We developed a novel silorane-based biomaterial (SBB) for use as an orthopedic cement. SBB is comprised of non-toxic silicon-based monomers, undergoes non-exothermic polymerization, and has weight-bearing strength required of orthopedic cements. We sought to compare the antibiotic release kinetics of this new cement to that of commercially available PMMA bone cement. We also evaluated each material's inherent propensity to support the attachment of bacteria under both static and dynamic conditions. One gram of either rifampin or vancomycin was added to 40g batches of PMMA and SBB. Pellets were individually soaked in PBS. Eluate was collected and tested daily for 14 days using HPLC. Compressive strength and modulus were tested over 21 days. Bioassays were used to confirm the bioactivity of the antibiotics eluted. We measured the growth and maturation of staphylococcus aureus (SA) biofilm on the surface of both PMMA and SBB disks over the course of 72 hours in a static well plate and in a dynamic biofilm reactor (CDC Biofilm Reactor). N=4 at 24, 48, and 72 hours. A luminescent strain of SA (Xen 29) was employed allowing imaging of bacteria on the discs. SBB eluted higher concentrations of vancomycin than did PMMA over the course of 14 days (p<0.001). A significant 55.1% greater day 1 elution was observed from SBB. Silorane cement was able to deliver rifampin in clinically favorable concentrations over 14 days. On the contrary, PMMA was unable to deliver rifampin past day 1. The incorporation of rifampin into PMMA severely reduced its mechanical strength (p<0.001) and modulus (p<0.001). Surface bacterial radiance of PMMA specimens was significantly greater than that of SBB specimens at all time points (p<0.05). The novel silorane-based cement demonstrated superior antibiotic release and, even without antibiotic incorporation, demonstrated an innate inhabitation to bacterial attachment and biofilm

Aims. Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading. Methods. For each cement (PMMA or SBB), three formulations were prepared (rifampin-added, vancomycin-added, and control) and made into pellets (6 mm × 12 mm) for testing. Antibiotic elution into phosphate-buffered saline was measured over 14 days. Compressive strength and modulus of all cement pellets were tested over 14 days. Results. The SBB cement was able to deliver rifampin over 14 days, while PMMA was unable to do so. SBB released more vancomycin overall than did PMMA. The mechanical properties of PMMA were significantly reduced upon rifampin incorporation, while there was no effect to the SBB cement. Vancomycin incorporation had no effect on the strength of either cement. Conclusion. SBB was found to be superior in terms of rifampin and vancomycin elution. Additionally, the incorporation of these antibiotics into SBB did not reduce the strength of the resultant SBB cement composite whereas rifampin substantially attenuates the strength of PMMA. Thus, SBB emerges as a potential weight-bearing alternative to PMMA for the local delivery of antibiotics. Cite this article: Bone Joint Res 2021;10(4):277–284

Introduction Polymethylmethacrylate (PMMA) has been widely used in orthopaedic procedures for fixation of joint replacements or enhancing the fixation of implants. However, the use of PMMA has been associated with cardiovascular deterioration and even death. More recently, PMMA has also been used for augmenting osteoporotic vertebral bodies which have fractured or are at risk of fracture. The main complication is PMMA leakage into adjacent structures. Transient hypotension and fatal fat embolism (FE) have also been reported. The pathomechanism of cardiovascular deterioration after the injection of PMMA (i.e. FE) remains a highly controversial subject. The exact role of PMMA in the development of FE remains unclear. The aim of the present study was to elucidate the acute effects of injecting PMMA compared with bone wax into vertebral bodies on the cardiovascular system using an established animal model for vertebroplasty (VP) (Aebli, N, et al. Spine. 2002). Methods In 8 skeletally mature mixed-bred ewes (2–4 years) 6.0ml PMMA (CMW3-Depuy) or bone wax (Bone Wax, Ethicon) were injected unilaterally, through an open approach into the L1 & L2 pedicles. Blood pressure, heart rate, and cardiac output were measured. Results The major difference between the cardiovascular response of the PMMA and that of the bone wax group was the recovery in Pulmonary Artery Pressure (PAP) and Pulmonary Vascular Resistance (PVR). Three minutes post-injection, PAP had fully recovered to baseline values in the wax group. However in the PMMA group, PAP had only recovered by 52% after 3 min and fully recovered after 10 min. Discussion The augmentation of vertebral bodies resulted in transient cardiovascular changes regardless of the material used. However, the recovery of PAP and PVR values took significantly longer with the PMMA group. The peak response was a result of pulmonary vasoconstriction triggered by a reflex reaction to the embolisation of bone marrow particles or by vasoactive cytokines. The peak response was therefore mainly associated with the increase in intraosseous pressure during the augmentation causing release of bone marrow contents into the and not the cement monomer. The cement monomer however plays a role in the cardiovascular complications during FE. The delayed recovery of PAP and PVR in the PMMA group may be due to a vasoconstriction effect of the cement monomer on the pulmonary vascular system. Potentially serious cardiovascular complications may occur during VP regardless of the material used. The injection of PMMA may cause prolonged pulmonary hypertension during vertebro- and also arthroplasty. Continuous invasive cardiovascular monitoring may be required in patients with impaired cardiovascular and pulmonary function

Thermal damage to bone related to the exothermic polymerisation of bone cement (PMMA) remains a concern. A series of studies were conducted to examine PMMA bone interface during cemented arthroplasty. In vitro and in vivo temperature distributions were performed in the laboratory and human and animal surgery. In vivo (10 patients) measurements of cement temperature during cementing of BHR femoral prosthesis using thermocouples. Intra-operative measurement of cement temperature in BHR in the presence of femoral head cysts was examined in patients. The BHR femoral heads were sectioned to assess cement mantle as well as position of thermocouples. An additional study was performed in sheep with PMMA implanted into cancellous defects. Thermocouples were used to monitor temperature in the cement as well as adjacent bone. Histology and CT was used to assess any thermal damage. The exothermic reaction of PMMA during polymerization does indeed result in an increase in temperature at the interface with bone. The in vivo study recorded a maximum temperature of 49.12C for approximately three minutes in the cancellous bone underneath the BHR prosthesis. This exposure is probably not sufficient to cause significant injury to the femoral head. The maximum temperature of the cement on the surface of the bone was 54.12C, whereas the maximum recorded in the cement in the mixing bowl was 110.2C. In the presence of artificial cysts within the bone, however, temperatures generated within the larger cysts, and even at the bone-cement interface of these cysts, reached levels greater than those previously shown to be harmful to bone. This occurred in one case even in the 1 cc cyst. Routine histology revealed a fibrous layer at the cement bone interface in the sheep study. Fluorescent microscopy demonstrated bone label uptake adjacent to the defect site. Histology did not reveal thermal necrosis in the defects in terms of bony necrosis. CT data was used to measure the amount of PMMA placed into each defect. This analysis revealed a range of volumes that did not seem to influence the histology. The heat of cement polymerisation in resurfacing as performed in our study is not sufficient to cause necrosis. This may reflect the ability of the body to rapidly conduct heat away by acting as a heat sink. The temperature-conducting properties of the metal prosthesis are also likely to be important

Introduction. Temporary use of antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in two-stage revisions is considered to be standard of care for patients with a chronic infection of a joint replacement. Spacers should be wear resistant and load-bearing to avoid prolonged immobilisation of the patient and to reduce morbidity. Most cement spacers contain barium sulphate or zirconium dioxide as radio-opaque substrate. Both are quite hard materials that may negatively influence the wear behaviour of the spacer. Calcium carbonate is another radio-opaque substrate with lower hardness potentially increasing the wear resistance of the spacer materials. The purpose of the study was to compare a prototype PMMA knee spacer (calcium carbonate loaded) with a commercially available spacer (containing barium sulphate) regarding the wear performance and particle release in a knee wear simulator. Material and Methods. Spacer K (TECRES, Italy) was used as barium sulphate (10%) containing spacer material. A prototype material (Heraeaus Medical, Germany) with 15% calcium carbonate was compared. Both were gentamicin impregnated, ready-made for clinical application (preformed) and consist of a tibial and a femoral component. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance to ISO 14243–1 with a 50% reduced axial force (partial weight bearing). Tests were carried out at 37 °C in closed chambers filled with calf serum. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, gravimetric wear measurements according to ISO 14243–2 and wear particle analysis according to ASTM F1877–05 were performed. Results. Fig. 1 presents the results of the gravimetric wear measurements. For the Spacer K cement a mean articular wear mass of 375.53±161.22 mg was determined after 500.000 cycles (femoral components: 149.55±17.30 mg, tibial components: 225.98±153.01 mg). The prototype cement showed lower mean total wear of 136.32±37.58 mg (femoral components: 74.32±33.83 mg, tibial components: 61.99±15.74 mg). However, a statistically significant lower wear rate was only seen for the femoral components (p=0,027). In Fig. 2 isolated PMMA wear particles are shown and the morphological characteristics are given in Tab. 1. Discussion and conclusion. The prototype material showed better wear performance in terms of gravimetric wear and particle release. Thus calcium carbonate seems to be a promising material as radio-opaque substrate in PMMA spacers. Nevertheless, the wear amount released from both spacer materials is much higher as compared to conventional total knee replacements with polyethylene inserts. In this context biological reactions against PMMA particles and an increased release of cytokines have been reported in vitro [1] and furthermore, the promotion of osteolysis has been shown in vivo in the presence of PMMA particles [2]. As a clinical consequence we suggest excessive debridement during removal of the cement spacer components to reduce the risk of third body wear for the final joint replacement. Beside the wear performance further studies are essential to prove the mechanical stability and the antibiotic release kinetics for the prototype cement

Introduction and Aims: Polymethylmethacrylate (PMMA) has been widely used in orthopaedic surgery including more recently vertebroplasty. The reported rate of complications following vertebroplasty is low and mainly related to PMMA leakage. The aim of this study was to elucidate the acute cardiovascular effects of PMMA or bone wax in a vertebroplasty animal model. Method: Eight skeletally mature sheep were used and PMMA or bone wax were injected unilaterally into L1 and L2 at 10-minute intervals. Arterial, central venous, pulmonary artery and left ventricular pressures were recorded using Statham pressure transducers and Swan Ganz catheters were used for monitoring cardiac output. Results: Augmentation resulted in a two-phase response regardless of which material was used. First the mean arterial blood pressures started to drop after approximately two seconds. Secondly the pulmonary artery pressure and central venous pressure increased after approximately 11 seconds, whereas cardiac output and left ventricular pressure decreased. There was no significant change in heart rate for both groups. There was a significant difference (p< 0.05) in the pulmonary artery pressure values in the PMMA group compared to the basal values at one, three and five minutes, whereas in the wax group the pulmonary artery pressure recovered within three minutes. Conclusion: Augmentation resulted in a two-phase cardiovascular response regardless of which material was used. Peak responses were similar for both groups, but pulmonary artery pressure and cardiac output recovered quicker in the wax group. The late recovery of pulmonary artery pressure and cardiac output in the PMMA group may be due to a vasoconstriction effect of the cement monomer

Aims: PMMA is currently used as grouting agent of arthroprostheses and for filling of bone cavities after bone curettage. It is moreover used as a carrier of antibiotics in the local treatment of bone infections and it has been proposed as a carrier of antiblastic drugs in the local treatment of bone metastases. The aim of this study is to analyse the biological properties and compressive strenght of PMMA-Methotrexate mixture to be used for the local treatment of bone metastases. Methods: Cylinders of PMMA containing Methotrexate in different concentrations were manufactured according to ASTM F-451. Cylinders of PMMA were used as control. The porosity of the cylinders was characterised by SEM. Drug elution rate in saline solution was measured by HPLC. The biological activity of Methotrexate was analysed on human breast cancer cells using MTT test at different time (from 5 minutes to 30 days). Compressive tests was performed in conformity to ASTM F-451 on PMMA- Methotrexate samples and control as-made and after 30 days of aging in saline. Results: SEM analysis showed the presence of granules of Methotrexate on the surface of as-made cylinders that can be readily released from PMMA cylinders. The release occurred in large amount within 24 hours after immersion. We observed a relative release rate is more sustained in samples containing the drug in lower concentration. Also the biological activity was time dependent: cell death decreased progressively from 60% at 24 hours to 10% at 30 days. Compressive tests showed no statistical differences between PMMA cylinders containing Methotrexate and controls before and after aging in saline. Conclusions: The results show that PMMA-Metho-trexate may be considered an interesting option in the treatment of bone metastases because cement allows mechanical resistance after bone curettage or resection and Methotrexate improves locally anticancer activity

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this. We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks. The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss. Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines

Antibiotic-loaded PMMA spacers are used with increased frequency in two-stage revision arthroplasty. The release of aminoglycosides and vancomycin, the most commonly used antibiotics, is prompt, and concentrations are inhibitory. The release kinetic from PMMA bone cement shows a biphasic profile, consisting in an initially high and rapid drug release followed by a slower but sustained phase. However, this general profile of drug release kinetics from PMMA spacers in vitro may have great variability in terms of drug amount, modality, and duration of elution. Initial drug concentration, cement surface area and porosity are essential and well-known factors in determining the drug release. Moreover, viscosity, vacuum-preparation and the different technical characteristics of commercially available spacers are additional factors of variability. Industrial preformed spacers are considered superior to custom-made devices because of uniform mixing and standardized procedures. Spacers produced by different manufacturers vary in their mechanical properties and antibiotic elution characteristics. Small changes in the formulation of a bone cement can also affect these properties. Similar bone cements produced by various brands release different amount of drugs. Gentamicin diffuses from Palacos in a larger amount and for a longer period than from Simplex and CMV. Spacers produced in France (Synicem™) and in Argentina (Subiton™) elute less total amount of gentamicin than those produced in Italy (Spacer G™) and show a delayed peak drug release. The low initial release of antibiotic can contribute to unsatisfactory antimicrobial effect and to the risk of selection of resistant bacteria. Some spacers release gentamicin for longtime (months), while others release antibiotic for only two weeks. In the last years an evolution of PMMA spacers production occurred and modifications in the polimerization process of cement can increase cement porosity and antibiotic elution from spacers. The current commercial preformed spacers for 10 days elution (Spacer G™, prepared with Cemex HP) release more gentamicin (34.1 mg) than previous models, which were prepared with Cemex SP (16.4 mg). Furthermore, they maintain a high elution rate (1.4–1.6 mg/day after one month). The combination of Gentamicin and Vancomycin mantains an elution pharmacokinetic profile that is superimposable to that of Gentamicin and Vancomycin alone, with synergistic effects against multiresistant bacteria in prosthetic infection site. In conclusion, the antibiotic release from PMMA spacers of various brands is not equivalent. The old elution data are no longer valid for new preparations. Consequently, this additional factor of variability should be considered in clinical practice and literature data utilisation

Introduction. Antibiotic loaded polymethyle methacrylate spacers are commonly used in the management of septic hip replacements. Aim. The aim of this study was to determine wear patterns on the articulating surfaces of these spacers, as well as to determine the extent of PMMA particulate debris generation. Method. We took tissue specimens around the acetabulae in 12 cases at the time of the second stage procedure for septic total hip revisions. These were subjected to histological analysis to determine the extent of PMMA particulate debris contamination. We also performed a basic explant retrieval analysis of the articulating surfaces of the PMMA spacers to determine any specific wear patterns. Results. We found numerous PMMA particles in the acetabular soft tissues biopsied. The particle concentration was highest in the area of the acetabular fovea. We could also demonstrate specific wear patterns on the spacers that could be correlated with the generally mismatched articulating couple between the spacer and the bony acetabulum. We could also demonstrate some boney destruction present in the acetabulum with long-term spacer use. Conclusions. We concluded that significant amounts of PMMA particulate debris are generated by these articulating antibiotic spacers. The total volume of this debris may be determined by specific wear patterns on the spacers’ surfaces. We recommend a thorough debridement to decrease the PMMA particle load generated. Consideration in respect of the bearing surface implanted after the explantation of the PMMA spacer should take into account the effect of the debris on the bearing surfaces. We also make recommendations in respect of the design of these PMMA spacers

Two-stage exchange revision is the gold standard in treating an infected total hip arthroplasty. The new emerging gold standard appears to be using an antibiotic impregnated spacer made from polymethylmeta-crylate (PMMA) bone cement between two stages. However, a consensus has not been reached on the antibiotic to use in the cement and its dose. Vancomycin an aminoglycoside is widely used for this purpose in the PMMA cement in doses such as 3 to 9 gr per 40 gr polymer powder. The purpose of this study was to see if Vancomycin is as effective in safer low doses of 1 gr per 40 gr polymer powder.Between 1997 and 2002, twenty-six patients were treated for an infected hip arthroplasty with a two-stage exchange arthroplasty using a Vancomycin impregnated polymethylmetacrylate (PMMA) bone cement spacer. During the first stage all prosthetic material was removed and after debridement, irrigation an articulating spacer was made from PMMA cement (Surgical Simplex, Howmedica, Rutherford, NJ, USA). One gram of Vancomycin HCl (Vancomycin, Eli Lilly, USA) powder was added to each 40 gr polymer powder prior to curing the cement. After the first stage parenteral antibiotics were administered for six weeks. When erythrocyte sedimentation rate and the CRP returned to a normal level, the patient underwent the second stage were a cementless prosthesis was inserted. Intra-operative cultures and frozen sections obtained during the second stage were negative in all patients indicating successful treatment of the infection. Mean follow up after the second stage was 36 (range 24 to 74) months. Two patients had a reinfection after four months. These two patients were infected with gram-negative micro-organisms. This gave us a 92 percent infection eradication rate at 3 years. None of the patients suffered from Vancomycin related side effects.In this study we used a lower dose (1 gr per 40 gr polymer powder) of Vancomycin in the PMMA spacer instead of the commonly used 3 to 9 gr per 40 gr polymer powder. The reason for this was our concerns for nephrotoxicity and allergic reactions frequently associated with use of Vancomycin. Antibiotics are used in cement spacers as a disinfecting agent and sterilizer of dead spaces. As Vancomycin is highly effective when used in PMMA due to its elution dynamics and thermostability we believed it would be effective even in low doses. In all patients the infection appeared to be cured after the first stage. This was demonstrated with negative intraoperative cultures and frozen sections. However, we had two reinfections in patients that initially were infected with gram-negative organism, which Vancomycin is not as effective. Despite this we were able to sterilize the infected hip with a low dose approach in the first stage. Vancomycin is effective in low dose when used in PMMA cement spacers for infected total hip arthroplasties. This approach will decrease potential serious side effects of Vancomycin

Study Design: Comparative, prospective follow-up study. Objective: Comparison of outcome between patients treated with Percutaneous VertebroPlasty (PVP) using low viscosity PolyMethylMetAcrylate (PMMA) bone cement and patients treated with PVP using medium viscosity PMMA bone cement. Summary of background data. Viscosity is the characterizing parameter of PMMA bone cement, currently the standard augmentation material in PVP, and influences interdigitation and cement distribution inside the vertebral body, injected volume and extravasation, thereby affecting the clinical outcome of PVP. In PVP, low, medium and high viscosity PMMA bone cements are used interchangeably. However, effect of viscosity of cement on clinical outcome in patients with Osteoporotic Vertebral Compression Fractures (OVCFs) has not yet been explicit subject of investigation. Methods: Follow-up was conducted using a 0–10 Pain Intensity Numerical Rating Scale (PI-NRS) and the Short Form 36 (SF-36) Quality of Life (QoL) questionnaire before PVP and at 7 days (PI-NRS only), 1 month, 3 months and 12 months after PVP. Cement leakage was analyzed on direct post-operative CT-scanning. Injected cement volume was measured using a calibrated DICOM-viewer and the degree of interdigitation was assessed. At six and 52 weeks and at suspicion, patients were analyzed for the incidence of new fractures. Results: Thirty consecutive patients received PVP using low viscosity PMMA bone cement (OsteoPal-V. ®. ) for 62 OVCFs, followed by 34 patients who received PVP using medium viscosity PMMA bone cement (Disc-O-Tech. ®. ) for 67 OVCFs. Baseline characteristics were comparable between groups. Viscosity qualification was stated by the manufacturer. results regarding PI-NRS and SF-36 were comparable between both groups. Postoperative comparison of injected cement volume, degree of interdigitation, proportion of bipedicular procedures, incidence of new vertebral fractures and complications revealed no substantial differences between both groups. In the low viscosity group a significantly greater proportion of vertebrae showed cement extravastion (81,0% versus 71,6%, p = 0,029). Multiple logistic analysis revealed no definitive predictive factors for the occurrence of cement leakage (yes/ no) (Odds Ratio [95% CI], P):. Severity (acc to Genant et al): 1.82 [0,69 – 4.89], 0.229. Fracture Type (Genant et al): 1.22 [0.64 – 2.32], 0.550. Injected Volume: 0.98 [0.76 – 1.27], 0.875. Spinal Region: 0.87 [0.48 – 1.55], 0.628. Cement Viscosity: 0.42 [0.16 – 1.10], 0.076. Conclusion: No major differences in clinical outcome after PVP in OVCFs using low and medium viscosity PMMA bone cement were found. Viscosity of PMMA bone cement is likely to influence cement extravastion, although this could not be confirmed

Introduction: Patients with spinal metastases often have patterns of disease requiring both an anterior and posterior surgical decompression and stabilisation. Subtotal spondylectomy and circumferential stabilisation can be safely performed via a single posterior transpedicular approach. Polymethyl-methacrylate bone cement (PMMA) has been widely used in spinal column reconstruction with mixed results. PMMA is a potential means for local drug delivery in the prevention of locally recurrent disease. The biomechanical characteristics of anterior reconstruction using PMMA have not been adequately evaluated. Purpose: To evaluate the stability of an anterior cement construct following total spondylectomy and to compare this reconstruction against alternative stabilisation techniques. Methods: Ten fresh-frozen human cadaveric spines (T9-L3) were used. After intact analysis, a total spondylectomy was performed at T12. Three potential reconstruction techniques were tested for their ability to restore stiffness to the specimen: (1) multi-level posterior pedicle screw instrumentation from T10-L2 {MP1} [Depuy Acromed], (2) anterior instrumentation [ATL Z-plate II™, Medtronic, Sofamor Danek Instruments] and rib graft at T11-L1 with multi-level posterior instrumentation from T10-L2 {AMPI}, and (3) anterior cement [Simplex P] and pins construct (T12) with multi-level posterior instrumentation from T10-L2 {CMPI}. Each of the three potential reconstruction techniques was tested on each specimen in random order. Non-destructive testing was performed under load control. The specimen was positioned vertically for axial compression and torsion testing, and horizontal for flexion/extension and lateral bending tests. A customised jig was manufactured for this latter purpose. Results: Only circumferential stabilisation techniques (AMPI, CMPI) restored stiffness to a level equivalent or higher to that of the intact spine in all loading modes (p< 0.05). CMPI provided more stability to the specimen than AMPI in compression and flexion testing (p< 0.05). Posterior instrumentation alone (MPI) did not restore stiffness to the intact level in compression and flexion testing (p< 0.005). Conclusions: Circumferential reconstruction using an anterior cement construct provides equal or more stability than the intact spine in all testing modes. Posterior stabilisation alone is an inadequate method of reconstruction following total spondylectomy. PMMA has the advantage over traditional anterior reconstruction techniques in that it can be inserted using a single posterior approach and offers the potential value of local drug delivery

Purpose: This study investigates the synergistic use of fusidic acid with vancomycin, and linezolid in poly-methylmethacrylate (PMMA) cement for the treatment of orthopedic MRSA and MRSE infections. Alone, Vancomycin is typically eluted in limited quantities from cement. The purpose of this study was to. combine FA and Vancomycin, and Linezolid alone in PMMA cement and characterize antibiotic elution, and. to improve drug release using polyethylene glycol (PEG) and NaCl in PMMA cement. Method: Standardized 1g pellets of Palacos cement were manufactured containing Vancomycin and FA or Linezolid at increasing concentrations in three batches: without additive, with increasing concentrations of PEG, and with increasing concentrations of NaCl. The pellets were incubated in phosphate buffered saline and sampled at regular intervals. Drug analysis was performed with high pressure liquid chromatograpy. Results: Total drug release at 2.5% loading of Vancomycin alone was 0.84% and of FA was 2.35%. Linezolid showed comparable release profiles. Vancomycin and FA combined yeilded Vancomycin release of 6.2% and FA of 8.4%. The addition of 30% PEG increased release of Vancomycin and Fusidic Acid by six-fold. The addition of 18% NaCl increased total Vancomycin release by 11-fold but had no effect on FA release. Conclusion: Linezolid, Vancomycin and FA can be combined in PMMA and have favorable release profiles. The addition of PEG and NaCl dramatically increases the release of antibiotics, with the exception of FA and NaCl. These strategies may be useful in the management of MRSA/MRSE infections

Introduction: morcelized defatted bone-Bank graft (MOD-B) has been employed in 249 patients for different diseases in Rizzoli Institute from 1998 to 2002. 82 hip revisions, 51 spine fusions, 50 osteolitic bone cavities, 47 non-unions). Good results obtained with MOD-B have been the reason for different researches of his properties like an antibiotic carrier and, in the same time, a particular new bone graft. Material and Methods:. MOD-B with antibiotic powder and PMMA Cylinders (A-MB-C) have been placed in saline solution and plasma for 4 weeks, compared with cylinders made with PMMA and antibiotic. The mechanical resistance of A-MB-C to compressive test has been performed subsequently. About biocompatibility, A-MB-C were implanted in sheep’s Ilium. After 3 moths an histologic evaluation has been performed. Results:. The MOD-B + antibiotic + PMMA have released the higher quantity of antibiotic for all the 4 weeks. The A-MB-C resistance has been of 13.6 MPa, the same resistance of cancellous bone in the man’s femur. The histological result with a fluoroscopic microscope has been an osteogenesis in the full section of the cylinders. Conclusions: morcelized defatted bone-Bank graft is an important opportunity to restore bone loss lesions but, with a septic situation, it is not so easy obtain good results. A very important goal would be to have a graft with good antibiotic deliver system, good mechanical compressive strength and the potential capacity to become new living bone

Pain is the main symptom of acetabular osteolysis and is frequently associated with pathologic fractures. Surgical procedures requiring an aggressive approach, and as a consequence high morbidity, are rarely indicated. The minimally invasive approach may be effective in treating tumours and is capable of reducing the mechanical pain. PMMA has been widely used in neoplastic and spinal surgery as a bone filler because of its mechanical and biologic behaviours. Recently percutaneous injection of PMMA was proposed for the treatment of neoplastic acetabular osteolysis. The technique was tested in four patients affected by secondary ostheolytic lesions. The patients were evaluated clinically (HHS, Womac, SF-12) and radiographically (X-ray and CT) at 18 months. All the patients demonstrated a durable and significant improvement in terms of pain and restoration of function. The radiographic examinations (X-ray and CT) confirm these results. Complications (temporary increase in pain and fever) were only observed in one patient. The preliminary results demonstrate the reliability and effectiveness of this procedure. Clinical results showed a significant reduction in pain and the capability of restoring function. The indications can be extended also to the acetabular lesion at a distance from the weight-bearing zone, reducing pain and the risk of pathologic fractures. The technique was demonstrated to be effective and showed only minor and self-resolving complications. It is useful in patients in whom major surgery is contraindicated and clinical improvement is necessary to improve the quality of life

The use of PMMA cement vertebroplasty for the treatment of severe disabling focal back pain as a result of osteoporotic compression fractures is well established. However clinical experience of this treatment is limited in New Zealand. This study reports a technique and indications for this treatment and early clinical results. A prospective study of eight cases of severe disabling focal back pain due to osteoporotic compression fractures was undertaken. These were treated with percutaneous transpedicle vertebroplasty. The patient’s pain was assessed before and after the treatment using a visual analogue pain scale. All eight patients reported an improvement in pain immediately and at one month following the procedure. A sustained improvement in pain followed the vertebroplasty. This is consistent with other case reports in the literature although in this study the response appears to be less dramatic than that reported in other series

Introduction. Radio-opaque additives for Orthopaedic Bone Cement, like BaSO4 or ZrO2, are now routinely used because of the valuable help in identifying cement location around an implant on the x-ray films. A new bone cement formulation was devised with the aim to improve the reparative response of bone tissue surrounding a cemented implant, soon after the operation: a 6% NaF 6% BaSO4 preparation “Fluoride Bone Cement©” (Tecres, I) was tested in-vivo versus a 9% BaSO4 preparation “CemexRX©” (Tecres, I). NaF stimulating action towards bone repair is prompt by the formation of fluoroapatite and the stimulation of osteoblast differentiation. NaF-added cement acts like a “drug-release device” for fluoride ions.

Materials & Methods. Eighteen outbred male New Zealand White rabbits of approximately 3,2 kg of weight have been used. They were divided into six groups of three units. Gropus A1, A2, A3 were implanted with cement without fluoride “CemexRX©” while groups B1, B2, B3 had “Fluoride Bone Cement©”. Retrieval occurred after 17 days (A1, B1); 33 days (A2, B2); 60 days (A3, B3). The surgical implantation site selected was the distal femural canal (meta-epiphyseal region). The canal in the right femur was filled with cement while the canal in the left femur was used as a surgical control (“sham” operation). Sections of 100 micron of thickness were taken by a rotating diamond-saw microtome (Leitz Wetzlar) and analyzed by polarized light and ultra-violet fluorescence microscopy (Nikon Miscroscope). One hundred and twenty sections were obtained for each femur.

Results. Calcein green fluorescent labelling showed that no real endosteal osteogenic response was evidenced the day after surgery, for both cement preparations, while periosteal response was normal. This was the consequence of the biological insult of the intramedullary polymerization of the cement. Xylenol orange showed that all the contra-lateral femurs (“sham”) had a normal endosteal and periosteal osteogenesis at all times. Both cement preparations continued to show a limited end-osteal response after 17 days and a slow recovery after 33 days, with better pictures in favour of NaF cement. After 60 days recovery in endosteal osteogenesis was adequate but, again, NaF cement showed the highst number of good pictures.

Conclusions. Adding NaF promoted the better recovery in endosteal osteogenic response observed in comparison with NaF-free cement. To differentiate the biological response it was essential to compare a high number of sections (120) in comparable locations, in a contralateral “sham” operated control in the very same animal. This procedure, costly and demanding, seems to be a right methodological approach.

Aims

Two-stage exchange revision total hip arthroplasty (THA) performed in case of periprosthetic joint infection (PJI) has been considered for many years as being the gold standard for the treatment of chronic infection. However, over the past decade, there have been concerns about its safety and its effectiveness. The purposes of our study were to investigate our practice, collecting the overall spacer complications, and then to analyze their risk factors.

Knee sepsis following TKR can have devastating consequences for patient as well as surgeon. A two stage revision is a well accepted technique in TKR sepsis with the introduction of a temporary antibiotic cement spacer being the most popular procedure although irrigation techniques are popular in SA.

From a total of 111 revisions TKR from my practice 26 (23%) were 2 stage revisions for joint sepsis following TKR. 3 cases were early, 10 intermediate and 13 late onset sepsis cases. Most common organism was S. Aureus (7/26) and S. Epidermidis (7/26) although numerous other organisms were seen.

In all cases a two stage revision with a Palacos R cements spacer plus parenteral antibiotics were used. Prosthesis used for revision was primary knee prosthesis in 8 cases and revision (stemmed) prosthesis in 18 cases. Follow up range from 13 years to 6 months (average 6.8 years) with only one case of recurrent sepsis (3.8%) which went on to an arthrodesis. Time from debridement and spacer placement to revision TKR varied from 3 weeks to 10 months (average 2.1 months).

This paper shows that meticulous debridement followed by standard antibiotic cement spacer technique with additional parenteral antibiotics is indeed the gold standard approach without necessitating additional irrigation techniques.

To evaluate and compare the stability of an anterior cement construct following total spondylectomy for meta-static disease against alternative stabilization techniques.

After intact analysis of ten cadaveric spines (T9–L3), a T12 spondylectomy was performed. Three reconstruction techniques were tested for their ability to restore stiffness to the specimen using non-destructive tests:

1) multilevel posterior pedicle screw instrumentation (PPSI) from T10–L2 {MPI}, 2) anterior instrumentation from T11–L1 with PPSI {AMPI}, and 3) anterior cement and pins construct (T12) with PPSI {CMPI}.

Circumferential stabilization {AMPI, CMPI} restored stiffness to a level of the intact spine. CMPI provided more stability to the specimen than AMPI. MPI alone did not restore stiffness to the intact level.

Circumferential reconstruction using an anterior cement construct following total spondylectomy is biomechanically superior to posterior stabilisation alone.

Introduction: In two-stage revision of an infected total hip replacement a preformed temporary antibiotic-loaded polymethylmethacrylate spacer may be required in order to allow weightbearing and joint motion while ensuring antibiotic local release.

Methods: 29 patients with infected hips were treated by a two-stage procedure including removal of prosthesis and implantation of a spacer. The device comprised a stem with 3 available head sizes pre-coated by bone cement supplemented with gentamicin (2.5% w/w) and vancomycin (2.5% w/w). Joint motion and weight-bearing were allowed when the bone stock ensured an adequate stability to the spacer. Systemic antibiotics were administered for 8 weeks. The spacer remained in situ for an average of 155 (range 70–272) days. Reimplantation was performed when recovery of clinical and serological signs of infection was obtained. Patients’ evaluation included clinical assessment (HHS), standard x-ray and laboratory parameters.

Results: mean follow-up was 52 months (range 36–100). Healing of the infection was obtained in 27/29 cases (93.1%). 5 patients required resection-arthroplasty (2 persistent infections, 2 inadequate bone stock, 1 recurrent infection). In 4 cases the spacer dislocated, being treated by non-surgical reduction. The reimplanted patients (24) showed no clinical or laboratory signs of infection recurrence, with a mean HHS score of 79 (range 53 to 100); no radiographic signs of loosening were observed.

Discussion: the use of a preformed antibiotic-loaded spacer in two-stage revisions, allowing a local antibiotic release together with some degree of joint motion, appears to enhance infection’s treatment improving patients’ quality of life and functional recovery.

We retrospectively compared the outcome after the treatment of giant cell tumours of bone either with curettage alone or with adjuvant cementation. Between 1975 and 2008, 330 patients with a giant cell tumour were treated primarily by intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246) compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On multivariate analysis both the stage of disease and use of cement were independent significant factors associated with local recurrence. The use of cement was associated with a higher risk of the subsequent need for joint replacement. In patients without local recurrence, 18.1% (13 of 72) of those with cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9 of 12) of those with previous cementation required a joint replacement, compared with 45.2% (33 of 73) of those without cement (p = 0.044).

The augmentation of fixation with bone cement is increasingly being used in the treatment of severe osteoporotic fractures. We investigated the influence of bone quality on the mechanics of augmentation of plate fixation in a distal femoral fracture model (AO 33 A3 type). Eight osteoporotic and eight non-osteoporotic femoral models were randomly assigned to either an augmented or a non-augmented group. Fixation was performed using a locking compression plate. In the augmented group additionally 1 ml of bone cement was injected into the screw hole before insertion of the screw. Biomechanical testing was performed in axial sinusoidal loading. Augmentation significantly reduced the cut-out distance in the osteoporotic models by about 67% (non-augmented mean 0.30 mm (sd 0.08) vs augmented 0.13 mm (sd 0.06); p = 0.017). There was no statistical reduction in this distance following augmentation in the non-osteoporotic models (non-augmented mean 0.15 mm (sd 0.02) vs augmented 0.15 mm (sd 0.07); p = 0.915). In the osteoporotic models, augmentation significantly increased stability (p = 0.017).

Cite this article: Bone Joint J 2013;95-B:1406–9.

Background: Polymethylmethacrylate (PMMA) is a potent stimulant of inflammatory response. This study investigated the role of Prostaglandin E2 (PGE2), Platelet activating factor (PAF) and histamine and their specific antagonists in bone changes.

Materials: 120 white-male-wistar rats were divided into ten groups. Using sterile technique, a 2mm drill hole was made in the tibia 1cm distal to the knee joint bilaterally. The left tibia was filled with Simplex particulate cement polymer (PMMA) and the right tibia was used as control. The first nine groups respectively received terfenadine 1mg/kg, 10mg/kg and 25mg/kg, alprazolam 0.08mg/kg, 0.32mg/kg and 0.64mg/kg, and naproxen 1mg/kg, 5mg/kg and 25mg/kg; however, the tenth group received no drug and served as control. The animals were killed after 16 weeks and implant areas were harvested aseptically and studied by one pathologist.

Results: Our study revealed that the cellular reaction in the left side was statistically more than the right one in all cases (p< 0.05). Also, a significant decrease in histiocytes and giant cells was seen just in those groups that had received 10mg/kg and 25mg/kg of terfenadine, 0.32mg/kg and 0.64mg/kg of alprazolam and 5mg/kg and 25mg/kg of naproxen (P< 0.05) while administration of 1mg/kg naproxen resulted in significant decrease only in giant cells (P< 0.05) but not in histiocytes.

Discussion: Previous studies have suggested that particulate debris, PGE2 production and inflammatory response are associated with arthroplasty loosening. This experiment has demonstrated that the increased cellular reaction by the membrane surrounding particulate cement polymer can be suppressed by administration of PGE2, PAF and histamine specific inhibitors. The use of these agents may be indicated in retarding the bone loss associated with early prosthetic loosening.

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in. sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use

Osteosarcoma and other types of bone cancers often require bone resection, and backfill with cement. A novel silorane-based cement without PMMA's drawbacks, previously developed for dental applications, has been reformulated for orthopedic use. The aim of this study is to assess each cement's ability to elute doxorubicin, maintain its potency, and maintain suitable weight-bearing strength. The silorane-based epoxy cement was synthesized using a platinum-based Lamoreaux's catalyst. Four groups of cement were prepared. Two PMMA groups, one without any additives, one with 200 mg of doxorubicin. Two silorane groups: one without any additive, one with doxorubicin, added so that the w% of drug into both cements were equal. Pellets 6 × 12 mm were used for testing (ASTM F451). n=10. Ten pellets from each group were kept dry. All others were placed into tubes containing 2.5 mL of PBS and stored at 37 °C. Elution from doxorubicin-containing groups were collected every day for 7 days, with daily PBS changeout. Antibiotic concentrations were determined via HPLC. Compressive strength and compressive modulus of all groups were determined for unsoaked specimens, and those soaked for 7 and 14 days. MTT assays were done using an MG63 osteosarcoma cell line. Both cements were able to elute doxorubicin over 7 days in clinically-favorable quantities. For PMMA samples, the incorporation of doxorubicin was shown to significantly affect the compressive strength and modulus of the samples (p<0.01). Incorporation of doxorubicin into silorane had no significant effect on either (p>.05). MTT assays indicated that doxorubicin incorporated into the silorane cement maintained its effectiveness whereas that into PMMA did not. At the dosing used, both cements remained above the 70 MPa. Both PMMA and silorane-based cements can deliver doxorubicin. Doxorubicin, however, interacts chemically with PMMA, inhibiting polymerization and lowering the chemotherapeutic's effectiveness

Polymethylmethacrylate (PMMA) bone cement is strong in compression, however it tends to fail under torsion. Sufficient pressurisation and subsequent interdigitation between cement and bone are critical for the mechanical interlock of cemented orthopaedic implants, and an irregular surface on the acetabular cup is necessary for reasonable fixation at the cup-cement interface. There is limited literature investigating discrepancies in the failure mechanisms of cemented all-polyethylene acetabular cups with and without cement spacers, under torsional loading. In vitro experimental comparison of three groups of polyethylene acetabular prosthesis (PAP) cemented into prepared sawbone hemipelvises:. * PAP without PMMA spacers maintaining an equal cement mantle circumferentially. (Group 1 n=3). * PAP without PMMA spacers cemented deliberately ‘bottoming-out’ the implant within the acetabulum. (Group 2 n=3). * PAP with PMMA spacers. (Group 3 n=3). The constructs were tested to torstional failure on a custom designed setup, and statistical analysis done by a one-way ANOVA and Tukey-Welsh test. Group 3 demonstrated superior torsional resistance with a statistically significant torque of 145Nm (SD±12Nm) at failure, compared to group 2 (109Nm, SD±7Nm) and group 1 (99Nm, SD±8Nm). Group 3 experienced failure predominantly at the bone-cement interface, in contrast, Groups 1 and 2 exhibited failure predominantly at the cup-cement interface. There was no significant difference between Group 1 and 2. Qualitative analysis of the failure mode indicates the efficient redistribution of stress throughout the cement mantle, consistent with the greater uniformity of cement. PMMA spacers increase the resistance to torsional failure at the implant-cement interface. Acetabular components without spacers (Groups 1 and 2) failed at the implant-cement interface before the cement-bone interface, at a statistically significantly lower level of torque to failure. Although the PMMA spacers may reduce cement interdigitation at the cement-bone interface the torsional forces required to fail are likely supraphysiological

Great strides have been made in the early detection and treatment of cancer which is resulting in improved survivability and more Canadians living with cancer. Approximately 80% of primary breast, lung, and prostate cancers metastasize to the spine. Poly-methyl methacrylate (PMMA) bone cement is one of the most commonly used bone substitutes in spine surgery. In clinical practice it can be loaded with various drugs, such as antibiotics or chemotheraputic drugs, as a means of local drug delivery. However, studies have shown that drugs loaded into PMMA cement tend to release in small bursts in the first 48–72 hours, and the remaining drug is trapped without any significant release over time. The objective of this study is to develop a nanoparticle-functionalized PMMA cement for use as a sustained doxorubicin delivery device. We hypothesize that PMMA cement containing mesoporous silica nanoparticles will release more doxorubicin than regular PMMA. High viscosity SmartSet ™ PMMA cement by DePuy Synthes was used in this study. The experimental group consisted of 3 replicates each containing 0.24 g of mesoporous silica nanoparticles, 1.76 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The control group consisted 3 replicates each containing 2.0 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The experimental group contained an average of 8.18 ± 0.008 % (W/W) mesoporous silica nanoparticles. Each replicate was casted into a cylindrical block and incubated in a PBS solution which was changed at predetermined intervals for 45 days. The concentration of eluted doxorubicin in each solution was measured using a florescent plate reader. The mechanical properties of cement were assessed by unconfined compression testing. The effect of the doxorubicin released from cement on prostate and breast tumor cell metabolic activity was assessed using the Alamar Blue test. After 45 days the experimental group released 3.24 ± 0.25 % of the initially loaded doxorubicin which was more than the 2.12 ± 0.005% released by the control group (p 0.03). There was no statistically significant difference in Young's elasticity modulus between groups (p 0.53). Nanoparticle functionalized PMMA suppressed the metabolic activity of prostate cancer by more than 50 percent but did not reach statistical significance. Nanoparticle functionalized PMMA suppressed the metabolic activity of breast cancer cells by 69 % (p < 0.05). Nanoparticle-functionalized PMMA cement can release up to 1.53 times more doxorubicin than the standard PMMA. The use of mesoporous silica nanoparticles to improve drug release from PMMA cement shows promise. In the future, in vivo experiments are required to test the efficacy of released doxorubicin on tumor cell growth

Treatment of bone infection often includes a burdensome two-stage revision. After debridement, contaminated implants are removed and replaced with a non-absorbable cement spacer loaded with antibiotics. Weeks later, the spacer is exchanged with a bone graft aiding bone healing. However, even with this two-stage approach infection persists. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoinductive calcium phosphate scaffold (CPS) is effective in single-stage revision of an infected non-union with segmental bone loss in rabbits. A 5 mm defect was created in the radius of female New Zealand White rabbits. The bone fragment was replaced, stabilized with cerclage wire and inoculated with Staphylococcus aureus (MSSA). After 4 weeks, the infected bone fragment was removed, the site debrided and a spacer implanted. Depending on group allocation, rabbits received: 1) PMMA spacer with gentamycin; 2) CPS loaded with rifampin and vancomycin and 3) Non-loaded CPS. These groups received systemic cefazolin for 4 weeks after revision. Group 4 received a loaded CPS without any adjunctive systemic therapy (n=12 group1-3, n=11 group 4). All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or histology. Covariance analysis (ANCOVA) and multiple regression were performed. All animals were culture positive at revision surgery. Half of the animals in all groups had eliminated the infection by end of study. In a historical control group with empty defect and no systemic antibiotic treatment, all animals were infected at euthanasia. There was no significant difference in CFU counts between groups at euthanasia. Our results show that treating an osteomyelitis with segmental bone loss either with CPS or PMMA has a similar cure rate of infection. However, by not requiring a second surgery, the use of CPS may offer advantages over non-resorbable equivalents such as PMMA

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence. Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated. The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells. Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection

Introduction. The medical field has long held largely anecdotal beliefs that polymethyl methacrylate (PMMA) vapors are dangerous to a growing fetus, and as such, women who are pregnant should avoid exposure. This study investigates the perceptions of female orthopedic surgeons regarding PMMA cement exposure during pregnancy, and if it influences 1) currently held beliefs / practices and 2) clinical and career choices. Methods. A 23-question survey was distributed via e-mail to active members of the Ruth Jackson Orthopaedic Society and a private social media group for women in orthopedics. Questions included demographics, current usage of PMMA, previous exposure during pregnancy and/or breastfeeding, and beliefs regarding current or future willingness of exposure. Additionally, questions were asked regarding PMMA training and whether beliefs influenced specialty choices. Results. There were 278 survey responses received, of which 256 met inclusion criteria. 73% currently utilize PMMA in training/practice, and >90% of survey respondents reported awareness of risks surrounding PMMA in pregnancy. PMMA training was found to have a weak positive correlation with those who remained in the room while pregnant. 43.6% would leave the room in the future if PMMA were being used while they were pregnant, with 26.2% leaving if they were breastfeeding. 24.9% would leave if they were the primary surgeon on the case, and 8.4% admitted that PMMA exposure during pregnancy factored into which subspecialty they chose. Conclusion. This survey demonstrates a lack of consensus amongst female orthopedic surgeons regarding the risks posed by remaining in a room during pregnancy and breastfeeding while PMMA is used. Despite 90% of respondents claiming awareness of the risks of PMMA, beliefs and education practices should be examined to determine if they match the available literature. It is plausible that beliefs regarding this exposure are deterring individuals from pursuing specialties where PMMA is used regularly. For any tables or figures, please contact the authors directly

In chronically infected fracture non-unions, treatment requires extensive debridement to remove necrotic and infected bone, often resulting in large defects requiring elaborate and prolonged bone reconstruction. One approach includes the induced membrane technique (IMT), although the differences in outcome between infected and non-infectious aetiologies remain unclear. Here we present a new rabbit humerus model for IMT secondary to infection, and, furthermore, we compare bone healing in rabbits with a chronically infected non-union compared to non-infected equivalents. A 5 mm defect was created in the humerus and filled with a polymethylmethacrylate (PMMA) spacer or left empty (n=6 per group). After 3 weeks, the PMMA spacer was replaced with a beta-tricalcium phosphate (chronOs, Synthes) scaffold, which was placed within the induced membrane and observed for a further 10 weeks. The same protocol was followed for the infected group, except that four week prior to treatment, the wound was inoculated with Staphylococcus aureus (4×10. 6. CFU/animal) and the PMMA spacer was loaded with gentamicin, and systemic therapy was applied for 4 weeks prior to chronOs application. All the animals from the infected group were culture positive during the first revision surgery (mean 3×10. 5. CFU/animal, n= 12), while at the second revision, after antibiotic therapy, all the animals were culture negative. The differences in bone healing between the non-infected and infected groups were evaluated by radiography and histology. The initially infected animals showed impaired bone healing at euthanasia, and some remnants of bacteria in histology. The non-infected animals reached bone bridging in both empty and chronOs conditions. We developed a preclinical in vivo model to investigate how bacterial infection influence bone healing in large defects with the future aim to explore new treatment concepts of infected non-union

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Introduction. Degeneration of the cervical spine can lead to neurological symptoms that require surgical intervention. Often, an anterior cervical discectomy (ACD) with fusion is performed with interposition of a cage. However, a cage substantially increases health care costs. The polymer polymethylmethacrylate (PMMA) is an alternative to cages, associated with lower costs. The reported high-occurrence of non-fusion with PMMA is often seen as a drawback, but evidence for a correlation between radiological fusion and clinical outcome is absent. To investigate if the lower rate of fusion with PMMA has negative effects on long-term clinical outcome, we assessed the clinical results of ACD with PMMA as a intervertebral spacer with a 5–10 year follow-up. Methods. A retrospective cohort study among all patients who underwent a mono-level ACD with PMMA for degenerative cervical disease, between 2007–2012, was performed. Patients filled out an online questionnaire, developed to assess clinical long-term outcome, complications and re-operation rates. The primary outcome measure was the Neck Disability Index (NDI), secondary outcome measures were re-operation and complication rates. Results. Of 196 eligible patients, 90 patients were assessed (response rate 53%). The average NDI score at follow-up (mean 7.5 years) was 19.0 points ± 18.0 points. Complications occurred in 10% and re-operation in 8.8%. Conclusion. This study provides evidence of good long-term clinical results of ACD with PMMA, as the results were similar with long-term outcomes of ACD with a cage as spacer. Therefore, the results of this study may suggest that the use of PMMA is an lower-cost alternative. No conflicts of interests. No funding obtained

Objectives. Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. Methods. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. Results. In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. Conclusion. Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection. Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387–396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1

Abstract. Objectives. The principle of osteoporotic vertebral compression fracture (OVCF) is fixing instability, providing anterior support, and decompression. Contraindication for vertebroplasty is anterior or posterior wall fracture. The study objectives was to evaluate the efficacy and safety of vertebroplasty with short segmented PMMA cement augmented pedicle screws for OVCF with posterior/anterior wall fracture patients. Methods. A retrospective study of 24 patients of DGOU type-4 (vertebra plana) OVCF with posterior/anterior wall fracture, were treated by vertebroplasty and short segment PMMA cement augmented pedicle screws fixation. Radiological parameters (kyphosis angle and compression ratio) and clinical parameters Visual analogue scale (VAS) and Oswestry disability index (ODI) were analysed. Results. A significant improvement was noted in VAS (preoperative, 7.90 ±0.60; final follow-up 2.90 ± 0.54) and ODI (77.10 ± 6.96 to 21.30 ± 6.70), (P < 0.05). Neurological improvement was noted in all patients. Kyphosis corrected significantly from preoperative 23.20±5.90 to 5.30±1.40 postoperative with 5% (3.30± 2.95) loss of correction at final follow-up. Anterior vertebral height restored significantly from 55.80±11.9% t0 87.6±13.1% postoperative with 4.5±4.0% loss at final follow-up. One case had cement leakage was found, but the patient is asymptomatic. No implant-related complication was seen. No iatrogenic dural or nerve injury. Conclusions. Treatment with vertebroplasty with cement augmented screw fixation and direct decompression is a great option in treating such a complex situation in fragile age with fragile bones because It provides anterior support with cementing that avoids corpectomy. Short segment fixation has less stress risers at the junctional area

Objectives. The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content. Methods. Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties. Results. Compared with control, the rifampin-incorporated cement had a prolonged setting time and a reduction in exothermic output during polymerization. The rifampin cement showed significantly reduced strength and was below the orthopaedic weight-bearing threshold of 70 MPa. Based on the radical scavenging assay and strength tests, the hydroquinone structure within rifampin was identified as the polymerization inhibitor. Conclusion. The incorporation of rifampin into PMMA bone cement interferes with the cement’s radical polymerization. This interference is due to the hydroquinone moiety within rifampin. This combination alters the cement’s handling and curing properties, and lowers the strength below the threshold for weight-bearing applications. Additionally, the incomplete polymerization leads to increased toxic monomer output, which discourages its use even in non-weight-bearing applications. Cite this article: G. A. Funk, E. M. Menuey, K. A. Cole, T. P. Schuman, K. V. Kilway, T. E. McIff. Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement. Bone Joint Res 2019;8:81–89. DOI: 10.1302/2046-3758.82.BJR-2018-0170.R2

Aim. The preparation of antibiotic-containing polymethyl methacrylate (PMMA), as spacers generates a high polymerization heat, which may affect their antibiotic activity; it is desirable to use bone cement with a low polymerization heat. Calcium phosphate cement (CPC) does not generate heat on polymerization, and comparative elution testings are reported that vancomycin (VCM)-containing CPC (VCM-CPC) exceeded the antibiotic elution volume and period of PMMA (VCM-PMMA). Although CPC alone is a weak of mechanical property spacer, the double-layered, PMMA-covered CPC spacer has been created and clinically used in our hospital. In this study, we prepared the double-layered spacers: CPC covered with PMMA and we evaluated its elution concentration, antimicrobial activity and antibacterial capability. Method. We prepared spherical, double-layered, PMMA-coated (CPC+PMMA; 24 g CPC coated with 16 g PMMA and 2 g VCM) and PMMA alone (40 g PMMA with 2 g VCM) spacers (5 each). In order to facilitate VCM elution from the central CPC, we drilled multiple holes into the CPC from the spacer surface. Each spacer was immersed in phosphate buffer (1.5 mL/g of the spacer), and the solvent was changed daily. VCM concentrations were measured on days 1, 3, 7, 14, 28, 56, and 84. Antimicrobial activity against MRSA and MSSA was evaluated by the broth microdilution method. After measuring all the concentration, the spacers were compressed at 5 mm/min and the maximum compressive load up to destruction was measured. Results. The VCM concentration of the CPC+PMMA spacer exceeded that of the PMMA spacer at all-time points; in particular, it was approximately 7.3 times (109.30 vs. 15.03 μg/mL) and approximately 9.1 times (54.47 vs. 6.50 μg/mL) greater on days 14 and 28, respectively. Using the broth microdilution method, we found that the CPC+PMMA spacer had higher antimicrobial activity than the PMMA model. On day 56, the PMMA spacer lost the capability to inhibit bacterial growth, but the CPC+PMMA spacer maintained this ability. The average maximum compressive load for the CPC+PMMA was 7.28 kN, and that of PMMA was 16.21 kN. Conclusions. The CPC+PMMA spacer was superior to PMMA alone in VCM elution volume and duration, so CP- C+PMMA may be effective for the treatment of MRSA and MSSA infection. The double-layered, antibiotic-loaded cement spacer may maintain antibacterial capability and sufficient strength

Aim. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded polymethylmethacrylate (PMMA) against multidrug resistant bacteria from osteomyelitis (OM) and prosthetic joint infection (PJI) isolates. Method. We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2mm), BAG-S53P4 granules (0.5–0.8mm and <45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 hours of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. Results. Inhibition of bacterial growth started soon after 48 hours of incubation, reached zero CFU/ml between 120 and 168 hours of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p< 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. Moreover, despite no difference was observed between both Vancomycin - or Gentamicin-loaded PMMA and BAG groups, there was statistical difference between the effectiveness of all treatments (BAG included) against gram-positive cocci and gram-negative bacilli, the latter of which requiring longer time frames for the cultures to yield no bacterial growth. Conclusions. BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI, although presenting differences between its effectiveness against different bacterial groups

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483

The burden of periprosthetic joint infection (PJI) continues to rise and the management of this dreaded complication continues to pose challenges to the orthopaedic community. Dr Buchholz from the Endo Klinik has been credited for reporting the initial observation that addition of antibiotic to polymethylmethacrylate (PMMA) cement lead to better ability to deliver higher concentrations of antibiotic to the joint milieu and avoid administration of high doses of systemic antibiotics with potential for systemic toxicity. Addition of antibiotics to PMMA cement has continued to be an important aspect of managing patients with chronic PJI. The rationale for this practice is that higher doses of local antibiotics can be reached without placing the patients at risk of systemic toxicity. Whether a one-stage or a two-stage exchange arthroplasty is being performed, antibiotics that can withstand the exothermic reaction of PMMA and are able to elude from cement are added at various doses to the PMMA for later delivery. Although this practice continues to be almost universal, there are a few unknowns. First of all, a recent study raised a valid question regarding this practice. Though intuitively logical, addition of antibiotics to PMMA spacers has not been scrutinised by any level 1 study and hence one is not able to prove that this practice does indeed accomplish its intended objectives of reducing recurrence or persistence of infection. Orthopaedic community is advised to seek avenues to generate this much-needed evidence. The other main unknown is how much, and in some instances which antibiotic, needs to be added to the PMMA cement. Some authorities have declared that antibiotics can be added at high doses, with an average total dose of 10.5 g of vancomycin (range, 3–16 g) and 12.5 g of gentamicin (range, 3.6–19.2 g) in one study, to PMMA cement without the fear of systemic toxicity. In recent years, renal toxicity and other systemic adverse effects have been attributed to addition of high doses of antibiotics to cement. I have personally witnessed such adverse reactions in a few patients. Although initially I was inclined to “blame” the concurrent administration of systemic antibiotics for the renal toxicity that patients developed following insertion of spacer, selective nephrotoxicity (i.e. reaction to aminoglycoside that was only present in the spacer and not systemically administered) and resolution of the nephrotoxicity upon removal of antibiotic spacer, convinced me that our nephrology colleagues have a valid reason to be concerned about addition of high doses of antibiotics to PMMA spacers. What has become clear is that high viscosity cements containing MA-MMA copolymers have been shown to have better antibiotic elution profiles than other PMMA formulations. So when fashioning a spacer in the operating room the surgeon needs to be aware of the differences in elution profile of antibiotics from PMMA and individualise the dose of antibiotics being added to spacer based on the type and viscosity of cement being used and the renal status of the patient. Thus, systemic toxicity caused by addition of antibiotics to cement spacer appears to be a real issue in some circumstances and this needs to be born in mind when managing patients with PJI. There are numerous other issues related to the use of antibiotic cement spacers. In the hip, the lack of adequate offset and limited portfolio of products result in laxity in the soft tissue and subsequent dislocation of the hip. In addition, the dose and type of antibiotic in the premanufactured spacers, at least in the US, are inadequate to lead to a substantial delivery of antibiotics in the local tissues. Because of these issues, I prefer to fabricate “customised” spacers for each patient that I operate on

Introduction. The management of open long bone fractures is well described and has been standardised through a number of well-established guidelines. However, there is no consensus regarding the application of local antibiotics into the open fracture site as a means of reducing infection rates. Materials & Methods. A systematic review and meta-analysis were undertaken as per PRISMA guidelines. PROSPERO Registration CRD42022323545. PubMed, EMBASE, Scopus and CENTRAL were the databases assessed. The Newcastle Ottawa Scale and the Rob 2 Tool were used to assess bias. A qualitative synthesis of all included studies and meta-analysis of suitable subgroups was undertaken. Results. In total, 12 studies (11 observational, 1 RCT) assessing 2431 open fractures were included for analysis. All compared the addition of a local antibiotic therapy to a standard treatment versus the standard treatment alone. The methods of delivery were vancomycin powder (4 papers), tobramycin polymethylmethacrylate beads (4 papers), gentamicin coated intramedullary (IM) nails (2 papers), gentamicin injections (1 paper) and antibiotic released IM core cement (1 paper). The addition of vancomycin powder did not decrease infection rates in comparison to intravenous antibiotics alone (OR 1.3, 95% CI (0.75 – 2.26)). Antibiotic coated IM Nails appear to have an association with lower infection rates than standard IM Nails. PMMA antibiotics have shown varied results in reducing infection rates depending on the individual studies. Conclusions. There are numerous methods available to deliver antibiotics locally to an open fracture site. Further high-quality research is required to provide a definitive conclusion on their efficacy irrespective of delivery method

The enhancement of current bone cement properties is a challenging issue that has been the focus of much research. Developing bone composites with high level of cytocompatibility, mechanical and antibacterial properties is a challenging task. We overcome this challenge by designing a nanocomposite that contain two-dimensional (2D) nanosheets. To develop our novel bone cement nanocomposite, 2D nanosheets were synthesized, mixed in different ratios, and then added to the PMMA matrix. The results reveal that the incorporation of 2D nanosheets into the PMMA matrix leads to increase in the antibacterial properties of the bone cement composite against E. coli bacteria. In addition, the 2D nanosheets improve the compression strength of the bone cement nanocomposite significantly. We also show that nanosheets increased the bioactivity of the bone cements. Finally, MTT assay results indicate that PMMA as a control sample has the lowest cytocompatibility, however, our novel nanocomposites have the highest amount of cytocompatibility. Thus, the current study suggests that 2D nanosheets are potential filler components for the next generation of PMMA bone cement nanocomposites. The findings of this work reveal that the excellent performance of the proposed bone composite can result in a paradigm shift in design of state-of-the art bone cement composites

A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer. We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body. The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone. In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed. In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation. The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures

Multiple studies have established an inverse relationship between ambient theatre temperatures and polymethyl methacrylate (PMMA) cement setting times. It is also known that allowing cement to equilibrate to ambient theatre temperatures restores expected setting characteristics. One overlooked entity is the transport and storage conditions of cement. This is important in tropical regions, where extreme temperature and humidity may cause rapid cement setting times, resulting in potentially significant intra-operative complications. This study investigated the relationship between extreme transport and storage conditions of Antibiotic Simplex cement (Stryker), and the effect on setting times at Cairns Hospital, Far North Queensland, Australia. Fifty units of cement were divided evenly into a control arm and four experimental arms. The experimental arms were designed to mimic potential transport and storage conditions. They included seven days of storage in a medication fridge, on the hospital loading dock, in a cane shed, and in a Toyota Landcruiser parked outdoors during January 2022. Humidity and temperature readings were recorded. The samples in each group were evenly distributed to equilibrate to theatre conditions for 1 hour and 24 hours. Setting time was recorded when a no. 15 scalpel blade was unable to mark the surface. All three ‘hot’ exposures setting times were significantly faster for both 1 hour (ρ=0.001) and 24 hours (ρ=0.024) equilibration times. The difference in setting times for the ‘cold’ exposure was not significant for either equilibration times (ρ=1). To our knowledge, this is the first study investigating cement setting times in tropical climates. Further studies are required to address the effect of these conditions on biomechanical strength of PMMA cement. We conclude that extreme heat and humidity during transport and storage have a statistically significant effect on cement setting times

Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation. Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation. We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically

Objectives. Understanding lumbar facet joint involvement and biomechanical changes post spinal fusion is limited. This study aimed to establish an in vitro model assessing mechanical effects of fusion on human lumbar facet joints, employing synchronized motion, pressure, and stiffness analysis. Methods and Results. Seven human lumbar spinal units (age 54 to 92, ethics 15/YH/0096) underwent fusion via a partial nucleotomy model mimicking a lateral cage approach with PMMA cement injection. Mechanical testing pre and post-fusion included measuring compressive displacement and load, local motion capture, and pressure mapping at the facet joints. pQCT imaging (82 microns isotropic) was carried out at each stage to assess the integrity of the vertebral endplates and quantify the amount of cement injected. Before fusion, relative facet joint displacement (6.5 ± 4.1 mm) at maximum load (1.1 kN) exceeded crosshead displacement (3.9 ± 1.5 mm), with loads transferred across both facet joints. After fusion, facet displacement (2.0 ± 1.2 mm) reduced compared to pre-fusion, as was the crosshead displacement (2.2 ± 0.6 mm). Post-fusion loads (71.4 ± 73.2 N) transferred were reduced compared to pre-fusion levels (194.5 ± 125.4 N). Analysis of CT images showed no endplate damage post-fusion, whilst the IVD tissue: cement volume ratio did not correlate with the post-fusion behaviour of the specimens. Conclusion. An in vitro model showed significant facet movement reduction with stand-alone interbody cage placement. This technique identifies changes in facet movement post-fusion, potentially contributing to subsequent spinal degeneration, highlighting its utility in biomechanical assessment. Conflicts of interest. None. Sources of funding. This work was funded by EPSRC, under grant EP/W015617/1

Objectives. Investigate the incorporation of an antibiotic in bone cement using liposomes (a drug delivery system) with the potential to promote osseointegration at the bone cement interface whilst maintaining antibiotic elution, anti-microbiological efficacy and cement mechanical properties. Prosthetic joint infection and aseptic loosening are associated with significant morbidity. Antibiotic loaded bone cement is commonly used and successfully reduces infection rates; however, there is increasing resistance to the commonly used gentamicin. Previous studies have shown gentamicin incorporated into bone cement using liposomes can maintain the cement's mechanical properties and improve antibiotic elution. The phospholipid phosphatidyl-l-serine has been postulated to encourage surface osteoblast attachment and in a liposome could improve osseointegration, thereby reducing aseptic loosening. Preliminary clinical isolate testing showed excellent antimicrobial action with amoxicillin therefore the study aims were to test amoxicillin incorporated into bone cement using liposomes containing phosphatidyl-l-serine in terms of antibiotic elution, microbiological profile and mechanical properties. Methods. Amoxicillin was encapsulated within 100nm liposomes containing phosphatidyl-L-serine and added to PMMA bone cement (Palacos R (Heraeus Medical, Newbury, UK)). Mechanical testing was performed according to Acrylic Cement standards (ISO BS 5833:2002). Elution testing was carried out along with microbiological testing utilising clinical isolates. Results. Liposomal encapsulated amoxicillin PMMA bone cement exceeded minimum ISO BS 5833:2002 standards, had better elution at 12.9% when compared with plain amoxicillin (p=0.036 at 48 hours) or commercial gentamicin cement (Palacos R+G, Heraeus Medical, Newbury, UK – previous studies showed 6% elution over the same time period). Amoxicillin showed superior antimicrobial action when compared with gentamicin of the same concentration. However, liposomal encapsulated amoxicillin in solution and liposomal encapsulated amoxicillin in PMMA were both less effective than free amoxicillin in bacterial growth inhibition. The liposomal amoxicillin also seemed to decrease the cement setting time. Conclusions. Phosphatidyl-l-serine containing liposomes maintained the cement's mechanical properties and seemed to have better antibiotic elution, however, had less effective antibacterial action than plain amoxicillin. This difference in antibacterial action requires further investigation along with investigation of osteoblast attachment to phosphatidyl-l-serine containing liposomes within cement. Plain amoxicillin, for those not penicillin allergic, seems to be a credible alternative to gentamicin for incorporation in PMMA bone cement. It has shown superior antibacterial action, which may improve infection rates, whilst maintaining the cement's mechanical properties

Aims. Tissue responses to debris formed by abrasion of polymethylmethacrylate (PMMA) spacers at two-stage revision arthroplasty for prosthetic joint infection are not well described. We hypothesised that PMMA debris induces immunomodulation in periprosthetic tissues. Patients and Methods. Samples of tissue were taken during 35 two-stage revision arthroplasties (nine total hip and 26 total knee arthroplasties) in patients whose mean age was 67 years (44 to 85). Fourier transform infrared microscopy was used to confirm the presence of PMMA particles. Histomorphometry was performed using Sudan Red and Haematoxylin-Eosin staining. CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype the inflammatory cells. All slides were scored semi-quantitatively using the modified Willert scoring system. Results. The mean CD-68 scores did not show any significant change during the six weeks between the stages. Perivascular and diffuse scores showed significant difference in CD-3, CD-20, CD-11(c) and IL-17. At the time of re-implantation, a shift in the pattern of the expression of dendritic cells towards a perivascular arrangement and towards the periphery of PMMA particles was observed. Positive microbiological cultures were found at the time of re-implantation in three patients. Five further revisions were required for other reasons. Conclusion. Our results represent a biological reaction of the synovial tissues to spacers with a less diffuse expression of dendritic cells and an increased expression of perivascular lymphocytes. The use of spacers in two-stage revision for infection probably induces an immunomodulation of synovial tissues. Cite this article: Bone Joint J 2016;98-B:1062–8