Effect Of Calcium Phosphate Cement Research Articles

Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression

Calcium phosphate cements (CPC) are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability, suitable to be used in minimally invasive treatment of bone defects. However the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties, in particular its osteoinductivity. Hyaluronic acid reinforced calcium phosphate cements (HA/CPC) showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its osteoinductivity. In our study, the compressive strength of HA/CPC increased significantly when the cement was added 1% hyaluronic acid (denoted as 1-HA/CPC). In the meantime, hyaluronic acid obviously promoted ALP activity, osteogenic related protein and mRNA expression of hBMSCs (human bone marrow mesenchymal stem cells) in vitro, cement group of HA/CPC with 4% hyaluronic acid adding (denoted as 4-HA/CPC) showed optimal enhancement in hBMSCs differentiation. After being implanted in rat tibial defects, 4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors, comparing to pure CPC and 1-HA/CPC groups. The underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid incorporation. These results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.

Effects of calcium phosphate cement combined with hyaluronic acid/curcumin on the proliferation and osteogenesis of osteoblasts

After using hyaluronic acid (HA) to modify curcumin (CUR), the effects of calcium phosphate cement (CPC) combined with HA/CUR on the proliferation and osteogenesis of osteoblasts were investigated. First, HA and CUR were esterified and covalently combined to prepare HA/CUR, and the characteristics were observed and the infrared spectrum was tested. Then, HA, CUR, and HA/CUR were mixed with CPC according to 5% ( W/ W) to prepare HA-CPC, CUR-CPC, and HA/CUR-CPC, respectively. Setting time detection, scanning electron microscope observation, injectable performance test, and compression strength test were conducted; and the CPC was used as a control. Osteoblasts were isolated and cultured from the skull of newborn Sprague Dawley rats, and the 2nd generation cells were cultured with the 4 types of bone cement, respectively. The effects of HA/CUR-CPC on the proliferation and osteogenesis of osteoblasts were estimated by the scanning electron microscopy observation, live/dead cell fluorescence staining, cell counting, osteopontin (OPN) immunofluorescence staining, alkaline phosphatase (ALP) staining,and alizarin red staining. Infrared spectroscopy test showed that HA and CUR successfully covalently combined. The HA/CUR-CPC group had no significant difference in initial setting time, final setting time, injectable rate, and compressive strength when compared with the other 3 groups ( P>0.05); scanning electron microscope observation showed that HA/CUR was scattered on CPC surface. After co-culture of bone cement and osteoblasts, scanning electron microscopy observation showed that the osteoblasts, which had normal morphology and the growth characteristics of osteoblasts, clustered and adhered to HA/CUR-CPC. There was no significant difference in cell survival rate between HA/CUR-CPC group and other groups ( P>0.05), and the number of cells significantly increased ( P<0.05); the degrees of OPN immunofluorescence staining, ALP staining, and alizarin red staining were stronger than other groups. HA/CUR-CPC has good biocompatibility and mechanical properties, which can promote the proliferation and osteogenesis of osteoblasts.

Improving osteogenesis of calcium phosphate bone cement by incorporating with manganese doped β-tricalcium phosphate.

Lack of osteogenic capacity limits the bone repair effect of calcium phosphate cement (CPC). In present work, bivalent manganese ion (Mn2+) doped β-tricalcium phosphate (Mn-TCP) was incorporated into CPC to enhance its osteogenic ability. The incorporation of Mn-TCP promoted the hydration reaction of CPC. The presence of Mn2+ made the hydration products finer. When adding 10wt% Mn-TCP in CPC (Mn-CPC-1), the setting time of CPC was shortened, whereas the strength and injectability were not changed. Mouse Bone marrow mesenchymal stem cells (mBMSCs) on Mn-CPC-1 and CPC with 20wt% Mn-TCP (Mn-CPC-2) presented better adhesion and spreading behaviors. Besides, Mn-CPC-1 promoted the gene levels of ALP, Col-I and OC while Mn-CPC-2 promoted the gene levels of Runx2 and OC. Cellular behaviors were related to two points: one was the increase of adsorption capacity of proteins (e.g. BSA) after changing the surface properties of bone cements; and the other was the biological role of Mn2+ released from CPC in osteogenesis. All the results indicated that CPC incorporated with 10wt% Mn-TCP has good osteogenesis and proper physicochemical properties, which will be a prospective biomaterial applying in the area of bone regeneration.

Preliminary evaluation of different biomaterials for defect healing in an experimental osteoporotic rat model with dynamic PET-CT (dPET-CT) using F-18-Sodium Fluoride (NaF)

The aim of the current study was to measure and compare the effect of calcium phosphate cement (CPC) and CPC enriched with strontium (SrCPC) for the healing of osteoporotic bone defects in the rat femur using 18F-Sodium Fluoride dPET-CT. Methods: Osteoporosis was induced by ovariectomy and a calcium restricted diet. After three months, rats were operated to create a 4mm defect in the distal metaphyseal femur with internal fixation. 7 Rats have been treated either with CPC (Group 2) or with SrCPC (Group 3) for bone replacement and defect healing. Furthermore, a control group of 7 rats without any biomaterial (Group 1) was used for reference. 18 weeks after osteoporosis induction and 6 weeks following femoral surgery, dPET-CT studies scan were performed with 18F-Sodium Fluoride. SUVs and a 2-tissue compartmental learning-machine model (K1-k4, VB, influx) were used for quantitative analysis. Results: VB, reflecting the fractional blood volume and k3, reflecting the formation of fluoroapatite were the most sensitive parameters for the characterisation of healing process and revealed the best differentiation for the control group and the CPC group (Group 2) as well as for the CPC with strontium carbonate group (Group 3) (p<0.05). VB was decreased by the order of Group1, Group 2 and Group3, while k3 was increased by the same order. Therefore, the data direct to a decreased fractional blood volume and increased fixation of fluoride in rats with these biomaterials. Conclusion: We found PET scanning using 18F-Sodium Fluoride to be a sensitive and useful method for evaluation of bone healing after replacement with CPC or SrCPC.

Potentiation of the antitumor effect of calcium phosphate cement containing anticancer drug and caffeine on rat osteosarcoma

BackgroundSeveral reports suggest diffusion of anticancer agents from bone cement may suppress tumor growth. New drug delivery systems have been developed that incorporate anticancer drugs into calcium phosphate cement (CPC) to maintain high concentrations of anticancer drugs at local sites. We investigated whether CPC implants containing anticancer drugs and caffeine, which enhance the cytocidal effect of anticancer drugs, would enhance their antitumor effects on rat osteosarcomas (SOSN2 cells). MethodsWe calculated the release of cisplatin (CDDP) and caffeine from the CPC and bone cement. The following CPCs were prepared: CPC-only, CPC containing caffeine, CPC containing cisplatin, and CPC containing cisplatin and caffeine. We performed cell growth inhibition assays on SOSN2 cells using culture media previously used to incubate each CPC. We transplanted SOSN2 cells into the tibias of rats, excised the tumor 3 days after transplantation, implanted each CPC and observed subsequent tumor growth. ResultsThe in vitro sustained-release test demonstrated greater amounts and more persistent release of CDDP and caffeine from CPC than from bone cement and also showed CPC could release the majority of its loaded CDDP and caffeine. Culture media containing CDDP and caffeine inhibited in vitro proliferation of SOSN2 cells, and this inhibitory effect was greater than the inhibition resulting from CDDP alone. Experiments with an in vivo rat model demonstrated greater tumor growth inhibition with CPC containing CDDP and caffeine than with CPC containing CDDP alone. ConclusionsThe study results suggest CPC containing CDDP and caffeine potentiate antitumor effects and may be effective as a local chemotherapeutic method of treating malignant bone tumors.

Effects of α-DT cement with hydroxypropyl cellulose on bone augmentation within a titanium cap in the rabbit calvarium

The present study was performed to evaluate the effects of calcium phosphate cement (alpha-DT cement) containing alpha-TCP, dicalcium phosphate anhydrous, and tetracalcium phosphate mixed with hydroxypropyl cellulose (HPC) for bone augmentation within a titanium cap in the rabbit calvarium. A total of 24 male adult Japanese white rabbits were used in this study. In each rabbit, one side of the cap was filled with alpha-DT cement (alpha-DT) or alpha-DT cement mixed with HPC (alpha-DTH), and the other side of the cap was left empty (control). After 1 and 3 months, newly generated tissue and mineralized bone areas were measured histomorphometrically. Significant differences in newly generated tissue and mineralized tissue were observed between the alpha-DT or alpha-DTH group and the control at 3 months. Furthermore, alpha-DTH showed significantly more mineralized tissue than alpha-DT group. Our findings indicated that although alpha-DT cement was effective for bone augmentation, alpha-DTH was more useful than alpha-DT for bone maturation.

Effects of calcium phosphate cement on the outcome of vertebroplasty for osteoporotic compression fractures; comparison between vartebroplasty using Biopex and Biopex-R

Effects of calcium phosphate cement on the outcome of vertebroplasty for osteoporotic compression fractures; comparison between vartebroplasty using Biopex and Biopex-R

3 インプラント周囲組織界面へのリン酸カルシウム骨セメントの影響(第503回 大阪歯科学会例会)

3 インプラント周囲組織界面へのリン酸カルシウム骨セメントの影響(第503回 大阪歯科学会例会)

Calcium phosphate cement–based vertebroplasty compared with conservative treatment for osteoporotic compression fractures: a matched case–control study

Few studies have been conducted to compare vertebroplasty and conservative treatment for osteoporotic vertebral compression fractures (OVCFs). To investigate the effects of calcium phosphate cement (CPC)-based vertebroplasty on relief of pain and augmentation of the fractured vertebral body (VB), the authors compared the results of CPC-assisted vertebroplasty with those of conservative treatment alone. Two groups of patients were examined: the vertebroplasty group (30 consecutive patients with primary OVCF) and the control group (30 patients matched for age, sex, interval from injury to treatment, and grade of the posterior wall defects of the fractured VB). Outcome measures included the visual analog scale (VAS) score of back pain and analgesic requirements, and the radiographically documented rate of the VB kyphosis. The follow-up duration was more than 12 months (mean 17 months). The mean VAS score at 12 months after injury was 0.67 cm in the vertebroplasty group and 1.97 cm in the control group, and the mean improvement rates in the VAS scores were 91.6 and 73.6%, respectively (p < 0.0001). The mean duration of analgesic requirement was 8.3 days in the vertebroplasty group and 62.2 days in the control group (p = 0.0005). The mean kyphosis rate at 12 months after injury was 72.9% in the vertebroplasty group and 58% in the control group, and the mean recovery rate of kyphosis was +8.4 and -21%, respectively (p < 0.0001). The authors conclude that CPC-assisted vertebroplasty provides better clinical and radiological results than conservative treatment for primary OVCF.

Enhancement of pedicle screw stability using calcium phosphatecement in osteoporotic vertebrae: in vivo biomechanical study

We conducted an experimental study using femalebeagles with and without ovariectomy-induced osteoporosisto determine the effect of calcium phosphate cement (CPC)on the mechanical stability of inserted pedicle screws. A drillhole was created from the base of the transverse process to thevertebral body; CPC was injected into the hole, and then ascrew was inserted into the same hole. In the presence ofosteoporosis evidenced by dual X-ray absorptiometry, the stabilityof the inserted screw augmented by CPC against pulloutand cephalocaudal forces were significantly greater by28% and 54% at 1 week after operation, 48% and 71% at 2weeks, and 56% and 68% at 4 weeks compared with thosewithout CPC. The pull-out strength increased progressivelywith time after surgery, probably reflecting new-bone growthfrom the surrounding cancellous bone, which was in directcontact with the CPC, as shown in the histologic study. Ateach time point the cephalocaudal rigidity was similar and thepull-out strength greater than that for the screws insertedwithout CPC in nonporotic dogs. These findings suggest thatCPC augments the stability of the inserted pedicle screws andincreases the stiffness of fixed osteoporotic motion segmentsusing instrumentation.

α-Tricalcium phosphate cement: “in vitro” cytotoxicity

Calcium phosphate-based bioceramics have revolutionized orthopedic and dental repair of damaged parts of the bone system. Among these materials, calcium phosphate-based cements, with hydraulic setting, stand out due to their biocompatibility and in situ hardening, which allow easy manipulation and adaptation to the shape and dimensions of bone defects. An investigation was made of the in vitro cytotoxic effect of calcium phosphate cement based on α-tricalcium phosphate, immersed for different lengths of time in simulated body fluid (SBF), based on the ISO-10993 “Biological Evaluation of Medical Devices” standard. The culture medium was Chinese hamster ovary (CHO) cells in contact with diluted cement extracts. The results revealed that the calcium phosphate cement used was cytotoxic and that the material's cytotoxicity decreased the longer the cement was immersed in SBF.