Calcium Phosphate Cement Research Articles

Indications and Limitations of Carbonated Calcium Phosphate Cement for Secondary Contouring Cranioplasty: A Long-Term Institutional Experience.

Abstract The authors describe our long-term institutional experience utilizing carbonated calcium phosphate (CCP) cement for secondary cranioplasty refinements with the goals to The authors conducted a retrospective cohort study of patients undergoing secondary cranioplasty for forehead reshaping utilizing CCP between June 2007 and August 2018. Exclusion criteria included < 3-month follow-up. The primary outcome was aesthetic forehead correction determined by Whitaker classification, while secondary outcomes included complications and reoperations. In total, 107 patients met inclusion with a median age of 15.5 years. The majority of bony deficits were limited to the frontal region (90.7%), required onlay application (87.7%) of large (96.0 cm2) partial thickness (85.7%) cranial defects, in a clean setting (99.0%), and ASA grade II (69.7%). Median Whitaker classification decreased from 2.3 [IQR: 2, 2.3] preoperatively to 1.0 [1.0, 1.3] postoperatively (P < 0.01). There was no difference in Whitaker classification between early and late postoperative timepoints (P < 0.17). The complication rate was 13.2%, with the majority related to infection (5/14). Factors associated with complications included frontal sinus proximity (OR 3.6, P < 0.04) and the use of interposition titanium mesh for full-thickness reconstruction (OR 6.4, P < 0.02). CCP remains an effective alloplastic bone substitute with a complication rate of 13.2% in patients undergoing secondary, onlay cranioplasty. Early postoperative Whitaker classification may predict long-term aesthetic results. Complications may arise years following implantation, warranting long-term follow-up.

Strength and Biocompatibility of Heparin-Based Calcium Phosphate Cement Grafted with Ferulic Acid.

The biomimetic synthesis of carbonated apatites by biomolecule-based templates is a promising way for broadening apatite applications in bone tissue regeneration. In this work, heparin was used as an organic template to prepare uniform carbonate-based apatite nanorods (CHA) and graft ferulic acid (F-CHA) for enhanced bone mineralization. Next, by combining calcium phosphate cement (CPC) with different F-CHA/CPC ratios, a new type of injectable bone cement combined with F-CHA bioactive apatite was developed (CPC + F-CHA). The physicochemical properties, biocompatibility, and mineralization potential of the CPC + F-CHA composites were determined in vitro. The experimental results confirmed the preparation of highly biocompatible CHA and the compatibility of F-CHA with CPC. Although CPC + F-CHA composites with F-CHA (2.5 wt%, 5 wt%, and 10 wt%) showed a significant reduction in compressive strength (CS), compositing CPC with 10 wt% F-CHA yielded a CS suitable for orthopedic repair (CS still larger than 30 MPa). Spectroscopic and phase analyses revealed that the phase of the hydrothermally synthesized CHA product was not modified by the heparin template. Injection and disintegration tests indicated that the CPC + F-CHA composites have good biocompatibility even at 10 wt% F-CHA. D1 osteoprogenitor cells were cultured with the composites for 7 days in vitro, and the CPC + 10%F-CHA group demonstrated significantly promoted cell mineralization compared with other groups. Given these results, the use of over 10% F-CHA in CPC composites should be avoided if the latter is to be applied to load-bearing areas. A stress-shielding device may also be recommended to stabilize these areas. These newly developed biocompatible CPC + F-CHA have great potential as osteoconductive bone fillers for bone tissue engineering.

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

Selenium-modified calcium phosphate cement can accelerate bone regeneration of osteoporotic bone defect.

The purpose is to observe whether local administration with selenium (Se) can enhance the efficacy of calcium phosphate cement (CPC) in the treatment of osteoporotic bone defects. Thirty ovariectomized (OVX) rats with two defects were generated and randomly allocated into the following graft study groups: (1) OVX group (n = 10), (2) CPC group (n = 10); and (3) Se-CPC group (n = 10). Then, these selenium-modified calcium phosphate cement (Se-CPC) scaffolds were implanted into the femoral epiphysis bone defect model of OVX rats for 12 weeks. Micro-CT, history, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and to explore the possible mechanism. Micro-CT and histological analysis evaluation showed that the Se-CPC group presented the strongest effect on bone regeneration and bone mineralization when compared with the CPC group and the OVX group. Protein expressions showed that the oxidative stress protein expressions, such as SOD2 and GPX1 of the Se-CPC group, are significantly higher than those of the OVX group and the CPC group, while Se-CPC remarkably reduced the expression of CAT. RT-qPCR analysis showed that the Se-CPC group displayed more OPG than the OVX and CPC groups (p < 0.05), while Se-CPC exhibited less RANKL than the OVX and CPC groups (p < 0.05). Our current study demonstrated that Se-CPC is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local oxidative stress and through OPG/RANKL signaling pathway.

A bone replacement-type calcium phosphate cement that becomes more porous in vivo by incorporating a degradable polymer

This study investigated whether mixing low viscosity alginic acid with calcium phosphate cement (CPC) causes interconnected porosity in the CPC and enhances bone replacement by improving the biological interactions. Furthermore, we hypothesized that low viscosity alginic acid would shorten the setting time of CPC and improve its strength. CPC samples were prepared with 0, 5, 10, and 20% low viscosity alginic acid. After immersion in acetate buffer, possible porosification in CPC was monitored in vitro using scanning electron microscopy (SEM), and the setting times and compressive strengths were measured. In vivo study was conducted by placing CPC in a hole created on the femur of New Zealand white rabbit. Microcomputed tomography and histological examination were performed 6 weeks after implantation. SEM images confirmed that alginic acid enhanced the porosity of CPC compared to the control, and the setting time and compressive strength also improved. When incorporating a maximum amount of alginic acid, the new bone mass was significantly higher than the control group (P = 0.0153). These biological responses are promising for the translation of these biomaterials and their commercialization for clinic applications.

Adapting the Pore Size of Individual, 3D-Printed CPC Scaffolds in Maxillofacial Surgery.

Three dimensional (3D) printing allows additive manufacturing of patient specific scaffolds with varying pore size and geometry. Such porous scaffolds, made of 3D-printable bone-like calcium phosphate cement (CPC), are suitable for bone augmentation due to their benefit for osteogenesis. Their pores allow blood-, bone- and stem cells to migrate, colonize and finally integrate into the adjacent tissue. Furthermore, the pore size affects the scaffold’s stability. Since scaffolds in maxillofacial surgery have to withstand high forces within the jaw, adequate mechanical properties are of high clinical importance. Although many studies have investigated CPC for bone augmentation, the ideal porosity for specific indications has not been defined yet. We investigated 3D printed CPC cubes with increasing pore sizes and different printing orientations regarding cell migration and mechanical properties in comparison to commercially available bone substitutes. Furthermore, by investigating clinical cases, the scaffolds’ designs were adapted to resemble the in vivo conditions as accurately as possible. Our findings suggest that the pore size of CPC scaffolds for bone augmentation in maxillofacial surgery necessarily needs to be adapted to the surgical site. Scaffolds for sites that are not exposed to high forces, such as the sinus floor, should be printed with a pore size of 750 µm to benefit from enhanced cell infiltration. In contrast, for areas exposed to high pressures, such as the lateral mandible, scaffolds should be manufactured with a pore size of 490 µm to guarantee adequate cell migration and in order to withstand the high forces during the chewing process.

Bioactive Glass Modified Calcium Phosphate Cement with Improved Bioactive Properties: A Potential Material for Dental Pulp-Capping Approaches

Direct pulp capping (DPC) is one of the treatment plans for deep caries with mechanical pulp exposure that can replace invasive treatments. This study aimed to assess the apatite-forming ability and solubility of a calcium phosphate cement (CPC) modified with bioactive glass (BG) as a potential bioactive material for DPC.Three different biomaterials including CPC, BG, and CPC/BG composite were used in this study. For bioactivity evaluation, specimens were immersed in simulated body fluid (SBF) for 5 time periods (3, 7, 14, 21 and 28 days). The samples were analyzed by SEM, EDS and XRD to confirm the formation of hydroxyapatite. The solubility was calculated by measuring the initial and final mass according to the ISO 6876 specifications.According to the results of this study, SEM observations and XRD analysis revealed higher formation of hydroxyapatite crystals in the CPC/BG Group and also at the shorter time than those in the CPC and BG groups. Concerning solubility, the CPC group showed the most solubility after 7 days and the BG group showed the lowest one. At this time the difference between CPC and BG groups was statistically meaningful (p value=0.003). After 30 days the CPC/BG group exhibited the lowest solubility value. At the day 30, the CPC and BG groups showed significant difference in their solubility (p value=0.04).).Based on the results, addition of BG to CPC improved bioactivity properties of CPC material and did not affect its solubility adversely. The CPC/BG composite seems to be a promising material for DPC. Further in vivo studies are needed to prove its clinical success.

Clinical observations of vancomycin-loaded calcium phosphate cement in the 1-stage treatment of chronic osteomyelitis: a randomized trial.

This study sought to explore the clinical effects of vancomycin-loaded calcium phosphate cement (CPC) in the treatment of chronic osteomyelitis. Ninety-eight patients with chronic osteomyelitis, who were treated at our Department from December 1st, 2014 to December 1st, 2015, were randomly allocated into the research group or the control group. Each group comprised 49 patients. Patients in the research group (Group A) received a 1-stage treatment of vancomycin-loaded CPC after debridement, while those in the control group (Group B) received an irrigation and drainage device that administered irrigated antibiotics. The treatment effects, recurrence rates, and safety outcomes of the two groups were observed. Patients in the two groups were followed up with for a period of 12 months. The control group without recurrence in one case. There was some systemic adverse postoperative effects and safety issues. The X-ray film showed that CPC filling is good and part of the degradation of osteogenesis. Some patients in the research group the CPC particles were absorbed, the bone defect area was healed, after One-year postoperatively. Further, the cure rate was high. One-stage vancomycin-loaded CPC implantation osteomyelitis lesions fill the die cavity, enable patients to continue to fight infection, induce bone defect osteogenesis, reduce the recurrence of chronic osteomyelitis, and are an effective method for treating chronic osteomyelitis. Chinese Clinical Trial Registry website (ChiCTR2100044724).

Effects of pullulan on the biomechanical and anti-collapse properties of dicalcium phosphate dihydrate bone cement.

In this work, a modified dicalcium phosphate dihydrate (DCPD) bone cement with unique biodegradable ability in a calcium phosphate cement system was prepared by the hydration reaction of monocalcium phosphate monohydrate and calcium oxide and integration with pullulan (Pul), a non-toxic, biocompatible, viscous, and water-soluble polysaccharide that has been successfully used to improve defects in DCPD bone cement, especially its rapid solidification, fragile mechanical properties, and easy collapse. The effect of different contents of Pul on the structure and properties of DCPD were also studied in detail. The modified cement was characterised by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet-visible absorption, X-ray photoelectron spectroscopy analysis, and rheological property measurements. The results indicated that Pul promoted the hydration formation of DCPD, and interface bonding occurred between Pul and DCPD. With increasing content of Pul, the setting time of the DCPD bone cement increased from 2.6 min to 42.3 min, the compressive strength increased from 0 MPa to 20.4 MPa, and the anti-collapse ability also improved owing to the strong interface bonding, implying that the DCPD bone cement improved by Pul has better potential for application in the field of non-loading bone regenerative medicine compared to unmodified DCPD bone cement.

Bioresorbable porous β-tricalcium phosphate chelate-setting cements with poly(lactic-co-glycolic acid) particles as pore-forming agent: fabrication, material properties, cytotoxicity, and in vivo evaluation

ABSTRACT Calcium-phosphate cements (CPCs) have been used as bone filling materials in orthopaedic surgery. However, CPCs are set using an acid-base reaction, and then change into stable hydroxyapatite (HAp) in a living body. Therefore, we developed bioresorbable chelate-setting β-tricalcium phosphate (β-TCP) cements based on surface modifications of inositol phosphate (IP6). In order to improve the bioresorbability, we fabricated IP6/β-TCP cements hybridized with poly(lactic-co-glycolic acid) (PLGA) particles as a pore-forming agent. The compressive strengths of the cements with the amounts of 5 and 10 mass% PLGA particles were 23.2 and 22.8 MPa, respectively. There was no significant difference from cements without PLGA (23.4 MPa). The setting times of the cement specimens with PLGA particles (30 min) were a little longer than those without PLGA particles (26.3 min). The lack of cytotoxicity of the cement specimens was confirmed using osteoblast-like cells (MC3T3-E1). Cylindrical defects were made by drilling into the tibia of mini-pigs and injecting the prepared cement pastes into the defects. Twelve weeks after implantation the specimens were stained with toluidine blue and histologically evaluated. Histological evaluation of cement specimens with PLGA particles showed enhanced bioresorbability. Newly-formed bone was also observed inside cement specimens with PLGA particles. The IP6/β-TCP cement specimens with PLGA particles had excellent material properties, such as injectability, compressive strength, high porosity, no cytotoxicity in vitro, bioresorption and bone formation abilities in vivo. Organic-inorganic hybridized CPCs are expected to be valuable as novel biodegradable paste-like artificial bone fillers.

Efficacy of calcium phosphate cementing in the surgical treatment of Sanders Type II and III calcaneal fractures using screw fixation with sinus tarsi approach.

This study aimed to determine the effectiveness of calcium phosphate cementing in the surgical treatment of Sanders type II and III calcaneal fractures using screw fixation with sinus tarsi approach. In this retrospective study, 85 feet of 84 patients (74 males, 10 females; mean age 43 [17-61] years) in whom screw fixation was performed using the sinus tarsi approach for Sanders type II or III calcaneal fractures were included. The mean follow-up was 28 (14-39) months. Patients were categorized into 2 groups on the basis of whether calcium phosphate cement (CPC) was used. Group 1 had 37 patients with CPC (38 calcaneal fractures) and group 2 had 47 patients without CPC (47 calcaneal fractures). In the clinical assessment, the American Orthopedic Foot Ankle Society (AOFAS) hind foot score and the Maryland Foot Score (MFS) were used at the final follow-up. In the radiological assessment, Bohler's angle on plain radiograph and posterior facet step-off on computed tomography were measured pre-and postoperatively. At the final follow-up, the mean Bohler's angle was 26.2° (20°-33°) in group 1 and 26° (17°-30°) in group 2 (P = 0.85). The mean posterior facet step-off was 1.6 (0-5) mm in group 1 and 1.5 (0-5) mm in group 2 (P = 0.85). The mean AOFAS score was 83.8 (59-100) in group 1 and 85.8 (60-100) in group 2 (P = 0.5). The mean MFS was 86.3 (66-100) in group 1 and 87.7 (66-100) in group 2 (P = 0.62). Evidence from this study have shown that CPC may have no significant effect on clinical and radiological outcomes in the surgical treatment of Sanders type II and III calcaneal fractures using screw fixation with sinus tarsi approach.

Effect of the Addition of Alginate and/or Tetracycline on Brushite Cement Properties.

Calcium phosphate cements have the advantage that they can be prepared as a paste that sets in a few minutes and can be easily adapted to the shape of the bone defect, which facilitates its clinical application. In this research, six formulations of brushite (dicalcium phosphate dihydrated) cement were obtained and the effect of the addition of sodium alginate was analyzed, such as its capacity as a tetracycline release system. The samples that contain sodium alginate set in 4 or 5 min and showed a high percentage of injectability (93%). The cements exhibit compression resistance values between 1.6 and 2.6 MPa. The drug was released in a range between 12.6 and 13.2% after 7 days. The antimicrobial activity of all the cements containing antibiotics was proven. All samples reached values of cell viability above 70 percent. We also observed that the addition of the sodium alginate and tetracycline improved the cell viability.

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.

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.

Soluble phosphate salts as setting aids for premixed calcium phosphate bone cement pastes

Recently, premixed calcium phosphate cement pastes have been proposed as biomaterials for bone tissue repair and regeneration. Use of premixed pastes saves the time and removes an extra step during a medical operation. α-Tricalcium phosphate (α-TCP) based cements set to form calcium deficient hydroxyapatite which has a moderate bioresorbtion speed. α-TCP cements require a setting aid, usually a sodium or potassium phosphate salt, to speed up the setting process. Within the current research we investigated which setting aid has significant advantage, if α-TCP is used in form of non-aqueous premixed paste. This approach offers the application of simple ingredients to produce a premixed calcium phosphate cement. The following properties of cement formulations were evaluated: cohesion, phase composition, microstructure, pH value of the liquid surrounding the cement, and compressive strength.Compositions using mixture of basic and acidic potassium phosphate salts (KH2PO4 and K2HPO4) in sufficient amounts give the best overall results (adequate cohesion and pH of the surrounding liquid, hydrolysis of starting materials within 48 h, and compressive strength of 12 ± 3 MPa). Cement prepared with basic sodium phosphate salt (Na2HPO4) as setting aid had considerably higher compressive strength 22 ± 1 MPa, but the pH of the surrounding liquid was basic (9.0).

Clinical study of calcium phosphate cement loaded with recombinant human bone morphogenetic protein 2 combined with calcium phosphate cement loaded with antibiotic for chronic osteomyelitis with bone defect

To compare the effectiveness of calcium phosphate cement (CPC) loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) combined with CPC loaded with antibiotic versus CPC loaded with antibiotic alone in one stage for chronic osteomyelitis with bone defect. A single-blind prospective randomized controlled clinical trial was conducted. Between April 2018 and April 2019, 80 patients of chronic osteomyelitis with bone defect in accordance with the random number table were randomly divided into two groups, 40 in the trial group (CPC loaded with rhBMP-2 combined with CPC loaded with antibiotic) and 40 in the control group (CPC loaded with antibiotic). There was no significant difference in gender, age, disease duration, lesion, and preoperative white blood cells (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) between the two groups ( P>0.05). All patients were implanted the corresponding CPC and external fixator after lesion clearance in the two groups. The postoperative WBC count, platelet count, ESR, CRP, hospital stay, cure rate of osteomyelitis, repaired bone defect volume, the time of external fixator removal, and the time of full weight-bearing of the affected limb were compared between the two groups. All patients were followed up 12-24 months, with an average of 18.4 months. There was no significant difference in WBC count, platelet count, ESR, and CRP between the two groups at 4 weeks after operation ( P>0.05). There were significant differences in WBC count, platelet count, and CRP in the two groups between 1 week before operation and 4 weeks after operation ( P<0.05). And the ESR showed no significant difference between pre- and post-operation in the two groups ( P>0.05). In the trial group, the anaphylactic exudate occurred in 1 patient with tibial osteomyelitis and the incision healed after oral administration of loratadine. The incisions of other patients healed by first intention in the two groups. One case of distal tibial osteomyelitis recurred in each group, and 1 case of humeral osteomyelitis recurred in the control group. The cure rates of osteomyelitis were 97.5% (39/40) in the trial group and 95% (38/40) in the control group, showing no significant difference between the two groups ( χ 2 =0.000, P=1.000). There was no significant difference in the repaired bone defect volume and hospital stay between the two groups ( P>0.05). X-ray film and CT showed that the bone defects were repaired in the two groups. The time of external fixator removal and the time of full weight-bearing of the affected limb were significantly shorter in the trial group than in the control group ( P<0.05). Application of CPC loaded with rhBMP-2 and antibiotic in one stage is effective for the chronic osteomyelitis with bone defect, which can accelerate the bone regeneration in situ to repair bone defect, reduce the trauma, shorten the course of treatment, and obtain good function of the affected limb.

Calcium phosphate-based materials regulate osteoclast-mediated osseointegration

Calcium phosphate-based materials (CaP) have been widely used as bone graft substitutes with a decent osseointegration. However, the mechanism whereby cells function and repair the bone defect in CaP micro-environment is still elusive. The aim of this study is to find the mechanism how osteoclast behaviors mediate bone healing with CaP scaffolds. Recent reports show that behaviors of osteoclast are closely related with osteogenesis, thus we make a hypothesis that active osteoclast behaviors induced by CaP facilitate bone healing. Here, we found a new mechanism that CaP can regulate osteoclast-mediated osseointegration. Calcium phosphate cement (CPC) is selected as a representative CaP. We demonstrate that the osteoclast-mediated osseointegration can be strongly modulated by the stimulation with CaP. An appropriate Ca/P ratio in CaP can effectively promote the RANKL-RANK binding and evoke more activated NF-κB signaling transduction, which results in vigorous osteoclast differentiation. We observe significant improvement of bone healing in vivo, owing to the active coupling effect of osteoclasts. What is more noteworthy is that the phosphate ions released from CaP can be a pivotal role regulating osteoclast activity by changing Ca/P ratio readily in materials. These studies suggest the potential of harnessing osteoclast-mediated osteogenesis in order to develop a materials-manipulated approach for improving osseointegration.

Application of Graphene-Based Nanomaterials Combined with Early Exercise Rehabilitation Training in the Treatment of Patients with Infectious Bone Defects

Methods of treating bone defects include autogenous bone and allogeneic bone transplantation, tissue engineering technology, gene therapy, growth factor and adjuvant therapy of physical therapy, etc. However, most treatment schemes have obvious disadvantages. The purpose of this paper is to study the application of graphene-based nanomaterials combined with early exercise rehabilitation training in the treatment of patients with infectious bone defects. The biomedical properties and biomedical applications of graphene are briefly introduced through literature research and investigation, and bone defect diseases and commonly used treatment methods are analyzed. Graphene is used in many biomedical fields, such as disease diagnosis, biosensing, antibacterial and antiviral materials, cancer targeting, photothermal therapy, drug delivery, cell electrical stimulation, tissue engineering, stem cell technology, DNA sequencing and fluorescent (FL) tracking molecular probes. The effects of graphene-based nanomaterials and rehabilitation exercise on the treatment of infectious bone defects were compared through controlled experiments. The results show that although the repair effect of graphene-based nano-materials is not as good as that of autogenous bone, the difference is not significant, and it is better than calcium phosphate cement. After rehabilitation exercise, the curative effect of graphene experimental group was improved. In the 12th week, the tensile strength reached 5.78 N, and the torsional strength reached 0.93 N m, which exceeded the group of autogenous bone without rehabilitation exercise. This paper discusses the strength-related repair effect, but the in vivo toxicity of graphene needs further study.

Combined use of calcium phosphate cement, mesenchymal stem cells and platelet-rich plasma for bone regeneration in critical-size defect of the femoral condyle in mini-pigs.

Aim: To investigate the outcome of autologous bone marrow mesenchymal stem cells (BMMSCs) and platelet-rich plasma in combination with calcium phosphate cement (CPC) scaffold to reconstruct femoral critical bone defects in mini-pigs. Materials & methods: Scanning electron microscopy, micro-computed tomography evaluation and quantitative histological assessment were used. Results & conclusion: BMMSCs were attached to the CPC scaffold after 7 days of culture and decreased the residual CPC material in each group at 12 weeks compared with 6 weeks. The newly formed bone area was higher in the CPC+SC+P group than in the CPC group at each time point (all p < 0.05). The strategy of CPC combined with BMMSCs and platelet-rich plasma might be an effective method to repair bone defects.

Influence of polyacrylic acid (PAA)/Na2HPO4 mixture on biphasic calcium phosphate cement: Enhancing strength and cell viability

AbstractThis study has investigated the effect of combination of new liquid phase mixture of disodium hydrogen phosphate (Na2HPO4) and polyacrylic acid (PAA) on the compressive strength, setting time, bioactivity, and cytotoxicity of biphasic calcium phosphate cement. The PAA was known as one of water‐soluble and biocompatible polymers to improve the mechanical performances of the bone cement, but it usually inhibits the phase conversion to hydroxyapatite after the cement has already set. The aim of this work was to evaluate the incorporation of the mixture of PAA and Na2HPO4 into biphasic cement. We have found the crucial concentration for adding PAA/Na2HPO4 at 30:70 v/v% to enhance the mechanical strength, cell viability, and maintain bioactivity. The phase composition and crosslinking reaction between PAA and alpha‐tricalcium phosphate (α‐TCP) powder were detected by XRD and FTIR techniques. The beta‐tricalcium phosphate (β‐TCP) was added in the formula to achieve the biphasic cement, which composed of β‐TCP and apatite/calcium deficient‐hydroxyapatite (CD‐HA) in the final product. The biphasic granule commercial product was used as comparison in the cell viability test. This work had been confirmed that the cement was a nontoxic material. Therefore, our results suggest that the PAA/Na2HPO4 could be beneficial for further clinical applications.