Carbonated Hydroxyapatite Powder Research Articles

The Effect of Power Rate Microwave Heating on Limestone Carbonated Hydroxyapatite Scaffold Using Gas Foaming Method

Microwave heating was used with a gas foaming method for fabricating limestone carbonated hydroxyapatite scaffold (SCHA). Carbonated hydroxyapatite (CHA) was produced from limestone as a calcium source using the co-precipitation method. For further treatment, 0.6 gr CHA powder was mixed in 1 ml H2O2 solution as a blowing agent. The slurry-foam-like CHA was heated in a microwave with different levels of heating power from 180 W to 720 W. The SCHA samples were characterized using X-ray diffraction (XRD), Fourier-transform infrared (FTIR), and Scanning electron microscope (SEM). The crystallinity and crystallite size were affected due to different rates of heating power in the microwave-assisted method. The increasing temperature decreased the crystallite size from 37.49 to 33.97(nm). However, other crystallinity trends were observed at 180 W because the lower power heating needed a longer time to be formed SCHA. The different power rates have an insignificant contribution to the morphology of the scaffolds.

Investigation of Microwave Sintering of B-Type Carbonated Hydroxyapatite Bioceramics

B-type carbonated hydroxyapatite (CBHA) is potentially an excellent biodegradable bioceramic for bone repair. However, conventional sintering results in formation of undesired phases. Therefore, microwave sintering of CBHA was investigated to assess the possibility to reduce formation of unwanted phases. Pellets with 0.8 mol% of B-type carbonate were sintered in a multimode instrumented cavity under static air with short thermal cycles. They were prepared from a CBHA powder alone and from a mixture of CBHA and carbon powder to generate a local in-situ CO2 atmosphere. XRD, FT-IR, SEM and BET analyses indicated that CBHA densification with increase temperature lead to decomposition into apatite. The addition of carbon powder to the CBHA that generate a CO2-rich atmosphere around the samples did not prevent the decomposition. Efficient control of temperature and atmosphere composition is required to improve microwave sintering of CBHA bioceramics.

Preparation and morphological investigation on bioactive ion-modified carbonated hydroxyapatite-biopolymer composite ceramics as coatings for orthopaedic implants

Bioactive ions (Mg, Sr, Zn) doped carbonated hydroxyapatite powders (dHAp) and pure carbonated hydroxyapatite (HAp) powders were prepared by wet chemical precipitation method. The bioactive ions were incorporated into the HAp matrix by co-precipitation from solution containing the appropriate amount of chloride salt of different ions. The morphology of pure HAp was mainly needle-like in nanometre size and the particles were disordered showing quasi-amorphous structure. The ion doping changed the morphology of particles, the dHAp particles had distorted spheroid shapes. Owing to the ion addition, the crystallinity of particles decreased. Particle aggregations can also be observed in both types of samples. HAp and dHAp loaded biopolymer polyvinylpyrrolidone (PVP) composite materials have also been developed by novel electrospinning technique. It has been shown that both the HAp and dHAp particles can be successfully incorporated into the PVP fibre web matrix and simultaneously the bioceramic powders were attached to the surface of polymer fibres. The surface of fibres was not fully covered with the particles. The ceramic powder addition to the polymer solution caused the polymer fibres to become more entangled and the diameters of fibres varied over a wider range compared to the base polymer fibres without bioceramic powder addition.

Synthesis, Structural and Biomedical Characterization of Hydroxyapatite/Borosilicate Bioactive Glass Nanocomposites

In this work, a borosilicate glass sample (5SiO2–45B2O3–20Na2O–25CaO–5Ag2O) was added to nano-sized carbonated hydroxyapatite (CHA) powders with different contents up to 20 wt% to improve the bioactivity, antibacterial effect, physical and mechanical properties of the resulting nanocomposites. The CHA and BG nanocomposite powders were mixed, milled with a high-energy ball mill, then pressed into pellets under hydraulic pressure, and finally sintered in muffle at 650 ºC. Subsequently, the sintered samples were subjected to X-ray diffraction (XRD) technique, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) to examine their structure, chemical composition and microstructure, respectively. Furthermore, the physical and mechanical properties of the sintered nanocomposites were also measured. Moreover, the in vitro bioactivity of the prepared nanocomposites was tested after being soaked in a simulated body fluid (SBF) solution for 10 days and their surfaces were then examined with XRD and SEM. In addition, the antibacterial behavior of these samples was tested against E. coli and S. aureus by the disc-diffusion method. The results obtained indicated that the sample with the highest BG content possessed the best bioactivity, antibacterial effect, physical and mechanical properties. Based on these results, the prepared nanocomposites can be used in various biomedical applications.

Effect of sintering temperature on the morphology, crystallinity and mechanical properties of carbonated hydroxyapatite (CHA)

Effect of sintering temperature on the physical and mechanical properties of synthesized B-type carbonated hydroxyapatite (CHA) over a range of temperature in CO2 atmosphere has been investigated. The B-type CHA in nano size was synthesized at room temperature by using a direct pouring wet chemical precipitation method. The synthesized CHA powders were subsequently consolidated by sintering treatment from 800 to 1100 °C. The sintered CHA samples were evaluated using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrometry, X-ray fluorescence (XRF), carbon-hydrogen-nitrogen-sulfur-oxygen (CHNS/O) elemental analyzer, Field emission scanning electron microscopy (FESEM), and Vicker's indentation technique. The results obtained from XRD and FESEM indicated that the synthesized B-type CHA powders were nanometer in size. The crystallinity and crystallite size of the sintered CHA samples were increased due to increasing sintering temperature. The heat treatment between 800 °C and 1000 °C has resulted in coarsening and increased hardness of the sintered CHA samples. However, these properties began to deteriorate when sintering beyond 1100 °C due the formation of calcium oxide.

Faster synthesis of A-type carbonated hydroxyapatite powders prepared by high-temperature reaction

Synthesis of A-type carbonated hydroxyapatite (CHA) materials has typically involved heating of a hydroxyapatite composition for 24 h or greater. In this study, a hydroxyapatite powder was heated at 800, 900 or 1000 °C for 1, 8 or 16 h in dry CO2. Samples heated for 8 and 16 h at 900/1000 °C were fully-carbonated A-type CHAs. After only one hour at 1000 °C, the carbonate content approached 95% of the theoretical maximum. Preparing compositions with more than 95% of the theoretical maximum with reduced thermal energy (1000 °C for 1 h, or 900 °C for 8 h) results in powders with higher surface areas and a reduced level of sintering, compared to powders prepared with typical thermal treatments reported for A-type CHAs, such as 1000 °C for 16 h. As far as the authors are aware, these are the shortest heating times reported for the preparation of fully-carbonated A-type CHAs which is significant for future applications of such powders, particularly in applications beyond medical devices such as chromatography, remediation and carbon capture.

Synthesis of Bio-composite CHA/PVA/Alginate as Bone Substitute Material

The main inorganic constituent of human bone is carbonated-hydroxyapatite (CHA). The CHA powder had been successfully synthesized by using chicken eggshell through microwave assisted precipitation methods. In the application, the biomaterials needed by orthopaedic doctors were in the form of scaffold. The addition of PVA and alginate to CHA can improve mechanical properties and affect the pores. The freeze-drying method was used to synthesize bio-composite scaffold. The FTIR result showed that spectrums correspond to functional group of PO4 3−, OH−, CO3 2− which were the characteristic of CHA. The elastic scaffold was produced in this research. The scaffold mechanical test results showed that the higher PVA content showed the higher mechanical properties. The phase composition was evaluated by XRD and indicated the presence of CHA. The morphology of the sample was evaluated by SEM which formed pores. These scaffolds showed good prospects for bone substitute material.

Carbonated Hydroxyapatite Derived from Snail Shells (<i>Pilla ampulacea</i>): The Influence of Sintering Temperature on Purity and Crystallography Properties

The aim of this work is to investigate the influence of sintering temperature on purity and crystallography properties of carbonated hydroxyapatite (CHAp). The CHAp was synthesized using a coprecipitation method. The snail shells (Pillaampulacea) were processed to yield calcium oxide as the calcium source in synthesis. The CHAp powder then was sintered for 2 h in an air atmosphere at 400, 600, 800, and 1000°C. An X-Ray diffractometer (XRD), Fourier transform infrared (FTIR), scanning electron microscope (SEM), and energy dispersive x-ray (EDX) are used to investigate the physicochemical properties of CHAp. XRD, FTIR, and EDS results show primary phase is carbonated hydroxyapatite. Calcium oxide as a secondary phase is detected starting from 800°C. The crystallinity and crystallite size are increased along the increasing of sintering temperature. Drastic enhancement on these properties is shown at 600–800°C. However, there is no simple relation to the sintering temperature and lattice parameters. These results show that sintering temperature has an important role in the purity and crystallography properties of the CHAp.

Development Carbonated Hydroxyapatite Powders from Oyster Shells (<i>Crassostrea gigas</i>) by Carbonate Content Variations

Carbonated hydroxyapatite (CHAp) is an inorganic mineral that more closely resembles the main component of composing human hard tissue in 2-8 wt% carbonate content. CHAp powders have been synthesized from oyster shells using the precipitation method. Oyster shells are one type of shellfish from the bivalve class which is rich in calcium carbonate content. In this research, CaO from oyster shells obtained from the decomposition process of CaCO3 was used as a source of calcium and diammonium hydrogen phosphate and ammonium bicarbonate as well as a precursor of phosphate and carbonate, respectively. In addition, carbonate content variations were x = 0, 0.3, 0.8 and 1.2 which were characterized by fourier transform infrared spectroscopy (FTIR), X-ray diffractometer (XRD), and scanning electron microscope-energy dispersive X-Ray (SEM-EDX) to determine the functional groups, crystallographic properties, morphology and Ca/P molar ratio, respectively. Carbonate ion substitution in the hydroxyapatite crystal structure is known to decrease crystallinity and crystallite size. The theory is in accordance with the results obtained in this study with the crystallite size is 74.322, 46.933, 37.727, and 31.499 nm for 0.95, 2.7, 5.7, and 9.35 wt.% carbonate content, respectively.

Fabrication of Low Temperature Carbonated Hydroxyapatite Porous Scaffolds for Bone Tissue Engineering Applications

Three-dimensional (3D) porous carbonated hydroxyapatite (CHA) scaffolds were successfully prepared using polyurethane (PU) replication technique. Two sets of porous scaffolds were prepared using as-synthesized and as-calcined CHA powder as the main component of the slurry. The effect of the condition of starting material was investigated in terms of structure, phase purity, crystallinity and morphology of the fabricated porous scaffolds. Regardless of the condition of starting material used, the porous scaffolds fabricated was single phase B-type CHA and free of secondary phases. Interestingly, scaffolds made of as-calcined CHA powder (SC scaffolds) showed a smoother surface and more solidified struts when compared to as-synthesized CHA powder (SA scaffolds). This is attributed to the state of semi-crystalline phase of the as-calcined powder being amorphous phase. SC scaffold was found to be better scaffold with respect to handling, compaction strength and microstructure with better strut properties.

Effect of Sintering Temperature on Carbonated Hydroxyapatite Derived from Common Cockle Shells (Cerastodermaedule): Composition and Crystal Characteristics

Incorporation carbonate ion to hydroxyapatite (HAp) structure, known as carbonated hydroxyapatite (CHAp) is reported to reduce crystallinity, increase the solubility rate, and increase bioactivity. Sintered CHAp material is interesting because it may have a better biological response.CHAp derived from common cockle (Cerastoderma edule) shell have produced by precipitation method. This study aimed to investigate the effect of sintering temperature to compositon and crystal characteristics of CHAp. CHAp powder was sintered at 400, 600, and 800°C in air atmosphere.CHApas-preparedand sintered samples were analyzed using Energy Dispersive Spectrometry (EDS), Fourier Transform Infrared (FT-IR), and X-ray Diffractometer (XRD).EDS analysis showed that the Ca/P ratio of powder CHAp was around 1.67-1.94 (greater than the Ca/P ratioof HAp). For increasing of sintering temperature, carbonate and water content decreased, crystallinity and crystallite size increased.

Microwave–assisted precipitation of carbonated hydroxyapatite

Carbonated hydroxyapatite (CHA) is a bone implant material that has good solubility and resorption. In this study, CHA was synthesized and characterized using microwave–assisted precipitation method under different irradiation power and time. CHA powder was synthesized starting from calcium hydroxide, diammonium hydrogen phosphate, and calcium hydroxide. Chemical and physical analyses, XRD, FTIR, SEM, and EDX, were applied to investigate the composition, crystallinity, crystallite size and morphology of CHA powder. XRD patterns showed that CHAs had low characteristic peaks that indicating poor crystallinity. According to the crystallinity index, 450 W 30 minutes CHA with CI = 35.3% and SF = 2.908 was chosen as the best result because it was the closest result to the bone crystallinity reference. The crystallite size for all CHA samples reached 19.386 – 24.019 nm, were almost similar to the crystallite size for bone. FTIR and EDX affirmed that CHA bond existed. The carbonated hydroxyapatite was formed B type CHA with some additional A and AB type. CHA crystal was formed of nanorod particle. Hence the physical and chemical analyses suggest that CHA powder can be obtained using a microwave-assisted precipitation method with good results

Development Carbonated Hydroxyapatite Powders from Oyster Shells (Crassostrea gigas) by Sintering Time Controlling

Carbonated-hydroxyapatite (CHAp) is a hydroxyapatite substituted with carbonate ions and is known to resemble the hard bone structure of humans. CHAp was synthesized from biogenic material. Oyster shells (Crassostrea gigas) was biogenic materials that used as a calcium source. In addition, sodium bicarbonate and ammonium hydrogen phosphate were also used as sources of carbonate and phosphate. In this research, the oyster shells used were milled, calcined, and characterized to determine the phase changes from CaCO3 to CaO by decomposition process. CHAp powders which were synthesized by precipitation method, were sintered at 650 °C for 0.25, 0.5, 1, 2 and 4 hours. To find the quality of CHAp powders with different sintering time, characterization process using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffractometer (XRD), and Scanning Electron Microscope-Energy Dispersive X-Ray (SEM-EDX) has been successfully done. FTIR, XRD, and SEM-EDX was used to determine functional groups, to confirm the presence of carbonate groups, to analyse the crystallography, and to calculate the Ca/P molar ratio and carbonate content of CHAp powders. Based on the results of characterization process showed that the oyster shells weres successfully synthesized into CHAp and the length of sintering time effects of the crystallite size and crystallinities. CHAp powders sintered for 4 h have 41.385 % and 31.499 nm degree of crystallinity and crystallite size, respectively.

Microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite: therapeutic potential and effects on bone regeneration.

Background and objective: Tetracycline and its derivatives, combined with calcium phosphates, have been proposed as a delivery system to control inflammatory processes and chronic infections. The objective of this study was to evaluate the microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite (CHAMINO) as a biomimetic device to carry out target-controlled drug delivery for alveolar bone repair.Methods: CHAMINO microspheres were implanted in a rat central incisor socket after 7 and 42 days. New bone was formed in both groups between 7 and 42 days of implantation. However, the bone growth was significantly higher for the CHAMINO microspheres.Results: The minocycline (MINO) loading capacity of the nanocrystaline carbonated hydroxyapatite (CHA) nanoparticles was 25.1±2.2 µg MINO/mg CHA for adsorption over 24 hrs. The alginate microspheres containing minocycline-loaded CHA were biologically active and inhibited the Enterococcus faecalis culture growth for up to seven days of the MINO release. An osteoblastic cell viability assay based on the resazurin reduction was conducted after the cells were exposed to the CHAMINO powder and CHAMINO microspheres. Thus, it was found that the alginate extracts encapsulated the minocycline-loaded CHA microspheres and did not affect the osteoblastic cell viability, while the minocycline-doped CHA powder reduced the cell viability by 90%.Conclusion: This study concluded that the alginate microspheres encapsulating the minocycline-loaded nanocrystalline carbonated hydroxyapatite exhibited combined antibacterial activity against Enterococcus faecalis with cytocompatibility and osteoconduction properties. The significant improvement in the new bone formation after 42 days of implantation suggests that the CHAMINO microsphere has potential in clinical applications of bone regeneration.

Carbonated Hydroxyapatite Derived from Cerastoderma edule, Paphia undulata, and Meretrix meretrix Shells

Carbonated hydroxyapatite (CHAp) derived from three different shells, Cerastoderma edule, Paphia undulata, and Meretrix meretrix shells, have been synthesized by precipitation method. Calcium oxide from extracting shells, diammonium hydrogen phosphate, and ammonium bicarbonate was used to synthesis as the starting precursors. The CHAp materials were analyzed by Energy Dispersive Spectroscopy (EDS), Fourier Transform Infrared (FT-IR), and X-Ray Diffractometer (XRD). EDS analysis showed that the Ca/P ratio of CHAp powders were around 1.75-1.77 (bigger than the Ca/P ratio of HAp) and carbonate content of the powder CHAp was 3.10-4.05wt%. XRD data has produced diffraction patterns from the three different shells similar to the apatite structure. The position of the main peak (2θ) diffraction patterns detected at 31.99°, 32.23°, and 31.95°. The lattice parameter of a-axis and c-axis were obtained around 9.37 Å and 6.89 Å. Crystallite size of CHAp samples was 30-40 nm. The FTIR spectra showed that there are functional groups of OH-, PO43-, and CO32- at wave number around 3447, 571, and 873 cm−1. Based on the results of the analysis, it shows that the CHAp characteristics that had successfully produced from Cerastoderma edule, Paphia undulata, and Meretrix meretrix shells were B-type CHAp.

Physico-chemical properties of Co-Sr doped carbonated hydroxyapatite powders

Abstract The present study aimed to investigate the effects of ionic substitutions on the physico-chemical properties of carbonated hydroxyapatite (CHA) by incorporation of two biologically important cations, cobalt (Co2+) and strontium (Sr2+) ions into the apatite structure. Four different compositions of Co-Sr CHA powders with different combinations of Co2+ and Sr2+ were synthesized via nanoemulsion method at 25°C. The physico-chemical properties of the powders were investigated through several analytical techniques, i.e. X-Ray Diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy, Carbon, Hydrogen, Nitrogen (CHN) analyzer and Field Emission Scanning Electron Microscopy equipped with Energy Dispersive X-Ray (FESEM/EDX). Regardless of their compositions, the as-synthesized Co-Sr CHA powders remained as B-type CHA and no secondary phase detected. The amounts of carbonate present in the as-synthesized powders were found to be in a range of 1-5 wt%, which relatively close to the carbonate content found in natural human bone. The Ca/P ratios obtained for all the as-synthesized powders were relatively higher than the theoretical ratio of the stoichiometric HA (1.67). This proved that carbonate, strontium and cobalt ions were partially substituted into the apatite structure. All as-synthesized powders showed highly agglomerated nanoparticles when observed under FESEM. Co-Sr CHA 1 with 0.0082 wt% Co and 0.0547 wt% Sr was selected as the best formulation to be used in the next phase of our study in developing three-dimensional porous scaffolds.

Effect of Microwave Irradiation on the Synthesis of Carbonated Hydroxyapatite (CHA) from Chicken Eggshell

The main inorganic constituent of human bone is carbonated-hydroxyapatite (CHA). Chicken eggshells (CES) become potential waste which can be used for biomaterial synthesis because it contains of 94% calcium carbonate (CaCO3). This research aims to synthesize CHA by microwave assisted methods. CHA was successfully synthesized by mixing a calcium solution from CES with aqueous solution of NaHCO3 and H3PO4. Microwave assist offers many advantages such as fast reaction, easy reproducibility, high yield, high purity, efficient energy transformation, and throughout volume heating. After precipitation process, samples were irradiated in microwave oven for 30, 35, and 40 minutes by using microwave power 40, 200 and 400W. The functional groups of CHA powder was determined by FTIR. There are functional groups of phosphate (PO43−), hydroxyl (OH−), and carbonate (CO32−). The FTIR spectrum indicates that the prepared sample is B-type carbonated substituted HA because part of phosphate groups in the HA structure is replaced by carbonated groups. The phase composition was evaluated by XRD and indicated the presence of HA and CHA. The quantitative analysis showed that Ca/P ratio is 1.64, which indicates that the obtained product is non-stoichiometric HA. The successful synthesis of CHA is a critical step forward in our efforts to fabricate bone tissue engineering scaffold.

Porous Carbonated Hydroxyapatite Ceramics Obtained by the Original Method of “Ceramic Biscuit” for Medicine

Carbonated hydroxyapatite (CHA) owing to its chemical and phase composition that is similar to that of the inorganic component of native bone tissue is a promising material for reconstructive surgery to heal bone defects that are caused by trauma and extensive surgery. An original method for obtaining porous CHA ceramic granules was developed. To obtain a system of interconnected pores, a protein foam with sucrose was used. The optimum ratio of the protein foam to the ceramic CHA powder was found to be 3: 1 for production of porous ceramics with a homogeneous structure. The mechanical properties of the porous CHA ceramics that we obtained at different ratios between the protein foam and ceramic CHA powder were studied: as the concentration of the ceramic CHA powder increased in the mixture, the compressive strength of the CHA ceramics decreased from 6–7 to 2–3 MPa. The microstructure of the CHA ceramics is characterized by the presence of pores that are different in size, from fractions to tens of microns. In vitro studies of the porous CHA ceramics were performed. The evaluation of the influence of the granules on the growth of rat MMSCs in vitro revealed a decrease in the cell viability with an increase in the concentration of the granules. The reduced viability of the MMSCs in the presence of the granules can be associated with alkalization of the environment by the sintering additive.

Co-Sr doped carbonated hydroxyapatite: A biomaterial with enhanced mechanical and bioactivity properties

The present study is aimed at investigating the role of two biologically important cations, cobalt (Co2+) and strontium (Sr2+) doped into carbonated hydroxyapatite (CHA) crystal structure. Four different compositions of Co-Sr CHA powders were synthesized via nanoemulsion method at ambient temperature. Among the as-synthesized powders, Co-Sr CHA 1 (0.0082wt% Co, 0.0547wt% Sr) and Co-Sr CHA 2 (0.0085wt% Co, 0.0261wt% Sr) were chosen as the optimum compositions and used for fabrication of dense products. Sintering was then performed on the Co-Sr CHA compacted samples at 900°C in air, followed by cooled down in dry CO2 atmosphere at temperature of 200°C. Regardless of their compositions, the sintered samples remained as single phase B-type CHA. Co-Sr CHA 1 has the optimum mechanical properties where the relative density and diametral tensile strength (DTS) values obtained were 89.15% and 7.67 MPa, respectively. In vitro bioactivity test revealed that the formation of apatite layer were detected on the surface of all sintered samples after soaking in SBF solution for 7 days, with Co-Sr CHA 1 showing the fastest apatite formation as compared to CHA and Co-Sr CHA 2. Results obtained indicate that simultaneous doping of Co2+ and Sr2+ into CHA structure gives rise to improved mechanical strength as well as enhanced the bioactivity of the apatite.

Cyclotriphosphate associated to fluoride increases hydroxyapatite resistance to acid attack.

This study evaluated the effect of sodium trimetaphosphate (TMP) associated or not with fluoride (F) on the structure and dissolution of carbonated hydroxyapatite (CHA). Synthetic CHA powder (1.0 g) was suspended in solutions containing TMP at 0-10%, associated with 0, 1100, 4500, or 9000 ppm F, and the precipitates were submitted to a pH cycle (n = 6/group). Samples were analyzed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. F, calcium (Ca) and phosphorous (P) concentrations were determined in CHA, while P and F were analyzed in the supernatants. Data were submitted to analysis of variance, Student-Newman-Keuls' test and Pearson's correlation coefficient (α = 0.05). Solutions containing 1100 ppm F with TMP between 2-4% and 4500 and 9000 ppm F with TMP between 4 and 8% led to higher Ca/P ratio (p < 0.05) in CHA. Alkali-soluble F deposition was directly related to TMP concentrations whereas an inverse pattern was observed for acid-soluble F incorporation (p < 0.05). Greater P adsorption in the CHA structure was observed with increasing concentrations of TMP for the 0 and 1100 ppm F solutions (p < 0.05). All diffractograms and FTIR spectra showed a similar pattern to that for pure hydroxyapatite. Thus, when TMP and F are coadministered, TMP interferes with F deposition on CHA, and an ideal TMP:F ratio can enhance the precipitation of CHA with lower solubility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2553-2564, 2018.