Mechanical augmentation of the vertebral body by calcium phosphate cement injection

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

Spinal surgery for osteoporotic vertebral fractures using implants often results in implant failure owing to poor bone quality. We developed a new augmentation technique using calcium phosphate cement (CPC) for percutaneous pedicle screws (PPSs). This study evaluated the reinforcement effect of CPC on the initial fixation strength of PPSs in synthetic bone specimens. Using the X-NeedleⓇ, developed for screw hole preparation and CPC injection, a 40 mm deep pilot hole was created in 40×40×60 mm bone specimens. A commercially available CPC (BIOPEX-RⓇ) was mixed at a powder-to-liquid ratio of 12 g/3.4 mL, and 0.5 mL was injected into the pilot hole 6 minutes (min) after mixing. Screws were then inserted using the standard PPS technique. Pull-out strength (N) was measured seven times in four groups: without CPC (control group), immediately after CPC injection (CPC0 group), 10 mins after CPC injection (CPC10 group), and 24 hours after CPC injection (CPC24 group). Toggle tests were conducted six times in the control and CPC24 groups to measure the number of cycles/load (N) required to achieve 2 mm screw head displacement. In the pull-out test, the maximal pull-out strength in the CPC24 group was significantly greater than that in the control and CPC0 groups. Pull-out strength in the CPC10 and CPC24 groups increased to 121.1% and 165.1% of that of the control group, respectively. In the toggle test, the CPC24 group showed significantly higher values for both cycles and load compared to the control group. The X-NeedleⓇ enables simple, minimally invasive CPC injection into the pilot hole, facilitating PPS augmentation. Additionally, screws augmented with CPC showed increased pull-out and toggle strengths. PPS augmentation using CPC may serve as a preventive measure against implant failure in spinal surgery for patients with poor bone quality.

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.

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

Injectable and macroporous calcium phosphate cement scaffold

In orthopedic minimally invasive surgeries (MIS) such as percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP), calcium phosphate cements (CPCs) are an attractive alternative to bioinert polymethyl methacrylate (PMMA) due to their superior biocompatibility and osteoconductivity. However, the mechanical strength and injectability of CPCs often remain insufficient for load-bearing applications, limiting their broader use in these critical procedures. To address this challenge, we introduce a machine learning-assisted approach to enhance both the mechanical strength and injectability of CPCs by identifying specific polymers as superplasticizers. By optimizing its concentration and the liquid-to-powder (L/P) ratio, we developed an injectable brushite-based cement with an exceptional compressive strength of 79.5 ± 4.3 MPa, surpassing both traditional CPCs and PMMA in orthopedic applications. Zeta potential and adsorption studies reveal that these superplasticizers enhance cement paste dispersion via electrostatic repulsion. In vitro assays demonstrate excellent biocompatibility and osteogenic properties, while in vivo experiments further confirm the cement’s superior osteoinductive capability. The brushite cement regulates cellular metabolism and stem cell differentiation by enhancing energy metabolism and activating key signaling pathways such as phosphatidylinositol 3-kinase–AKT and mitogen-activated protein kinase–extracellular signal–regulated kinase. These findings offer a novel approach to fabricating CPCs with enhanced mechanical strength and osteogenic potential, addressing long-standing challenges in orthopedic MIS.

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.

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.

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.

Calcium phosphate cement (CPC) is a potentially useful alternative to polymethylmethacrylate (PMMA) for transpedicular injection into osteoporotic vertebral fractures. Unlike PMMA, CPC is both biocompatible and osteoconductive without producing heat from polymerization, but it has lower compressive strength compared to PMMA. This in vitro model experiment analyzed how different CPC powder-liquid ratios (P/L ratios) and injection methods may minimize blood contamination in the CPC and, thereby its reduction in compressive strength. (1) CPC of different P/L ratios of 4.0, 3.5, and 3.2 was equally mixed with different amounts of freshly obtained human venous blood, producing cylindrically shaped CPC samples. (2) Using a transpedicular vertebroplasty model containing blood in the bottom, CPC pastes of different P/L ratios were injected with the nozzle of an injection gun affixed either to the bottom (Bottom method) or to the top of the container (Top method). All cylindrical CPC samples thus obtained were immersed in simulated body fluid and then underwent compressive strength tests at 3 h-7 days post-immersion. In CPC equally mixed with blood, lower P/L ratios and a larger amount of blood contamination reduced compressive strength more significantly. Of the two methods of CPC injection, the 'Bottom method' produced significantly greater compressive strength values than the 'Top method'. When performing CPC-assisted vertebroplasty, a greater load bearing-support can be obtained by injecting CPC paste of a high P/L ratio of 4.0 into the deepest part of the space inside the vertebral body to minimize blood contamination.

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.

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.