Synthesis, structural, molecular docking, and in vitro biological activities of Cu-doped ZnO nanomaterials.

Copper-doped ZnO nanoparticles with the formula Zn1-x(Cu)O, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and structural properties were properly examined. Powdered X-ray diffraction (P-XRD) patterns revealed the formation of hexagonal wurtzite crystal structure in all samples, through atomic substitutional incorporation in the Cu-doped ZnO lattice. The presence of Cu ions and their dissolution in the host ZnO crystal structure was supported by FT-IR spectra. HR-TEM images were used to assess the average size, morphology, and shape regularity of the synthesized samples. The form and homogeneity of the ZnO changed when Cu ions were substituted, as evidenced by FE-SEM/EDX analysis. The presence of copper signals in the Cu-doped samples indicates that the doping was successful. The decrease in zeta potential with an increased copper doping percentage designates that the nanoparticles (NPs) are more stable, which could be attributed to an increase in the ionic strength of the aqueous solution. The synthesized NPs were evaluated for their substantial in vitro antioxidant properties. In addition, the antimicrobial efficacy of the materials was tested against pathogenic microorganisms. Regarding the anti-diabetic activity, the 7Cu ZnO sample showed the highest inhibitory effect on the α-amylase enzyme. No variations were observed in the activities of the acetylcholinesterase enzyme (AChE) and proteinase enzymes with ZnO and samples doped with different concentrations of Cu. Therefore, further studies are recommended to reveal the in-vitro anti-diabetic activity of the studied doped samples. Finally, molecular docking provided valuable insights into the potential binding interactions of Cu-doped ZnO with α-amylase, FabH of E. coli, and Penicillin-binding proteins of S. aureus. These outcomes suggest that the prepared materials may have an inhibitory effect on enzymes and hold promise in the battle against microbial infections and diabetes.

Doxorubicin loaded cerium substituted hydroxyapatite nanoparticles: A promising new therapeutic approach for bone regeneration, doxorubicin delivery, and cancer treatment.

The current study used the precipitation method to prepare pure calcium hydroxyapatite (HA) and cerium-substituted hydroxyapatite (Ce-HA) nanoparticles, where cerium ions were exchanged into the HA structure at different concentrations ranging from 3 to 7 wt%. X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurements, and zeta potential were used to examine the structural characteristics of the nanoparticles. Additionally, the antibacterial and antifungal effects of the produced materials on Gram-positive, Gram-negative, and fungal bacterial species were studied. Nanoparticles with cerium doping showed effective antibacterial and antifungal properties. All samples were tested for bioactivity in simulated body fluid (SBF), and the formation of an apatite layer on their surfaces was highlighted using SEM in conjunction with energy-dispersive X-rays (EDX).Doxorubicin (DOX) release from Ce-HA nanoparticles and pure HA was tested in phosphate-buffered saline (PBS) for up to 28 days. Both nanoparticles were able to release the drug while still being semi-fully loaded. Similarly, the cytotoxic effect of all produced samples on the MG-63 cell line was evaluated, and all samples showed good cytocompatibility. The cytotoxic effect of doxorubicin-loaded nanoparticles showed promising anticancer activity against bone cancer cells, especially samples with high cerium content. The resulting nanoparticles show excellent promising ability for the delivery of doxorubicin to bone cancer with the capacity for bone regeneration.

CuO nanoparticles for green synthesis of significant anti-Helicobacter pylori compounds with in silico studies.

Helicobacter pylori (H. pylori) is a universal health intimidation as mentioned by the World Health Organization. The primary causal agent linked to a number of illnesses, including inflammation and the development of stomach ulcers, is Helicobacter pylori. Since, H. pylori develops antibiotic resistance quickly, current H. pylori treatment approaches are becoming less effective. Our research aims to highlight novel formulation antibiotics using CuO-NPs as catalysts and studied their activity as anti-helicobacter pylori supported by computational studies (POM analysis and molecular docking) software. They were designed for anti-Helicobacter Pylori action. All compounds revealed a bactericidal effect better than the reference McFarland standards.

Prebiotic-mediated gastroprotective potentials of three bacterial levans through NF-κB-modulation and upregulation of systemic IL-17A.

This study aimed to investigate whether the gastroprotective effects of three types of bacterial levans are correlated with their prebiotic-associated anti-inflammatory/antioxidant potentials. Three levans designated as LevAE, LevP, and LevZ were prepared from bacterial honey isolates; purified, and characterized using TLC, NMR, and FTIR. The anti-inflammatory properties of levan preparations were assessed in LPS-stimulated RAW 264.7 cell lines, while their safety and gastroprotective potentials were assessed in Wistar rats. The three levans significantly reduced ulcer number (22.29-70.05 %) and severity (31.76-80.54 %) in the ethanol-induced gastric ulcer model compared to the control (P < 0.0001/each), with the highest effect observed in LevAE and levZ (200 mg/each) (P < 0.0001). LevZ produced the highest levels of glutathione; catalase activity, and the lowest MDA levels (P = 0.0001/each). The highest anti-inflammatory activity was observed in LevAE and levZ in terms of higher inhibitory effect on IL-1ß and TNF-α production (P < 0.0001 each); COX2, PGE2, and NF-κB gene expression. The three levan preparations also proved safe with no signs of toxicity, with anti-lipidemic properties as well as promising prebiotic activity that directly correlated with their antiulcer effect. This novel study highlights the implication of prebiotic-mediated systemic immunomodulation exhibited by bacterial levans that directly correlated with their gastroprotective activity.

Biphasic calcium phosphate doped with zirconia nanoparticles for reconstruction of induced mandibular defects in dogs: cone-beam computed tomographic and histopathologic evaluation.

The present study aimed to evaluate osteogenic potential and biocompatibility of combining biphasic calcium phosphate with zirconia nanoparticles (4Zr TCP/HA) compared to biphasic calcium phosphate (TCP/HA) for reconstruction of induced mandibular defects in dog model. TCP/HA and 4Zr TCP/HA scaffolds were prepared. Morphological, physicochemical, antibacterial, cytocompatibility characterization were tested. In vivo application was performed in 12 dogs where three critical-sized mandibular defects were created in each dog. Bone defects were randomly allocated into: control, TCP/HA, and 4Zr TCP/HA groups. Bone density and bone area percentage were evaluated at 12 weeks using cone-beam computed tomographic, histopathologic, histomorphometric examination. Bone area density was statistically increased (p < 0.001) in TCP/HA and 4Zr TCP/HA groups compared to control group both in sagittal and coronal views. Comparing TCP/HA and 4Zr TCP/HA groups, the increase in bone area density was statistically significant in coronal view (p = 0.002) and sagittal view (p = 0.05). Histopathologic sections of TCP/HA group demonstrated incomplete filling of the defect with osteoid tissue. Doping with zirconia (4Zr TCP/HA group), resulted in statistically significant increase (p < 0.001) in bone formation (as indicated by bone area percentage) and maturation (as confirmed by Masson trichrome staining) compared to TCP/HA group. The newly formed bone was mature and organized with more trabecular thickness and less trabecular space in between. Physicochemical, morphological and bactericidal properties of combining zirconia and TCP/HA were improved. Combining zirconia and TCP/HA resulted in synergistic action with effective osteoinduction, osteoconduction and osteointegration suggesting its suitability to restore damaged bone in clinical practice.

Formulation and evaluation of alginate-gelatin hydrogel scaffolds loaded with zinc-doped hydroxyapatite and 5-fluorouracil.

Alginate and gelatin are natural macromolecules used to formulate biocompatible drug delivery systems. Hydroxyapatite (HA) is an osteophilic ceramic used to prepare bone scaffolds. The current study aimed at preparing and characterizing HA, zinc-doped HA, and 5-fluorouracil(5-FU)-loaded alginate-gelatin-based hydrogel scaffolds using different crosslinking solutions. 5-FU incorporation efficiency, in-vitro drug release, antitumor bioassays, FTIR, X-ray-diffraction (XRD), High-Resolution Transmission, and Scanning-Electron Microscope (HR-TEM and SEM) studies were conducted. XRD showed the incorporation of Zn2+ into HA structure with a deformity in HA crystal lattice and inhibited crystal growth. FTIR-spectra represented the characteristic bands corresponding to HA structure. HR-TEM showed a decreased HA crystal size and rod-like crystallites that increased with increasing zinc content. Zn2+ content and 5-FU-loading caused significant effects on the scaffolds' thickness (p-value = 0.021 and 0.035, respectively). Burst 5-FU release within 10-15 min followed by 100 % release within 4 h was observed. Zinc content showed a significant positive effect on the cytotoxicity% of the blank and drug-loaded scaffolds. XRD and FTIR studies revealed that 5-FU was completely incorporated into the hydrogel with no chemical interaction. SEM-imaging showed interconnected pores and needle-shaped drug particles. The prepared formulations showed promising physico-chemical properties for targeted delivery of 5-FU in the form of biocompatible bone scaffolds.

Zinc oxide calcium silicate composite attenuates acute tramadol toxicity in mice.

BACKGROUND: Seizures are considered to be the most common symptom encountered in emergency- rushed tramadol-poisoned patients; accounting for 8% of the drug-induced seizure cases. Although, diazepam clears these seizures, the risk of central respiratory depression cannot be overlooked. Henceforth, three adsorbing composites were examined in a tramadol acute intoxication mouse model. METHODS: Calcium Silicate (Wollastonite) either non-doped or wet doped with iron oxide (3%Fe2O3) or zinc oxide (30% ZnO) were prepared. The composites' adsorption capacity for tramadol was determined in vitro. Tramadol intoxication was induced in Swiss albino mice by a parenteral dose of 120 mg/kg. Proposed treatments were administered within 1 min at 5 increasing doses, i.p. The next 30 min, seizures were monitored as an intoxication symptom. Plasma tramadol concentration was recorded after two hours of administration. RESULTS: The 3% Fe2O3-containing composite (CSFe3), was found to be composed of mainly wollastonite with very little alpha-hematite. On the other hand, hardystonite and wellimite were developed in the 30%ZnO-containing composite (CSZn3). Micro-round and irregular nano-sized microstructures were established (The particle size of CS was 56 nm, CSFe3 was 49 nm, and CSZn3 was 42 nm). The CSZn3 adsorption capacity reached 1497 mg of tramadol for each gram. Tramadol concentration was reduced in plasma and seizures were inhibited after its administration to mice at three doses. CONCLUSION: The calcium silicate composite doped with ZnO presented a good resolution of tramadol-induced seizures accompanied by detoxification of blood, indicating its potential for application in such cases. Further studies are required.

Osteogenic potential of calcium silicate-doped iron oxide nanoparticles versus calcium silicate for reconstruction of critical-sized mandibular defects: An experimental study in dog model.

Objective: To evaluate bioactivity and osteogenic potential of calcium silicate (CS)-doped iron oxide (Fe2O3) nanoparticles versus pure CS in the reconstruction of induced critical-sized mandibular defects. Design: CS-doped Fe2O3 was prepared; morphological and microstructure identification of nanoparticles were made. An in vivo randomised design was developed on 24 adult male dogs where four critical-sized mandibular defects were created in each dog. Bone defects were allocated into control, CS, CS-3% Fe2O3 and CS-10% Fe2O3 group. Dogs were euthanized at 1 and 3 months (12 dog/time) for histopathologic and histomorphometric evaluation. Results: At three months, bone formation and maturation were evident where mean ± SD percent of mature bone was 2.66 ± 1.8, 9.9 ± 2.5, 22.9 ± 4.9, and 38.6 ± 8.1 in control, CS, CS-3% Fe2O3, and CS-10% Fe2O3 groups respectively. A high significant (P < 0.001) increase in area percent of mature bone was recorded in CS, CS-3% Fe2O3, and CS- 10% Fe2O3 groups compared to control group (73%, 88% and 93.3% respectively). Significant increase (P < 0.001) in area of mature bone was recorded in CS-3% Fe2O3 and CS-10% Fe2O3 groups compared to CS group. A significant increase (P < 0.001) in area of mature bone formation was detected in CS-10% Fe2O3 group compared to other groups. Conclusion: CS-doped Fe2O3 has good osteoconductive, biocompatible properties with promoted bone regeneration. Fe2O3 has synergistic effect in combination with CS to promote bone formation. Increasing concentration of Fe2O3 nanoparticles resulted in improved osteogenesis and maturation. Results suggests that the novel CS-Fe2O3 alloplasts could be used for reconstruction of critical-sized bone defects.

TiO2 nanoparticle as catalyst for an efficient green one-pot synthesis of 1H-3-Indolyl Derivatives as significant antiviral activity.

Titanium dioxide nanoparticles (TiO2- NPs) are produced in large quantities for an extensive range of applications. They retain variable physicochemical properties, which influence their bioactivity. The condensation synthesis of 3-acetylindol, thiophene-2-carbaldehyde and malononitrile in the existence of TiO2 nanoparticle yields 2-amino-6-(1H-indol-3-yl)-4-(thiophen-2-yl)-4H-pyran-3-carbonitrile derivatives. The yielded compound 2 reacted with (formic acid, formamide, ethyl chloroacetate, chloroacetyl chloride, thiourea and sodium nitrite). This three-combination system is safe, ecologically friendly, and non-toxic. The proposed system helped in time preservation and reduction in chemical consumption. The synthesized compounds were screened for antiviral activity against Vero cells (HAV). Antiviral impact percent for samples 2, 5, 6 and 7 versus HAV were 81.98, 91.05, 9.21, and 21.95%, respectively. The viral efficacy of Sample 5 was the strongest against HAV.

A Novel Treatment of Schistosomiasis: Nano-Calcium Silicate Incorporating 5% Copper Oxide.

Purpose: Praziquantel (PZQ) is a well-known drug accredited by the World Health Organization (WHO) for the treatment of schistosomiasis. It shows poor efficiency in patients during the earliest infection phases. Therefore, the search for new alternative drugs was the intention of many researchers. Methods: In the current study, the effect of different concentrations (ranging from 0.07-10 µg∕mL) of calcium silicate (CS) containing 5% copper oxide [CS-5%CuO] on golden hamster infected by Schistosoma mansoni and Schistosoma haematobium (Egyptian strains) was evaluated in both in vitro and in vivo. To the best of our knowledge, this is a novel study in investigating the efficiency of CS-5%CuO against both strains of schistosomes. The worms of S. mansoni and S. haematobium were tested in RPMI-1640 medium in vitro. Results: The results declare that CS-5% CuO exhibited excellent anti-schistosomal activities on both in vitro and in vivo experiments for both Egyptians Schistosoma strains. The most potential effect of the CS-5% CuO was exhibited after 6 h by 10 µg∕mL with significant activity of (P value = 0.001). Conclusion: Therefore, CS-5%CuO may become an innovative treatment for the schistosomiasis.

Radiological evaluations of low cost wollastonite nano-ceramics graft doped with iron oxide in the treatment of induced defects in canine mandible.

Wollastonite with/without maghemite [(Fe2O3), 0, 3 and 10 wt%] was prepared by facile wet precipitation method. Effect of Fe2O3 presence in the obtained nano-ceramics on physical structure, morphology, size and the mechanical features was evaluated using X-ray diffraction, transmission electron microscope, and universal testing machine. Moreover, the in vitro biomineralization was examined using simulated body fluid (SBF) by means of scanning electron microscope/energy dispersive X-ray, Fourier transform infrared, and inductively coupled plasma. An in vivo study was conducted on 24 adult male mongrel dogs to test the biosafety of fabricated samples in the reconstruction of experimentally induced mandibular bone defects. Bone density was measured through cone beam computed tomography analysis conducted at 1 and 3 months following surgery. Wollastonite was the main phase in all the prepared samples however little maghemite was developed in Fe-containing samples. No remarkable changes were recognized for physical structure of obtained microcrystalline structures, however, a decrease in particle size was noted in the existence of Fe2O3 (10-15 nm) when compared to the pure wollastonite (30-50 nm). Mechanical features were dependent on the included Fe2O3 concentration within the wollastonite ceramic matrix. The degree of biomineralization of the samples immersed in SBF was elevated with the increase in Fe2O3 percentage. Clinically, the reconstruction of bone defects was uneventful without any adverse toxic effect. Bone density was significantly increased at 1 and 3 months (p < .001) in grafted defects compared to control ones. Increasing the doping concentrations of iron oxide was associated with significant increase (p < .001) of bone density in all induced defects. Due to the impressive healing effect of current fabricated nano-ceramics, they are recommended to be utilized as low cost bone graft alternatives.

Adipose tissue-derived mesenchymal stem cells and chitosan/poly (vinyl alcohol) nanofibrous scaffolds for cartilage tissue engineering.

Osteoarthritis (OA) has been defined as a chronic inflammatory joint disease characterized by progressive articular cartilage degeneration. Recently growing interest in regenerative medicine, using cell therapy and tissue engineering, where cellular components in combination with engineered scaffolds and bioactive materials were used to induce functional tissue regeneration. In the present study, nanofibrous scaffold based on chitosan (CS)/poly (vinyl alcohol) (PVA) were used to develop biologically functionalized biomaterial to mimic the extracellular matrix, allowing the human adipose tissue derived mesenchymal stem cells (ADSCs) to proliferate and differentiate to chondrogenic cells. The morphology of the nanofibrous mat was examined using field emission scanning electron microscope (FE/SEM). The characteristic functional groups and the nature of the chemical bonds between atoms were evaluated using Fourier transform infrared spectroscopy (FTIR) spectrum. Characterization of the seeded cells was morphologically evaluated by scanning electron microscopy and by flow cytometry for the expression of the stem cell surface markers. The differentiation potential was verified after chondrogenic induction by analyzing the expression of chondrogenic marker genes using real-time (RT PCR). Current study suggest significant potential for the use of ADSCs with the nanofibrous scaffolds in improving the osteoarthritis pathology.

Hydroxyapatite nanoparticles derived from mussel shells for in vitro cytotoxicity test and cell viability.

Hydroxyapatite (HA) nanoparticles derived from mussel shells were prepared using the wet precipitation method and were tested on human mesenchymal and epithelial cells. Shells and HA powder were characterized via X-ray diffraction analysis (XRD) and scanning electron microscopy along with energy dispersive X-ray spectroscopy (SEM/EDX), high resolution transmission electron microscopy (HR-TEM) and Fourier transform infrared spectroscopy (FTIR). The in vitro cytotoxic properties of HA and mussel shells were determined using sulphorhodamine B (SRB) assays for MCF-7 cells (HepG2) and colon (Caco-2) cells. Cell viability tests confirmed the nontoxic effects of synthesized HA and mussel shells on human mesenchymal stem cells (h-MSCs) and epithelial cells. Toxicity values were less than 50% of the cell's validity ratio based on analyses using different concentrations (from 0.01 to 1,000 µg). The results indicate that MSC and epithelial cell attachment and proliferation in the presence of both HA and shell occurred. The proliferation capability was established after 3 and 7 days. SEM images revealed that stem cells and epithelial cells attached to the scaffold indicated full and complete integration between the cells and the material. It seems that due to the ion exchange between bovine serum albumin solutions (BSA) and HA, the FTIR data confirmed an increase in the amide I and amide II bands, which indicates the compatibility of the BSA helix structure. This study sheds light on the importance of merging stem cells and nanomaterials that may lead to improvements in tissue engineering to develop novel treatments for various diseases.

Role of levan extracted from bacterial honey isolates in curing peptic ulcer: In vivo.

Peptic ulcer is one of the worldwide diseases where 10% of adults are affected by peptic ulcers at least once in their lifetime. The goal of this study was to evaluate the effect of levan in treating peptic ulcer. The bacterial honey isolates called Bacillus sp. levan was utilized. Levan was chemically characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), 1H and 13C NMR analysis. Levan was used to treat gastric ulcers induced in rats by oral administration of 5 mL/kg ethanol. Microscopic examination of stomach sections indicated that treatment with 200 mg/kg levan effectively healed the ulcers. Levan had no antimicrobial activity against a common cause of ulcers such as Helicobacter pylori bacteria. Rather, we proposed that the high adhesion (manifested as a protective coating) and prebiotic activity of levan may account for the observed beneficial effects. The immunohistochemical examination showed that levan led to a noticeable Bacillus sp. levan reduction in NF-κB in the upper gastric mucosa. The results concluded that the role of levan was more protective rather than preventive and suggested that levan could play a fundamental role in solving the peptic ulcer problems.

Novel, cost-effective, Cu-doped calcium silicate nanoparticles for bone fracture intervention: Inherent bioactivity and in vivo performance.

Copper (Cu)-doped calcium silicate nanoparticles were synthesized by a wet precipitation method as economical bone fracture filler. The aim was to improve the overall physicochemical properties, bioactivity, and biological performance of the bone fracture filler prepared herein. The synthesized nanoparticles were evaluated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The bioactivity of the prepared nanoparticles was investigated after immersion in simulated body fluid (SBF) by means of inductively coupled plasma (ICP), SEM coupled with energy dispersive X-rays (EDX), and FTIR. The size and bioactivity of the prepared nanoparticles after 15 days of immersion in SBF was dependent on the Cu concentrations. The fracture healing ability of the fabricated nanoparticles on adult aged male Wistar rats was enhanced by the presence of copper. All the obtained results are of high relevance for fabricating improved Cu-doped calcium silicate nanoparticles (∼50 nm) as low cost bone fracture filler. In addition, the in vivo study presented complete healing of the tibiae bone with normal architecture of bone tissue specifically calcium silicate nanoparticles doped with 3% and 5% Cu. Hence, the presence of copper is a promising tactic for improving the biological properties of calcium silicate. Therefore, the designed nanoparticles have huge potential for the treatment of bone fractures. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 388-399, 2019.

Immunotoxicity evaluation of novel bioactive composites in male mice as promising orthopaedic implants.

OBJECTIVE: In orthopaedics, novel bioactive composites are largely needed to improve the synthetic achievement of the implants. In this work, semiconducting metal oxides such as SiO2, TiO2, and ZrO2 particles (Ps) were used individually and in different ratios to obtain different biphasic composites. The immunotoxicity of these composites was tested to inspect the potential toxicity prior to their use in further medical applications. MATERIALS AND METHODS: In vitro mineralisation ability was inspected by soaking the composites in simulated body fluid (SBF). Additionally, in vivo experiments were performed consuming male mice using ISSR-PCR, micronucleus (MN) test, comet assay, glutathione peroxidase activity, and determination of albumin, globulin, lymphocyte population, ALT, and AST levels. Several groups of adult male albino mice were treated with 100, 200, and 400 mg/kg body weight of SiO2, TiO2, and ZrO2-Ps in pure or mixed forms. RESULTS: Our findings revealed that treatment of mice with low and medium doses of SiO2, TiO2, and ZrO2-Ps in pure or mixed form revealed values relatively similar to the control group. However, using 400 mg/kg especially from TiO2-Ps in genuine form or mixed with SiO2 showed proliferation in the toxicity rates compared with the high dose of SiO2 and ZrO2-Ps. CONCLUSIONS: The results suggest that TiO2 composite induced in vivo toxicity, oxidative DNA damage, bargain of the antioxidant enzymes, and variations in the levels of albumin, globulin, lymphocyte population, ALT, and AST in a dose-dependent manner. However, SiO2, and ZrO2 composites revealed a lower toxicity in mice compared with that of TiO2.

Fabrication and mechanical evaluation of hydroxyapatite/oxide nano-composite materials.

In the current study, the semiconducting metal oxides such as nano-ZnO and SiO2 powders were prepared via sol-gel technique and conducted on nano-hydroxyapatite (nHA) which was synthesized by chemical precipitation. The properties of fabricated nano-structured composites containing different ratios of HA, ZnO and SiO2 were examined using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM) and transmission electron microscope (TEM) techniques. The effect of the variation of ratios between the three components on mechanical, microstructure and in-vitro properties was assessed to explore the possibility of enhancing these properties. The results proved that the mechanical properties exhibited an increment with increasing the ZnO content at the extent of HA. In-vitro study proved the formation and nucleation of apatite onto the surface of the fabricated composites after one week of immersion. It is concluded that HA composites containing SiO2 or SiO2/ZnO content had a suitable mechanical properties and ability to form apatite particles onto the composite surface. Based on bioactivity behavior, Si-HA is more bioactive than pure hydroxyapatite and nano-arrangements will provide an interface for better bone formation. Therefore, these nano-composites will be promising as bone substitutes especially in load bearing sites.