanocomposites
  100. Biosynthesis of ZnO NPs from pumpkin seeds’ extract and elucidation of its anticancer potential against breast cancer
  101. Preliminary trials of the gold nanoparticles conjugated chrysin: An assessment of anti-oxidant, anti-microbial, and in vitro cytotoxic activities of a nanoformulated flavonoid
  102. Effect of micron-scale pores increased by nano-SiO2 sol modification on the strength of cement mortar
  103. Fractional simulations for thermal flow of hybrid nanofluid with aluminum oxide and titanium oxide nanoparticles with water and blood base fluids
  104. The effect of graphene nano-powder on the viscosity of water: An experimental study and artificial neural network modeling
  105. Development of a novel heat- and shear-resistant nano-silica gelling agent
  106. Characterization, biocompatibility and in vivo of nominal MnO2-containing wollastonite glass-ceramic
  107. Entropy production simulation of second-grade magnetic nanomaterials flowing across an expanding surface with viscidness dissipative flux
  108. Enhancement in structural, morphological, and optical properties of copper oxide for optoelectronic device applications
  109. Aptamer-functionalized chitosan-coated gold nanoparticle complex as a suitable targeted drug carrier for improved breast cancer treatment
  110. Performance and overall evaluation of nano-alumina-modified asphalt mixture
  111. Analysis of pure nanofluid (GO/engine oil) and hybrid nanofluid (GO–Fe3O4/engine oil): Novel thermal and magnetic features
  112. Synthesis of Ag@AgCl modified anatase/rutile/brookite mixed phase TiO2 and their photocatalytic property
  113. Mechanisms and influential variables on the abrasion resistance hydraulic concrete
  114. Synergistic reinforcement mechanism of basalt fiber/cellulose nanocrystals/polypropylene composites
  115. Achieving excellent oxidation resistance and mechanical properties of TiB2–B4C/carbon aerogel composites by quick-gelation and mechanical mixing
  116. Microwave-assisted sol–gel template-free synthesis and characterization of silica nanoparticles obtained from South African coal fly ash
  117. Pulsed laser-assisted synthesis of nano nickel(ii) oxide-anchored graphitic carbon nitride: Characterizations and their potential antibacterial/anti-biofilm applications
  118. Effects of nano-ZrSi2 on thermal stability of phenolic resin and thermal reusability of quartz–phenolic composites
  119. Benzaldehyde derivatives on tin electroplating as corrosion resistance for fabricating copper circuit
  120. Mechanical and heat transfer properties of 4D-printed shape memory graphene oxide/epoxy acrylate composites
  121. Coupling the vanadium-induced amorphous/crystalline NiFe2O4 with phosphide heterojunction toward active oxygen evolution reaction catalysts
  122. Graphene-oxide-reinforced cement composites mechanical and microstructural characteristics at elevated temperatures
  123. Gray correlation analysis of factors influencing compressive strength and durability of nano-SiO2 and PVA fiber reinforced geopolymer mortar
  124. Preparation of layered gradient Cu–Cr–Ti alloy with excellent mechanical properties, thermal stability, and electrical conductivity
  125. Recovery of Cr from chrome-containing leather wastes to develop aluminum-based composite material along with Al2O3 ceramic particles: An ingenious approach
  126. Mechanisms of the improved stiffness of flexible polymers under impact loading
  127. Anticancer potential of gold nanoparticles (AuNPs) using a battery of in vitro tests
  128. Review Articles
  129. Proposed approaches for coronaviruses elimination from wastewater: Membrane techniques and nanotechnology solutions
  130. Application of Pickering emulsion in oil drilling and production
  131. The contribution of microfluidics to the fight against tuberculosis
  132. Graphene-based biosensors for disease theranostics: Development, applications, and recent advancements
  133. Synthesis and encapsulation of iron oxide nanorods for application in magnetic hyperthermia and photothermal therapy
  134. Contemporary nano-architectured drugs and leads for ανβ3 integrin-based chemotherapy: Rationale and retrospect
  135. State-of-the-art review of fabrication, application, and mechanical properties of functionally graded porous nanocomposite materials
  136. Insights on magnetic spinel ferrites for targeted drug delivery and hyperthermia applications
  137. A review on heterogeneous oxidation of acetaminophen based on micro and nanoparticles catalyzed by different activators
  138. Early diagnosis of lung cancer using magnetic nanoparticles-integrated systems
  139. Advances in ZnO: Manipulation of defects for enhancing their technological potentials
  140. Efficacious nanomedicine track toward combating COVID-19
  141. A review of the design, processes, and properties of Mg-based composites
  142. Green synthesis of nanoparticles for varied applications: Green renewable resources and energy-efficient synthetic routes
  143. Two-dimensional nanomaterial-based polymer composites: Fundamentals and applications
  144. Recent progress and challenges in plasmonic nanomaterials
  145. Apoptotic cell-derived micro/nanosized extracellular vesicles in tissue regeneration
  146. Electronic noses based on metal oxide nanowires: A review
  147. Framework materials for supercapacitors
  148. An overview on the reproductive toxicity of graphene derivatives: Highlighting the importance
  149. Antibacterial nanomaterials: Upcoming hope to overcome antibiotic resistance crisis
  150. Research progress of carbon materials in the field of three-dimensional printing polymer nanocomposites
  151. A review of atomic layer deposition modelling and simulation methodologies: Density functional theory and molecular dynamics
  152. Recent advances in the preparation of PVDF-based piezoelectric materials
  153. Recent developments in tensile properties of friction welding of carbon fiber-reinforced composite: A review
  154. Comprehensive review of the properties of fly ash-based geopolymer with additive of nano-SiO2
  155. Perspectives in biopolymer/graphene-based composite application: Advances, challenges, and recommendations
  156. Graphene-based nanocomposite using new modeling molecular dynamic simulations for proposed neutralizing mechanism and real-time sensing of COVID-19
  157. Nanotechnology application on bamboo materials: A review
  158. Recent developments and future perspectives of biorenewable nanocomposites for advanced applications
  159. Nanostructured lipid carrier system: A compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery
  160. 3D printing customized design of human bone tissue implant and its application
  161. Design, preparation, and functionalization of nanobiomaterials for enhanced efficacy in current and future biomedical applications
  162. A brief review of nanoparticles-doped PEDOT:PSS nanocomposite for OLED and OPV
  163. Nanotechnology interventions as a putative tool for the treatment of dental afflictions
  164. Recent advancements in metal–organic frameworks integrating quantum dots (QDs@MOF) and their potential applications
  165. A focused review of short electrospun nanofiber preparation techniques for composite reinforcement
  166. Microstructural characteristics and nano-modification of interfacial transition zone in concrete: A review
  167. Latest developments in the upconversion nanotechnology for the rapid detection of food safety: A review
  168. Strategic applications of nano-fertilizers for sustainable agriculture: Benefits and bottlenecks
  169. Molecular dynamics application of cocrystal energetic materials: A review
  170. Synthesis and application of nanometer hydroxyapatite in biomedicine
  171. Cutting-edge development in waste-recycled nanomaterials for energy storage and conversion applications
  172. Biological applications of ternary quantum dots: A review
  173. Nanotherapeutics for hydrogen sulfide-involved treatment: An emerging approach for cancer therapy
  174. Application of antibacterial nanoparticles in orthodontic materials
  175. Effect of natural-based biological hydrogels combined with growth factors on skin wound healing
  176. Nanozymes – A route to overcome microbial resistance: A viewpoint
  177. Recent developments and applications of smart nanoparticles in biomedicine
  178. Contemporary review on carbon nanotube (CNT) composites and their impact on multifarious applications
  179. Interfacial interactions and reinforcing mechanisms of cellulose and chitin nanomaterials and starch derivatives for cement and concrete strength and durability enhancement: A review
  180. Diamond-like carbon films for tribological modification of rubber
  181. Layered double hydroxides (LDHs) modified cement-based materials: A systematic review
  182. Recent research progress and advanced applications of silica/polymer nanocomposites
  183. Modeling of supramolecular biopolymers: Leading the in silico revolution of tissue engineering and nanomedicine
  184. Recent advances in perovskites-based optoelectronics
  185. Biogenic synthesis of palladium nanoparticles: New production methods and applications
  186. A comprehensive review of nanofluids with fractional derivatives: Modeling and application
  187. Electrospinning of marine polysaccharides: Processing and chemical aspects, challenges, and future prospects
  188. Electrohydrodynamic printing for demanding devices: A review of processing and applications
  189. Rapid Communications
  190. Structural material with designed thermal twist for a simple actuation
  191. Recent advances in photothermal materials for solar-driven crude oil adsorption
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Heruntergeladen am 2.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/ntrev-2022-0127/html
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