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1.
Int J Nanomedicine ; 19: 4515-4531, 2024.
Article En | MEDLINE | ID: mdl-38803996

Introduction: There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth. Methods: A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca2+, P2+, and Sr2+ ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag2+ ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen. Results: The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity. Discussion: In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag2+ ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties.


Acetabulum , Anti-Bacterial Agents , Silver , Strontium , Titanium , Titanium/chemistry , Titanium/pharmacology , Silver/chemistry , Silver/pharmacology , Strontium/chemistry , Strontium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Acetabulum/injuries , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Osseointegration/drug effects , Mice , Surface Properties , Fractures, Bone/therapy , Durapatite/chemistry , Durapatite/pharmacology , Osteoblasts/drug effects , Hydroxyapatites/chemistry , Hydroxyapatites/pharmacology , Prostheses and Implants , Ions/chemistry , Ions/pharmacology , Humans , Cell Line
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124289, 2024 Aug 05.
Article En | MEDLINE | ID: mdl-38692101

Biphasic calcium phosphate (BCP), consisting of bioceramics such as HAp + ß-TCP and Ca10(PO4)6(OH)2 + Ca3(PO4)2, is a popular choice for optimizing performance due to its superior biological reabsorption and osseointegration. In this study, BCP was produced by calcining the bones of tilapia fish (Oreochromis niloticus) reared in net cages and slaughtered at an age ranging from 15 to 420 days. The bones were cleaned and dried, calcined at 900 °C for 8 h, and then subjected to high-energy grinding for 3 h to produce BCP powders. After the calcination process, the crystalline phase's hydroxyapatite (HAp) and/or beta-tricalcium phosphate (ß-TCP) were present in the composition of the bioceramic. The age-dependent variation in phase composition was confirmed by complementary vibrational spectroscopy techniques, revealing characteristic peaks and bands of the bioceramic. This variation was marked by an increase in HAp phase and a decrease in ß-TCP phase. Thermogravimetric Analysis (TGA) and Differential Thermal Analysis (DTA) from 25 to 1400 °C showed the characteristic mass losses of the material, with a greater loss observed for younger fish, indicating the complete removal of organic components at temperatures above 600 °C. Comparison of the results obtained by X-Ray Diffraction (XRD) and Rietveld refinement with Raman spectroscopy showed excellent agreement. These results showed that with temperature and environment control and adequate fish feeding, it is possible to achieve the desired amounts of each phase by choosing the ideal age of the fish. This bioceramic enables precise measurement of HAp and ß-TCP concentrations and Ca/P molar ratio, suitable for medical orthopedics and dentistry.


Bone and Bones , Ceramics , Spectrum Analysis, Raman , Animals , Ceramics/chemistry , Bone and Bones/chemistry , Tilapia/metabolism , X-Ray Diffraction , Hydroxyapatites/chemistry , Spectroscopy, Fourier Transform Infrared , Calcium Phosphates/chemistry , Thermogravimetry
3.
Biomed Mater ; 19(4)2024 Jun 11.
Article En | MEDLINE | ID: mdl-38815599

Literature on osteoimmunology has demonstrated that macrophages have a great influence on biomaterial-induced bone formation. However, there are almost no reports clarifying the osteo-immunomodulatory capacity of macrophage-derived extracellular vesicles (EVs). This study comprehensively investigated the effects of EVs derived from macrophages treated with biphasic calcium phosphate (BCP) ceramics (BEVs) on vital events associated with BCP-induced bone formation such as immune response, angiogenesis, and osteogenesis. It was found that compared with EVs derived from macrophages alone (control, CEVs), BEVs preferentially promoted macrophage polarization towards a wound-healing M2 phenotype, enhanced migration, angiogenic differentiation, and tube formation of human umbilical vein endothelial cells, and induced osteogenic differentiation of mesenchymal stem cells. Analysis of 15 differentially expressed microRNAs (DEMs) related to immune, angiogenesis, and osteogenesis suggested that BEVs exhibited good immunomodulatory, pro-angiogenic, and pro-osteogenic abilities, which might be attributed to their specific miRNA cargos. These findings not only deepen our understanding of biomaterial-mediated osteoinduction, but also suggest that EVs derived from biomaterial-treated macrophages hold great promise as therapeutic agents with desired immunomodulatory capacity for bone regeneration.


Bone Regeneration , Cell Differentiation , Ceramics , Extracellular Vesicles , Human Umbilical Vein Endothelial Cells , Macrophages , Mesenchymal Stem Cells , MicroRNAs , Osteogenesis , Bone Regeneration/drug effects , Extracellular Vesicles/metabolism , Humans , Macrophages/metabolism , Macrophages/drug effects , Osteogenesis/drug effects , Ceramics/chemistry , Ceramics/pharmacology , MicroRNAs/metabolism , Animals , Cell Differentiation/drug effects , Mice , Mesenchymal Stem Cells/cytology , RAW 264.7 Cells , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Hydroxyapatites/chemistry , Hydroxyapatites/pharmacology , Neovascularization, Physiologic/drug effects , Cell Movement/drug effects
4.
Colloids Surf B Biointerfaces ; 238: 113880, 2024 Jun.
Article En | MEDLINE | ID: mdl-38581836

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.


Alloys , Calcium , Magnesium , Zinc , Alloys/chemistry , Alloys/pharmacology , Corrosion , Animals , Zinc/chemistry , Zinc/pharmacology , Magnesium/chemistry , Mice , Calcium/chemistry , Calcium/metabolism , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Surface Properties , Materials Testing , Cell Proliferation/drug effects , Hydroxyapatites/chemistry , Cell Line , Durapatite/chemistry , Durapatite/pharmacology
5.
ACS Appl Mater Interfaces ; 16(13): 15687-15700, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38511302

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.


Integrins , Osteogenesis , Cytokines , Angiogenesis , Endothelial Cells , Hydroxyapatites/chemistry , Strontium/pharmacology , Strontium/chemistry , Signal Transduction , Ions/pharmacology
6.
Molecules ; 29(3)2024 Jan 31.
Article En | MEDLINE | ID: mdl-38338415

Tissue engineering is an interdisciplinary field of science that has been developing very intensively over the last dozen or so years. New ways of treating damaged tissues and organs are constantly being sought. A variety of porous structures are currently being investigated to support cell adhesion, differentiation, and proliferation. The selection of an appropriate biomaterial on which a patient's new tissue will develop is one of the key issues when designing a modern tissue scaffold and the associated treatment process. Among the numerous groups of biomaterials used to produce three-dimensional structures, hydroxyapatite (HA) deserves special attention. The aim of this paper was to discuss changes in the double electrical layer in hydroxyapatite with an incorporated boron and strontium/electrolyte solution interface. The adsorbents were prepared via dry and wet precipitation and low-temperature nitrogen adsorption and desorption methods. The specific surface area was characterized, and the surface charge density and zeta potential were discussed.


Boron , Hydroxyapatites , Humans , Hydroxyapatites/chemistry , Tissue Scaffolds/chemistry , Durapatite , Biocompatible Materials/chemistry , Strontium/chemistry , Surface Properties
7.
J Mech Behav Biomed Mater ; 151: 106385, 2024 Mar.
Article En | MEDLINE | ID: mdl-38246094

Porous biphasic calcium phosphate (BCP) ceramics are widely used in bone tissue engineering, and the mechanical properties of BCP implants must be reliable. However, the effects of pore structure (e.g., shape and size) on the mechanical properties are not well understood. In this study, we used molecular dynamics simulations to investigate the influence of pore shape and size on the mechanical behavior of BCP nanoparticles. BCP void models with cylindrical and cuboid pores ranging from 2 to 16 nm in diameter were constructed, and the elastic moduli were calculated. In addition, uniaxial tensile and compressive tests were performed on the models. We found that the pore size had a more significant impact on the mechanical properties of BCP than pore shape. Further, the elastic moduli decreased nonlinearly with increasing pore size. In addition, the tensile and compressive strength also decreased with the increase in pore size, but the ductility improved. Furthermore, deformation and fracture were more likely to occur near the pores and at the phase interfaces as a result of high atomic local strain in the calcium-deficient hydroxyapatite area. The results of this work reveal the effects of pore parameters on the mechanical properties of porous BCP at the nanometer level, which may aid the design of improved porous and multiphase CaP-based biomaterials for bone regeneration.


Molecular Dynamics Simulation , Nanoparticles , Calcium Phosphates/chemistry , Hydroxyapatites/chemistry , Durapatite/chemistry , Porosity , Nanoparticles/chemistry
8.
Int J Dev Biol ; 67(4): 137-146, 2023.
Article En | MEDLINE | ID: mdl-37975329

For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown that strontium (Sr) can safely and effectively help prevent and treat bone diseases, including osteoporosis. These findings have resulted in the concept of integrating Sr and HA for bone disease management. The doped Sr can improve the physicochemical properties of HA and enhance its angiogenic and bone regeneration ability. Nevertheless, no study has reviewed the design strategy of Sr-doped HA (Sr-HA) to understand its biological roles. Therefore, in this article, we review recent developments in Sr-HA preparation and its effect on osteogenesis and angiogenesis in vitro and in vivo along with key suggestions for future research and development.


Angiogenesis , Osteogenesis , Humans , Hydroxyapatites/chemistry , Hydroxyapatites/pharmacology , Durapatite/chemistry , Durapatite/pharmacology , Strontium/pharmacology , Strontium/chemistry
9.
Int J Biol Macromol ; 252: 126478, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-37625758

The objective of this study is to explore the potential role of alginate (Alg) in the crystallization of metal-substituted hydroxyapatite, with application in orthopaedic reconstruction. The alginate at different concentrations (0.5 and 1.0 wt%) facilitated in situ mineralization of hydroxyapatite (HA) and strontium-substituted HA (SHA, 10 and 30 mol%). The incorporation of the biopolymer and dopant induced notable changes in HA, including reduced crystal size from 31.0 to 16.4 nm and increased lattice volume from 577.3 to 598.0 Å3. The superior affinity of alginate for Sr2+ than for Ca2+ resulted in higher residual alginate in Alg/SHA (13.0 to 19.0 %) compared to Alg/HA (7.1 to 8.2 %). This residual alginate influenced composite properties: surface charge decreased from -26.5 to -45.7 mV, microhardness increased from 0.33 to 0.54 GPa, and dissolution increased from 0.17 to 0.39 %. The in vitro studies revealed that strontium substitution as well as the organization and crystallographic aspects of apatite regulated osteoblastic cell survival, proliferation, differentiation, and biomineralization. The findings suggest that an alginate concentration of 0.5 wt% is optimal for the crystallization of SHA with 10 mol% substitution, and its resulting composite possesses the ideal biomechanical properties to imitate native bone.


Durapatite , Hydroxyapatites , Hydroxyapatites/chemistry , Durapatite/chemistry , Strontium/chemistry , Alginates
10.
Int J Biol Macromol ; 248: 125927, 2023 Sep 01.
Article En | MEDLINE | ID: mdl-37481177

The influence of carbohydrates on the crystallization of metal-substituted hydroxyapatite predicts its relevance to natural bone growth. This study demonstrates the role of carbohydrates in the crystallization of strontium-substituted hydroxyapatite (SHAP). The increasing order of hydroxyl groups, dextrose (monosaccharide) < maltose (disaccharide) < starch (polysaccharide), coordinated with Ca2+/Sr2+ and thus guided SHAP crystallization, with crystal size reduced from 35 to 19 nm, lattice volume increased from 518 to 537 Å3, and residual carbohydrates increased from 1.8 to 20.2 %. The variation in residual carbohydrates is due to their interaction with apatite and/or aqueous insolubility. Compared to pure SHAP, the starch-SHAP with higher residual starch showed increased water uptake from 1.23 ± 0.18 to 4.26 ± 0.21 % and degradation from 0.22 ± 0.06 to 1.53 ± 0.14 %, but decreased microhardness from 0.73 ± 0.12 to 0.38 ± 0.01 GPa and protein affinity from 4.82 ± 0.01 to 0.81 ± 0.01 µg/mg. However, its microhardness value was bone-like, and the reduced protein adsorption was masked by the rich osteogenic behaviour. In vitro cellular response demonstrated that the residual carbohydrate and strontium augmented osteocompatibility, proliferation, differentiation and biomineralization. The result concludes that carbohydrates drive SHAP crystallization, and starch-SHAP replicates natural bone.


Maltose , Tissue Engineering , Starch , Crystallization , Hydroxyapatites/chemistry , Durapatite/chemistry , Strontium/chemistry , Glucose
11.
BMC Microbiol ; 23(1): 193, 2023 07 18.
Article En | MEDLINE | ID: mdl-37464289

BACKGROUND: Hydroxyapatites (HAp) are widely used as medical preparations for e.g., bone replacement or teeth implants. Incorporation of various substrates into HAp structures could enhance its biological properties, like biocompatibility or antimicrobial effects. Silver ions possess high antibacterial and antifungal activity and its application as HAp dopant might increase its clinical value. RESULTS: New silicate-substituted hydroxyapatites (HAp) doped with silver ions were synthesized via hydrothermal methods. The crystal structure of HAp was investigated by using the X-ray powder diffraction. Antifungal activity of silver ion-doped HAp (with 0.7 mol%, 1 mol% and 2 mol% of dopants) was tested against the yeast-like reference and clinical strains of Candida albicans, C. glabrata, C. tropicalis, Rhodotorula rubra, R. mucilaginosa, Cryptococcus neoformans and C. gattii. Spectrophotometric method was used to evaluate antifungal effect of HAp in SD medium. It was shown that already the lowest dopant (0.7 mol% of Ag+ ions) significantly reduced fungal growth at the concentration of 100 µg/mL. Increase in the dopant content and the concentration of HAp did not cause further growth inhibition. Moreover, there were some differences at the tolerance level to Ag+ ion-doped HAp among tested strains, suggesting strain-specific activity. CONCLUSIONS: Preformed studies confirm antimicrobial potential of hydroxyapatite doped with silver. New Ag+ ion-HAp material could be, after further studies, considered as medical agent with antifungal properties which lower the risk of a surgical-related infections.


Anti-Infective Agents , Durapatite , Durapatite/chemistry , Durapatite/pharmacology , Antifungal Agents/pharmacology , Silver/pharmacology , Silver/chemistry , Hydroxyapatites/chemistry , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Ions
12.
J Mater Sci Mater Med ; 34(6): 27, 2023 May 19.
Article En | MEDLINE | ID: mdl-37204535

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.


Bone Substitutes , Hydroxyapatites , Animals , Dogs , Bone Regeneration , Bone Substitutes/chemistry , Calcium Phosphates/chemistry , Hydroxyapatites/chemistry , Mandible/surgery
13.
Int J Mol Sci ; 24(6)2023 Mar 12.
Article En | MEDLINE | ID: mdl-36982504

The reconstruction of bones following tumor excision and radiotherapy remains a challenge. Our previous study, performed using polysaccharide-based microbeads that contain hydroxyapatite, found that these have osteoconductivity and osteoinductive properties. New formulations of composite microbeads containing HA particles doped with strontium (Sr) at 8 or 50% were developed to improve their biological performance and were evaluated in ectopic sites. In the current research, we characterized the materials by phase-contrast microscopy, laser dynamic scattering particle size-measurements and phosphorus content, before their implantation into two different preclinical bone defect models in rats: the femoral condyle and the segmental bone. Eight weeks after the implantation in the femoral condyle, the histology and immunohistochemistry analyses showed that Sr-doped matrices at both 8% and 50% stimulate bone formation and vascularization. A more complex preclinical model of the irradiation procedure was then developed in rats within a critical-size bone segmental defect. In the non-irradiated sites, no significant differences between the non-doped and Sr-doped microbeads were observed in the bone regeneration. Interestingly, the Sr-doped microbeads at the 8% level of substitution outperformed the vascularization process by increasing new vessel formation in the irradiated sites. These results showed that the inclusion of strontium in the matrix-stimulated vascularization in a critical-size model of bone tissue regeneration after irradiation.


Bone Regeneration , Polymers , Rats , Animals , Hydroxyapatites/chemistry , Osteogenesis , Strontium/chemistry
14.
Biomed Mater ; 18(2)2023 02 28.
Article En | MEDLINE | ID: mdl-36805546

Strontium is a kind of element which can promote the increase of bone density and benefit the growth of bone tissue. This study combined strontium hydroxyapatite (Sr-HAp) with magnesium oxychloride cement (MOC) to prepare a bioactive material with good osteogenic activity and degradability. The results revealed that the incorporation of 10 wt.% Sr-HAp densified the structure of MOC, slowed down the degradation rate of hydration product phase 5 in water, and enhanced the water resistance of MOC. After soaking for 28 days, the compressive strength of Sr-HAp/MOC decreased by 53%, which was lower than that of MOC (93%) and HAp/MOC (61%) without adding Sr-HAp. During the degradation processin vitro, Sr-HAp/MOC continuously released Sr2+and the cumulative concentration of Sr2+releasedin vitroafter seven days of immersion was 1.27 ± 0.15 ppm. When Sr-HAp/MOC was soaking in simulated body fluid, Sr-HAp induced the growth and deposition of bone-like component hydroxyapatite crystals on MOC's surface, improving MOC's bioactivity. After implantation of femur defect in rats, the new bone tissue grew from outside to inside around Sr-HAp/MOC, which showed Sr-HAp/MOC had better osteogenic activity. MOC was containing 10 wt.% Sr-HAp can not only provide strong support for bone defects but also have the potential to promote bone regeneration.


Hydroxyapatites , Magnesium , Rats , Animals , Materials Testing , Hydroxyapatites/chemistry , Osteogenesis , Strontium/chemistry , Bone Cements/chemistry , Water
15.
J Biomed Mater Res B Appl Biomater ; 111(6): 1207-1223, 2023 06.
Article En | MEDLINE | ID: mdl-36718607

Cuttlebone (CB) is a marine waste-derived biomaterial and a rich source of calcium carbonate for the biosynthesis of the calcium phosphate (CaP) particles. The current study aimed to synthesize CB derived biphasic calcium phosphate (CB-BCP) and investigate biological activity of the CB-CaP: hydroxyapatite (CB-HA), beta-tricalcium phosphate (CB-b-TCP) and biphasic 60:40 (w/w) HA/b-TCP (CB-BCP) with the human dental pulp stem cells (hDPSCs). The particles were synthesized using solid state reactions under mild condition and properties of the particles were compared with a commercial BCP as a reference material. Morphology, particle size, physicochemical properties, mineral contents, and the ion released patterns of the particles were examined. Then the particle/cell interaction, cell cytotoxicity and osteogenic property of the particles were investigated in the direct and indirect cell culture models. It was found that an average particles size of the CB-HA was 304.73 ± 4.19 nm, CB-b-TCP, 503.17 ± 23.06 nm and CB-BCP, 1394.67 ± 168.19 nm. The physicochemical characteristics of the CB-CaP were consistent with the HA, b-TCP and BCP. The highest level of calcium (Ca) was found in the mineral contents and the preincubated medium of the CB-BCP and traces of fluoride, magnesium, strontium, and zinc were identified in the CB-CaP. The cell cytotoxicity and osteogenic property of the particles were dose dependent. The particles adhered on cell surface and were internalized into the cell cytoplasm. The CB-BCP and CB-HA indirectly and directly promote osteoblastic differentiations of the hDPSCs in stronger levels than other groups. The CB-BCP and CB-HA were potential bioactive bone substitute materials.


Bone Substitutes , Humans , Bone Substitutes/pharmacology , Bone Substitutes/chemistry , Hydroxyapatites/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Durapatite/chemistry , Calcium Phosphates/pharmacology , Calcium Phosphates/chemistry
16.
J Phys Chem B ; 126(46): 9726-9736, 2022 11 24.
Article En | MEDLINE | ID: mdl-36378585

Biphasic calcium phosphate (BCP) is used as a bone substitute and bone tissue repair material due to its better control over bioactivity and biodegradability. It is crucial to stabilize the implanted biomaterial while promoting bone ingrowth. However, a lack of standard experimental and theoretical protocols to characterize the physicochemical properties of BCP limits the optimization of its composition and properties. Computational simulations can help us better to learn BCP at a nanoscale level. Here, the Voronoi tessellation method was combined with simulated annealing molecular dynamics to construct BCP nanoparticle models of different sizes, which were used to understand the physicochemical properties of BCP (e.g., melting point, infrared spectrum, and mechanical properties). We observed a ∼20 to 30 Å layer of calcium-deficient hydroxyapatite at the HAP/ß-TCP interface due to particle migration, which may contribute to BCP stability. The BCP model may stimulate further research into BCP ceramics and multiphasic ceramics. Moreover, our study may facilitate the optimization of compositions of BCP-based biomaterials.


Molecular Dynamics Simulation , Nanoparticles , Biomimetics , Hydroxyapatites/chemistry , Calcium Phosphates/chemistry , Durapatite/chemistry , Ceramics/chemistry , Biocompatible Materials/chemistry , Nanoparticles/chemistry
17.
ACS Appl Mater Interfaces ; 14(42): 47491-47506, 2022 Oct 26.
Article En | MEDLINE | ID: mdl-36251859

Adequate new bone regeneration in bone defects has always been a challenge as it requires excellent and efficient osteogenesis. Calcium phosphate (CaP) bioceramics, including hydroxyapatite (HA) and biphasic calcium phosphates (BCPs), have been extensively used in clinical bone defect filling due to their good osteoinductivity and biodegradability. Here, for the first time, we designed and fabricated two porous CaP bioceramic granules with core-shell structures, named in accordance with their composition as BCP@HA and HA@BCP (core@shell). The spherical shape and the porous structure of these granules were achieved by the calcium alginate gel molding technology combined with a H2O2 foaming process. These granules could be stacked to build a porous structure with a porosity of 65-70% and a micropore size distribution between 150 and 450 µm, which is reported to be good for new bone ingrowth. In vitro experiments confirmed that HA@BCP bioceramic granules could promote the proliferation and osteogenic ability when cocultured with bone marrow mesenchymal stem cells, while inhibiting the differentiation of RAW264.7 cells into osteoclasts. In vivo, 12 weeks of implantation in a critical-sized femoral bone defect animal model showed a higher bone volume fraction and bone mineral density in the HA@BCP group than in the BCP@HA or pure HA or BCP groups. From histological analysis, we discovered that the new bone tissue in the HA@BCP group was invading from the surface to the inside of the granules, and most of the bioceramic phase was replaced by the new bone. A higher degree of vascularization at the defect region repaired by HA@BCP was revealed by 3D microvascular perfusion angiography in terms of a higher vessel volume fraction. The current study demonstrated that the core-shell structured HA@BCP bioceramic granules could be a promising candidate for bone defect repair.


Calcium Phosphates , Hydrogen Peroxide , Animals , Porosity , Calcium Phosphates/pharmacology , Calcium Phosphates/chemistry , Bone Regeneration , Hydroxyapatites/chemistry , Osteogenesis , Durapatite/pharmacology , Durapatite/chemistry , Alginates
18.
J Biomater Appl ; 37(4): 600-613, 2022 Oct.
Article En | MEDLINE | ID: mdl-35775433

Many studies have reported on the conversion of natural resources into xenografts with hydroxyapatite (HA) as major component, but the extraction of biphasic calcium phosphate (HA/ß-TCP) from animal bones and transformation into bone graft substitutes are rarely reported. In this research, two kinds of fish bones were made into granular porous biphasic calcium phosphate bone graft substitutes with particle sizes between 500 to 1000 µm through a series of preparation procedures (Salmo salar calcined at 900°C named Sa900 and Anoplopoma fimbria calcined at 800°C named An800). The chemical composition was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The morphology and porous structure of the scaffolds were comparatively analyzed by scanning electron microscopy (SEM) and mercury porosimeter. The specific surface area of materials was measured by the nitrogen adsorption technique based on BET theory. Cytotoxicity and ectopic osteogenesis were also carried out to investigate the biocompatibility and osteoinductive potential of these materials. The results showed that both fishbone-derived scaffolds were composed of HA and ß-TCP with different proportions, and numerous interconnected pores with different sizes were observed at the surface of materials. An800 had higher total porosity reaching 74.8% with higher interconnectivity and micropores mostly distributed at 0.27 µm and 0.12 µm, while Sa900 had a higher specific surface area and higher intraparticle porosity with nanopores mostly distributed at 0.07 µm. CCK-8 assays and Live/dead staining demonstrated excellent biocompatibility. Material-induced osteoid formation were observed on the interface of both internal pores and periphery of materials after implantation in muscle pouch of Wistar rats for 8 weeks which indicated some extent of osteoinductive potential of materials. The possible mechanism of material-induced osteogenesis and the effects of chemical composition, surface topography, and spatial structure on osteogenesis were also discussed in this paper.


Bone Substitutes , Mercury , Animals , Bone Substitutes/chemistry , Calcium Phosphates/chemistry , Durapatite/chemistry , Humans , Hydroxyapatites/chemistry , Mercury/pharmacology , Nitrogen , Osteogenesis , Porosity , Rats , Rats, Wistar
19.
Macromol Biosci ; 22(8): e2200092, 2022 08.
Article En | MEDLINE | ID: mdl-35645042

Poly(lactic-co-glycolic acid) (PLGA)-based porous structures have a widespread application in bone defects. To solve its flaws in the bone application, hydroxyapatite (HA) is often introduced into PLGA-based systems, and ion doping endows HA with more biological activity. In osteoporotic bone defects, the decreased activity of osteoblasts and the hyperactive osteoclasts results in slow bone repair. Strontium (Sr) can promote bone regeneration and inhibit bone resorption and has been used in the treatment of osteoporosis. Magnesium (Mg) cannot only enhance the regeneration of bone tissue but also vessels. In this study,the aim is to fabricate a multifunctional porous structure that can promote osteogenesis, and angiogenesis and inhibit osteoclasts for repairing osteoporotic bone defects. PLGA cage-like structures loaded with Sr- and Mg-doped HA (Sr/Mg@HA/PLGA-CAS) are prepared; they have large pores, suitable hydrophilicity, and can continuously release Mg2+ and Sr2+ , which facilitate cell adhesion and growth. The results show that Sr/Mg@HA/PLGA-CAS can motivate the osteogenic activity of osteoblast precursor cells and angiogenic ability of endothelial cells, and suppress osteoclast differentiation in vitro. This study indicates that Sr/Mg@HA/PLGA-CAS can assist osteogenesis, and angiogenesis while restraining osteoclast differentiation, which may have a potential application value in osteoporotic bone defects.


Magnesium , Osteoporosis , Bone Regeneration , Durapatite/chemistry , Durapatite/pharmacology , Endothelial Cells , Humans , Hydroxyapatites/chemistry , Magnesium/pharmacology , Osteogenesis , Osteoporosis/drug therapy , Strontium/chemistry , Strontium/pharmacology , Tissue Scaffolds/chemistry
20.
Colloids Surf B Biointerfaces ; 217: 112620, 2022 Sep.
Article En | MEDLINE | ID: mdl-35738077

Three luminescent Eu-containing phosphate materials (Ca-doped europium phosphate monohydrate, Eu-doped carbonated-apatite, and europium phosphate monohydrate) were prepared and analyzed on the level of bulk structure and surface properties and compared to the biomimetic non-luminescent counterpart hydroxyapatite. Europium-containing phosphate materials exhibited nanosized dimensions but different luminescence emissions and luminescence lifetimes depending on their crystalline structures (i.e., lanthanide phosphate or apatites) and chemical composition. The introduction of Eu in the crystal lattice leads to a notable decrease in the overall Lewis acidity of the surface cationic sites detected by CO probing. Further, the mixed Eu/Ca-containing materials surfaces were found to be very similar to the reference hydroxyapatite in terms of water adsorption energy, while the pure europium phosphate resulted to have the notably higher energy values of direct interaction of water molecules with the surface cations with no detected propagation of this effect towards water overlayers.


Europium , Luminescence , Europium/chemistry , Hydroxyapatites/chemistry , Luminescent Measurements , Phosphates , Water
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