Strontium-doped Calcium Polyphosphate Research Articles

3D Molybdenum Disulfide Nanospheres Loaded with Metformin to Enhance SCPP Scaffolds for Bone Regeneration.

Conventional strontium-doped calcium polyphosphate (SCPP) ceramics have attracted a lot of attention due to good cytocompatibility and controlled degradation. However, their poor mechanical strength, brittleness, and difficulty in eliminating unavoidable postoperative inflammation and bacterial infections in practical applications limit their further clinical application. In this study, carboxylated molybdenum disulfide nanospheres (MoS2-COOH) were first prepared via a one-step hydrothermal method. The optimal doping concentration of MoS2-COOH was then incorporated into SCPP to overcome its poor mechanical strength. To further enhance the anti-inflammatory properties of scaffolds, metformin (MET) was loaded onto MoS2-COOH through covalent bond cross-linking (MoS2-MET). Then MoS2-MET was doped into SCPP (SCPP/MoS2-MET) according to the previously obtained concentration, resulting in the controlled and sustained release of MET from the SCPP/MoS2-MET scaffolds for 21 days in vitro. The SCPP/MoS2-MET scaffolds were shown to have good biological activity in vitro to promote stem cell proliferation and the potential to promote mineralization in vitro. It also showed good osteoimmunomodulatory activity could reduce the expression of proinflammatory factors and effectively induce the differentiation of BMSCs under inflammatory conditions, upregulating the expression of relevant osteoblastic cytokines. In addition, SCPP/MoS2-MET scaffolds could effectively inhibit Staphylococcus aureus and Escherichia coli. In vivo experiments also demonstrated better osteogenic potential of SCPP/MoS2-MET scaffolds compared with the other scaffold-samples. Thus, the introduction of carboxylated molybdenum disulfide nanospheres is a promising approach to improve the properties of SCPP and may provide a new modification strategy for inert ceramic scaffolds and the construction of multifunctional composite scaffolds for bone tissue engineering.

Research on essential performance of oxidized chitosan-crosslinked acellular porcine aorta modified with bioactive SCPP/DOPA for esophageal scaffold with enhanced mechanical strength, biocompatibility and anti-inflammatory

Acellular porcine aorta (APA) is an excellent candidate for an implanted scaffold but needs to be modified with appropriate cross-linking agent to increase its mechanical property and storage time in vitro as well as to give itself some bioactivities and eliminate its antigenicity for acting as a novel esophageal prosthesis. In this paper, a polysaccharide crosslinker (oxidized chitosan, OCS) was prepared by oxidizing chitosan using NaIO4 and further used to fix APA to prepare a novel esophageal prosthesis (scaffold). And then the surface modification with dopamine (DOPA) and strontium-doped calcium polyphosphate (SCPP) were performed one after another to prepare DOPA/OCS-APA and SCPP-DOPA/OCS-APA to improve the biocompatibility and inhibit inflammation of the scaffolds. The results showed that the OCS with a feeding ratio of 1.5:1.0 and a reaction time of 24 h had a suitable molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. Compared with glutaraldehyde (GA) and genipin (GP), OCS-fixed APA could provide a more suitable microenvironment for cell proliferation. The vital cross-linking characteristics and cytocompatibility of SCPP-DOPA/OCS-APA were evaluated. Results suggested that SCPP-DOPA/OCS-APA exhibited suitable mechanical properties, excellent resistance to enzymatic degradation/acid degradation, suitable hydrophilicity, and the ability to promote the proliferation of Human normal esophageal epithelial cells (HEECs) and inhibit inflammation in vitro. In vivo tests also confirmed that SCPP-DOPA/OCS-APA could diminish the immunological response to samples and had a positive impact on bioactivity and anti-inflammatory. In conclusion, SCPP-DOPA/OCS-APA could act as an effective, bioactive artificial esophageal scaffold and be expected to be used for clinical in the future.

A novel CPC composite cement reinforced by dopamine coated SCPP fibers with improved physicochemical and biological properties.

Traditional CPC cements have attracted wide attentions in repairing bone defects for injectability, easy plasticity and good osseointegration. However, its further application was limited by poor mechanical properties, long setting time and unsatisfactory biocompatibility. To solve these problems, polydopamine (DOPA) coated strontium-doped calcium polyphosphate (SCPP) fibers were added into CPC cements for the first time. A doping amount at fiber weight fraction of 0%, 1%, 2% and 5% was designed to develop a multifunctional composite fitting for bone tissues' regeneration and reconstruction and the optimum amount was selected through subsequent physicochemical and biological characterizations. The results implied DOPA coating successfully formed stable connections between SCPP fibers and CPC matrix, which simultaneously reinforced biomechanical strength and tenacity (5% SCPP/D/CPC samples exhibited more prominent mechanical property than others). In addition, 5% D/SCPP fibers doped composite cements were characterized as markedly-improved cytocompatibility: Sr2+ introduction induced cytoactive and significantly accelerated proliferation, attachment and spreading of osteoblasts. Besides, it also stimulated the secretion of OT, Col-I and ALP from seeded MG63, which was a critical character for further inducing osteogenic process, mineralization and bone tissues formation. The promoted cytocompatibility and improved osteogenesis-related growth factors' secretion could be attributed to constant and controllable release of Sr2+ and this deduction was approved by ICP analysis. In addition, Sr doping made this novel cement had a potential efficacy to inhibit aseptic loosening. In a word, present studies all demonstrated 5% SCPP/D/CPC composites could be a potential candidate material employed in bone regeneration and reconstruction for excellent mechanical property and cytocompatibility.

A promising material for bone repair: PMMA bone cement modified by dopamine-coated strontium-doped calcium polyphosphate particles.

Polymethyl methacrylate (PMMA) bone cement has been widely used in clinics as bone repair materials for its excellent mechanical properties and good injection properties. However, it also has defects such as poor biological performance, high temperature, and the monomer has certain toxicity. Our study tried to modify the PMMA bone cement by doping with various particle weight fractions (5, 10 and 15%) of SCPP particles and polydopamine-coated SCPP particles (D/SCPP) to overcome its clinical application disadvantages. Our study showed that all results of physical properties of samples are in accordance with ISO 5833. The 15% D/SCPP/PMMA composite bone cement had much better biocompatibility compared with pure PMMA bone cement and SCPP/PMMA composite bone cement due to the best cell growth-promoting mineralization deposition on the surface of 15% D/SCPP/PMMA composite bone cements and Sr2+ released from SCPP particles. Our research also revealed that the reaction temperature was found to be reduced with an increase in doped particles after incorporating the particles into composite bone cements. The novel PMMA bone cements modified by D/SCPP particles are promising materials for bone repair.

Double-Layer Microsphere Incorporated with Strontium Doped Calcium Polyphosphate Scaffold for Bone Regeneration.

To design and prepare a novel controlled release system for sustained release of two drugs. In this study, a double-layer microsphere was incorporated with strontium-doped calcium polyphosphate (SCPP) scaffold to facilitate bone regeneration and achieve skull repair. The double-layer microsphere combining tetracycline loaded sodium alginate and matrix metalloproteinase-2 (MMP-2) loaded chitosan was manufactured by electrospinning, which were further adhered to SCPP scaffold. The characteristics of microstructure were observed through scanning electron microscope. Loading efficiencies and the optimal ratio of microsphere of the obtained controlled release system were investigated. In addition, the cytotoxicity and the effects on osteoblast proliferation and expressions of osteogenesis-related factors were examined in vitro. Thereafter, the compound material with the controlled release system was implanted in the skull defect of rabbit to evaluate its properties of promoting bone regeneration. The results indicated that this novel controlled release system with SCPP scaffold and the double-layer microspheres loaded with tetracycline and MMP-2 could be a promising material for bones repair.

In vitro study of strontium doped calcium polyphosphate-modified arteries fixed by dialdehyde carboxymethyl cellulose for vascular scaffolds

Dialdehyde carboxymethyl (DCMC) was select as an optimal crosslinking reagent for its excellent biocompatibility, appropriate degradable property and suitable chemical reactivity in our previous research. However, similar to other traditional crosslinking reagent, the endothelialization of biological vascular scaffolds fixed by DCMC was not sufficient enough. To overcome this limitation presented in DCMC-fixed arteries, a novel strategy was developed by introducing SCPP into arteries to investigate effects of strontium doped calcium polyphosphate (SCPP)-doping on the properties of DCMC-fixed arteries, especially on the endothelialization of fixed arteries. After modifying and crosslinking, their chemical structures, mechanical properties, stability, and cytocompatibility were examined. The result obtained from EDS analysis indicated SCPP was successfully introduced into DCMC-fixed arteries. Compared with purely DCMC-crosslinked ones, DCMC/SCPP modification has no significant effect on mechanical strength of fixed arteries, but a slight tend to improve the stability of fixed samples in D-Hanks solution. Moreover, MTT assay, SEM observation and live/dead assay implied that DCMC/SCPP modification could effectively stimulate HUVECs’ adhesion and proliferation, and thus promote endothelialization process of fixed arteries. In this study, micron-sized SCPP particles were firstly applied to modify DCMC-crosslinked porcine arteries, and the results demonstrated this method could improve the endothelialization of fixed arteries. Therefore, DCMC/SCPP-modified arteries with excellent physicochemical properties and biocompatibility should be a promising materials for fabricating vascular scaffolds.

A promising scaffold with excellent cytocompatibility and pro-angiogenesis action for dental tissue engineering: Strontium-doped calcium polyphosphate.

Angiogenesis is of great importance in dental tissue engineering. Therefore, it is quite necessary for dental tissue engineering to develop a new scaffold with bioactivity to induce angiogenesis. This study was performed to determine the ability of 1% strontium-doped calcium polyphosphate (SCPP) to induce angiogenesis by detecting the levels of VEGF and bFGF from cultured human dental pulp cells (hDPCs). Results of scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) tests indicated the growth of hDPCs on 1%SCPP scaffolds was more superior than that on calcium polyphosphate (CPP) and hydroxyapatite (HA) scaffolds. The detection of MTT indicated 1%SCPP could accelerate proliferation of hDPCs. Further analyzed with ELISA demonstrated the protein levels of VEGF, bFGF from cultured hDPCs on 1%SCPP scaffolds were significantly higher than that on CPP and HA scaffolds. These findings above suggested 1%SCPP could be a promising scaffold for dental tissue engineering to induce angiogenesis.

The co-culture of peripheral blood-derived endothelial progenitor cells and mesenchymal stem cells on three-dimensional porous strontium-doped calcium polyphosphate scaffold for construction of vascularized engineering bone

Event Abstract Back to Event No Records Found Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Google Google Scholar PubMed Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Repairing defect and preventing collapse of femoral head in a steroid-induced osteonecrotic of femoral head animal model using strontium-doped calcium polyphosphate combined BM-MNCs.

We investigated the synergism between strontium-doped calcium polyphosphate (SCPP) and autologous bone marrow mononuclear cells (BM-MNCs) in treating osteonecrosis of the femoral head (ONFH). ONFH was confirmed histopathologically at 2 weeks after methylprednisolone acetate injection and the rabbits were treated with morselized autogenous cancellous compacted bone graft (group I), SCPP combined with BM-MNCs (group II), and calcium polyphosphate (group III), respectively. The amount of newly formed bone in group II increased dramatically by 4, 8, and 12 weeks and much more than that in group III (P<0.05). VEGF expression in group I was significantly higher than in group II (P=0.023), and its expression in group II was significantly higher than in group III (P=0.017). At 12 weeks, group II had articular cartilage collapse and group III had joint-space narrowing. The mean histological and radiological scores for repaired defects in group II were significantly higher than those in group III (P=0.000) but lower than those in group I (P=0.000). The implantation of a combination of SCPP and BM-MNCs enhances VEGF expression and promotes osteogenesis, which may improve angiogenesis and allow incorporation and remodeling into new trabecular bone without mechanical weakening.

Coculture of peripheral blood-derived mesenchymal stem cells and endothelial progenitor cells on strontium-doped calcium polyphosphate scaffolds to generate vascularized engineered bone.

Vascularization of engineered bone tissue is critical for ensuring its survival after implantation and it is the primary factor limiting its clinical use. A promising approach is to prevascularize bone grafts in vitro using endothelial progenitor cells (EPC) derived from peripheral blood. Typically, EPC are added together with mesenchymal stem cells (MSC) that differentiate into osteoblasts. One problem with this approach is how to promote traditional tissue engineering bone survival with a minimally invasive method. In this study, we examined the effectiveness of administering to stimulate the release of peripheral blood stem cells and their co-culturing system for generating prevascularized engineered bone. Cells were isolated by Ficoll density gradient centrifugation and identified as EPC and MSC based on morphology, surface markers, and functional analysis. EPC and MSC were cocultured in several different ratios, and cell morphology and tube formation were assessed by microscopy. Expression of osteogenesis and vascularization markers was quantified by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction, and histochemical and immunofluorescence staining. Increasing the proportion of EPC in the coculture system led to greater tube formation and greater expression of the endothelial cell marker CD31. An EPC:MSC ratio of 75:25 gave the highest expression of osteogenesis and angiogenesis markers. Cocultures adhered to a three-dimensional scaffold of strontium-doped calcium polyphosphate and proliferated well. Our findings show that coculturing peripheral blood-derived EPC and MSC may prove useful for generating prevascularized bone tissue for clinical use.

The inhibitory effect of strontium-doped calcium polyphosphate particles on cytokines from macrophages and osteoblasts leading to aseptic loosening in vitro

Aseptic loosening is a common cause of joint implant failure in humans. In order to enhance implant stability, we need to develop a new material that not only promotes the wear resistance of components of an artificial joint, but also possesses the pharmaceutical efficacy of protecting patients against aseptic loosening. Strontium-doped calcium polyphosphate (SCPP) has been found to have this potential ability. The goal of this study is to respectively quantify the levels of TNF-α (for macrophages), receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) (for osteoblasts) when osteoblasts and macrophages are challenged with various particles (including SCPP). In this study, the osteoblasts ROS 17/2.8 and macrophages RAW 264.7 were challenged with various wear particles (8% SCPP, the molar percentage of Sr in SCPP is 8%, UHMWPE, hydroxyapatite (HA) and CPP). The secretion of TNF-α (from RAW 264.7), OPG and RANKL protein (from ROS 17/2.8) was analyzed by ELISA. The OPG and RANKL mRNA from ROS 17/2.8 was detected by RT-PCR. The data of ELISA indicated that the amount of TNF-α challenged with 8% SCPP particles was more than three-fold lower than that of all other test groups. The ratio of OPG/RANKL in the 8% SCPP group was significantly increased compared to that of all other test groups. The results of OPG and RANKL mRNA expression showed the same tendency as the ELISA results. In general, this study showed that 8% SCPP particles can inhibit the expression of TNF-α and RANKL, promote the expression of OPG so that SCPP can inhibit bone resorption and promote bone formation, and then inhibit aseptic loosening. Thus SCPP could be a promising material for the construction of artificial joints.

Effects of strontium-doped calcium polyphosphate on angiogenic growth factors expression of co-culturing system in vitro and of host cell in vivo

Efforts to induce angiogenesis have been dedicated to developing novel strategies to fabricate an ideal scaffold for bone tissue engineering. In order to mimic the environment of the repair process in vivo, this study was performed to investigate the effect of strontium-doped calcium polyphosphate (SCPP) on angiogenesis-related behaviors of umbilical vein endothelial cells and osteoblasts co-cultured in vitro. The results indicate that, compared with those in calcium polyphosphate (CPP) and hydroxyapatite (HA) group, cells attached and spread better with a significantly improved cell proliferation in SCPP group. More importantly, in vitro co-culture demonstrated a significant improvement in the VEGF and bFGF expression levels in SCPP groups. The results also demonstrated that SCPP could effectively enhance VEGF and bFGF expression from host cell in vivo and thereby inducing angiogenesis in implanted scaffolds. SCPP could be used as a potential material with stimulating angiogenesis, which would provide a novel thought for resolving the problem of angiogenesis in bone tissue engineering.

Effect of erythromycin‐doped calcium polyphosphate scaffold composite in a mouse pouch infection model

We previously showed that strontium-doped calcium polyphosphate (SCPP) scaffold with poly(vinyl alcohol) (PVA) coating extended the impregnated erythromycin (EM) release. In this study, we examined the bactericidal effect of EM-doped SCPP (SCPP(EM) ) scaffolds with PVA coating in a Staphylococcus aureus (S. aureus) infected mouse pouch. SCPP scaffolds with or without 5% EM, and SCPP(EM) scaffolds coated with PVA (with or without 5% EM) were prepared. Scaffolds were implanted in the pouch of BALB/c mice, followed by inoculation of 1 × 10(3) colony-forming units of S. aureus. Mice were sacrificed 14 days after surgery. Pouch tissues and scaffolds were collected for histology, scanning electron microscopy, and microbiological analysis. In the absence of SCPP scaffolds, the pouch infection was eliminated by the host immune surveillance. In the presence of SCPP scaffolds, both the pouch tissues and scaffolds were infected, but SCPP(EM) scaffolds successfully inhibited bacterial growth. Although PVA coating of SCPP(EM) scaffolds enhanced bacterial growth, incorporation of EM into PVA coating inhibited growth. In conclusion, BALB/c mice were capable of eradicating a low grade S. aureus infection. SCPP protected S. aureus growth from host immune surveillance. Though PVA coating sustained EM release in vitro, it was unable to inhibit bacterial growth because PVA gel matrix provided a temporary shelter for bacteria to grow and slowed the EM release from SCPP scaffold. To guarantee a sufficient inhibition of bacterial growth at the initial stage, embedding EM or other antibiotics in the PVA coating is also essential.

Stimulations of strontium-doped calcium polyphosphate for bone tissue engineering to protein secretion and mRNA expression of the angiogenic growth factors from endothelial cells in vitro

The vascularization of tissue-engineered bone is the key problem needed solving before application of tissue-engineered bone in clinical practice. Meanwhile, endothelial cells are the major and important source of seed cells in bone tissue engineering, and significant on promoting vascularization in tissue-engineered bone. Vascularization (namely angiogenesis) is a process mainly controlled by several angiogenic growth factors (VEGF, bFGF and MMP-2) which can be secreted by endothelial cells. Therefore, the research on the stimulations of SCPP to the secretion of the angiogenic growth factors from endothelial cells is very important. This study was performed to determine the ability of strontium-doped calcium polyphosphate (SCPP) to induce angiogenesis by detecting the protein secretion levels and mRNA expression of VEGF, bFGF and MMP-2 from cultured endothelial cells. As a control, we also researched the effect of HA on the mRNA expressions and protein secretion of angiogenic growth factors from cultured endothelial cells. We cultured endothelial cells with SCPP scaffolds containing various concentration of strontium and HA. The results obtained in the MTT and SEM tests indicated that endothelial cells on SCPP scaffold exhibited higher proliferation rate and were easy to get a good spread than them on CPP, the best state of growth and proliferation of cells could be observed on 8%SCPP. The results of ELISA demonstrated that the protein levels of VEGF, bFGF and MMP-2 from cultured endothelial cells increased with the increasing Sr doped in calcium polyphosphate in SCPP groups, the peaks appeared on 8%SCPP. All SCPP groups showed a better ability to stimulate the protein secretion of VEGF, bFGF and MMP-2 from endothelial cells relative to CPP group and HA group. The results of RT-PCR suggested that the 8%SCPP group exhibited a significantly higher mRNA expression of VEGF, bFGF and MMP-2 relative to CPP group and HA group. In conclusion, the results of this study demonstrated that 8%SCPP had obvious promotion for secretion and mRNA expression of angiogenic growth factors from cultured endothelial cells.

Preparation and properties of plasma sprayed strontium-doped calcium polyphosphate coating for bone tissue engineering

The purpose of this study was to scale-up the usage of strontium-doped calcium polyphosphate (SCPP) to major load-bearing applications in bone substitute application. SCPP powders were used to prepare biological coatings on titanium (Ti) substrates by plasma-spraying under a series of different conditions. Microstructure and bonding strength (with titanium substrates) of the SCPP coatings were investigated by an inductively coupled plasma-mass spectrometer, X-ray diffraction analysis, a scanning electron microscope and a strength test machine. The results showed the main crystal type of coating remained β-crystal SCPP. The surface and cross-sectional morphologies of coatings showed that the SCPP coatings were fairly dense. The bonding strength between the SCPP and Ti was higher than normal plasma spraying coatings. Furthermore, the research on the interactions between ROS17/2.5 cells and various SCPP coatings-Ti substrates indicated that the coating-implants possessed good cytocompatibility with osteoblasts. Therefore, SCPP is considered to be a biological coating material with good prospect in clinical application.

Application of strontium-doped calcium polyphosphate scaffold on angiogenesis for bone tissue engineering

The key factor for regenerating large segmental bone defects through bone tissue engineering is angiogenesis in scaffolds. Attempts to overcome this problem, it is a good strategy to develop a new scaffold with bioactivity to induce angiogenesis in bone tissue engineering. In our previous research, the ability of strontium-doped calcium polyphosphate (SCPP) to stimulate the release of angiogenic growth factors from cultured osteoblasts was studied. This study was performed to determine the ability of SCPP to induce angiogenesis within in vitro co-culture model of human umbilical vein endothelial cells (HUVEC) and osteoblasts co-cultured. The bioactivity of developed scaffolds to induce angiogenesis in vivo was also researched in this paper. Co-cultured model has been developed in vitro and then cultured with SCPP scaffold as well as calcium polyphosphate (CPP) scaffold and hydroxylapatite (HA) scaffold. The results showed that the optimal ratio of HUVEC and osteoblasts co-cultured model for in vitro angiogenesis was 5:1. The model could maintain for more than 35days when cultured with the scaffold and show the best activity at 21st day. Compared with those in CPP and HA scaffold, the formation of tube-like structure and the expression of platelet endothelial cell adhesion molecule in co-cultured model is better in SCPP scaffold. The in vivo immunohistochemistry staining for VEGF also showed that SCPP had a potential to promote the formation of angiogenesis and the regeneration of bone. SCPP scaffold could be served as a potential biomaterial with stimulating angiogenesis in bone tissue engineering and bone repair.

Cell-mediated degradation of strontium-doped calcium polyphosphate scaffold for bone tissue engineering

Bio-ceramic porous scaffolds used in bone tissue engineering are incorporated in vivo by a process of cellular in-growth, followed by cell-mediated degradation and replacement of these scaffolds, in which macrophages and osteoclasts play the key role. Calcium polyphosphate (CPP) is an inorganic polymeric bioceramic which has been increasingly studied as a bone graft. The solution-mediated chemical degradation of strontium-substituted calcium polyphosphate (SCPP) scaffolds is well established in vitro, but an in vitro model of cell-mediated SCPP scaffold degradation has not been investigated. Herein, RAW264.7 (a murine monocyte/macrophage cell line) and osteoclasts were cultured on CPP and SCPP scaffolds. The weight loss and release amount of Sr2+, Ca2+ and PO43− in a degradation medium indicated that macrophages could accelerate the degradation of SCPP. According to the results from MTT assay and scanning electron microscopy, it was found that a low dose of strontium was beneficial to the proliferation of macrophages, while strontium inhibited the activity of osteoclasts. This study will aid in developing SCPP scaffolds for in vivo bone tissue engineering.

Acceleration of segmental bone regeneration in a rabbit model by strontium-doped calcium polyphosphate scaffold through stimulating VEGF and bFGF secretion from osteoblasts

The development of suitable bioactive three-dimensional scaffold for the promotion of bone regeneration is critical in bone tissue engineering. The purpose of this study was to investigate in vivo osteogenesis of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds for bone repair, as well as the relationship between osteogenic properties of SCPP scaffolds and the secretion of bFGF and VEGF from osteoblasts stimulated by SCPP. Besides, the advantages of scaffolds seeded with mesenchymal stem cells (MSCs) for bone repair were also studied. Firstly, the bone repair evaluation of scaffolds was performed on a rabbit segmental bony defects model over a period of 16weeks by histology combined with X-ray microradiography. And then, in order to avoid the influence from the other factors such as hypoxia which emerge in vivo study and affect the secretion of VEGF and bFGF from host cells, human osteoblast-like cells (MG63) were seeded to SCPP, CPP and HA scaffolds in vitro to determine the ability of these scaffolds to stimulate the secretion of angiogenic growth factors (VEGF and bFGF) from MG63 and further explore the reason for the better osteogenic properties of SCPP scaffolds. The histological and X-ray microradiographic results showed that the SCPP scaffolds presented better osteogenic potential than CPP and HA scaffolds, when combined with MSCs, the SCPP scaffolds could further accelerate the bone repair. And the amounts of VEGF measured by ELISA assay in SCPP, CPP and HA groups after cultured for 7days were about 364.989pg/mL, 244.035pg/mL and 232.785pg/mL, respectively. Accordingly, the amounts of bFGF were about 27.085pg/mL, 15.727pg/mL and 8.326pg/mL. The results revealed that the SCPP scaffolds significantly enhanced the bFGF and VEGF secretion compared with other scaffolds. The results presented in vivo and in vitro study demonstrated that the SCPP could accelerate bone formation through stimulating the secretion of VEGF and bFGF from osteoblasts, making it attractive for bone regeneration.

A novel strontium‐doped calcium polyphosphate/erythromycin/poly(vinyl alcohol) composite for bone tissue engineering

It is our goal to develop bactericidal bone scaffolds with osteointegration potential. In this study, poly(vinyl alcohol) (PVA) coating (7%) was applied to an erythromycin (EM)-impregnated strontium-doped calcium polyphosphate (SCPP) scaffold using a simple slurry dipping method. MicroCT analysis showed that PVA coating reduced the average pore size and the percentage of pore interconnectivity to some extent. Compressive strength tests confirmed that the PVA coating significantly increased material elasticity and slightly enhanced the scaffold mechanical strength. It was also confirmed that the PVA coatings allowed a sustained EM release that is controlled by diffusion through the intact PVA hydrogel layer, irrespective of the drug solubility. PVA coating did not inhibit the EM bioactivity when the scaffolds were immersed in simulated body fluid for up to 4 weeks. EM released from SCPP-EM-PVA composite scaffolds maintained its capability of bacterial growth (S. aureus) inhibition. PVA coating is biocompatible and nontoxic to MC3T3 preosteoblast cells. Furthermore, we found that SCPP-EM-PVA composite scaffolds and their eluants remarkably inhibited RANKL-induced osteoclastogenesis in a murine RAW 264.7 macrophage cell line. Thus, this unique multifunctional bioactive composite scaffold has the potential to provide controlled delivery of relevant drugs for bone tissue engineering.

In vitro study in stimulating the secretion of angiogenic growth factors of strontium-doped calcium polyphosphate for bone tissue engineering

Angiogenesis of tissue-engineered bone remains a limited factor for the engineering of larger bone tissue constructs. Attempts to stimulate angiogenesis, using recombinant protein or gene transfer of angiogenic growth factors, have been proposed; however, these approaches have been associated with some problems regarding such as complex technique, expensive prices as well as safety problems and short half-life of angiogenic growth factors. This study was performed to determine the ability of strontium-doped calcium polyphosphate (SCPP) to induce angiogenesis via researching its effect on the mRNA expressions and protein secretion of VEGF and bFGF in/from cultured osteoblasts (ROS17/2.8 cells). We cultured osteoblasts with SCPP scaffolds containing various doses of strontium as well as calcium polyphosphate (CPP) scaffold. Through the detection of MTT and SEM, we have found that SCPP could promote cell proliferation and maintain their morphology. The results of RT-PCR and ELISA indicated that, compared with those in CPP group, the mRNA expression as well as protein levels of VEGF and bFGF in/from cultured osteoblasts were dose-dependent increasing in response to increasing strontium before reaching the peak in SCPP groups, and 8% SCPP showed the optimal promoting role. Therefore, SCPP containing proper dose of strontium could be served as a potential biomaterial with stimulating angiogenesis in bone tissue engineering and bone repair.