Injectable Calcium Phosphate Cement Research Articles

Mesoporous Bioactive Glass-Incorporated Injectable Strontium-Containing Calcium Phosphate Cement Enhanced Osteoconductivity in a Critical-Sized Metaphyseal Defect in Osteoporotic Rats.

In this study, the in vitro and in vivo bone formation behavior of mesoporous bioactive glass (MBG) particles incorporated in a pasty strontium-containing calcium phosphate bone cement (pS100G10) was studied in a metaphyseal fracture-defect model in ovariectomized rats and compared to a plain pasty strontium-containing calcium phosphate bone cement (pS100) and control (empty defect) group, respectively. In vitro testing showed good cytocompatibility on human preosteoblasts and ongoing dissolution of the MBG component. Neither the released strontium nor the BMG particles from the pS100G10 had a negative influence on cell viability. Forty-five female Sprague-Dawley rats were randomly assigned to three different treatment groups: (1) pS100 (n = 15), (2) pS100G10 (n = 15), and (3) empty defect (n = 15). Twelve weeks after bilateral ovariectomy and multi-deficient diet, a 4 mm wedge-shaped fracture-defect was created at the metaphyseal area of the left femur in all animals. The originated fracture-defect was substituted with pS100 or pS100G10 or left empty. After six weeks, histomorphometrical analysis revealed a statistically significant higher bone volume/tissue volume ratio in the pS100G10 group compared to the pS100 (p = 0.03) and empty defect groups (p = 0.0001), indicating enhanced osteoconductivity with the incorporation of MBG. Immunohistochemistry revealed a significant decrease in the RANKL/OPG ratio for pS100 (p = 0.004) and pS100G10 (p = 0.003) compared to the empty defect group. pS100G10 showed a statistically higher expression of BMP-2. In addition, a statistically significant higher gene expression of alkaline phosphatase, osteoprotegerin, collagen1a1, collagen10a1 with a simultaneous decrease in RANKL, and carbonic anhydrase was seen in the pS100 and pS100G10 groups compared to the empty defect group. Mass spectrometric imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the release of Sr2+ ions from both pS100 and pS100G10, with a gradient into the interface region. ToF-SIMS imaging also revealed that resorption of the MBG particles allowed for new bone formation in cement pores. In summary, the current work shows better bone formation of the injectable pasty strontium-containing calcium phosphate bone cement with incorporated mesoporous bioactive glass compared to the bioactive-free bone cement and empty defects and can be considered for clinical application for osteopenic fracture defects in the future.

Injectable periodontal ligament stem cell-metformin-calcium phosphate scaffold for bone regeneration and vascularization in rats.

Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo. hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste. Five groups were tested: (1) CPC control; (2) CPC +hPDLSC-fibers +0% Met (CPC + hPDLSCs + 0%Met); (3) CPC +hPDLSC-fibers +0.1% Met (CPC + hPDLSCs + 0.1%Met); (4) CPC +hPDLSC-fibers +0.2% Met (CPC + hPDLSCs + 0.2%Met); (5) CPC +hPDLSC-fibers +0.4% Met (CPC + hPDLSCs + 0.4%Met). The injectability, mechanical properties, metformin release, and hPDLSC osteogenic differentiation and bone mineral were determined in vitro. A rat cranial defect model was used to evaluate new bone formation. The novel construct had good injectability and physical properties. Alginate fibers degraded in 7 days and released hPDLSCs, with 5-fold increase of proliferation (p＜0.05). The ALP activity and mineral synthesis of hPDLSCs were increased by Met delivery (p＜0.05). Among all groups, CPC+hPDLSCs+0.1%Met showed the greatest cell mineralization and osteogenesis, which were 1.5-10folds those without Met (p＜0.05). Compared to CPC control, CPC+hPDLSCs+0.1%Met enhanced bone regeneration in rats by 9 folds, and increased vascularization by 3 folds (p＜0.05). The novel injectable construct with hPDLSC and Met encapsulation demonstrated excellent efficacy for bone regeneration and vascularization in vivo in an animal model. CPC+hPDLSCs+0.1%Met is highly promising for dental and craniofacial applications.

In Vitro and In Vivo Evaluation of Injectable Strontium-Modified Calcium Phosphate Cement for Bone Defect Repair in Rats

Calcium phosphate cement (CPC) has been widely studied, but its lack of osteoinductivity and inadequate mechanical properties limit its application, while strontium is able to promote bone formation and inhibit bone resorption. In this study, different proportions of tristrontium silicate were introduced to create a novel strontium-modified calcium phosphate cement (SMPC). The physicochemical properties of SMPC and CPC were compared, and the microstructures of the bone cements were characterized with scanning electron microscopy assays. Then, the effect of SMPC on cell proliferation and differentiation was examined. Furthermore, local inflammatory response and osteogenesis after SMPC implantation were also confirmed in the study. Finally, a rat model of isolated vertebral defects was used to test the biomechanical properties of the cements. The results showed that SMPC has better injectability and a shorter setting time than CPC. Meanwhile, the addition of tristrontium silicate promoted the mechanical strength of calcium phosphate cement, and the compressive strength of 5% SMPC increased to 6.00 ± 0.74 MPa. However, this promotion effect gradually diminished with an increase in tristrontium silicate, which was also found in the rat model of isolated vertebral defects. Furthermore, SMPC showed a more preferential role in promoting cell proliferation and differentiation compared to CPC. Neither SMPC nor CPC showed significant inflammatory responses in vivo. Histological staining suggested that SMPCs were significantly better than CPC in promoting new bone regeneration. Importantly, this osteogenesis effect of SMPC was positively correlated with the ratio of tristrontium silicate. In conclusion, 5% SMPC is a promising substitute material for bone repair with excellent physicochemical properties and biological activity.

Strontium-doped apatitic bone cements with tunable antibacterial and antibiofilm ability.

Injectable calcium phosphate cements (CPCs) represent promising candidates for the regeneration of complex-shape bone defects, thanks to self-hardening ability, bioactive composition and nanostructure offering high specific surface area for cell attachment and conduction. Such features make CPCs also interesting for functionalization with various biomolecules, towards the generation of multifunctional devices with enhanced therapeutic ability. In particular, strontium-doped CPCs have been studied in the last years due to the intrinsic antiosteoporotic character of strontium. In this work, a SrCPC previously reported as osteointegrative and capable to modulate the fate of bone cells was enriched with hydroxyapatite nanoparticles (HA-NPs) functionalized with tetracycline (TC) to provide antibacterial activity. We found that HA-NPs functionalized with TC (NP-TC) can act as modulator of the drug release profile when embedded in SrCPCs, thus providing a sustained and tunable TC release. In vitro microbiological tests on Escherichia coli and Staphylococcus aureus strains proved effective bacteriostatic and bactericidal properties, especially for the NP-TC loaded SrCPC formulations. Overall, our results indicate that the addition of NP-TC on CPC acted as effective modulator towards a tunable drug release control in the treatment of bone infections or cancers.

Novel injectable calcium phosphate scaffold with human periodontal ligament stem cell encapsulation in microbeads for bone regeneration

Objectives: 1) Develop a novel construct of human periodontal ligament stem cells (hPDLSCs) encapsulated in degradable alginate microbeads (DAMB) with human platelet lysate (hPL) and injectable calcium phosphate cement (ICPC); 2) Investigate the proliferation and osteogenic differentiation of hPDLSCs in ICPC with hPL as a xeno-free supplement and animal serum replacement for bone tissue engineering applications.Methods: hPDLSCs were encapsulated in alginate-fibrin microbeads (DAMB + fibrin), alginate-hPL degradable microbeads (DAMB + hPL), or alginate-fibrin-hPL microbeads (DAMB + fibrin + hPL). The proliferation and osteogenic differentiation of hPDLSCs were investigated in culturing with the ICPC scaffold.Results: Flexural strength of ICPC was 8.4 ± 0.91 MPa, and elastic modulus was 1.56 ± 0.1 GPa, exceeding those of cancellous bone. hPDLSCs had higher viability in DAMB + fibrin + hPL group than in DAMB + fibrin. ALP was 69.97 ± 16.96 mU/mg for ICPC + DAMB + fibrin + hPL group, higher than 30.68 ± 2.86 mU/mg of ICPC + DAMB + fibrin (p < 0.05) and 4.12 ± 1.65 mU/mg of control (p < 0.01). At 7 days, osteogenic gene expressions (ALP, RUNX2, COL1, and OPN) in ICPC + DAMB + fibrin + hPL and ICPC + DAMB + fibrin were 4–11 folds that of control. At 21 days, the hPDLSC-synthesized bone mineral amounts in ICPC + DAMB + fibrin + hPL and ICPC + DAMB + fibrin were 13.2 folds and 11.1 folds that of control group, respectively.Conclusion: The novel injectable CPC scaffold encapsulating hPDLSCs and hPL is promising to protect and deliver hPDLSCs. The hPL-based medium significantly enhanced the osteogenic differentiation of hPDLSCs in ICPC + DAMB + fibrin + hPL construct, suggesting a promising xeno-free approach for bone tissue regeneration applications.

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Some cancers have tropism for bone: breast, prostate, lung, kidney, and thyroid cancers are the most common. Bone metastases can be treated with surgical resection and the resulting bone defects can be filled with injectable biomaterials. Among these, calcium phosphates may be the biomaterials of choice because of their ability to locally release anticancer active ingredients. Herein, we propose the synthesis of injectable calcium phosphate cement (CPC) loaded with gallium maltolate (GaM). It is an extremely promising anticancer drug with also antibiotic and anti-inflammatory properties. This synthesis was based on commercial cement whose main component was α-tri-calcium phosphate (α-TCP), and the final product obtained after hardening was calcium-deficient apatite (CDA). Two formulations were prepared, containing 3.5% and 7% by mass of GaM (CPC-3.5G and CPC-7G respectively). Powder x-ray diffraction (pXRD), Fourier transform infrared (FTIR) spectroscopy, and magic-angle spinning nuclear magnetic resonance (NMR MAS) 31P analyses showed that the direct incorporation of GaM did not modify the final cement composition. Textural properties, such as setting time, injectability, workability, and cohesiveness, were well preserved or even improved. Additionally, the mechanical strength, although slightly reduced, remained perfectly compatible with surgical use. In vitro kinetics studies of GaM-loaded CPCs showed a controlled release of GaM (49% at 60 days for CPC-3.5G and 58% at 116 days for CPC-7G) following Fick’s law. Raman imaging was used to visualize its diffusion within the cement during in vitro release experiments. Finally, the structural integrity of the gallium complex in the CPC was confirmed using NMR MAS 71Ga.

Fabrication of Radio-Opaque and Macroporous Injectable Calcium Phosphate Cement.

The aim of this work was the development of injectable radio-opaque and macroporous calcium phosphate cement (CPC) to be used as a bone substitute for the treatment of pathologic vertebral fractures. A CPC was first rendered radio-opaque by the incorporation of zirconium dioxide (ZrO2). In order to create macroporosity, poly lactic-co-glycolic acid (PLGA) microspheres around 100 μm were homogeneously incorporated into the CPC as observed by scanning electron microscopy. Physicochemical analyses by X-ray diffraction and Fourier transform infrared spectroscopy confirmed the brushite phase of the cement. The mechanical properties of the CPC/PLGA cement containing 30% PLGA (wt/wt) were characterized by a compressive strength of 2 MPa and a Young's modulus of 1 GPa. The CPC/PLGA exhibited initial and final setting times of 7 and 12 min, respectively. Although the incorporation of PLGA microspheres increased the force necessary to inject the cement and decreased the percentage of injected mass as a function of time, the CPC/PLGA appeared fully injectable at 4 min. Moreover, in comparison with CPC, CPC/PLGA showed a full degradation in 6 weeks (with 100% mass loss), and this was associated with an acidification of the medium containing the CPC/PLGA sample (pH of 3.5 after 6 weeks). A cell viability test validated CPC/PLGA biocompatibility, and in vivo analyses using a bone defect assay in the caudal vertebrae of Wistar rats showed the good opacity of the CPC through the tail and a significant increased degradation of the CPC/PLGA cement a month after implantation. In conclusion, this injectable CPC scaffold appears to be an interesting material for bone substitution.

Porous CDHA microspheres laden brushite-based injectable bone substitutes for improved bone regeneration.

Porous CDHA microspheres were incorporated into innovative injectable calcium phosphate cement (CPC) to enhance the rate of degradation and bioactivity of bone regeneration. With varying content of CDHA microspheres, the final setting time varied between 12 and 17 min, which is adequate for surgeons to accomplish the implantation. Compressive strength ranged between 6 and 8MPa, until the addition of porous CDHA microsphere into CPC reached 20 vol %, but decreased dramatically after 30 vol % addition. Therefore, CPC with 20 vol % addition of porous CDHA microspheres was found appropriate for in vitro degradation and cytocompatibility studies. Histological assessment identified new bone formation around the injected bone substitute without significant inflammatory reactions. In vivo analysis of rat femoral defects revealed a threefold higher bone formation in CPC/CDHA 20 vol % than in CPC, due to the more cell migration and penetration into CPC by the existence of porous CDHA microspheres. Based on the promising results obtained, this novel injectable bone substitute may be useful in bone regeneration.

Enhanced Osteogenesis of Dental Pulp Stem Cells In Vitro Induced by Chitosan-PEG-Incorporated Calcium Phosphate Cement.

The use of bone graft materials is required for the treatment of bone defects damaged beyond the critical defect; therefore, injectable calcium phosphate cement (CPC) is actively used after surgery. The application of various polymers to improve injectability, mechanical strength, and biological function of injection-type CPC is encouraged. We previously developed a chitosan–PEG conjugate (CS/PEG) by a sulfur (VI) fluoride exchange reaction, and the resulting chitosan derivative showed high solubility at a neutral pH. We have demonstrated the CPC incorporated with a poly (ethylene glycol) (PEG)-grafted chitosan (CS/PEG) and developed CS/PEG CPC. The characterization of CS/PEG CPC was conducted using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The initial properties of CS/PEG CPCs, such as the pH, porosity, mechanical strength, zeta potential, and in vitro biocompatibility using the WST-1 assay, were also investigated. Moreover, osteocompatibility of CS/PEG CPCs was carried out via Alizarin Red S staining, immunocytochemistry, and Western blot analysis. CS/PEG CPC has enhanced mechanical strength compared to CPC, and the cohesion test also demonstrated in vivo stability. Furthermore, we determined whether CS/PEG CPC is a suitable candidate for promoting the osteogenic ability of Dental Pulp Stem Cells (DPSC). The elution of CS/PEG CPC entraps more calcium ion than CPC, as confirmed through the zeta potential test. Accordingly, the ion trapping effect of CS/PEG is considered to have played a role in promoting osteogenic differentiation of DPSCs. The results strongly suggested that CS/PEG could be used as suitable additives for improving osteogenic induction of bone substitute materials.

Histological Assessment of Injectable Macro-porous Calcium Phosphate Cement (CPC) Versus Autogenous Bone Graft on Healing of Osseous Defect (Experimental Animal Study)

Objective: The aim of this study is to evaluate histologically the healing potential of injectable macro-porous Calcium Phosphate Cement and autogenous bone. (Normal bone healing) on surgically induced bone defect on femur bone of rabbit. Materials and Methods: Twelve adult white male New Zealand rabbits were selected for this study. Rabbits were divided into two groups and the two groups according to a two evaluation periods divided into 2 subgroups. Rabbits were anesthetized with intramuscular anethesia, and two osseous defects had been created in the distal aspect of the femur bone.one of this defects injected by a grafting material (SI-HPMC CPC) and the other left empty as control (normal healing).Animal were sacrificed after two sacrifice dates and the femur bone excised for histological and statistical evaluation.esults: Rabbits from each group were sacrificed after 2 and 4 weeks. The femur bone containing the induced defect was dissected. Each femur bone was excised using hard tissue microtome. Each slice was then fixed in 10% neutral buffered formalin. The formalin-fixed bone samples were decalcified in 15% buffered formic acid solution and processed for routine histological examination using hematoxylin and eosin stain under light microscope.. Conclusion: According to our results in the present study, we can consider Si-HPMC CPC a viable alternative to the autogenous bone in the healing of osseous bone defects . In the present study, the new and simple method to prepare macroporous CPCs using Si-HPMC a foaming agent in connected syringe , result

Calcium phosphate-based composite cement: Impact of starch type and starch pregelatinization on its physicochemical properties and performance in the vertebral fracture surgical models in vitro.

Calcium phosphate cement (CPC) modified with native and pregelatinized normal corn and waxy maize starches was studied. Effects of starch pregelatinization and starch type on the physicochemical properties of CPC were investigated. CPC modified with pregelatinized normal corn starch (CPB-PNC) or pregelatinized waxy maize starch (CPB-PW) was evaluated by two vertebral fracture surgical models in vitro. Both granular and pregelatinized starches significantly improved the setting times and injectability of CPC, but only the pregelatinized starches improved the anti-collapsibility and compressive strength of CPC significantly. CPB-PW, whose micro-structure was compact and uniform, showed the best physicochemical properties. Addition of starch did not inhibit the hydro-reaction of CPC. Unmodified CPC had very poor dispersibility and could not apply in the tests of the surgical models. Pregelatinized starch especially waxy maize starch improved the dispersibility of CPC and showed good dispersion area, volume, improved pull-out force and maximum torque in the Sawbones sponge model. Similarly, in the minimally invasive kyphoplasty model, CPB-PNC and CPB-PW could disperse in the osteoporotic sheep vertebrae and improve the compressive strength of the sheep vertebral body. In conclusion, starch pregelatinization and starch botanical source affect the physicochemical properties of CPC significantly. Bone cements modified by different starches also performed differently in surgical models for osteoporotic vertebral fracture. Pregelatinized waxy maize starch may be a better candidate for CPC modification comparing to the pregelatinized normal corn starch.

Physicochemical, setting, rheological, and mechanical properties of a novel bio-composite based on apatite cement, bioactive glass, and alginate hydrogel

Calcium phosphate cements (CPC) have been widely investigated as bone substitutes, owing to their attractive features in terms of physicochemical and biocompatibility properties. However, the clinical applicability of this group of biomaterials is still critically limited by its poor strength and rheological properties in terms of injectability and cohesion. The present work aims to develop novel composite cement based on calcium phosphate cement (CPC) and bioactive glass (BG), associated with sodium alginate hydrogel (Alg). The composition, microstructure, setting, rheological, and mechanical properties of this composite cement were further investigated. Evaluation of setting properties showed that BG participates crucially in the setting reaction as a calcium and phosphate provider and serves as a setting accelerator. Thus, the setting time appears lower in these cements than in the reference CPC cement: it decreases from 75 to 42 min as the BG content increases from 10 to 25 wt% and is delayed from 42 to 73 min while the Alg amount augmented from 1 to 5 wt%. The rheological evaluation revealed that injectability was slightly improved with increasing BG content compared to the injectability of CPC, reaching a value close to 100% when combined with Alg hydrogel. The anti-washout property appeared to be weak for the CPC with or without BG, which are disintegrated in solution. The cohesiveness was significantly improved by introducing Alg hydrogel; furthermore, the addition of 5 wt% of alginate hydrogel induced an increase in the compressive strength about twice (7.2 MPa) higher than that of the reference CPC (4.0 MPa). According to the above findings, the addition of BG acts as a setting accelerator leading to a fast apatite formation, while the introduction of Alg hydrogel as a rheological promoting agent improves the injectability and cohesion. The combination of BG and Alg as additives increased the compressive strength compared to the reference cement.

Bioactive small molecules in calcium phosphate scaffold enhanced osteogenic differentiation of human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) are exciting for regenerative medicine due to their multi-potent differentiation. SB431542 bioactive molecule can activate bone morphogenetic protein-signalling in osteoblasts. The objectives were to: (1) develop a novel injectable calcium phosphate cement (CPC)-SB431542 scaffold for dental/craniofacial bone engineering; and (2) investigate cell proliferation and osteo-differentiation of hiPSC-derived mesenchymal stem cells (hiPSC-MSCs) on CPC-SB431542 scaffold. Three groups were tested: CPC control; CPC with SB431542 inside CPC (CPCSM); CPC with SB431542 in osteogenic medium (CPC+SMM). SB431542 in CPC promoted stem cell proliferation and viability. hiPSC-MSCs differentiated into osteogenic lineage and synthesized bone minerals. CPC with SB431542 showed much greater osteo-expressions and more bone minerals than those without SB431542. In conclusion, hiPSC-MSCs on CPC scaffold containing SB431542 showed excellent osteo-differentiation and bone mineral synthesis for the first time. CPC was a suitable scaffold for delivering stem cells and SB431542 to promote bone regeneration in dental/craniofacial applications.

Characterization and In Vitro Evaluations of Injectable Calcium Phosphate Cement Doped with Magnesium and Strontium.

Injectable calcium phosphate cement is a promising biomaterial for hard tissue repair due to its osteoinductivity, biocompatibility properties, and its use to correct defect areas involving narrow cavities with limited accessibility by the minimally invasive technique. Microwave-synthesized hydroxyapatite (HA) was used for the preparation of cement. In recent years, both magnesium and strontium calcium phosphate cements have exhibited rapid setting, improved mechanical strength, and a good resorption rate. A big step still remains to develop injectable magnesium and strontium phosphate cements with ideal self-setting properties, adequate mechanical strength, and good biocompatibility for clinical applications. In this study, both magnesium and strontium were doped with synthesized semiamorphous and crystalline hydroxyapatite (HA). The powder mixture was mixed with Na2HPO4, NaH2PO4, and a carboxymethyl cellulose (CMC) solution to develop the novel magnesium and strontium calcium phosphate cement. The setting time, physiochemical properties of hardened cement, microstructure, mechanical strength, and injectability of the prepared cement were studied. The toxicity evaluation and cell adhesion, which are necessary to identify the suitability of the material for different applications, were quantified and investigated using fibroblast cells. The setting time of cement was reduced substantially for magnesium- or strontium-doped cement by 2 min. The phase composition of the hardened cement expresses the semiamorphous or crystalline phase of HA with additives. Smooth and complete injection of cement paste was observed in semiamorphous HA-based cement. The intercellular reactive oxygen stress (ROS) of the Sr2+-doped cement sample showed varied degrees of toxicity to cells in terms of different concentrations. The Mg2+-doped cement showed significant attachment of cells after treatment at varying incubation times.

Bone cements for therapy and regeneration for minimally invasive treatment of neoplastic bone defects.

Although calcium phosphate cements (CPCs) have been clinically used to repair bone defects caused by bone tumor resection, traditional CPCs cannot kill the remaining tumor cells after surgery and prevent cancer recurrence. In this study, a multifunctional injectable metal-organic framework (MOF) cobalt coordinated tetrakis(4-carboxyphenyl)porphyrin (Co-TCPP)-modified calcium phosphate cement (Co-TCPP/CPC) was prepared for the minimally invasive treatment of neoplastic bone defects. The incorporation of Co-TCPP not only retained the good injectability of bone cements, but also shortened the setting time, improved the compressive strength, and endowed them with excellent photothermal properties. The hyperthermia effect induced by the presence of Co-TCPP well induced the therapeutic effect against bone tumors both in vitro and in vivo. Moreover, Co-TCPP/CPC exhibited desirable osteogenesis and angiogenesis by promoting bone and vascular regeneration in vivo. Therefore, the Co-TCPP composite bone cement demonstrated its great potential for bone tumor therapy and tissue regeneration, representing a multifunctional biomaterial for the treatment of neoplastic bone defects.

Setting Characteristics and High Compressive Strength of an Anti-washout, Injectable Calcium Phosphate Cement Combined with Thermosensitive Hydrogel.

In this work, a thermosensitive poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel was introduced into calcium phosphate cement (CPC) to enhance the anti-washout property of CPC. The effects of the hydrogel on the setting time, injectability, anti-washout property and compressive strength of CPC were thoroughly investigated. The results showed that the hydrogel significantly increased the injectability and anti-washout property of CPC, meanwhile maintained the setting time with an acceptable range. Moreover, the hydrogel improved the initial compressive strength of CPC. The composite cement with 20% v/v hydrogel in the liquid phase showed fine crystals of hydration product, a more compact microstructure and lower porosity compared with control CPC. The analysis of X-ray diffraction (XRD), infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated that suitable volume ratio of hydrogel (20% v/v) in the setting liquid of CPC could promote the formation of hydroxyapatite in the early hydration period. The degradation behavior of the cement was characterized by immersion tests in simulated body fluid. The hydrogel had no adverse effect on the degradation rate of CPC over the immersion period of 23 days. This study indicated that incorporating PLGA-PEG-PLGA hydrogel could be a promising strategy to reinforce the handing properties and initial compressive strength of calcium phosphate cement.

Deposition of Hydroxyapatite on Silica Made from Rice Husk Ash to Produce the Powder Component of Calcium Phosphate Cement

Hydroxyapatite (HA) has been deposited on silica (SiO2) particles to produce HA-SiO2 composite that will be used as the powder component of calcium phosphate cement. HA was expected to be on the composite surface to maintain its bioactivity. SiO2 was made by the sol-gel method, in which silicate solution was extracted from rice husk ash with NaOH solution. Deposition of HA on SiO2 was carried out by wet chemical deposition method at various Ca/Si molar ratio (in a range of 5–25) followed by calcination at 600 °C for 2 h. Results showed that HA was successfully deposited on SiO2 particles. The cell parameters of the HA crystals were slightly distorted by the presence of SiO2 and HA in the composite had a bigger cell volume than pure HA. The crystallite size of HA in the composites increased with the increase of the Ca/Si ratio but the values were smaller than pure HA. SiO2 acted as a morphology directing agent. At low Ca/Si ratio, the HA-SiO2 particles were in a form of short rod-like particles with sizes of < 50 nm, while at high Ca/Si ratio, a mixture of short and long rod-like particles with the size of < 100 nm was obtained. The zeta potential of composites was almost similar to pure HA. These properties indicated that HA-SiO2 composites support the bioactivity of injectable calcium phosphate cement.

Effects of zirconia additives on β-tricalcium-phosphate cement for high strength and high injectability

Injectable calcium phosphate cements (CPCs) exhibit many advantages as bone substitution materials. However, the strength of injectable CPCs after setting are often insufficient. In our previous studies, mechano-chemically modification of β-tricalcium phosphate cement powder through a planetary ball-milling process exhibited simultaneous improvement in the strength and injectability of CPC. Two plausible effects of this process are: changes in the CPC powder properties and zirconia abrasion powder contamination from the milling pot and balls. The objective of the present study is to separately evaluate these two effects on the strength and injectability of CPCs.The calculated injectability of the cement paste with and without the addition of zirconia powder were higher than 65% at 6 h after mixing. These values were much higher than that of the CPC paste without mechano-chemically modification, and similar to that of CPC with zirconia abrasion powder contamination. By contrast, the compression strength of the set CPC with zirconia powder additives were higher than that without the addition, and similar to that of CPC with zirconia abrasion powder contamination. These results suggest that the changes in the CPC powder properties due to mechano-chemically modification mainly affected the injectability of the CPC paste, and the zirconia abrasion powder contamination of the CPC powder affected the strength of the set CPC.

Combination of biocompatible hydrogel precursors to apatitic calcium phosphate cements (CPCs): Influence of the in situ hydrogel reticulation on the CPC properties.

In the field of bone regenerative medicine, injectable calcium phosphate cements (CPCs) are used for decades in clinics, as bone void fillers. Most often preformed polymers (e.g., hyaluronic acid, collagen, chitosan, cellulose ethers…) are introduced in the CPC formulation to make it injectable and improve its cohesion. Once the cement has hardened, the polymer is simply trapped in the CPC structure and no organic subnetwork is present. By contrast, in this work a CPC was combined with organic monomers that reticulated in situ so that a continuous biocompatible 3D polymeric subnetwork was formed in the CPC microstructure, resulting in a higher permeability of the CPC, which might allow to accelerate its in vivo degradation. Two options were investigated depending on whether the polymer was formed before the apatitic inorganic network or concomitantly. In the former case, conditions were found to reach a suitable rheology for easy injection of the composite. In addition, the in situ formed polymer was shown to strongly affect the size, density, and arrangement of the apatite crystals formed during the setting reaction, thereby offering an original route to modulate the microstructure and porosity of apatitic cements.

Preshearing is an in situ setting modification method for inorganic bone cements

AbstractThe flow behaviour and injectability of calcium phosphate cements are outcomes of the complex interplay between time‐dependent processes of dissolution, nucleation and crystal growth. Their dependence on shear strains, frequencies and rates has been revealed by rheological investigation of the setting processes of a brushite cement under torsional flow. Various oscillatory torsional strain amplitudes and frequencies were seen to promote dissolution or delay crystal intergrowth compared to quiescently set cement samples. Oscillatory torsional strain amplitudes higher than the linear viscoelastic strain limit resulted in a pronounced lag in crystal intergrowth. Dissolution was enhanced and setting was promoted with increasing frequency and strain amplitude within the linear viscoelastic strain range. Changing the preshearing mode to steady torsion increased energy spent to microstructural deformation, counteracting the beneficial vibratory effect on cement setting kinetics, and produced a net retardation by the disruption of the crystal network structure. Such deformation history can be created in the cement suspension prior to injection during clinical practice by precise adjustment of the preshearing modes and parameters to enable the orthopaedic surgeon tailor the setting time, flow behaviour and injectability of calcium phosphate cements in situ without altering the cement chemistry, hence bioactivity.