Polymerization Of Bone Cement Research Articles

Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release

Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.

High-purity butoxydibutylborane catalysts enable the low-exothermic polymerization of PMMA bone cement with enhanced biocompatibility and osseointegration.

Polymethyl methacrylate (PMMA) based biomaterials have been widely utilized in clinics. However, currently, PMMA catalyzed by benzoyl peroxide (BPO) exhibits disquieting disadvantages including an exothermic polymerization reaction and a lack of bioactivity. Here, we first designed three industrial-scale synthesis methods for high-purity butoxydibutylborane (BODBB), achieving purity levels greater than 95% (maximum: 97.6%) and ensuring excellent fire safety. By utilizing BODBB as a catalyst, the highest polymerization temperature of PMMA bone cement (PMMA-BODBB) reached only 36.05 °C, ensuring that no thermal damage occurred after implantation. Compared to PMMA catalyzed by BPO and partially oxidized tributylborane (TBBO, catalyst of Super Bond C&B), PMMA-BODBB exhibited superior cell adhesion, proliferation, and osteogenesis, attributed to the reduced release of free radicals and toxic monomer, and moderate bioactive boron release. After injection into a 5 mm defect in the rat cranial bone, PMMA-BODBB demonstrated the highest level of osteointegration. This work not only presents an industrial-scale synthesis of high-purity BODBB, but also offers an innovative PMMA biomaterial system with intrinsic biocompatibility and osseointegration, paving the way for the next generation of PMMA-based biomaterials with broader applications.

Effect of commonly used lavage solutions on the polymerization of bone cement

IntroductionLittle is known about the impact irrigation solutions have on the material properties of cement used in hip and knee arthroplasty. We sought to compare the effect of three commonly used lavage solutions on cement polymerization. MethodsTen groups were used for cure and mechanical testing: two cement controls, and eight cement groups mixed with test solutions. Test solutions included a commercially available benzalkonium chloride/citric acid solution (BCS), chlorhexidine gluconate (0.05%) (CHG), povidone-iodine 0.35%, and normal saline added at cement mixing onset. Cement dough-time, set-time, and compression testing were performed following The American Society for Testing and Materials guidelines. ResultsPovidone-iodine had shorter dough-time (1min 34sec, sd 1min 5sec) versus controls (1min 56sec, sd 1min 35sec), p=0.0419. Cement exposed to all lavage samples had significantly reduced set-time. Compressive strength was reduced for all surgical lavages (p<0.001). Pairwise testing revealed that all lavage treatments reduced offset strength versus controls (p<0.001). ConclusionBone cement exposed to lavage solutions during the cement mixing-phase showed accelerated set-times and decreased compressive strength. If bone is not dry, and cement has not finished mixing at the time of application, cement curing time may be shortened. Additionally, bone cement should reach dough phase prior to pre-closure surgical lavage. Level of evidenceIII; case control study

Pulsatile Lavage During Cementation of Total Knee Arthroplasty - Is Fixation Impaired? A Cadaver Study.

Increasing economic pressure in modern healthcare necessitates an increase in efficiency in total knee arthroplasty (TKA) while maintaining high-quality outcomes. Removal of debris using pulsatile lavage (PL) during cement polymerization may considerably reduce the operative duration. However, water can penetrate the interface, resulting in impaired implant fixation. The aim of the present study was to investigate the impact of early-onset PL during bone cement polymerization on implant fixation and operative duration. Cemented implantation of tibial trays was performed in 20 fresh-frozen human tibiae from 10 donors in a matched-pair study design in two groups: 1) PL during cement polymerization; and 2) PL after completion of the polymerization process. The cement penetration depth was analysed by computed tomography (CT), and the pull-out force was measured to evaluate primary implant fixation. The duration of the procedure was recorded for both groups. Comparable pull-out forces were observed in the experimental (2,213 N) and control groups (2,350 N; p=0.68). The mean depth of cement penetration was similar in both groups. PL during cement polymerization could decrease the operative duration by 10 min. The application of PL during cement polymerization could significantly reduce operative duration and had no adverse effect on the mechanical fixation of the tibial component.

Stability of enoxaparin sodium in polymethyl methacrylate bone cement

Objective To investigate the polymerization process of polymethyl methacrylate (PMMA) bone cement, and the effects of exothermy on the stability of enoxaparin sodium (ES) added. Methods 8 000 AXaIU enoxaparin sodium was added to 40 g Palacos® R PMMA bone cement and the enoxparin sodium cement cylindrical test specimen was prepared according to ISO5833: 2002 Surgical Implants-Acrylic Resin Bone Cement standard. It was leached with pH 7.4 Tris-HCL buffer for 24 h. The antithrombotic activity and anticoagulant activity of the extract were determined and compared with the standard enoxaparin sodium dissolution. Results The release system of 8000 AXaIU enoxaparin sodium added to 40 g Palacos® R PMMA bone cement had an anti-Ⅹa factor activity of 0.847 AXaIU/ml for 24 h, which had obvious antithrombotic activity, could significantly prolong rabbit plasma recalcification time and exert good anticoagulant activity. After the ES pure powder or ES-PMMA bone cement was treated at 75 ℃ for 10 min, there was no significant change in anti-Ⅹa factor activity or anticoagulant activity. Conclusion ES can withstand PMMA bone cement polymerization and exothermic process, maintain its own anti-thrombation and anticoagulant effect, and has the potential to be compounded into PMMA bone cement. Key words: Sodium enoxaparin; Polymethyl methacrylate; Bone cement; Polymerization; Thermal stability

Heat conduction analysis during bone cement polymerization and assessment of thermal damage

Heat conduction analysis during bone cement polymerization and assessment of thermal damage

Synthesis and Characterization of an Injectable and Hydrophilous Expandable Bone Cement Based on Poly(methyl methacrylate).

Poly(methyl methacrylate) (PMMA), the most common bone cement, has been used as a graft substitute in orthopedic surgeries such as vertebroplasty. However, an undesirable minor crack in the bone-cement interface provoked by shrinkage during polymerization and high elastic modulus of conventional PMMA bone cement dramatically increases the risk of vertebral body refracture postsurgery. Thus, herein, a hydrophilous expandable bone cement was synthesized based on a PMMA commercial cement (Mendec Spine Resin), acrylic acid (AA), and styrene (St). The two synthesized cements (PMMA-PAA, PMMA-PAA-PSt) showed excellent volumetric swelling in vitro and cohesive bone-cement contact in rabbit femur cavity defect. The elastic modulus and compressive strength of the new cements were lower than PMMA. Furthermore, the in vitro analysis indicated that the new cements had lower cytotoxicity than PMMA, including superior proliferation and lower apoptotic rates of Sprague-Dawly rat-derived osteoblasts. Western blotting for protein expression and RT-PCR analysis of osteogenesis-specific genes were conducted on SD rat-derived osteoblasts from both PMMA and new cements films; the results showed that new cements enhanced the expression of osteogenesis-specific genes. Scanning electron microscopy demonstrated improved morphology and attachment of osteoblast on new cement discs compared to the PMMA discs. Additionally, the histological morphologies of the bone-cement interface from the rabbit medial femoral condyle cavity defect model revealed direct and cohesive contact with the bone in the new cement groups in contrast to a minor crack in the PMMA cement group. The sign of a new bone growing into the cement has been found in the new cements after 12 weeks, thereby indicating the osteogenic capacity in vivo. In conclusion, the synthesized hydrophilous expandable bone cements based on PMMA and poly(acrylic acid) (PAA) are promising candidates for vertebroplasty.

Evidence appraisal of Koh BTH, Tan JH, Ramruttun AK, Wang W. Effect of storage temperature and equilibration time on polymethyl methacrylate (PMMA) bone cement polymerization in joint replacement surgery.: J Orthop Surg Res. 2015;10(1):178. doi:10.1186/s13018-015-0320-7.

Evidence appraisal of Koh BTH, Tan JH, Ramruttun AK, Wang W. Effect of storage temperature and equilibration time on polymethyl methacrylate (PMMA) bone cement polymerization in joint replacement surgery.: J Orthop Surg Res. 2015;10(1):178. doi:10.1186/s13018-015-0320-7.

Effect of storage temperature and equilibration time on polymethyl methacrylate (PMMA) bone cement polymerization in joint replacement surgery

BackgroundIn cemented joint arthroplasty, the handling characteristics (doughing, working, and setting times) of polymethyl methacrylate (PMMA) bone cement is important as it determines the amount of time surgeons have to optimally position an implant. Storage conditions (temperature and humidity) and the time given for PMMA cement to equilibrate to ambient operating theater (OT) temperatures are often unregulated and may lead to inconsistencies in its handling characteristics. This has not been previously studied. Hence, the purpose of this study was to investigate the effect of storage temperatures on the handling characteristics of PMMA cement and the duration of equilibration time needed at each storage temperature to produce consistent and reproducible doughing, setting, and working times.MethodsSmartSet® HV cement was stored at three different controlled temperatures: 20 °C (control), 24 °C, and 28 °C for at least 24 h prior to mixing. The cement components were then brought into a room kept at 20 °C and 50 % humidity. Samples were allowed to equilibrate to ambient conditions for 15, 30, 45, and 60 min. The cement components were mixed and the dough time, temperature-versus-time curve (Lutron TM-947SD, Lutron Electronics, Inc., Coopersburg, PA), and setting time were recorded. Analysis was performed using the two-way ANOVA test (IBM SPSS Statistics V.22).ResultsAt 20 °C (control) storage temperature, the mean setting time was 534 ± 17 s. At 24 °C storage temperature, the mean setting time was 414 ± 6 s (p < 0.001*) with 15 min of equilibration, 446 ± 11 s (p < 0.001*) with 30 min of equilibration, 501 ± 12 s (p < 0.001*) with 45 min of equilibration, and 528 ± 15 (p > 0.05) with 60 min of equilibration. At 28 °C storage temperature, the mean setting time was 381 ± 8 s (p < 0.001*) with 15 min of equilibration, 432 ± 30 s (p < 0.001*) with 30 min of equilibration, 487 ± 9 (p < 0.001*) with 45 min of equilibration, and 520 ± 16 s (p > 0.05) with 60 min of equilibration.ConclusionsThis study reflects the extent to which storage temperatures and equilibration times can potentially affect the handling characteristics of PMMA cement. We recommend institutions to have a well-regulated temperature and humidity-controlled facility for storage of bone cements and a protocol to standardize the equilibration time of cements prior to use in the OT to improve consistency and reproducibility of the handling characteristics of PMMA cement.

E131 人工膝関節全置換術における骨セメント重合発熱の熱伝導解析 : CT画像に基づいた三次元有限要素モデルによる検討(OS-04:バイオトランスポートと生体熱工学)

E131 人工膝関節全置換術における骨セメント重合発熱の熱伝導解析 : CT画像に基づいた三次元有限要素モデルによる検討(OS-04:バイオトランスポートと生体熱工学)

Temperature Control of Bone Cement for Enhancing Applicability and Safety in Vertebroplasty

Vertebroplasty has been widely accepted in treatment of osteoporotic vertebral fractures. Polymerization of bone cement stabilizes the fractured vertebra by increasing its mechanical strength, thereby providing symptomatic pain relief. Many factors affect the reaction of polymerization of polymethylmethacrylate and, therefore, the reaction rate and injection permeability of bone cement. This may increase the probability of a surgeon missing the crucial period, leading to the increase of the risks of uneven cement distribution, cement leakage and premature hardening of cement. Hypothermic manipulation of bone cement is expected to reduce reaction rate and hence, extending the handling time. However, in a manner of reducing the environmental temperature of bone cement, there are still uncertainties on handling time, cement distribution pattern and injection permeability of cement. This study is thus designed to investigate the efficacy of temperature control for enhancing applicability and safety of bone cement.

Optimisation of a two-liquid component pre-filled acrylic bone cement system: a design of experiments approach to optimise cement final properties.

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery-acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery.

The effect of temperature on the viability of human mesenchymal stem cells

IntroductionImpaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs.MethodsThe viability of human MSCs was measured after incubating them at temperatures of 38°C, 48°C and 58°C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37°C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue™ assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett’s test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue™) and cell viability (Trypan Blue).ResultsResults showed that cell metabolism was not severely affected up to 48°C/150 seconds, while cells in the 58°C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48°C/150 seconds were compared with the control group.ConclusionsThe study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48°C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations.

Isoniazid Could Be Used for Antibiotic-loaded Bone Cement for Musculoskeletal Tuberculosis: An In Vitro Study

Antibiotic-loaded bone cement (ALBC) has been used in serious cases of musculoskeletal tuberculosis, but the type and amount of antibiotic that should be used in ALBC have not been determined. We therefore determined the (1) elution characteristics and (2) antimycobacterial activity of isoniazid- and rifampicin-loaded bone cement. A total of 240 elution samples of each of three discs from 40 g bone cement mixed with one of eight dosages: 1 g, 2 g, and 4 g isoniazid, 1 g, 2 g, and 4 g rifampicin, and a combination of 1 + 1 g or 2 + 2 g of isoniazid and rifampicin. The polymerization of rifampicin-loaded bone cement was delayed to mean 122.5 ± 31.1 minutes. We measured the quantity of isoniazid and rifampicin and the antimycobacterial activity on Days 1, 3, 7, 14, and 30. Isoniazid eluted in almost all the samples while rifampicin was detected only on Day 1 with 2 g (0.7 ± 0.4 ug/mL/day), and until Day 14 with 4 g (0.1 ± 0.0 ug/mL/day). Most of the samples containing isoniazid showed antimycobacterial activity while the samples containing rifampicin showed antimycobacterial activity only on Day 1 with 1 g (0.52 ± 0.18 ug/mL), until Day 14 with 2 g (0.03 ± 0.00 ug/mL), and until Day 30 with 4 g (1.84 ± 1.90 ug/mL). Rifampicin was unsuitable for ALBC because of its delayed polymerization. Isoniazid eluted and showed antimycobacterial activity for 30 days. The data suggest isoniazid could be considered for use in ALBC for musculoskeletal tuberculosis if used with systemic treatment. For preventing resistance and systemic toxicity, a combination with a second-line drug and an in vivo study would be needed.

E121 骨セメントの重合実験(一般講演(6))

E121 骨セメントの重合実験(一般講演(6))

1F04 骨セメント重合熱による骨組織の熱的損傷 : 1次元解析モデルによる評価(GS17-1:バイオヒート・マストランスポート(1))

1F04 骨セメント重合熱による骨組織の熱的損傷 : 1次元解析モデルによる評価(GS17-1:バイオヒート・マストランスポート(1))

Chemical and physical properties of bone cement for vertebroplasty

Vertebral compression fracture is the most common complication of osteoporosis. It may result in persistent severe pain and limited mobility, and significantly impacts the quality of life. Vertebroplasty involves a percutaneous injection of bone cement into the collapsed vertebrae by fluorescent guide. The most commonly used bone cement in percutaneous vertebroplasty is based on the polymerization of methylmethacrylate monomers to polymethylmethacrylate (PMMA) polymers. However, information on the properties of bone cement is mostly published in the biomaterial sciences literature, a source with which the clinical community is generally unfamiliar. This review focuses on the chemistry of bone cement polymerization and the physical properties of PMMA. The effects of altering the portions and contents of monomer liquid and polymer powders on the setting time, polymerization temperature, and compressive strength of the cement are also discussed. This information will allow spine surgeons to manipulate bone cement characteristics for specific clinical applications and improve safety.

Heat distribution of polymerisation temperature of bone cement on the spinal canal during vertebroplasty

In the last 15 years, vertebroplasty and kyphoplasty have become established operative procedures for treating osteoporotic vertebral-body fractures and vertebral bodies afflicted with metastases. These procedures are quickly performed with few personnel and material resources and have a low rate of complications. However, cases of neurological impairment are reported in the scientific literature. We analysed whether potentially harmful heat is radiated/conducted by the polymerisation temperature of polymethylmethacrylate (PMMA) bone cement in the spinal canal. We performed vertebroplasty on 25 vertebral bodies and measured the temperature distribution during polymerisation of bone cement within the spinal canal using heat probes placed in the respective areas. The vertebral bodies were located in a circulating water bath at 37°C. During polymerisation of the bone cement, a temperature rise was measured. The peak temperature was reached after few minutes. Temperature curves differed; a maximum temperature of up to 43.16°C was detected for a few seconds only. When vertebroplasty is performed correctly, there is no temperature development that could eventually damage the spinal cord or spinal nerves.

Cement leakage causes potential thermal injury in vertebroplasty

BackgroundPercutaneous vertebroplasty by injecting PMMA bone cement into the fractured vertebrae has been widely accepted in treatment of spinal compression fracture. However, the exothermic polymerization of bone cement may cause osseous or neural tissue injury. This study is thus designed to evaluate the potential risk of thermal damage in percutaneous vertebroplasty.MethodTwelve porcine vertebrae were immersed in 37°C saline for the experiment. In the first stage of the study, vertebroplasty without cement leakage (control group, n = 6) was simulated. The anterior cortex, foramen, posterior cortex and the center of the vertebral body were selected for temperature measurement. Parameters including peak temperature and duration above 45°C were recorded. In the second stage, a model (n = 6) simulating bone cement leaking into the spinal canal was designed. The methods for temperature measurement were identical to those used in the first stage.ResultsIn Stage 1 of the study (vertebroplasty of the porcine vertebral body in the absence of cement leakage), the average maximal temperature at the anterior cortex was 42.4 ± 2.2°C; at the neural foramen 39.5 ± 2.1°C; at the posterior cortex 40.0 ± 2.5°C and at the vertebral center, 68.1 ± 3.4°C. The average time interval above 45°C was 0 seconds at the anterior cortex; at the neural foramen, 0 seconds; at the posterior cortex, 0 seconds and at the vertebral center, 223 seconds. Thus, except at the core of the bone cement, temperatures around the vertebral body did not exceed 45°C. In Stage 2 of the study (cement leakage model), the average maximal temperature at the anterior cortex was 42.7 ± 2.4°C; at the neural foramen, 41.1 ± 0.4°C; at the posterior cortex, 59.1 ± 7.6°C and at the vertebral center, 77.3 ± 5.7°C. The average time interval above 45°C at the anterior cortex was 0 seconds; at the neural foramen, 0 seconds; at the posterior cortex, 329.3 seconds and at the vertebral center, 393.2 seconds. Based on these results, temperatures exceeded 45°C at the posterior cortex and at the vertebral center.ConclusionsThe results indicated that, for bone cement confined within the vertebra, curing temperatures do not directly cause thermal injury to the nearby soft tissue. If bone cement leaks into the spinal canal, the exothermic reaction at the posterior cortex might result in thermal injury to the neural tissue.

Femoral and obturator nerves palsy caused by pelvic cement extrusion after hip arthroplasty.

Cement extrusion into the pelvis with subsequent palsy of the obturator and femoral nerves is a rare entity after hip replacement surgery. Cemented fixation of the acetabular cup has been considered as a safe and reliable standard procedure with very good long term results. We present a case of fifty year old female patient after hip arthroplasty procedure which suffered an obturator and femoral nerve palsy caused by extrusion of bone cement into the pelvis. Postoperative X-rays and CT-scan of the pelvis demonstrated a huge mass consisted of bone cement in close proximity of femoral and obturator nerves. The surgery charts reported shallow and weak bony substance in postero-superior aspect of the acetabulum. This weak bony acetabular substance may have caused extrusion of bone cement during press-fitting of the polyethylene cup into the acetabulum, and the following damage of the both nerves produced by polymerization of bone cement. The bone cement fragment has been surgically removed 3 weeks after arthroplasty. The female patient underwent intensive postoperative physical therapy and electro stimulation which resulted in full recovery of the patient to daily routine and almost normal electromyography results.