Rheological properties of an apatitic bone cement during initial setting.

4:25 Repair of osteoporotic vertebral compression fracture by transpedicular injection of bioactive calcium phosphate cement into the vertebral body

The aim of this study was to evaluate the clinical applicability and biological behavior of a newly developed injectable calcium phosphate (Ca-P) cement as bone filler for gaps around oral implants. Twenty-four step-like implants, creating gaps of 1 and 2 mm, were inserted into the trabecular bone of the medial femoral condyles of six goats. Four different situations were tested: (1) implant + gaps; (2) implant + gaps, but covered with a polylactic acid membrane; (3) implant + gaps that were filled with Ca-P cement; and (4) implant + gaps that were filled with Ca-P cement and covered with a membrane. All implants were left in place for 12 weeks. Histological and quantitative histomorphometrical measurements demonstrated that implants + gaps had generally poor bone contact at the implant base. Furthermore, fibrous encapsulation was observed in the gap part. In contrast, the presence of a membrane promoted bone ingrowth into the gap and also the bone contact at the implant base. Injection of Ca-P cement resulted in an almost complete filling of the gaps around the implant. The cement surface was completely covered by bone. Active resorption and remodeling of cement particles was observed, suggesting a pattern of slow resorption associated with full replacement with newly formed bone. Additional use of a membrane did not result in adjunctive benefits. Bone-to-implant contact at the implant base was comparable with the implants provided only with a membrane. In conclusion, the Ca-P cement used here showed excellent clinical handling properties combined with a superior bone behavior. On the other hand, the degradation rate of the material was still very slow. This current characteristic can hamper the final clinical applicability of the material as gap filler for periimplant or periodontal defects.

Mechanical augmentation of the vertebral body by calcium phosphate cement injection

Mechanical and rheological properties and injectability of calcium phosphate cement containing poly (lactic-co-glycolic acid) microspheres

Enhancement of initial stability of press-fit femoral stems using injectable calcium phosphate cement: an in vitro study in dog bones

The bone regenerative properties of calcium phosphate cements (CPCs) may be improved by the addition of growth factors, such as recombinant human transforming growth factor-beta1 (rhTGF-beta1). Previously, we showed that rhTGF-beta1 in CPC stimulated the differentiation of preosteoblastic cells from adult rat long bones. The intermixing of rhTGF-beta1 in CPC, which was subsequently applied to rat calvarial defects, enhanced bone growth around the cement and increased the degradation of the cement. However, it is unknown whether the addition of rhTGF-beta1 changes the material properties of CPC and what the characteristics of the release of rhTGF-beta1 from CPC are. Therefore, we determined in this study the release of rhTGF-beta1, in vitro, from the cement pellets as implanted in the rat calvariae. The possible intervening effects of rhTGF-beta1 intermixing on the clinical compliance of CPC were studied through an assessment of its compressive strength and setting time, as well as its crystallinity, calcium-to-phosphorus ratio, porosity, and microscopic structure. We prepared CPC by mixing calcium phosphate powder (58% alpha-tricalcium phosphate, 25% anhydrous dicalcium phosphate, 8.5% calcium carbonate, and 8.5% hydroxyapatite) with a liquid (3 g/mL). The liquid for standard CPC consisted of water with 4% disodium hydrogen phosphate, whereas the liquid for modified CPC was mixed with an equal amount of 4 mM hydrochloride with 0.2% bovine serum albumin. The hydrochloride liquid contained rhTGF-beta1 in different concentrations for the release experiments. Most of the rhTGF-beta1 incorporated in the cement pellets was released within the first 48 h. For all concentrations of intermixed rhTGF-beta1 (100 ng to 2.5 mg/g of CPC), approximately 0.5% was released in the first 4 h, increasing to 1.0% after 48 h. Further release was only about 0.1% from 2 days to 8 weeks. CPC modification slightly increased the initial setting time at 20 degrees C from 2.6 to 5 min but had no effect on the final setting time of CPC at 20 degrees C or the initial and final setting times at 37 degrees C. The compressive strength was increased from 18 MPa in the standard CPC to 28 MPa in the modified CPC only 4 h after mixing. The compressive strength diminished in the modified CPC between 24 h and 8 weeks from 55 to 25 MPa. No other significant change was found with the CPC modification for rhTGF-beta1. X-ray diffraction revealed that standard and modified CPCs changed similarly from the original components, alpha-tricalcium phosphate and anhydrous dicalcium phosphate, into an apatite cement. The calcium-to-phosphorus ratio, as determined with an electron microprobe, did not differ for standard CPC and modified CPC. Standard and modified CPCs became dense and homogeneous structures after 24 h, but the modified CPC contained more crystal plaques than the standard CPC, as observed with scanning electron microscopy (SEM). SEM and back- scattered electron images revealed that after 8 weeks the cements showed equally and uniformly dense structures with microscopic pores (<1 microm). Both CPCs showed fewer crystal plaques at 8 weeks than at 24 h. This study shows that CPC is not severely changed by its modification for rhTGF-beta1. The prolonged setting time of modified cement may affect the clinical handling but is still within acceptable limits. The compressive strength for both standard and modified cements was within the range of thin trabecular bone; therefore, both CPCs can withstand equal mechanical loading. The faster diminishing compressive strength of modified cement from 24 h to 8 weeks likely results in early breakdown and so might be favorable for bone regeneration. Together with the beneficial effects on bone regeneration from the addition of rhTGF-beta1 to CPC, as shown in our previous studies, we conclude that the envisaged applications for CPC in bone defects are upgraded by the intermixing of rhTGF-beta1. Therefore, the combination of CPC and rhTGF-beta1 forms a promising synthetic bone graft.

Destructive biomechanical tests using fresh cadaveric thoracolumbar vertebral bodies. To evaluate the compression strength of human vertebral bodies injected with a new calcium phosphate (CaP) cement with improved infiltration properties for augmentation of the vertebral bodies before compression fracture and also for vertebroplasty in comparison with polymethylmethacrylate (PMMA) injection. Vertebroplasty is the percutaneous injection of PMMA cement into the vertebral body. While PMMA has high mechanical strength, it cures fast and thus allows only a short handling time. Other potential problems of using PMMA injection may include damage to surrounding tissues by a high polymerization temperature or by the unreacted toxic monomer, and the lack of long-term biocompatibility. Bone mineral cements, such as calcium carbonate and CaP cements, have longer working time and low thermal effect. They are also biodegradable while having a good mechanical strength. However, the viscosity of injectable mineral cements is high, and the infiltration of these cements into vertebral body has been questioned. Recently, the infiltration properties of a CaP cement have been significantly improved, which is ideal for the transpedicular injection to the vertebral bodies for vertebroplasty or augmentation of osteoporotic vertebral body strength. The bone mineral densities of 30 vertebral bodies (T2-L1) were measured using dual-energy x-ray absorptiometry. Ten control specimens were compressed at a loading rate of 15 mm/min to 50% of their original height. The other specimens had 6 mL of PMMA (n = 10) or the new CaP (n = 10) cement injected through the bilateral pedicle approach before being loaded in compression. Additionally, after the control specimens had been compressed, they were injected with either CaP (n = 5) or PMMA (n = 5) cement using the same technique, to simulate vertebroplasty. Loading experiments were repeated with the displacement control of 50% vertebral height. Load to failure was compared among groups and analyzed using analysis of variance. Mean bone mineral densities of all five groups were similar and ranged from 0.56 to 0.89 g/cm2. The size of the vertebral body and the amount of cement injected were similar in all groups. Load to failure values for PMMA, the new CaP, and vertebroplasty PMMA were significantly greater than that of control. Load to failure of the vertebroplasty CaP group was higher than control but not statistically significant. The mean stiffness of the vertebroplasty CaP group was significantly smaller than control, PMMA, and the new CaP groups. The mean height gains after injection of the new CaP and PMMA cements for vertebroplasty were minimal (3.56% and 2.01%, respectively). Results of this study demonstrated that the new CaP cement can be injected and infiltrates easily into the vertebral body. It was also found that injection of the new CaP cement can improve the strength of a fractured vertebral body to at least the level of its intact strength. Thus, the new CaP cement may be a good alternative to PMMA cement for vertebroplasty, although further in vivo animal and clinical studies should be done. Furthermore, the new CaP may be more effective in augmenting the strength of osteoporotic vertebral bodies for preventing compression fractures considering our biomechanical testing data and the known potential for biodegradability of the new CaP cement.

The study aim was to develop and apply an experimental technique to determine the biomechanical effect of polymethylmethacrylate (PMMA) and calcium phosphate (CaP) cement on the stiffness and strength of augmented vertebrae following traumatic fracture. Twelve burst type fractures were generated in porcine three-vertebra segments. The specimens were randomly split into two groups (n=6), imaged using microCT and tested under axial loading. The two groups of fractured specimens underwent a vertebroplasty procedure, one group was augmented with CaP cement designed and developed at Queen's University Belfast. The other group was augmented with PMMA cement (WHW Plastics, Hull, UK). The specimens were imaged and re-tested . An intact single vertebra specimen group (n=12) was also imaged and tested under axial loading. A significant decrease (p<0.01) was found between the stiffness of the fractured and intact groups, demonstrating that the fractures generated were sufficiently severe, to adversely affect mechanical behaviour. Significant increase (p<0.01) in failure load was found for the specimen group augmented with the PMMA cement compared to the pre-augmentation group, conversely, no significant increase (p<0.01) was found in the failure load of the specimens augmented with CaP cement, this is attributed to the significantly (p<0.05) lower volume of CaP cement that was successfully injected into the fracture, compared to the PMMA cement. The effect of the percentage of cement fracture fill, cement modulus on the specimen stiffness and ultimate failure load could be investigated further by using the methods developed within this study to test a more injectable CaP cement.

In the present study, ZrO2 was added into the injectable calcium phosphate cements (CPCs) to improve their mechanical strength. Different mass fractions of ZrO2 (5 %, 10 %, 15 %, 20%) were mixed with the powder components consisted of tricalcium phosphate (α-TCP) and hydroxyapatite (HA). Then formed the paste via adding the liquid component consisted of citric acid. The compressive strength, the injectability, the initial setting time and finial time of CPC were measured, respectively. X-ray diffraction (XRD) was employed to analyse the phase of as-prepared CPC. Scanning Electron Microscope (SEM) and Energy dispersive spertrum (EDS) were used to observe the morphology and indicate the element components of CPC. The compressive strength of ZrO2-CPC was higher than that of CPC without added ZrO2. The compressive strength got the maximal when the mass fraction of ZrO2 was 15%. It had no effect on the injectability with adding ZrO2, which were 89 % to 92 %. It had a slight down-regulation of the initial and final setting time with adding ZrO2. SEM showed that there was amounts needle-like substance in CPC, which might be related to the improvement of compressive strength of CPC. XRD showed that there were HA, a few of α-TCP and ZrO2 diffraction peaks in CPCs. The present results indicate that it is feasible to improve the compressive strength of injectable CPC via adding ZrO2.

Critical review: Injectability of calcium phosphate pastes and cements.

Calcium phosphate cement (CPC) sets in situ with intimate adaptation to the contours of defect surfaces, and forms an implant having a structure and composition similar to hydroxyapatite, the putative mineral in teeth and bones. The objective of the present study was to develop an injectable CPC using dicalcium phosphate dihydrate (DCPD) with a high solubility for rapid setting. Two agents were incorporated to impart injectability and fast-hardening to the cement: a hardening accelerator (sodium phosphate) and a gelling agent (hydroxypropyl methylcellulose, HPMC). The cement with DCPD was designated as CPC(D), and the conventional cement was referred to as CPC(A). Using water without sodium phosphate, CPC(A) had a setting time of 82 +/- 6 min. In contrast, CPC(D) exhibited rapid setting with a time of 17 +/- 1 min. At 0.2 mol/L sodium phosphate, setting time for CPC(D) was 15 +/- 1 min, significantly faster than 40 +/- 2 min for CPC(A) (Tukey's at 0.95). Sodium phosphate decreased the paste injectability (measured as the paste mass extruded from the syringe divided by the original paste mass inside the syringe). However, the addition of HPMC dramatically increased the paste injectability. For CPC(D), the injectability was increased from 65% +/- 12% without HPMC to 98% +/- 1% with 1% HPMC. Injectability of CPC(A) was also doubled to 99% +/- 1%. The injectable and rapid-setting CPC(D) possessed flexural strength and elastic modulus values overlapping the reported values for sintered porous hydroxyapatite implants and cancellous bone. In summary, the rapid setting and relatively high strength and elastic modulus of CPC(D) should help the graft to quickly attain strength and geometrical integrity within a short period of time postoperatively. Furthermore, the injectability of CPC(D) may have potential for procedures involving defects with limited accessibility or narrow cavities, when there is a need for precise placement of the paste, and when using minimally invasive surgical techniques.

Biomechanical Cadaveric Study. To characterize the pullout strength of calcium phosphate cement augmented screws between 0 and 6 minutes after cement injection. Earlier studies with calcium phosphate cement on pedicle screws inserted into a metal mold or sawbone have shown that the augmentation strength can be affected by the time between cement injection and screw insertion. However, these studies only compared soft cement to completely hardened cement with extended waiting times. These extended waiting times are impractical in live spinal surgeries. Twenty-four pedicle screws were inserted and pulled out axially from cadaveric bone to make revision models. The 24 screw holes were randomly divided into 4 groups, with each group having 6 holes. For each group, identical pedicle screws were inserted at 0, 2, 4, and 6 minutes after injection with bioresorbable calcium phosphate cement (CPC). After 24 hours, the augmented screws were pulled out axially and their pullout strengths were compared. The difference between secondary pullout strength and primary pullout strength increased up to 4 minutes after cement injection but decreased after 6 minutes but without statistical difference among the 4 time settings (P>0.3). The augmented screws had similar fixation strength regardless of the time between cement mixture and screw insertion as long as they are inserted within 6 minutes. Augmentation power tends to increase up to 4 minutes after cement injection but decreases after 6 minutes.

Axial pullout tests using fresh cadaveric thoracolumbar vertebral bodies. To evaluate the effect of a new injectable calcium phosphate cement on the axial pullout strength of both revised and augmented pedicle screws in comparison with polymethyl methacrylate and in terms of injection method. Failure of pedicle screws by loosening and back out remains a significant clinical problem and is of particular concern for patients with low bone quality. Polymethyl methacrylate was shown to significantly improve the screw pullout strength. However, polymethyl methacrylate is known to have a high polymerization temperature, which may damage surrounding tissues, and a short handling time, and it lacks long-term biocompatibility. Bone mineral cements such as calcium phosphate have a longer working time, very low thermal effect, and are biodegradable as well as having good mechanical strength. Recently, new calcium phosphate cement with improved infiltration properties for better injectability has been introduced, but its performance in augmenting the pedicle screw fixation has not been tested yet. The bone mineral densities of 52 vertebral bodies (T11-L5) were measured using dual-energy x-ray absorptiometry. In each vertebral body, a 6.5-mm-diameter and 45 +/- 5-mm-long pedicle screw was inserted into either the right or left pedicle, representing an initial intact implantation. These intact screws were pulled axially until failure at 10 mm/min. Following failure of the intact pedicle, 3.0 cc of cement was injected into the failed screw hole, representing a revision case, and the prepared screw hole in the contralateral intact pedicle representing an augmentation case. The cement was injected either to the distal tip of the screw hole (calcium phosphate-1 group, n = 19) or along the entire length of the screw hole (calcium phosphate-2 group, n = 20), and the screws were inserted. The cement was then allowed to cure for 24 hours at room temperature before both screws were pulled to failure. In 13 specimens, polymethyl methacrylate was injected along the entire length of the screw hole (polymethyl methacrylate group). Kruskal-Wallis and Mann-Whitney tests were used to compare the screw pullout strengths for study groups, whereas linear relationships between variables were assessed with scatter plots and Spearman correlation coefficients with a significance level of 0.05. Mean bone mineral densities of all groups were similar. A significant positive correlation was seen between bone mineral density and intact pullout strength. In revision, the pullout strength of calcium phosphate-1 was similar to that of intact, whereas the pullout strength of calcium phosphate-2 and polymethyl methacrylate was significantly greater than that of intact. In augmentation, all 3 injection methods significantly improved the pullout strength over intact. Injection of the calcium phosphate cement along the entire screw length was found to produce significantly higher pullout strengths than injection only at the distal tip of the screw in revision case. Injection of polymethyl methacrylate produced significantly higher pullout strengths than the injection of calcium phosphate by either method in both revision and augmentation. Results of this study demonstrate that the new calcium phosphate cement can improve the axial pullout strength of revised and augmented pedicle screws when injected along the entire length of the screw. This suggests that the injection method may be crucial for revision of failed pedicle screws. Considering inherent properties more favorable for in vivo application, such as nonexothermal polymerization and longer working time, and significant improvement in pullout strength, the new calcium phosphate cement may be a good alternative to polymethyl methacrylate for the augmentation of pedicle screw fixation.

Bone response to fast-degrading, injectable calcium phosphate cements containing PLGA microparticles

Calcium phosphate cements (CPCs) can be a suitable scaffold material for bone tissue engineering because of their osteoconductivity and perfect fit with the surrounding tissue when injected in situ. However, the main disadvantage of hydroxyapatite (HA) forming CPC is its slow degradation rate, which hinders complete bone regeneration. A new approach is to use hydraulic apatite cement with mainly α/β-tricalciumphosphate (TCP) instead of α-TCP. After hydrolysis the α/β-TCP transforms in a partially non-absorbable HA and a completely resorbable β-TCP phase. Therefore, α-TCP material was thermally treated at several temperatures and times resulting in different α/β-TCP ratios. In this experiment, we developed and evaluated injectable biphasic calcium phosphate cements (BCPC) in vitro. Biphasic α/β-TCP powder was produced by heating α-TCP ranging from 1000-11250°C. Setting time and compressive strength of the CPCs were analyzed after soaking in PBS for 6 weeks. Results demonstrated that the phase composition can be controlled by the sintering temperature. Heat treatment of α-TCP, resulted in 100%, 75% and 25% of α-to β-TCP transformation, respectively. Incorporation of these sintered BCP powder into the cement formulation increased the setting time of the CPC paste. Compressive strength decreased with increasing β-TCP content. In this study, biphasic CPCs were produced and characterized in vitro. This injectable biphasic CPC presented comparable properties to an apatitic CPC.