Hydroxyapatite Biomaterials Research Articles

Design of biphasic Fe and Zn doped hydroxyapatite: Novel strategy for combating osteomyelitis infections

Hydroxyapatite (HA) bioceramics are widely used materials for orthopaedic applications, offering enhanced cellular adhesion and differentiation. However, the lack of antibacterial features makes the HA biomaterials prone to bacterial infections in in-vivo conditions. The osteomyelitis-like conditions are often treated with prolonged doses of antibiotics and may require surgical removal. Such problems can be tackled by inducing the antibacterial characteristics in the biomaterials which prevent such infections. Various research studies have been conducted to improve the mechanical and antibacterial characteristics of biomaterials like HA through doping. The present study focuses on the synthesis, characterization, and antibacterial study of Zn and Fe doped HA (ZFHAp) for application in the treatment of osteomyelitis. Response Surface Methodology (RSM) based Central Composite Design (CCD) approach was used to optimize the process parameters using the Design Expert software. The analyses indicated the presence of Calcium Iron Hydrogen Phosphate (CIHP) and Parascholzite (PS) as major phases. The optimized experimental conditions were estimated as 0.09 M Zn and 0.04 M Fe at 65 °C, corresponding to 71.29 % and 28.71 % of the CIHP and PS phases, respectively. The synthesized nanopowder showed mixed morphology comprising spherical and rod-shaped particles due to biphasic composition. The ZFHAp sample showed a broad-spectrum antibacterial activity, with IC50 values of 4.02 mg/ml and 4.79 mg/ml against E. coli and S. aureus, respectively. The optimized sample showed excellent biocompatibility with the osteoblast-like cells (MG-63) with improved biomineralization properties. The antibacterial and osteoinductive characteristics of the synthesized biphasic Fe and Zn doped HA suggest its potential application against osteomyelitis-related conditions.

Hydroxyapatite biomaterials: a comprehensive review of their properties, structures, clinical applications, and producing techniques

Abstract Before employing a biomedical material in medical applications, a researcher must possess comprehensive knowledge regarding its chemical, physical, biological, structural, and mechanical properties. Hydroxyapatite (HAp, Ca10(PO4)6(OH)2) is a vital constituent of the calcium orthophosphate group. The material exhibits good dielectric and biological compatibility, diamagnetic behavior, thermal stability, osteoconductivity, and bioactivity. Additionally, it has a Ca:P molar ratio of 1.67. Because HAp has a chemical composition that is quite similar to normal bone and teeth, it has the potential to be used as a material for implant implantation in fractured portions of the human skeletal system. Many ways for generating HAp nanoparticles have been found as a result of the increasing usage of HAp in medicine. The conditions under which HAp is generated determine its physical and chemical properties, crystalline structure, and form. This study provides detailed information on the HAp’s characteristics and manufacturing procedures, as well as revealing the structure and its properties.

The effect of dental material type and masticatory forces on periodontitis-derived subgingival microbiomes

Restorative dental materials can frequently extend below the gingival margin, serving as a potential haven for microbial colonization, and altering the local oral microbiome to ignite infection. However, the contribution of dental materials on driving changes of the composition of the subgingival microbiome is under-investigated. This study evaluated the microbiome-modulating properties of three biomaterials, namely resin dental composites (COM), antimicrobial piezoelectric composites (BTO), and hydroxyapatite (HA), using an optimized in vitro subgingival microbiome model derived from patients with periodontal disease. Dental materials were subjected to static or cyclic loading (mastication forces) during biofilm growth. Microbiome composition was assessed by 16S rRNA gene sequencing. Dysbiosis was measured in terms of subgingival microbial dysbiosis index (SMDI). Biomaterials subjected to cyclic masticatory loads were associated with enhanced biofilm viability except on the antibacterial composite. Biomaterials held static were associated with increased biofilm biomass, especially on HA surfaces. Overall, the microbiome richness (Chao index) was similar for all the biomaterials and loading conditions. However, the microbiome diversity (Shannon index) for the HA beams was significantly different than both composites. In addition, beta diversity analysis revealed significant differences between composites and HA biomaterials, and between both loading conditions (static and cyclic). Under static conditions, microbiomes formed over HA surfaces resulted in increased dysbiosis compared to composites through the enrichment of periopathogens, including Porphyromonas gingivalis, Porphyromonas endodontalis, and Fretibacterium spp., and depletion of commensals such as Granulicatella and Streptococcus spp. Interestingly, cyclic loading reversed the dysbiosis of microbiomes formed over HA (depletion of periopathogenes) but increased the dysbiosis of microbiomes formed over composites (enrichment of Porphyromonas gingivalis and Fusobacterim nucleatum). Comparison of species formed on both composites (control and antibacterial) showed some differences. Commercial composites enriched Selenomonas spp. and depleted Campylobacter concisus. Piezoelectric composites effectively controlled the microbiome viability without significantly impacting the species abundance. Findings of this work open new understandings of the effects of different biomaterials on the modulation of oral biofilms and the relationship with oral subgingival infections.

Synthesis and characterization of luminescent cerium-doped hydroxyapatite

Hydroxyapatite (HAp) biomaterials are intended for use as bone substitutes, target functional agents in theranostics or bioimaging due to affinity for hard tissues, biocompatibility, and bioactivity. This study is devoted to HAp doped with cerium, having distinctive feature to change the oxidation state (3+/4+), which affects the physico-chemical and optical properties of the obtained powders. Cerium-doped HAp nanopowders with Ce content up to 0.5 wt% were obtained through precipitation technique and then were heat treated. The following conditions for heat treating were used: (i) heating in air atmosphere, (ii) hot pressing, (iii) heating in a carbon filling. For characterization, the complex methodology was implemented, including X-ray diffraction (XRD) analysis and high temperature XRD, X-ray absorption near edge structure (XANES) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, inductively coupled plasma atomic emission spectrometry (ICP-AES), transmission electron microscopy (TEM), electron paramagnetic resonance (EPR) spectroscopy, and, finally, photoluminescence (PL) spectroscopy. It was shown that the monophase cerium-HAp is stable up to a temperature of 1000 °C in the oxidizing atmosphere, above 1000 °C cerium(4+) oxide forms. Using reducing atmosphere during heating prevents the transition of Ce3+ to Ce4+. PL, EPR and XANES studding clarified obviously the Ce3+ content in the materials obtained under different processing conditions. It was shown, that Ce-HAp powders produced by precipitation and hot pressing contain Ce3+ and exhibit luminescence. The significant luminescence of hot pressed Ce-HAps was caused by a higher concentration of Ce3+ ions and incorporation of carbonate ions as a result of the processing.

CHARACTERIZATION OF HYDROXYAPATITE FROM CHANNA STRIATA AND SCOMBEROMORUS COMMERSON FISH BONE BY HEAT TREATMENT

Hydroxyapatite (HAp) biomaterials have been successfully obtained from Channa striata and Scomberomorus commerso fish bone. Heat treatment was chosen as the method to get it. Heat treatment was done at 400oC, 600oC, and 800oC. The X-ray diffractometer (XRD) was used to determine the crystalline phase and crystallography properties. Based on XRD data and JCPDS 09-0432, all samples showed the phase of HAp. However, the β-TCP phase has been found in samples from Scomberomorus commerso, which calcined at 600oC and 800oC. The crystallite size of HAp from Channa striata fish bone increased as followed by higher temperature, and Scomberomorus commerso has the same crystallite size on samples that calcined at 600oC and 800oC. The microstrain of both samples has the same trend: the higher the temperature, the lower the microstrain. The temperature also affected the crystallinity sample; the higher the calcined temperature, the improved crystallinity. Fourier Transform Infrared (FTIR) data determined the functional groups of samples. The functional groups that appeared were OH-, PO43-, and CO32-. The mass of samples before calcined differs from after calcined, where the mass after calcined is smaller than before. The higher the temperature we used, the more decreased yield percentage we got.

Chemical, structure and thermal characterisation of biowaste fish bone parts for orthopaedic coatings

ABSTRACT Fish bone waste is a valuable source of natural hydroxyapatite (HA). In this study, different sections of Nile tilapia (Oreochromis niloticus); head bone (T-HEB), otolith bone (T-OTB), operculum bone (T-OPB), and spine bone (T-SPB) were considered for potential natural HA biomaterial. The findings show that the T-OTB powder had a lower size particle distribution with 16.99 µm (d0.5) while T-OPB had the highest one with 148.14 µm (d0.5). Irregular particle morphology was observed for T-OPB, T-OTB, and T-SPB except for T-HEB powder, which owns needle-sharped particles. The phase analysis and the presence of the functional groups of OH−, CO3−2, and PO3− 4 belonging to HA confirmed the formation of HA for previous samples. In contrast, the T-OTB powder was mostly composed of CaO fitting with aragonite peaks according to elemental and phase analyses. The thermal analysis revealed that the volatile/organic compounds were removed completely above 622 °C for T-HEB, T-OPB, and T-SPB and the total mass loss of them was less than 2.17%. While this temperature was 864 °C for T-OTB and total mass loss was higher at 44.5%. The Ca/P ratio of T-HEB, T-OPB, and T-SPB powders was found to be 0.49 higher than the stochiometric HA. The findings suggest that T-HEB, T-OPB, and T-SPB powders can be used in the area of orthopaedic coatings.

Synthesis of Nanocrystalline Hydroxyapatite Biomaterial from Waste Eggshells by Precipitation Method

Synthesis of Nanocrystalline Hydroxyapatite Biomaterial from Waste Eggshells by Precipitation Method

Embryotoxicity and visual-motor response of functionalized nanostructured hydroxyapatite-based biomaterials in zebrafish (Danio rerio)

Hydroxyapatite (HA) is a biomaterial widely used in biomedical applications. Many studies have shown that ionic substituents can be incorporated into HA to produce a mineral composition more similar to natural bone tissue with more favorable biological characteristics for application in bone regeneration. However, its potentially toxic effects need to be evaluated before full approval for human use. For this purpose, an embryotoxicity test was performed on zebrafish according to OECD guideline 236. Zebrafish embryos were exposed to 1 or 3 microspheres of alginate containing nanoparticles of HA and carbonate (CHA), strontium (SrHA), and zinc-substituted HA (ZnHA) from 4 to 120 h post-fertilization (hpf). Lethality and developmental endpoints were evaluated. In addition, larval behavior at 168 hpf was also analyzed to observe whether biomaterials adversely affect optomotor and avoidance responses (neurotoxicity), as well as the oxidative stress pattern through qPCR. After 120 h exposure to all microspheres with different patterns of crystallinity, porosity, nanoparticle size, surface area, and degradation behavior, there was no mortality rate greater than 20%, indicating the non-embryotoxic character of these biomaterials. All experimental groups showed positive optomotor and avoidance responses, which means that embryo exposure to the tested biomaterials had no neurotoxic effects. Furthermore, larvae exposed to one SrHA microsphere showed a better optomotor response than the control. Furthermore, the biomaterials did not change the pattern of mRNA levels of genes related to oxidative stress even after 120 hpf. The growing number of new HA-based biomaterials produced should be accompanied by increased studies to understand the biosafety of these compounds, especially in alternative models, such as zebrafish embryos. These results reinforce our hypothesis that ion-substituted HA biomaterials do not impose toxicological effects, cause development and neuromotor impairment, or increase oxidative stress in zebrafish embryos being useful for medical devices and in the process of bone regeneration.

Screening of Hydroxyapatite Biomaterials for Alveolar Augmentation Using a Rat Calvaria Critical-Size Defect Model: Bone Formation/Maturation and Biomaterials Resolution.

Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomaterials appear to be the preferred technologies among clinicians for bone augmentation procedures in preparation for implant dentistry. The aim of this study was to screen candidate HA biomaterials intended for alveolar ridge augmentation relative to their potential to support local bone formation/maturation and to assess biomaterial resorption using a routine critical-size rat calvaria defect model. Eighty adult male Sprague Dawley outbred rats obtained from a approved-breeder, randomized into groups of ten, were used. The calvaria defects (ø8 mm) either received sham surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA (Cerabone, DirectOss, 403Z013), and bovine (403Z014) or synthetic HA/ß-TCP (Reprobone, Ceraball) constructs. An 8 wk healing interval was used to capture the biomaterials' resolution. All biomaterials displayed biocompatibility. Strict HA biomaterials showed limited, if any, signs of biodegradation/resorption, with the biomaterial area fraction ranging from 22% to 42%. Synthetic HA/ß-TCP constructs showed limited evidence of biodegradation/erosion (biomaterial area fraction ≈30%). Mean linear defect closure in the sham-surgery control approximated 40%. Mean linear defect closure for the Bio-Oss reference control approximated 18% compared with 15-35% for the candidate biomaterials without significant differences between the controls and candidate biomaterials. None of the candidate HA biomaterials supported local bone formation/maturation beyond the native regenerative potential of this rodent model, pointing to their limitations for regenerative procedures. Biocompatibility and biomaterial dimensional stability could suggest their potential utility as long-term defect fillers.

The Effect of Germanium-Loaded Hydroxyapatite Biomaterials on Bone Marrow Mesenchymal Stem Cells Growth.

Hydroxyapatite (HA) is a hard mineral component of mineralized tissues, mainly composed of calcium and phosphate. Due to its bioavailability, HA is potentially used for the repair and regeneration of mineralized tissues. For this purpose, the properties of HA are significantly improved by adding natural and synthetic materials. In this sense, the germanium (Ge) mineral was loaded in HA biomaterial by cold isostatic pressure for the first time and characterization and biocompatibility using bone marrow mesenchymal stem cells (BM-MSCs) were investigated. The addition of Ge at 5% improved the solubility (3.32%), stiffness (18.34 MPa), water holding (31.27%) and biodegradation (21.87%) properties of HA, compared to control. Compared to all composite biomaterials, the drug-releasing behavior of HA-3% Ge was higher at pH 1 and 3 and the maximum drug release was obtained at pH 7 and 9 with HA-5% Ge biomaterials. Among the different mediums tested, the DMEM-medium showed a higher drug release rate, especially at 60 min. HA-Ge biomaterials showed better protein adhesion and apatite layer formation, which ultimately proves the compatibility in BM-MSCs culture. Except for higher concentrations of HA (5 and 10 mg/mL), the different concentrations of Ge and HA and wells coated with 1% of HA-1% Ge had higher BM-MSCs growth than control. All these findings concluded that the fabricated HA biomaterials loaded with Ge could be the potential biomaterial for culturing mammalian cells towards mineralized tissue repair and regeneration.

Evaluation of swelling ability of scaffold combination of chitosan and hydroxypatite

Background: Tissue engineering is an important treatment strategy and used in current and future regenerative the-rapies. To achieve the success of tissue engineering, it is necessary to select a scaffold with certain characteristics. The ability to absorb water or swelling in the scaffold material is one of the properties related to architecture and cell activation. Swelling indicates the ability of the scaffold to absorb or retain water from the scaffold. The swelling ability is expected to absorb water from the surrounding tissue and have an impact on the morphology of the scaffold, espe-cially the combination of chitosan and hydroxyapatite on cell growth. Purpose: Knowing the ability of water absorption (swelling) on the scaffold combination of chitosan and hydroxyapatite for the purpose of bone tissue engineering. Method: Literature review with statistical review method that uses inclusion and exclusion criteria with article design used experimental laboratory in vitro and or experimental laboratory in vivo. Results: There are eight articles show-ing increased swelling ability and five articles showing decreased swelling ability. Conclusion: The combination of chitosan and hydroxyapatite biomaterials can increase and decrease the ability of water absorption on the scaffold so that affects the success of tissue engineering.

Uji Sitotoksisitas Hidroksiapatit Cangkang Telur Ayam Ras (Gallus gallus) terhadap Sel Fibroblas Ligamen Periodontal Manusia

Periodontitis is an inflammation disease of the periodontal tissues surrounding the teeth, include periodontal ligament fibroblast cell. The recently researches developed tissue engineering concept to accelerate regeneration and proliferation periodontal ligament cells. One of the major components of tissue engineering is scaffold. The hydroxyapatite is biomaterial that can be used as scaffold. The egg shell has the potential biowaste to be a source of hydroxyapatite biomaterial. Before being applied as a scaffold in the medical field, cytotoxicity testing needs to be done. This study aimed to examine toxicity effect of egg shell hydroxyapatite in various concentration toward human periodontal ligament fibroblast cells. This study used human periodontal ligament fibroblast primary cells (5x103) in microplate 96 wells which divided into 7 groups, control cells, control media without cells and the treatment groups with concentration egg shell hydroxyapatite100 μg/ml, 75 μg/ml, 50 μg/ml, 25 μg/ml dan 25 μg/ml and incubated for 24 hours. Cytotoxicity test was conducted using MTT assay. Optical density values describe the viability of living cells and the readings were done using ELISA readers, subsequently the data were analyzed using One way ANOVA. The number of human periodontal ligament cells at all concentration showed that the percentage of cell life is more than 90%. Egg shell hydroxyapatite at all concentrations tested is not toxic toward human periodontal ligament fibroblas cells.

Synthesis and Characterization of Biodegradable and Cytocompatible Polyurethane-Egg Shell Derived Hydroxyapatite Biomaterials

Synthesis and Characterization of Biodegradable and Cytocompatible Polyurethane-Egg Shell Derived Hydroxyapatite Biomaterials

Spectral analysis and biological activity assessment of silver doped hydroxyapatite

ABSTRACT In this study, the hydroxyapatite biomaterials are produced by the precipitation method and the role of silver doping within the different molar ratios of 2.0, 5.0, and 10.0% are investigated with some fundamental analysis, including powder XRD, SEM, EDS, FTIR, Raman, and material densities. In vitro biocompatibility assessment is conducted with cytotoxicity and agar diffusion tests. Moreover, genotoxicity tests determine whether the biomaterials produced cause the mutations or not. In addition, a hemolytic effect test examines the variation of hemolytic behavior of compounds. Also, the cell migration experiments inspect the influence of silver ion levels in biomaterials on many biological processes. The experimental results reveal that the honeycomb-patterned morphological structures are obtained for all the products. FTIR and Raman analyses reveal that the dramatic changes in the characteristic functional group peaks are obtained with the increment in the amount of silver ions. The experimental parts related to the biocompatibility assessment of the study show that there seems to be deterioration in biocompatibility as the silver ion-doping level increases in the system. To sum up, the ideal doping value for bone tissue engineering applications is found to be 2%.

Defect Induced Charge Redistribution and Enhanced Adsorption of Lysozyme on Hydroxyapatite for Efficient Antibacterial Activity.

Defects in hydroxyapatite (HA) have attracted increasing research interest due to their significant functions to increase the bioactivity and antibacterial ability of hard-tissue implants. However, little is known about the natural property and functional mechanism of the defects in HA. Herein, we reported on the defect property concerned with the coordination state and charge distribution in Al doped HA, as well as the consequent interface and protein capture ability for improved antibacterial activity. Systemic investigations suggested that Al replacing Ca in HA induced coordination defect with decreased coordination number and bond distance, caused charge transfer and redistribution of surrounding O atom and resulted in an increase in negative charge of coordinated O atoms. These O atoms coordinated with Al further served as docking sites for lysozyme molecules via electrostatic and H-bonding interaction. The capacity of lysozyme adsorption for Al-HA increased approximately 10-fold more than that of HA, which significantly increased the antibacterial activity through lysozyme-catalyzed splitting of cell wall of bacteria. Moreover, in vitro studies indicated that Al-HA materials showed good cytocompatibility. These findings not only provided new insights into the important effect of defects on the performances of HA biomaterials by modulation of the coordination state, charge distribution, and chemical activity, but also proposed a promising method for efficient antibacterial activity of HA biomaterials.

Synthesis and characterization of biodegradable and cytocompatible polyurethane-bovine-derived hydroxyapatite biomaterials

Polyurethane (PUR) is a well-established biocompatible material intended to augment the body regenerations. To enhance the compatibility, PUR was combined with bovine hydroxyapatite (BHA) extracted from waste bones. The HA consider as a chief bone mineral to maintain the rigidity of the structure. The PUR was synthesized by prepolymer process and mixed with BHA (5% and 10%) by solvent casting technique. The synthesis of PUR and composites was confirmed by characteristic bands from FTIR spectra. The crystallite size of BHA was 465A° with a hexagonal structure confirmed by XRD. Moreover, XRD supported the incorporation of BHA into PUR matrix. The thermal stability of composites was significantly enhanced by the addition of BHA into PUR. A rough morphology of composites was revealed by SEM which may support for end application. The biodegradability of composites was superior in simulated body fluid. In-vitro MTT antitumor bioassay established the cytocompatible nature of synthesized materials. The composites demonstrated enriched cell viability with an increase in the content of BHA. Hence, these results suggested a green and economic approach for synthesis of biodegradable and cytocompatible materials for tissue regeneration.

Chitosan and Hydroxyapatite Based Biomaterials to Circumvent Periprosthetic Joint Infections.

Every year, worldwide, millions of people suffering from joint pain undergo joint replacement. For most patients, joint arthroplasty reduces pain and improve function, though a small fraction will experience implant failure. One of the main reasons includes prosthetic joint infection (PJI), involving the prosthesis and adjacent tissues. Few microorganisms (MO) are required to inoculate the implant, resulting in the formation of a biofilm on its surface. Standard treatment includes not only removal of the infected prosthesis but also the elimination of necrotic bone fragments, local and/or systemic administration of antibiotics, and revision arthroplasty with a new prosthesis, immediately after the infection is cleared. Therefore, an alternative to the conventional therapeutics would be the incorporation of natural antimicrobial compounds into the prosthesis. Chitosan (Ch) is a potential valuable biomaterial presenting properties such as biocompatibility, biodegradability, low immunogenicity, wound healing ability, antimicrobial activity, and anti-inflammatory potential. Regarding its antimicrobial activity, Gram-negative and Gram-positive bacteria, as well as fungi are highly susceptible to chitosan. Calcium phosphate (CaP)-based materials are commonly utilized in orthopedic and dentistry for their excellent biocompatibility and bioactivity, particularly in the establishment of cohesive bone bonding that yields effective and rapid osteointegration. At present, the majority of CaP-based materials are synthetic, which conducts to the depletion of the natural resources of phosphorous in the future due to the extensive use of phosphate. CaP in the form of hydroxyapatite (HAp) may be extracted from natural sources as fish bones or scales, which are by-products of the fish food industry. Thus, this review aims to enlighten the fundamental characteristics of Ch and HAp biomaterials which makes them attractive to PJI prevention and bone regeneration, summarizing relevant studies with these biomaterials to the field.

Physicochemical changes of the chitosan/β-1,3-glucan/hydroxyapatite biocomposite caused by mesenchymal stem cells cultured on its surface in vitro

In the present study structural characteristics and physicochemical properties of tri-component biomaterial (consisting of chitosan, β-1,3-glucan and hydroxyapatite) seeded with mesenchymal stem cells were investigated with the use of diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). In this study we use non-conventional approach of DRIFT spectroscopy for investigating biomaterial changes under simulated physiological conditions. Particular cell-induced changes were intended to be properly evaluated with analytical methods. Abovementioned techniques allowed to precisely assess the changes on the surface of the biomaterial caused by two kinds of stem cells (ADSCs – Adipose tissue-Derived Stem Cells and BMDSCs – Bone Marrow-Derived Stem Cells) cultured directly on the surface of bioceramic-based biomaterial. The bioactivity and biocompatibility of designed bone biomaterial were demonstrated and hence it seems to be a promising scaffold used in tissue engineering. Designed chitosan, β-1,3-glucan, and hydroxyapatite biomaterial was proven to be non-toxic, surgically handy with cellular compatibility. The obtained results are interesting and promising in terms of spectroscopic methods suitability for qualitative assessment of material-cell interactions.

Efficient antibacterial activity of hydroxyapatite through ROS generation motivated by trace Mn(iii) coupled H vacancies.

Hydroxyapatite (HA) has attracted wide attention for medical application due to its biocompatibility and bioactivity. However, the infection problems of HA remain among the leading reasons for implantation failure. Thus, it is urgent to endow HA biomaterials with antibacterial activity. Herein, the high antibacterial activity was achieved by introducing trace Mn3+ and H vacancy couples in HA through a facile heat-treatment strategy in air. The theoretical results indicated that Mn3+ was preferentially substituted for the Ca(2) site in the HA structure with a charge-compensating H vacancy appearing at the adjacent OH- site. The antibacterial tests showed that Mn-HA possessed antibacterial activity towards both E. coli and S. aureus with trace Mn content at the ppm level, and implied that Mn3+ and centers may play an important role in the antibacterial process. The Mn3+ and couples in Mn-HA, serving as oxidative and reductive centers respectively, could then collectively participate in the CoQ/CoQH2 redox cycling and synergistically facilitate the accumulation of CoQ˙- and ROS radicals. This enhanced ROS production was the main factor to endow Mn-HA with efficient antibacterial activity. Moreover, the in vitro bioactivity assay showed that Mn-HA materials exhibited enhanced osteogenic activity and good biocompatibility. Therefore, this work not only provides a feasible method to control the oxidation state of Mn elements in HA, but also proposes a novel trace Mn3+-doped HA for potential applications in tissue engineering.

Design of hydroxyapatite bioceramics with micro-/nano-topographies to regulate the osteogenic activities of bone morphogenetic protein-2 and bone marrow stromal cells.

Biomimicking the nanostructure of natural bone apatite to enhance the bioactivity of hydroxyapatite (HA) biomaterials is an eternal topic in the bone regeneration field. In the present study, we designed four kinds of HA bioceramics with micro- to nanosized grains and investigated the effects of bioceramic topographies on the structures of bone morphogenetic protein-2 (BMP-2) and the effects on the responses of bone marrow stromal cells (BMSCs). Compared to the samples with submicron-scale crystalline particles, HA bioceramics with grain sizes of 104.6 ± 27.8 nm exhibited increased roughness, improved hydrophilicity and enhanced mechanical properties. The synergistic effects of these surface characteristics could well maintain the conformation of BMP-2, facilitate cell adhesion and spreading, and activate the osteogenic differentiation of BMSCs. Furthermore, SBF immersion and in vivo canine intramuscular implantation confirmed that the HA bioceramics with nanotopography also processed excellent bone-like apatite forming ability and outstanding osteoinductivity. In summary, these findings suggest that the nanotopography of HA bioceramics is a critical factor to enhance their bioactivity and osteoinductivity.