Strontium-substituted Hydroxyapatite Research Articles

On the Ion Implantation Synthesis of Ag-Embedded Over Sr-Substituted Hydroxyapatite on a Nano-Topography Patterned Ti for Application in Acetabular Fracture Sites.

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. 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. 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. 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.

Effects of Sr and Mg doping on elastic, mechanical, and optical properties of hydroxyapatite: A first-principles study

Hydroxyapatite (HAp), with the chemical formula Ca10(PO4)6(OH)2, is a bioactive ceramic material typically used in the treatment of bone defects owing to the excellent biocompatibility and the ability to bond with bone tissues. Mechanical properties of HAp have drawn pronounced attention because of the crucial roles in the medical applications. Based on density functional theory (DFT), this work reports the structural, formation energy, mechanical, Vickers hardness, electronic properties, and optical properties of hydroxyapatite (HAp), strontium-substituted HAp (Sr-HAp), and magnesium-substituted HAp (Mg-HAp). The results reveal that the Sr2+ and Mg2+ ions mainly replace the Ca2+ ion at the Ca-1 site in HAp. Resistance to hydrostatic compression followed the order Mg-HAp > HAp > Sr-HAp. Sr-HAp has the capability to enhance thermal shock resistance and lattice thermal conductivity. In addition, the electronic properties of HAp change upon substitutional Sr2+ and Mg2+ doping. In comparison with pristine HAp, the energy gap of Sr-doped HAp relatively increases, whereas that of Mg-doped HAp decreases. Nevertheless, both Sr-HAp and Mg-HAp remain insulators. Intriguingly, Sr-HAp possesses the improved hardness by 11.31 % owing to the hybridization of the Sr (4p) and O (2p) states, which contributed to its high shear modulus and high hardness. Beyond that, we further investigate their optical properties. The presence of Mg states at approximately 10 eV in the conduction band leads to enhanced absorption within the 14 – 20 eV for Mg-doped HAp. Similarly, the presence of a deep Sr(4p) level in Sr-HAp amplifies absorption within the 20–25 eV range. These findings have raised a potential avenue for selectively boosting the optical absorption of HAp, thus improving its photocatalytic properties.

Layer by layer assembly of strontium substituted nanowire hydroxyapatite and hybrid of carbon derivatives as potential biomaterial for bone metastasis treatment

To devise a highly effective implant for addressing bone metastasis with the unique capability of self-oxygen generation, a multifunctional film was engineered using a Layer-by-Layer technique. The film, comprised of strontium-substituted hydroxyapatite nanowires (SrwHAP) and a graphitic carbon nitride/graphene oxide (g-CN/GO) hybrid, was meticulously designed. To optimize the film's interaction with mesenchymal stem cells (MSCs), the number of layers was adjusted. Subsequent surface coating involved extracellular matrix (ECM) derived from osteogenic cells. The final film, ((CN/GO). SrwHAP)2. ECM, exhibited pronounced MSC attachment and an accelerated proliferation rate. Key osteogenic markers such as alkaline phosphatase activity, mineralization, RUNX2, and osteocalcin expression remarkably increased when compared to the glass substrate. Notably, the presence of LED irradiation yielded further enhancements in proliferation and osteogenic markers, attributed to the photocatalytic properties of the (CN/GO) hybrid alongside O2 generation. Direct co-culturing of MSCs and breast cancer cells (MCF7) on its surface, coupled with LED irradiation not only bolstered the osteogenic potential of MSCs but also reduced tumor colonies over time. Impressively, ((CN/GO). SrwHAP)2. ECM also demonstrated potent antibacterial properties against Gram-positive bacteria (Staphylococcus aureus). Based on the results obtained, ((CN/GO). SrwHAP)2. ECM emerges as a promising candidate for addressing bone defects in patients afflicted by breast cancer bone metastasis.

Alginate templated synthesis, characterization and in vitro osteogenic evaluation of strontium-substituted hydroxyapatite

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.

Dextrose, maltose and starch guide crystallization of strontium-substituted hydroxyapatite: A comparative study for bone tissue engineering application

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.

Enhanced bone regeneration via local low-dose delivery of PTH1-34 in a composite hydrogel.

Introducing bone regeneration-promoting factors into scaffold materials to improve the bone induction property is crucial in the fields of bone tissue engineering and regenerative medicine. This study aimed to develop a Sr-HA/PTH1-34-loaded composite hydrogel system with high biocompatibility. Teriparatide (PTH1-34) capable of promoting bone regeneration was selected as the bioactive factor. Strontium-substituted hydroxyapatite (Sr-HA) was introduced into the system to absorb PTH1-34 to promote the bioactivity and delay the release cycle. PTH1-34-loaded Sr-HA was then mixed with the precursor solution of the hydrogel to prepare the composite hydrogel as bone-repairing material with good biocompatibility and high mechanical strength. The experiments showed that Sr-HA absorbed PTH1-34 and achieved the slow and effective release of PTH1-34. In vitro biological experiments showed that the Sr-HA/PTH1-34-loaded hydrogel system had high biocompatibility, allowing the good growth of cells on the surface. The measurement of alkaline phosphatase activity and osteogenesis gene expression demonstrated that this composite system could promote the differentiation of MC3T3-E1 cells into osteoblasts. In addition, the in vivo cranial bone defect repair experiment confirmed that this composite hydrogel could promote the regeneration of new bones. In summary, Sr-HA/PTH1-34 composite hydrogel is a highly promising bone repair material.

Enhanced tissue infiltration and bone regeneration through spatiotemporal delivery of bioactive factors from polyelectrolytes modified biomimetic scaffold.

Efficient healing of bone defect is closely associated with the structured and functional characters of tissue engineered scaffolds. However, the development of bone implants with rapid tissue ingrowth and favorable osteoinductive properties remains a challenge. Herein, we fabricated polyelectrolytes modified-biomimetic scaffold with macroporous and nanofibrous structures as well as simultaneous delivery of BMP-2 protein and trace element strontium. The hierarchically structured scaffold incorporated with strontium-substituted hydroxyapatite (SrHA) was coated with polyelectrolyte multilayers of chitosan/gelatin via layer-by-layer assembly technique for BMP-2 immobilization, which endowed the composite scaffold with sequential release of BMP-2 and Sr ions. The integration of SrHA improved the mechanical property of composite scaffold, while the polyelectrolytes modification strongly increased the hydrophilicity and protein binding efficiency. In addition, polyelectrolytes modified-scaffold significantly facilitated cell proliferation in vitro, as well as enhanced tissue infiltration and new microvascular formation in vivo. Furthermore, the dual-factor loaded scaffold significantly enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells. Moreover, both vascularization and new bone formation were significantly increased by the treatment of dual-factor delivery scaffold in the rat calvarial defects model, suggesting a synergistic effect on bone regeneration through spatiotemporal delivery of BMP-2 and Sr ions. Overall, this study demonstrate that the prepared biomimetic scaffold as dual-factor delivery system has great potential for bone regeneration application.

Effect of pectin on the crystallization of strontium substituted HA for bone reconstruction application

The biomacropolymers of bone extracellular matrix (ECM) guide the growth of hydroxyapatite (HA) with various ionic substitutions. Pectin, a plant polysaccharide with chemical similarities to ECM, was investigated for its potential to promote the crystallization of strontium-substituted HA (SH). The influence of pectin (0.5 and 1.0 wt%) on the in situ mineralization of SH (10 and 30 mol% calcium substitution with strontium) was studied. The preferential affinity of pectin to strontium over calcium favoured the incorporation of strontium in apatite, decreased crystal size (18.85–26.22 nm) and retained more pectin residues (8–16%). The residual pectin strongly interacted with small SH particles, resulting in high microhardness (0.43–0.85 GPa) and high surface charge (−32.1 to −30.3 mV), while weak interaction with large HA particles resulted in low microhardness (0.15–0.25 GPa) and low surface charge (−35.4 to −34.6 mV). The in vitro cellular study using human osteoblast-like MG-63 cells demonstrated that inorganic size and material crystallinity play a vital role in regulating osteogenesis. The study suggests that the synchronization of low pectin concentration (0.5 wt%) and high strontium substitution in HA (30 mol%) offers the desired microhardness and in vitro osteogenic properties to emulate natural bone.

Influence of the Components and Orientation of Hydroxyapatite Fibrous Substrates on Osteoblast Behavior.

Synthetic hydroxyapatite has good biocompatibility, bioactivity and osteoconductive ability because its chemical properties and biological properties are similar to those of bioapatite in bone tissue. Strontium-substituted hydroxyapatite has better degradability than hydroxyapatite and can both promote osteogenesis and inhibit adipogenesis in mesenchymal stem cells. Hence, hydroxyapatite and strontium-substituted hydroxyapatite are widely used as bone graft materials, cell carriers and drug/gene delivery carriers. In addition, osteoblasts cultured on aligned nanofibrous substrates had higher expression of osteogenesis-related genes than did those cultured on random nanofibrous substrates. However, to date, no study has explored the effects of the components and orientation of hydroxyapatite nanofibrous substrates on osteoblastic behavior. In this study, a random hydroxyapatite nanofibrous substrate (R-HANF), a random strontium-substituted hydroxyapatite nanofibrous substrate (R-SrHANF), an aligned hydroxyapatite nanofibrous substrate (A-HANF) and an aligned strontium-substituted hydroxyapatite nanofibrous substrate (A-SrHANF) were successfully fabricated by using the electrospinning technique. The effect of fiber composition on osteoblast-like MG63 cells was assessed by evaluating cell morphology, cell proliferation and osteogenesis-related gene expression. The results showed that MG63 cells cultured on A-SrHANF had higher osteogenesis-related gene expression than those cultured on A-HANF. Additionally, MG63 cells were cultured on R-SrHANF and A-SrHANF to evaluate the effects of fiber orientation on cell behavior. On A-SrHANF, the cells aligned along the direction of the nanofibers, with typical bipolar morphologies, and exhibited higher osteogenesis-related gene expression than cells on R-SrHANF. Hence, the components and orientation of hydroxyapatite nanofibrous substrates are critical parameters affecting the osteogenesis process.

Physicochemical, osteogenic and antimicrobial properties of graphene oxide reinforced silver/strontium-doped hydroxyapatite on titanium for potential orthopedic applications

Variety of ion-doped apatite coatings, especially strontium substituted hydroxyapatite (SrHA), have attracted eventful attention for medical metal surface modifications due to their excellent cytocompatibility and organizational affinity. However, they are still not commercially used in clinics because of their inappropriate biomechanical properties, and lack of osteoinductivity and antibacterial capabilities. Here, silver (Ag) doped SrHA (SrAgHA)/graphene oxide (GO) composite coatings were fabricated on titanium (Ti) substrate via electrodeposition (ED) and this combination has been reported for the first time. Morphological observations revealed that GO facilitated HA pricker-like crystals to grow in longitudinal directions, changing into a bone-like microneedles structure. SrAgHA/GO showed good mechanical properties to ensure mechanical strength required for the bone repair coating. The roughness of samples decreased from 120 ± 19 μm for the SrAgHA/GO coated Ti to 527 ± 66 μm for HA coated Ti. Although the introduction of GO makes the composite coating have a significant decreased roughness, it has no effect on the hydrophilicity of the composite coating, which is almost superpotropic. Ion release evaluation demonstrated that the presence of GO slowed the release rate of Sr and Ag, which was beneficial to reduce the cytotoxicity accompanying high concentration of Ag release. Simultaneously, GO increased the surface hydrophilicity and mechanical strength of the SrAgHA/GO. In addition, the corrosion rates of investigated coatings increased in the following order: SrAgHA/GO<SrHA/GO<SrAgHA<HA<Ti. SrAgHA/GO coatings demonstrated an effective antibacterial effect against common bacteria in clinical. The co-doping of Sr and GO in SrAgHA/GO coatings can effectively mitigate the cytotoxicity of Ag and promote the cytocompatibility of HA. The SrAgHA/GO coating did not exhibit any cytotoxicity, which can greatly promote adhesion, extension, proliferation and early differentiation of osteoblasts. Therefore, high cytocompatibility, excellent antimicrobial activity, and good mechanical properties of the SrAgHA/GO-coated Ti samples combined with its exceptional corrosion resistance performance displayed the beautiful prospect of the SrAgHA/GO-coated Ti for applications in hard tissue implant.

Sr2+ Sustained Release System Augments Bioactivity of Polymer Scaffold

Strontium ion (Sr2+) enabled us to endow polymer bone scaffolds with bioactivity owing to its excellent osteoinductive capacity. Nevertheless, the burst release of Sr2+ hindered its further application. Herein, strontium substituted hydroxyapatite (SrHA) was constructed to achieve a sustained release system. Specifically, Sr2+ could substitute Ca2+ in a HA lattice framework through ion exchange due to their similar ion radius. The ionic bond formed by Sr2+ and surrounding ions could prevent the rapid escape of Sr2+ and thereby achieve the sustained release of Sr2+. Subsequently, SrHA was introduced into the poly-l-lactic (PLLA) scaffold fabricated by selective laser sintering. Results demonstrated that PLLA/SrHA scaffolds presented a sustained Sr2+ release with a cumulative concentration of 5.6 mg/L over 28 days. The released Sr2+ significantly promoted the cell proliferation and differentiation. Furthermore, the tensile and compressive strengths of PLLA/SrHA scaffolds were also greatly enhanced in comparison with that of PLLA scaffolds. These positive findings demonstrated that PLLA/SrHA scaffolds had considerable potential for bone repair.

Synthesis, characterization and in vitro evaluation of dendrimer-MWCNT reinforced SrHAP composite for bone tissue engineering

This study aimed to improve the mechanical, drug loading/release and bioactive characteristics of hydroxyapatite (HAP). The covalent functionalization of PAMAM dendrimer with MWCNT (d-MWCNT), and in situ synthesis of strontium substituted HAP (SrHAP) on d-MWCNT yielded a composite, d-MWCNT-SrHAP. The composite was characterized by FT-IR, XRD, HR-SEM, AFM, EDS, TGA and zeta potential. It was hydrophilic (water contact angle 25.25 ± 4.21°), porous (89.63 ± 2.4%), bioresorbable, mechanically strong (0.415 ± 0.04 GPa) and protein adsorbing. The d-MWCNT-SrHAP exhibited a 30-fold increase in curcumin loading and a 1.7-fold delay in burst release compared to SrHAP. Further, in vitro studies using human osteoblast-like MG-63 cells demonstrated that the curcumin-loaded composite, d-MWCNT-SrHAP-C, encouraged osteoblast survival, proliferation, differentiation and matrix mineralization. The desirable physico-chemical properties and in vitro bioactivity of the d-MWCNT-SrHAP-C composite strongly suggest its potential application as a drug delivery system in hard tissue engineering.

Preparing a Bioactive (Chitosan/Sodium Hyaluronate)/SrHA Coating on Mg–Zn–Ca Alloy for Orthopedic Implant Applications

The uncontrollable rapid degradation rate of the Mg alloy substrate limited its clinical application, and implant-associated infections have been reported to be the main reason for the secondary surgery of orthopedic implantation. The aim of this study was to produce a multifunctional coating on magnesium-based alloys that have improved corrosion resistance, bioactivity, and antibacterial properties through the preparation of polyelectrolytic multilayers (PEMs) consisting of chitosan (CS) and sodium hyaluronate (HA) on silane-modified strontium-substituted hydroxyapatite (hereafter referred to as Bil (SH + CS)/SrHA). The multifunctional coatings were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS). The results showed the polyelectrolyte complex SH/CS layer to be uniformly and tightly attached on to the surface of silane-treated SrHA. At the same time, a potentiodynamic polarization test and hydrogen evolution test showed the Bil (SH + CS)/SrHA coatings to exhibit superior corrosion resistance than bulk Mg-based alloys. The results of the cell–surface interactions revealed Bil (SH + CS)/SrHA coatings to be in favor of cell initial adhesion and more beneficial to the proliferation and growth of cells with the processing of co-culture. In addition, antibacterial tests demonstrated the strong bactericidal effect of Bil (SH + CS)/SrHA coatings against both Escherichia coli (E. coli) and Staphylococcus (S. aureus), suggesting that Bil (SH + CS)/SrHA coatings can successfully achieve multifunctionality with enhanced corrosion resistance, biocompatibility, and antibacterial properties.

The Effect of Strontium-Substituted Hydroxyapatite Nanofibrous Matrix on Osteoblast Proliferation and Differentiation.

Natural bone tissue consists primarily of bioapatite and collagen. Synthetic hydroxyapatite (HA) possesses good biocompatibility, bioactivity, and osteoconductivity due to its chemical and biological similarity to bioapatite. Hence, HA has been widely used as a bone graft, cell carrier and drug/gene delivery carrier. Moreover, strontium-substituted hydroxyapatite (SrHA) can enhance osteogenic differentiation and inhibit adipogenic differentiation of mesenchymal stem cells. Hence, SrHA has the potential to be used as a bone graft for bone regeneration. It is widely accepted that cell adhesion and most cellular activities are sensitive to the topography and molecular composition of the matrix. Electrospun polymer or polymer-bioceramic composite nanofibers have been demonstrated to enhance osteoblast differentiation. However, to date, no studies have investigated the effect of nanofibrous bioceramic matrices on osteoblasts. In this study, hydroxyapatite nanofiber (HANF) and strontium-substituted hydroxyapatite nanofiber (SrHANF) matrices were fabricated by electrospinning. The effect of the HANF components on MG63 osteoblast-like cells was evaluated by cell morphology, proliferation, alkaline phosphatase activity (ALP) and gene expression levels of RUNX2, COLI, OCN and BSP. The results showed that MG63 osteoblast-like cells exhibited higher ALP and gene expression levels of RUNX2, COLI, BSP and OCN on the SrHANF matrix than the HANF matrix. Hence, SrHANFs could enhance the differentiation of MG63 osteoblast-like cells.

Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration

Injectable nanoscale hydroxyapatite (nHA) systems are highly promising biomaterials to address clinical needs in bone tissue regeneration, due to their excellent biocompatibility, bioinspired nature, and ability to be delivered in a minimally invasive manner. Bulk strontium-substituted hydroxyapatite (SrHA) is reported to encourage bone tissue growth by stimulating bone deposition and reducing bone resorption, but there are no detailed reports describing the preparation of a systematic substitution up to 100% at the nanoscale. The aim of this work was therefore to fabricate systematic series (0–100 atomic% Sr) of SrHA pastes and gels using two different rapid-mixing methodological approaches, wet precipitation and sol-gel. The full range of nanoscale SrHA materials were successfully prepared using both methods, with a measured substitution very close to the calculated amounts. As anticipated, the SrHA samples showed increased radiopacity, a beneficial property to aid in vivo or clinical monitoring of the material in situ over time. For indirect methods, the greatest cell viabilities were observed for the 100% substituted SrHA paste and gel, while direct viability results were most likely influenced by material disaggregation in the tissue culture media. It was concluded that nanoscale SrHAs were superior biomaterials for applications in bone surgery, due to increased radiopacity and improved biocompatibility.

Synthesis of Silver- and Strontium-Substituted Hydroxyapatite with Combined Osteogenic and Antibacterial Activities.

Infection in bone transplantation process is attracting considerable attention. The current study synthesizes silver/strontium co-substituted hydroxyapatite (Ag/Sr-HA) nanoparticles with combined osteogenic and antibacterial activities. Different concentrations of silver-substituted hydroxyapatite (Ag-HA) nanoparticles were synthesized by hydrothermal method, and then their physicochemical properties were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), and energy-dispersive X-ray spectroscopy (EDS). Then, Sr was added as secondary element into Ag-HA to improve the biocompatibility of substrate. The antibacterial experiments indicated that Ag-HA had excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The effects of prepared samples on cell proliferation and differentiation were evaluated using MC3T3-E1 cells in vitro. The results showed that Sr substitution enhanced cell proliferation and differentiation, upregulated expression of osteogenic genes, and induced mineralization of cells. The substitution of Sr in Ag/Sr-HA nanoparticles can effectively alleviate the negative effects of Ag and enhance the biological activity of HA. Thus, the synthesized Ag/Sr-HA nanoparticles will serve as a potential candidate for application of biomedical implants with excellent osteogenic and antibacterial ability.

Strontium substituted hydroxyapatite with β-lactam integrin agonists to enhance mesenchymal cells adhesion and to promote bone regeneration

Multi-functionalization of calcium phosphates to get delivery systems of therapeutic agents is gaining increasing relevance for the development of functional biomaterials aimed to solve problems related to disorders of the muscolo-skeletal system. In this regard, we functionalized Strontium substituted hydroxyapatite (SrHA) with some β-lactam integrin agonists to develop materials with enhanced properties in promoting cell adhesion and activation of intracellular signaling as well as in counteracting abnormal bone resorption. For this purpose, we selected two monocyclic β-lactams on the basis of their activities towards specific integrins on promoting cell adhesion and signalling. The amount of β-lactams loaded on SrHA could be modulated on changing the polarity of the loading solution, from 3.5–24 wt% for compound 1 and from 3.2–8.4 wt% for compound 2. Studies on the release of the β-lactams from the functionalized SrHA in aqueous medium showed an initial burst followed by a steady-release that ensures a small but constant amount of the compounds over time. The new composites were fully characterized. Co-culture of human primary mesenchymal stem cells (hMSC) and human primary osteoclast (OC) demonstrated that the presence of β-lactams on SrHA favors hMSC adhesion and viability, as well as differentiation towards osteoblastic lineage. Moreover, the β-lactams were found to enhance the inhibitory role of Strontium on osteoclast viability and differentiation.

Effects of bioactive strontium-substituted hydroxyapatite on osseointegration of polyethylene terephthalate artificial ligaments

The insufficient bioactivity of polyethylene terephthalate (PET) artificial ligaments severely weakens the ligament-bone healing in anterior cruciate ligament (ACL) reconstruction, while osteogenic modification is a prevailing method to enhance osseointegration of PET artificial ligaments. In the present study, strontium-substituted hydroxyapatite (SrHA) nanoparticles with different strontium (Sr) contents were synthesized via microwave-hydrothermal method and subsequently were coated on the surface of PET artificial ligaments. The results of XRD, FT-IR, TEM and ICP-OES revealed that the doping of Sr ions had no great influences on the phase composition, morphology and particle size of HA, but affected its chemical compositions and crystallinity. The SEM images showed that nanoparticles were successfully deposited on the surface of PET grafts, the surface hydrophilicity of which was significantly improved by the prepared coatings. The in vitro study revealed that the osteogenic activity of rat bone marrow mesenchymal stem cells (rBMSCs) was affected by varying concentrations of Sr ions in coatings and the optimal osteogenic differentiation was observed in the 2SrHA-PET group, which significantly up-regulated the expression of BMP-2, OCN, Col-I and VEGF. The enhanced osteogenic ability of the 2SrHA-PET group was further demonstrated through an in vivo study, which obviously promoted ligament-bone integration compared with that of PET and HA-PET groups, thus improving the biomechanical strength of the graft-bone complex. This study confirms that SrHA coatings can facilitate osseointegration in the repair of ligament injury in rabbits and thus offers a prospective method for ACL reconstruction by using Sr-containing biomaterial-modified PET artificial ligaments.

A novel snail-inspired bionic design of titanium with strontium-substituted hydroxyapatite coating for promoting osseointegration

As the population ages, more and more people are suffering from osteoarthritis (OA), resulting in an increasing requirement for joint implants. Surface modification to improve the topology and composition of the implants has been proved to be an effective way to improve the primary stability and long-term success rate of joint implants. In this work, a bionic micro/nano-structure accompanied with a strontium-substituted hydroxyapatite (SrHA) coating was fabricated on titanium (Ti) surface via electrochemical corrosion, ultrasonic treatment, and hydrothermal deposition methods. The in vitro study demonstrated that the bionic structure and the bioactive apatite could synergistically increase the expressions of integrin-related gene (ITG α5β1) and osteoblastic genes (Col-I and OCN), and thus promote osteoblast growth. In addition, owing to the anti-bone resorption property of Sr2+, the coating could effectively inhibit osteoclast differentiation and proliferation. In a word, the prepared samples not only promoted osteogenesis but also inhibited osteoclastogenesis. The in vivo experiment via a rabbit model found that the bionic structured surface provided the pore for new bone ingrowth, which was beneficial to the mechanical interlocking between the implant and bone. Moreover, the bionic structure and bioactive SrHA coating had a synergistic effect on promoting bone formation, osseointegration, and bone-implant bonding strength. This study therefore presented a new strategy to fabricate bio-functionalized Ti-based implants for potential application in orthopedics field.

A combined experimental and molecular dynamics simulation study on doxorubicin adsorption on strontium-substituted hydroxyapatite hollow microspheres

Hydroxyapatite (HAp) materials with the functions of bone reconstruction as well as drug release have important applications in treatment of bone diseases. However, it still remains a challenge to synthesize ion-doped HAp with low crystallinity and high surface area to improve its biological responses and drug loading capacity. Herein, strontium-substituted hydroxyapatite (Sr-HAp) hollow microspheres that exhibit high drug loading efficiency and excellent biocompatibility are reported via a simple one-step hydrothermal method. The specific surface area of the as-prepared Sr-HAp microspheres can be as high as 214.69 m2/g. The simulation results show that there is no significant difference in the total binding energy between doxorubicin (DOX) and HAp as well as Sr-HAp. Both HAp and Sr-HAp show high DOX loading efficiency and sustained DOX release behavior. The binding between DOX and Sr-HAp is mainly through the electrostatic interaction between Ca or Sr ions on Sr-HAp surfaces and carbonyl-O or hydroxyl-O in DOX molecule. The findings provide insights into the design and development of drugs used in drug delivery system of HAp or ion-doped HAp materials.