Nano-hydroxyapatite / chitosan composite material was prepared via in situ Hybridization route. Surface chemical characterization on the nanocomposite was evaluated by Fourier transformed infrared (FTIR) and X-ray diffraction (XRD) surface topography, roughness and morphology of the samples were observed by atomic force microscopy (AFM) and scanning electron microscopy.
Original Description:
Original Title
Synthesis and Characterization of Hydroxyapatite-chitosan Nanocomposite Materials for Medical Engineering Applications
Nano-hydroxyapatite / chitosan composite material was prepared via in situ Hybridization route. Surface chemical characterization on the nanocomposite was evaluated by Fourier transformed infrared (FTIR) and X-ray diffraction (XRD) surface topography, roughness and morphology of the samples were observed by atomic force microscopy (AFM) and scanning electron microscopy.
Nano-hydroxyapatite / chitosan composite material was prepared via in situ Hybridization route. Surface chemical characterization on the nanocomposite was evaluated by Fourier transformed infrared (FTIR) and X-ray diffraction (XRD) surface topography, roughness and morphology of the samples were observed by atomic force microscopy (AFM) and scanning electron microscopy.
Synthesis and characterization of hydroxyapatite/chitosan nanocomposite
materials for medical engineering applications
M.R. Nikpour a,b , S.M. Rabiee a,c , M. Jahanshahi a,b, a Nanotechnology Research Institute, Babol University of Technology, Babol, Iran b Faculty of Chemical Engineering, Babol University of Technology, Babol, Iran c Faculty of Mechanical Engineering, Babol University of Technology, Babol, Iran a r t i c l e i n f o Article history: Received 9 July 2011 Received in revised form 7 October 2011 Accepted 13 January 2012 Available online 2 February 2012 Keywords: A. Nano-structures A. Polymermatrix composites A. Mechanical properties D. Electron microscopy a b s t r a c t Incorporation of hydroxyapatite (HA) withorganic polymer infavor of composites would be used inbioma- terial engineering. According to prior researches, because of its chemical similarity to natural bone andden- tal, this product could improve bioactivity and bone bonding ability. In this research, nano-hydroxyapatite/ chitosan composite material was prepared via in situ Hybridization route. The surface chemical character- ization on the nanocomposite was evaluated by Fourier transformed infrared (FTIR) and X-ray diffraction (XRD). Surface topography, roughness and morphology of the samples were observed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The characterization results conrmed homo- geneity, interaction and integration between the HA and chitosan matrix. It was indicated that composite samples consist of homogeneous aggregations around 40100 nm, in which many HA nanocrystals align along the chitosan molecules. HA grain gradually decreased in size when amount of chitosan increased from 0 to 6 g into 100 cc solution. It can be seen that by increasing chitosan, the aggregation of nanoparti- cles enhance and subsequently, improve the expected compatibility among HA ller and chitosan matrix. Furthermore, the mechanical compressive testing indicated that the synthesized composites have accept- able mechanical behavior for tissue substitution. The mechanistic of the biodegradable nanocomposite sys- tems, their preparation and characterization for medical usage are strongly discussed. 2012 Elsevier Ltd. All rights reserved. 1. Introduction Hydroxyapatite (HA, Ca 10 (PO 4 ) 6 (OH) 2 ) is an interesting biomate- rial withpotential orthopedic, dental, and maxillofacial applications due to its excellent biocompatibility, bioactivity, and osteoconduc- tivity [1]. HA powders, used for the treatment of bone defects, have the problemthat they easily migrate fromthe implanted sites. Also, in Compared to pure HA, polymeric nanocomposites are exhibited improved properties, such as modulus, strength, and stiffness [2,3]. Therefore, novel composites of HA and organic polymers that can compensate for the weak mechanical properties of HA have be- come of great interest [4,5]. Chitosan, (C 6 H 11 O 4 N) n is an N-deacety- lation product of chitin and is a unique polysaccharide based biopolymer that shares a number of chemical andstructural similar- ities with collagen and has been used as a skin grafting template, hemostatic agent, DNA and drug delivery vehicle, and as a wound healing material [611]. Also, chitosan (CTS) lms support the growth, function, and cellular activity of osteoblasts and chondro- cytes [12]. Inorganicorganic composite materials are increasingly important due to their extraordinary properties, which arise from the synergism between the properties of the components. These HA/chitosan nanocomposite has been developed as a good candi- date for tissue engineering, particularly bone and cartilage scaffolds [13,14]. HA particles have been incorporated into chitosan matrices to enhance the bioactivity of tissue engineering scaffolds for hard tissue regeneration [1521]. In addition, biomimetic inspiration fromnatural chitin composites has been used to study biominerali- zation phenomena in the formation of chitin based nanocomposites with silica, calcium carbonate, and HA [17,22]. Incorporation of HA with chitosan, the mineral component of bone, could improve the bioactivity andthe bone bonding ability of the HA/chitosancompos- ites [23]. Biomaterial scientists had paid their attention to investi- gate HA/chitosan composites with different HA content ranging, such as quick hardening past for bone repair [24,25], porous HA/ chitosan scaffold for tissue engineering [26]. Moreover, results from various papers exhibited that chitosan vast applied for HA surface modify and have an excellent benet [27,28]. In this study, the preparation of hydroxyapatite/chitosan nanocomposites using in situ hybridization method is attempted. However, evaluation and characterization of the products including morphology roughness, the effect of enhancement various 1359-8368/$ - see front matter 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.compositesb.2012.01.056
Corresponding author at: Nanotechnology Research Institute, Babol University
of Technology, Babol, P.O.BOX: 484, Iran. Tel./fax: +98 111 3220342. E-mail addresses: mmohse@yahoo.com, mjahan@nit.ac.ir (M. Jahanshahi). URL: http://nano.nit.ac.ir/IndexEn.aspx (M. Jahanshahi). Composites: Part B 43 (2012) 18811886 Contents lists available at SciVerse ScienceDirect Composites: Part B j our nal homepage: www. el sevi er. com/ l ocat e/ composi t esb component of chitosan on surface, dispersion, structural and parti- cle size nanoparticles-polymer matrix are investigated. In addition, mechanical behaviors of products are considered as well. 2. Materials and methods 2.1. Chemicals materials Chitosan from crab shells with a degree of deacetylation >85%, were purchased from SigmaAldrich Co. Acetic acid (HAc, 99.8%) obtained from Merck. Poly (ethylene glycol) (PEG) with moderate molecular weight of 400 that, was used as a agent in calcium ni- trate tetrahidrate (Ca(NO 3 ) 2 4H 2 O) solution to control the particle growth during precipitation, Cetyltrimethylammonium bromide (CTAB) that, has been used as a moisturing agent, Calcium nitrate tetrahidrate (Ca (NO 3 ) 2 4H 2 O), diammonium hydrogen phosphate ((NH 4 ) 2 HPO 4 ) and sodium hydroxide (NaOH), were supplied by Merck, respectively. 2.2. Preparation of hydroxyapatite/chitosan nanocomposites Chitosan was dissolved in 2% (v/v) acetic acid solution to obtain a polymer solution. Different composition of chitosan aqueous solution was prepared by dissolving the different amount chitosan powder into 100 cc distilled water containing acetic acid and stir- red for 24 h until a good suspension was achieved. Samples of this experiment consist of 0, 2, 4, 6 g of chitosan which are named as HC 0 , HC 2 , HC 4 , and HC 6 . All solutions were taken in such amount that Ca/P molar ratio was maintained at 1.67. Then Ca(NO 3 ) 2 4H 2 O of 0.5 M solution added in chitosan solution and vigorously stirred at room temperature with a mechanical stirrer (2500 rpm). Subse- quently, (NH 4 ) 2 HPO 4 suspension of 0.5 M were added drop wise into the prior mixture under extreme stirred until the better sus- pension was achieved. Stirring was continued up for another 24 h to obtain a homogeneous polymer solution. The resulting solution was held unstirred for another night to remove the air bubbles trapped in viscous liquid. In whole process, the pH value was adjusted to about 11 by using 2 M NaOHsolution and the reac- tion temperature was kept at 25 C. Finally the white gelatinous precipitate was separated by centrifuging the suspension at 3000 rpm for 30 min (Z-36HK Hermle, Germany). Then the mixture was dried in a freeze-dryer (FDE-0350, Korea) at 50 C for 48 h to make powder. The schematic diagram of the experimental setup is illustrated in Fig. 1. 2.3. Characterization 2.3.1. X-ray diffraction and FTIR analysis The crystal structure and the phase present in resulting pow- ders were analyzed with X-ray diffraction (XRD). This instrument (Philips PW 3710) works with voltage and current settings of 35 kV and 28.40 mA respectively, and uses Cu Ka radiation (1.5405 ). For qualitative analysis, XRD diagrams were recorded in the interval 20 6 2h 6 45 at scan speed of 2/min. The mean crystallite sizes D were determined according to the Scherrer equation that is, D = 0.9k/b cosh, where D is the average crystallite size in A, b is the peak broadening of the diffraction line measured at half of its maximum intensity in radian, k is the wavelength of X-rays, and h is the Braggs diffraction angle [23]. The structure of obtained product was determined by FTIR spectrum. These prod- ucts were analyzed by FTIR analysis (Perkin Elmer, USA) within scanning range of 4004000 cm 1 . The FTIR spectroscopy of this device has provided valuable information regarding the formation of HA powder and HA/chitosan nanocomposites. FTIR analysis has been done to identify the characteristic peaks of product. 2.3.2. Scanning electron microscopy Scanning electron microscopy (SEM, Hitachi S-4160) was used to characterize the morphology and particle size of nanocompos- ites materials. Prior to imaging, the samples mounted on alumi- num stubs were gold coated for better conductivity. 2.3.3. Atomic force microscopy Atomic force microscopy (AFM) images show the surface rough- ness, morphology and dispersion of powders were obtained with a JEOL 6330F eld emission atomic force microscopy. 2.3.4. Mechanical testing Compression tests were performed at room temperature by a universal testing machine (zwich/roell 2005) at a crosshead speed of 0.03 mm s 1 in the pressure of 10 Bar. The specimens were shaped into circular discs of approximately 5 mm diameter and Fig. 1. Scheme of nanocomposite preparation by in situ hybridization. Fig. 2. X-ray diffraction of synthesized composites with different amount of chitosan ratio. 1882 M.R. Nikpour et al. / Composites: Part B 43 (2012) 18811886 5 mm height. Elastic modulus was calculated as the slope of the initial linear portion of the stressstrain curve. The specimens at each sample were tested, and the data represented the average va- lue of three measurements. 3. Results and discussion 3.1. Crystal structure analysis and FTIR absorbance of nanoparticles on HA Fig. 2 shows the X-ray diffraction pattern of the pure HA and HA/chitosan nanocomposite samples. The use of synthesized n-HA powder with the CTS polymer as a matrix thus provides an effective means to produce nanocomposites. For HA nanoparticles, the existence of 2h peaks at approximately 23.2, 26, 29.3 and 32.2 corresponding to the diffraction planes (211), (002), (210) and (300) of the HA crystallites, respectively, that conrms the for- mation and presence of HA in products. These peaks refer to the b- TCP, HA, none reacted Ca(NO 3 ) 2 and b-TCP dual with HA together, respectively. It can be seen that crystalline structure refers in pre- pared products by in situ hybridization method. After composites formation, crystallization of the n-HA particles still existed, mean- while has decreased as shown in Fig. 2 that indicating the crystal- line characteristic peaks of HA were not alteration signicantly, which could be resulted from the interface binding between parti- cles and matrix. It is also noted that peaks in the precipitated HA/ chitosan nanocomposites became slightly broader and weaker as compared to the pure HA nanoparticles. The XRD peaks, (211), (002), (210) and (300) have shifted to higher 2h values in case of HA/CTS composites as compared to pure HAp (i.e., from 2h = 23.223.8, from 26 to 26.4, from 29.3 to 30.2 and from 32 to 32.8 in composite samples resp.), which these are possibly due to compression from the contracting polymeric matrix through inter- facial bonding. It seems the shift and decrease in crystallinity of each peak of the polymer as well as HA after composite formation clearly indicates the presence of bonding between HA particles and polymer matrix. The peak at 32.2 (300) of n-HA is weakened after composite formation, which also indicates the participation of n- HA in bonding with the polymer. It could be due to molecular interactions between HA and chitosan as well. Taking into account the broadening of each peak in XRD, mean crystallite size has been calculated using Scherrers equation that the approximate crystal- lite sizes of HC 0 , HC 2 , HC 4 , and HC 6 samples are found to be about less than 50 nm. Fig. 3 displays the FTIR spectra of various HA/chitosan compos- ites and pure HA samples. The absorption bands observed around Fig. 3. FTIR spectra of (a) HC 0 , (b) HC 2 , (c) HC 4 and (d) HC 6 samples. Fig. 4. SEM micrograph of (a) HC 0 , (b) HC 2 , (c) HC 4 and (d) HC 6 composites. M.R. Nikpour et al. / Composites: Part B 43 (2012) 18811886 1883 2917, 1642, 1456, and 1552 cm 1 were assigned to methylene (CH 2 ), amide I (C@O), amino (NH 2 ), and amide II (ANH) in nano- composite, respectively. The absorption bands observed around at 1099, 952, 839, and 563 cm 1 correspond to a phosphate group in HA while the stretching band (approximately between 2900 to 3700 cm 1 ) were assigned to OH group in HA. As carbonate bands around at 1457, 1433 and 840 cm 1 also was observed. A compar- ison of FTIR analysis for different samples was conrmed the effec- tive existence of HA nanoparticles surrounded at nanocomposite. The feature bands for HPO4 2 were assigned at 1131 cm 1 , 1062 cm 1 , 988 cm 1 , 876 cm 1 , 576 cm 1 , 528 cm 1 . It seems the magnitude of these bands becomes weaker and nally disap- pears with the development of in situ hybridization. Furthermore characteristic bands for PO 4 3 appeared at 963 cm 1 . 3.2. Morphological studies Fig. 4ad indicate the SEM micrographs of fracture surface of the pure HA and composite samples with different contents of chitosan. The composite samples approach exhibited same Fig. 5. AFM images of (a) HC 0 , (b) HC 2 , (c) HC 4 and (d) HC 6 samples. 1884 M.R. Nikpour et al. / Composites: Part B 43 (2012) 18811886 morphology and homogenous distribution of such kind of HA par- ticles within the chitosan matrix that visible in this Fig. 4bd. The micrographs show that with increase in amount of chitosan load- ing; the surface roughness for the composites is almost increased. As can be seen in the SEM image Fig. 4bd, many elliptic aggrega- tions are found in the composite. Furthermore, in the respective aggregate, there exist many small HA crystallites of 40100 nm. On the other hand, SEM clearly showed that the nanoparticles ex- hibit a uniform size distribution and spherical inorganic minerals are dispersed within polymeric matrices. Obviously, the particle sizes in these composites are quite uni- form that may signicant surface effective consociation or cover- ation chitosan. Maybe could gathered these harvest recognized to the surface improvement that modies the solubility of the nano- particles in the organic solvents, and prevent from augment parti- cles agglomeration. Fig. 5ad were used to determine surface topography and illustrate the surface properties of pure HA and nanocomposites in 3D and 2D topographies. The gures exhibit dispersed nanoparticles in the polymer matrix. As can be seen, pure HA has a relatively smooth and uniform surface. In this Fig. 5bd, HA/chitosan composites presents some different mor- phology as compared with that of pure HA. It can be seen; the HA particles are surrounded and embedded into the polymer chain of chitosan. Indicating the HA particles has a core effect on the polymerization of composites. It seems penetration of HA particles into the chitosan matrix leads to similar formations of aggregates and agglomerates on the surface of composites. In the other hand, the existence of these particles increases surface roughness negli- gibly along with the AFM images. The micrograph shows the pres- ence of agglomerations among the particles, which can be resulted from the interface binding between HA particles and the matrix, that it seems due to high specic surface energy of n-HA particles resulting in their aggregations too. Nanosized HA particles with homogeneous dispersion are well identied in case of HA/CTS composites. It give the impression the particle size of HA is also controlled by the biopolymer matrix in composite as depicted in the AFM micrograph. According to the obtained results, to add var- ious content of chitosan at the surface roughness of synthesized products make no diversity and from this achieved results it would be understood that the place which maximum value of chitosan existed, the most present of aggregation occur on the nanocompos- ite surface as well. we can see the HA particles in triple chitosan nanocomposites are covered with a continuous smooth chitosan layer and the particle sizes of composites are almost smaller due to the increasing values of chitosan. 3.3. Mechanical testing of n-HA/CTS composites For bone tissue engineering materials, the primary mechanical properties are usually imperative criterion in selecting the bone substitute materials. Hence, the compressive strength and com- pressive modulus of these synthesized materials were given in Table 1. From the records, it could be found that the compressive strength of the composites had a relation to the chitosan content in composites. The reason may be the large amount of n-HA which could reduce the degree of mechanical properties strength so that the structure of matrix may be inadequate to combine the higher proportion n-HA particles, resulting in reduced mechanical properties. The compressive strength of HC 2 , HC 4 and HC 6 are 11.45 1.41, 14.47 1.96, and 12.25 2.70 MPa, respectively and the average values of compressive modulus of these composites were found to be 1470 162, 1265 223 and 1163 251 MPa respectively. However, the compressive strength of HC 4 was the most acceptable (14.47 1.96 MPa) when compared with two other composites. This indicated amount of CTS in the composite is optimized but compressive modulus of HC 2 is more and subse- quently better than other indicated composites. It seems several factors can contribute to the observed mechanical response of these nanocomposites, such as particle size and particle size distri- bution of hydroxyapatite, the mechanical properties of biopolymer, the interfacial interactions between biopolymer and hydroxyapa- tite, and good distribution of n-HA in chitosan. The elastic moduli of specimens become weaker when the chitosan interaction with bioceramics and it will be good results for bone substitute materi- als. One example of the inuence of an elasticity high modulus of an implant material on surrounding bone is the dramatic bone loss around certain joint replacement prostheses. This bone loss has been attributed to the stress shielding resulting from the large dis- parity between the stiffness of the implant and the host bone [29]. It might be concluded that these composites can better support new bone tissue regeneration at the site of implantation and main- tain sufcient integrity for bone substitute. 4. Conclusions Nanocrystalline composites with various hydroxyapatite/chito- san ratios were successfully synthesized by in situ hybridization method. Structural, morphology, micrograph and chemical compo- sition of this synthesized powder were characterized by XRD, AFM, SEM and FTIR, respectively. Chitosan indicate strong adsorption interaction with this calcium phosphate material. We understand in the obtained composites, HA nanoparticles well pervaded in the matrix and from SEM and AFM, it was indicated that composite samples consist of homogeneous aggregations around 40100 nm, in which many HA nanocrystals align along the chitosan molecules. This homogeneous distribution of inorganic nanoparticles reveals strong interfacial interaction between the nanoparticles and the polymer matrix. 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