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Diabetes is associated with excessive inflammation, which negatively impacts the fracture healing process and delays bone repair. Previously, growing evidence indicated that activation of the nod-like receptor (NLR) family, such as nod-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome induces a vicious cycle of chronic low-grade inflammatory responses in diabetic fracture. Here, we describe the synthesis of a bone adhesive hydrogel that can be locally injected into the fracture site and releases a natural inhibitor of NLRP3 (rutin) in response to pathological cue reactive oxygen species activity (ROS). The hydrogel (denoted as RPO) was facilely formed by the cross-linking of rutin-functionalized gelatin, poly(vinyl alcohol), and oxidized starch based on the dynamic schiff base and boronate ester bond. Specifically, rutin is conjugated in the RPO hydrogel via a ROS linker and is released as the linker is cleaved by active ROS. In vitro studies demonstrate that RPO hydrogel effectively mitigates oxidative stress, alleviates mitochondrial dysfunction, and limits the overactivation of NLRP3 inflammasome in bone marrow derived macrophages, thereby promoting osteogenic differentiation of bone marrow mesenchymal stem cells. In a diabetic rat fracture model, RPO hydrogel significantly accelerates bone repair by modulating the inflammatory microenvironment. Our results demonstrate that local, on-demand NLRP3 inhibition for the treatment of diabetic fracture is achievable by using an injectable bioresponsive adhesive RPO hydrogel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The IEELEEELEAER peptide (PIE) identified from the protein hydrolysate of Mytilus edulis is reported to enhance osteoblast growth and differentiation, which also possesses a superior bone formation ability both in vitro and in vivo. Moreover, PIE bound to calcium spontaneously at the stoichiometry of 1:1, and there were amino nitrogen and carboxyl oxygen atoms in 2 glutamic acid residues at the calcium-binding sites in the PIE. The PIE-calcium complex facilitated calcium uptake through the Caco-2 cell monolayers. Incorporation of PIE into calcium phosphate cements enhanced calcium ion uptake and proliferation of osteoblasts and inhibit bacteria. This study suggest that calcium phosphate cements supplemented with PIE can serve as a potentially efficient material for bone graft used during spinal surgery., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of this study was to develop a biodegradable nanostructured electrospun layer based on collagen (COL), hydroxyapatite nanoparticles (HA), vancomycin hydrochloride (V), gentamicin sulphate (G) and their combination (VG) for the treatment of prosthetic joint infections and the prevention of infection during the joint replacement procedure. COL/HA layers containing different amounts of HA (0, 5 and 15 wt%) were tested for the in vitro release kinetics of antibiotics, antimicrobial activity against MRSA, gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis isolates and cytocompatibility using SAOS-2 bone-like cells. The results revealed that the COL/HA layers released high concentrations of vancomycin and gentamicin for 21 days and performed effectively against the tested clinically-relevant bacterial isolates. The presence of HA in the collagen layers was found not to affect the release kinetics of the vancomycin from the layers loaded only with vancomycin or its combination with gentamicin. Conversely, the presence of HA slowed down the release of gentamicin from the COL/HA layers loaded with gentamicin and its combination with vancomycin. The combination of both antibiotics exerted a positive effect on the prolongation of the conversion of vancomycin into its degradation products. All the layers tested with different antibiotics exhibited potential antibacterial activity with respect to both the tested staphylococci isolates and enterococci. The complemental effect of vancomycin was determined against both gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis in contrast to the application of gentamicin as a single agent. This combination was also found to be more effective against MRSA than is vancomycin as a single agent. Importantly, this combination of vancomycin and gentamicin in the COL/HA layers exhibited sufficient cytocompatibility to SAOS-2, which was independent of the HA content. Conversely, only gentamicin caused the death of SAOS-2 independently of HA content and only vancomycin stimulated SAOS-2 behaviour with an increased concentration of HA in the COL/HA layers. In conclusion, COL/HA layers with 15 wt% of HA impregnated with vancomycin or with a combination of vancomycin and gentamicin offer a promising treatment approach and the potential to prevent infection during the joint replacement procedures., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bone fractures at weight-bearing sites are challenging to treat due to the difficulty in maintaining articular congruency. An ideal biomaterial for fracture repair near articulating joints sets rapidly after implantation, stabilizes the fracture with minimal rigid implants, stimulates new bone formation, and remodels at a rate that maintains osseous integrity. Consequently, the design of biomaterials that mechanically stabilize fractures while remodeling to form new bone is an unmet challenge in bone tissue engineering. In this study, we investigated remodeling of resorbable bone cements in a stringent model of mechanically loaded tibial plateau defects in sheep. Nanocrystalline hydroxyapatite-poly(ester urethane) (nHA-PEUR) hybrid polymers were augmented with either ceramic granules (85% β-tricalcium phosphate/15% hydroxyapatite, CG) or a blend of CG and bioactive glass (BG) particles to form a settable bone cement. The initial compressive strength and fatigue properties of the cements were comparable to those of non-resorbable poly(methyl methacrylate) bone cement. In animals that tolerated the initial few weeks of early weight-bearing, CG/nHA-PEUR cements mechanically stabilized the tibial plateau defects and remodeled to form new bone at 16 weeks. In contrast, cements incorporating BG particles resorbed with fibrous tissue filling the defect. Furthermore, CG/nHA-PEUR cements remodeled significantly faster at the full weight-bearing tibial plateau site compared to the mechanically protected femoral condyle site in the same animal. These findings are the first to report a settable bone cement that remodels to form new bone while providing mechanical stability in a stringent large animal model of weight-bearing bone defects near an articulating joint., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Treatment for fractures of the tibial plateau is in most cases carried out by stable fixation in order to allow early mobilization. Minimally invasive technologies such as tibioplasty or stabilization by locking plate, bone augmentation and cement filling (CF) have recently been used to treat this type of fracture. The aim of this paper was to determine the mechanical behavior of the tibial plateau by numerically modeling and by quantifying the mechanical effects on the tibia mechanical properties from injury healing., Methods: A personalized Finite Element (FE) model of the tibial plateau from a clinical case has been developed to analyze stress distribution in the tibial plateau stabilized by balloon osteoplasty and to determine the influence of the cement injected. Stress analysis was performed for different stages after surgery., Findings: Just after surgery, the maximum von Mises stresses obtained for the fractured tibia treated with and without CF were 134.9 MPa and 289.9 MPa respectively on the plate. Stress distribution showed an increase of values in the trabecular bone in the treated model with locking plate and CF and stress reduction in the cortical bone in the model treated with locking plate only., Interpretation: The computed results of stresses or displacements of the fractured models show that the cement filling of the tibial depression fracture may increase implant stability, and decrease the loss of depression reduction, while the presence of the cement in the healed model renders the load distribution uniform., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The aim of this work was to develop an innovative drug delivery system potentially useful for the local delivery of Bisphosphonates to bone tissue. We propose the use of Solid Lipid Microparticles (MPs), up to now mainly used for oral and topical drug delivery, as carrier for bisphosphonates due to the favourable biocompatibility and lower toxicity of the lipids compared with many polymers. The delivery platform consisted of a biomimetic α-tricalcium phosphate-gelatin cement (CPC) enriched with alendronate loaded MPs (MPs-AL) produced by the spray congealing technology. Alendronate direct addition to cement composition is limited since Alendronate is able to sequester calcium from calcium phosphates, thus preventing the setting of the cements. At variance, this approach permitted to load a relatively high amount of the drug on the CPC and allowed the controlled release of the highly water soluble alendronate. A Design of Experiment (DoE) was employed for the screening of the effects of the formulation variables related to the presence of unloaded microparticle (MPs) on the cement most important mechanical properties. Then, MPs loaded with 10% w/w of alendronate were produced using five different carriers (Stearic Acid, Stearilic Alcohol, Cutina HR, Tristearin and Precirol ATO5). All MPs-AL exhibited a spherical shape, encapsulation efficiency higher than 90% and prevalent particle size ranging from 100 to 150μm. Solid state characterization (DSC, HSM and X-ray powder diffraction) demonstrated that encapsulation of alendronate into MPs did not alter its crystal structure. MPs-AL addition to the cement provoked a modest lengthening of the setting times and of the hardening reaction leading to the complete transformation of α-tricalcium phosphate into calcium-deficient hydroxyapatite, without significantly affect the cement mechanical properties. Moreover, the results of in vitro AL release study performed on cements enriched with MPs-AL showed that the system allows a controlled release of the drug over time., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Synthetic calcium phosphate bone graft substitutes are widely recognized for their biocompatibility and resorption characteristics in the treatment of large bone defects. However, due to their inherent brittleness, applications in load-bearing situations always require reinforcement by additional metallic implants. Improved mechanical stability would eliminate the need for non-resorbable metallic implants. In this context a new approach to obtain calcium phosphate scaffolds with improved mechanical stability by texturing the material in specific crystal orientations was evaluated. Texture and reduction of crystal size was achieved by recrystallizing α-TCP blocks into calcium deficient hydroxyapatite (CDHA) under hydrothermal conditions. SEM and XRD analysis revealed the formation of fine CDHA needles (diameter ≈ 0.1-0.5 μm), aligned over several hundreds of micrometers. The obtained microstructures were remarkably similar to the microstructures of the prismatic layer of mollusk shells or enamel, also showing organization at 5 hierarchical structure levels. Brazilian disc tests were used to determine the diametral tensile strength, σdts, and the work-of-fracture, WOF, of the textured materials. Hydrothermal incubation significantly increased σdts and WOF of the ceramic blocks as compared to sintered blocks. These improvements were attributed to the fine and entangled crystal structure obtained after incubation, which reduces the size of strength-determining critical defects and also leads to tortuous crack propagation. Rupture surfaces revealed intergranular tortuous crack paths, which dissipate much more energy than transgranular cracks as observed in the sintered samples. Hence, the refined and textured microstructure achieved through the proposed processing route is an effective way to improve the strength and particularly the toughness of calcium phosphate-based ceramics., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The high stiffness of bone cements used in vertebroplasty has been hypothesised to contribute to the propensity of adjacent vertebral fractures after treatment. Therefore, new low-modulus cements have been developed; however, there are currently no studies assessing the biomechanical aspects of vertebroplasty with these cements in an ex vivo non-prophylactic model. In this study, we induced wedge fractures through eccentric uniaxial compression to single whole-vertebrae, before and after augmentation with either standard or low-modulus cement. Compressive strength and stiffness of individual vertebrae were measured, on 19 samples from metastatic spines and 20 samples from elderly, osteopenic spines. While both cement types increased the strength of both the metastatic (+34% and +63% for standard and low-modulus cement, respectively) and the elderly vertebrae (+303% and +113%, respectively), none of them restored the initial stiffness of metastatic specimens (-51% and -46%, respectively). Furthermore, low-modulus cement gave a lower total stiffness (-13%) of elderly specimens whereas standard cement increased it above initial levels (+17%). Results show that vertebroplasty with low-modulus cement could provide restoration of the initial stiffness while increasing the strength of fractured elderly vertebrae and hence represent a treatment modality which is closer to pre-augmented behaviour. Also, this study indicates that stiffness-modified cement needs to be optimised for patient/pathology specific treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Acrylic bone cement has been an essential non-metallic implant used as fixing agent in the cemented total joint arthroplasty (THA). However, the currently available materials based mainly on polymethylmethacrylate (PMMA) still encounter certain limitations, such as time-consuming polymerization, thermal and chemical necrosis and troublesome revision procedure. Here from an alternative way, we proposed for the first time to adopt the injectable alloy cement to address such tough issues through introducing its unique liquid-solid phase transition mechanism. A typical cement along this way is thus made of an alloy Bi/In/Sn/Zn with a specifically designed low melting point 57.5 °C, which enables its rapid molding into various desired shapes with high plasticity and ultimate metallic behaviors. The fundamental characteristics including the mechanical strength, biocompatibility and phase transition-induced thermal effects have been clarified to demonstrate the importance of such alloy as unconventional cement with favorable merits. In addition, we also disclosed its advantage as an excellent contrast agent for radiation imaging on the bone interior structure which is highly beneficial for guiding the surgery and monitoring the therapeutic effects. Particularly, the proposed alloy cement with reversible phase transition feature significantly simplifies the revision of the cement and prosthesis. This study opens the way for employing the injectable alloy materials as reversible bone cement to fulfill diverse clinical needs in the coming time., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aseptic loosening of cemented tibial components in total knee arthroplasty (TKA) has been related to inadequate cement penetration into the trabecular bone bed during implantation. Recent postmortem retrieval work has also shown there is loss of interlock between cement and bone by resorption of trabeculae at the interface. The goal of this study was to determine if TKAs with more initial interlock between cement and bone would maintain more interlock with in vivo service (in the face of resorbing trabeculae) and have less micro-motion at the cement-bone interface. The initial (created at surgery) and current (after in vivo service) cement-bone interlock morphologies of sagittal implant sections from postmortem retrieved tibial tray constructs were measured. The implant sections were then functionally loaded in compression and the micro-motion across the cement-bone interface was quantified. Implant sections with less initial interdigitation between cement and bone and more time in service had less current cement-bone interdigitation (r(2)=0.86, p=0.0002). Implant sections with greater initial interdigitation also had less micro-motion after in vivo service (r(2)=0.36, p=0.0062). This work provides direct evidence that greater initial interlock between cement and bone in tibial components of TKA results in more stable constructs with less micro-motion with in vivo service., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A potential effective treatment for prevention of osteoporotic hip fractures is augmentation of the mechanical properties of the femur by injecting it with agents such as (PMMA) bone cement - femoroplasty. The operation, however, is only in research stage and can benefit substantially from computer planning and optimization. We report the results of computational planning and optimization of the procedure for biomechanical evaluation. An evolutionary optimization method was used to optimally place the cement in finite element (FE) models of seven osteoporotic bone specimens. The optimization, with some inter-specimen variations, suggested that areas close to the cortex in the superior and inferior of the neck and supero-lateral aspect of the greater trochanter will benefit from augmentation. We then used a particle-based model for bone cement diffusion simulation to match the optimized pattern, taking into account the limitations of the actual surgery, including limited volume of injection to prevent thermal necrosis. Simulations showed that the yield load can be significantly increased by more than 30%, using only 9 ml of bone cement. This increase is comparable to previous literature reports where gross filling of the bone was employed instead, using more than 40 ml of cement. These findings, along with the differences in the optimized plans between specimens, emphasize the need for subject-specific models for effective planning of femoral augmentation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Conventional water-free polymethylmethacrylate cements are not MRI visible due to the lack of free protons. A new MRI-visible bone cement was developed through the addition of a contrast agent and either a saline solution or a hydroxyapatite (Wichlas et al., 2010). The purposes of the study were to examine the influence of the two MRI-signal-inducing cements on the biomechanical behavior of cadaveric osteoporotic vertebral bodies after vertebroplasty and to compare the performance of the cements with conventional polymethylmethacrylate cement., Methods: Three different cements were used: standard polymethylmethacrylate cement and two modified MRI-signal-inducing cements that were mixed with either a 0.9% saline solution or a hydroxyapatite. The modulus of elasticity for the standard polymethylmethacrylate cement was 2040MPa, and the moduli for the MRI-signal-inducing cements that were mixed with a 0.9% saline solution and a hydroxyapatite were 1477 and 1225MPa, respectively. The lumbar vertebral bodies from nine osteoporotic spines (mean age=87 years, range=78-99 years) of female cadavers were examined. Three groups were formed: polymethylmethacrylate cement with saline solution (n=14), polymethylmethacrylate cement with hydroxyapatite (n=12) and polymethylmethacrylate cement (n=13). The vertebral bodies were biomechanically tested before and after vertebroplasty. Stiffness was chosen as the primary biomechanical parameter., Findings: The vertebral body stiffness was nearly two-fold greater after vertebroplasty, and this increase was statistically significant for every group. All the groups had similar vertebral body stiffness value before and after the vertebroplasty. The UNIANOVA test for multivariate analysis of variance showed no influence of lumbar level, injected cement volume and initial vertebral body stiffness., Interpretation: The elastic moduli of the cements appear to exert little influence on the biomechanical values when the cement is in the vertebral body. Based on the direct comparison with the classic polymethylmethacrylate cement, we believe that the implementation of such cements for MRI-guided vertebroplasties is feasible., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Injectable calcium phosphate cement (ICPC) has been applied to enhance the tendon-to-bone healing. However, its slow degradation delays the osteointegration of grafted tendon in bone tunnels. We therefore constructed a synthetic biomaterial of ICPC combined with recombined bone xenograft granules (RBX). In this study, the first stage study demonstrated that the ICPCB contained 3 mg BMPs (ICPCB-3) obtained a porous structure. More importantly, the values of ICPCB-3 were highest in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic genes, and newly ectopic bone-forming area (P < 0.05). Then, ICPCB-3 was used in an anterior cruciate ligament (ACL) reconstruction model. Ninety skeletal mature rabbits underwent bilateral ACL reconstructions and were assigned to 3 groups: control group, ICPC alone group, and ICPCB-3 group. Animals were sacrificed at 6, 12 and 24 weeks. The results showed compared with ICPC, ICPCB-3 composite markedly accelerated tendon-to-bone healing. In addition, little remnants were observed in ICPCB-3 group. Moreover, the maximum loads to failure of ICPCB-3 group was significantly higher than ICPC group at 24 weeks (P < 0.01). We conclude that the ICPCB composite, with a porous structure and better osteointegration effect, has direct clinical instruction to arthroscopic techniques of the ACL reconstruction., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Calcium phosphate cement scaffold (CPC) has been widely used as bone graft substitutes, but undesirable osteoinductivity and slow degradability greatly hamper their clinic application. To address these problems, a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium silicate/calcium phosphate cement scaffold (CSPC) with hierarchical pores was developed in this study. The CSPC scaffold with both interconnected macropores on the order of 200-500 μm and micropores of 2-5 μm was synthesized from CPC and calcium silicate (CS) by a NaCl particulate-leaching method. In vitro cell culture with C2C12 model cells, in vivo ectopic bone formation and rabbit femur cavity defect repair were performed to evaluate the osteogeneic capacity of the CSPC/rhBMP-2 scaffold. CPC, CSPC and CPC/rhBMP-2 scaffolds were parallelly investigated for comparison. The results demonstrated that the hierarchical macro/microporous structure, whether in presence of CS or rhBMP-2, highly favored the adhesion of C2C12 cells and bone in-growth into the CPC-based scaffolds. But, in comparison to the CPC-based scaffolds with CS or rhBMP-2 alone, the CSPC/rhBMP-2 scaffold strongly promoted osteogenic differentiation in vitro and osteogenetic efficacy in vivo. Further studies demonstrated that Si ions derived from CSPC contributed mainly to maintain the conformation of rhBMP-2 and thus stimulate the synergistic action of CS and rhBMP-2 in osteogenic differentiation and osteoinductivity. Additionally, the incorporation of CS was also beneficial for the dissolution of the scaffold. Those results suggest that the CSPC has superior properties for incorporation of rhBMP-2 and our developed CSPC/rhBMP-2 scaffold have great potential for future use in bone tissue regeneration., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Pyrophosphate ions are both inhibitors of HA formation and substrates for phosphatase enzymes. Unlike polyphosphates their hydrolysis results simultaneously in the complete loss of mineral formation inhibition and a localised elevation in orthophosphate ion concentration. Despite recent advances in our knowledge of the role of the pyrophosphate ion, very little is known about the effects of pyrophosphate on bone formation and even less is known about its local delivery. In this work we first developed a self setting pyrophosphate based calcium cement system with appropriate handling properties and then compared its in vivo degradation properties with those of a non-pyrophosphate containing control. Contrary to expectation, the presence of the pyrophosphate phase in the cement matrix did not inhibit mineralisation of the healing bone around the implant, but actually appeared to stimulate it. In vitro evidence suggested that enzymatic action accelerated dissolution of the inorganic pyrophosphate ions, causing a simultaneous loss of their mineralisation inhibition and a localised rise in supersaturation with respect to HA. This is thought to be a rare example of a biologically responsive inorganic material and these materials seem to be worthy of further investigation. Bioceramics to date have mainly been limited to orthophosphate, silicate and carbonate salts of calcium, here we report the successful application of a pyrophosphate material as a degradable osteoconductive bone repair cement., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Four cement applications were tested in this investigation. Two dicalcium phosphate dihydrate (DCPD-brushite) hydraulic cements, an apatite hydraulic fiber loaded cement, and a calcium sulfate cement (Plaster of Paris) were implanted in epiphyseal and metaphyseal cylindrical bone defects in sheep. The in vivo study was performed to assess the biocompatibility and bone remodeling of four cement formulations. After time periods of 2, 4, and 6 months, the cement samples were clinically and histologically evaluated. Histomorphometrically, the amount of new bone formation, fibrous tissue, and bone marrow and the area of remaining cement were measured. In all specimens, no signs of inflammation were detectable either macroscopically or microscopically. Cements differed mainly in their resorption time. Calcium sulfate was already completely resorbed at 2 months and showed a variable amount of new bone formation and/or fibrous tissue in the original drill hole over all time periods. The two DCPD cements in contrast were degraded to a large amount at 6 months, whereas the apatite was almost unchanged over all time periods., (Copyright © 2013. Published by Elsevier B.V.)

The objective of this study was to determine whether inclusion of magnesium oxide (MgO) in micro and nanoparticulate forms in poly methyl methacrylate (PMMA) cement has any influence on the fracture toughness of bone-cement interfaces. An interfacial fracture mechanics technique was used to compare the values of fracture toughness (KIC) among bone-PMMA, bone-PMMA with micro MgO particles and bone-PMMA with nano MgO particles interfaces. This study found that the values of KIC of bone-PMMA with micro MgO particles and bone-PMMA with nano MgO particles interfaces were significantly higher when compared to the values of KIC of the bone-PMMA interface (p<0.0001). Results indicated that the addition of the micro and nano MgO particles to PMMA improved the quality of bone-cement union., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Loosening of the tibial tray is cited as the most common cause of failure in total knee arthroplasty but the mechanism remains unclear. Post mortem specimens provide a unique opportunity to investigate the clinical condition., Methods: Twenty two cemented components were serially retrieved in situ at autopsy from a university clinic. They were investigated for mechanical stability by pull-out, which was related to cement morphology and bone quality from CT scans, and to polyethylene wear by score analysis. Implants were grouped into three types: a particular fixed bearing design (n=8), a particular rotating platform design (n=5) and other mixed designs (n=9)., Findings: Trends were observed for pull-out force to decrease with time in situ and increase with cement penetration but was unrelated to bone density or polyethylene wear. For the fixed bearing implants decreasing pull-out strength was related to an increasing proportion of failure at the bone-cement interface. For the mixed designs the opposite was observed. The rotating platform implants failed at the implant-cement interface., Interpretation: The analysis demonstrated that interface failure is dependent on the implant design, but that both the stem and the bone interfaces weaken with time in situ. Published findings for laboratory implantations have demonstrated that greater cement penetration improves fixation and this was reflected for clinical samples in this study., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Fracture healing and fracture fixation in the context of osteoporosis is extremely difficult. To inhibit osteoclast-induced bone resorption and associated implant loosening in this pathology, we describe a local delivery strategy to delivery RNA interfering technology to bone sites to target and down-regulate osteoclast formation and function. Resorbable polymer, poly(lactic-co-glycolic acid) (PLGA) microparticles were exploited as a passive phagocyte-targeting carrier to deliver RANK siRNA to both osteoclast precursors and osteoclasts - the professional phagocytes in bone. These natural phagocytes internalize micron-sized particles while most other non-targeted cells in bone cannot. PLGA-siRNA microparticles were dispersed within biomedical grade calcium-based injectable bone cement clinically used in osteoporosis as a bone augmentation biomaterial for fragility fracture prevention and fixation. siRNA released from this formulation in vitro retains bioactivity against the cell target, RANK, in cultured osteoclast precursor cells, inhibiting their progression toward the osteoclastic phenotype. These data support the proof-of-concept to utilize a clinically relevant approach to locally deliver siRNA to phagocytes in bone and improve fragility fracture healing in the context of osteoporosis. This local delivery system delivers siRNA therapeutics directly to osteoporosis sites from clinically familiar injected bone augmentation materials but could be extended to other injectable biomaterials for local siRNA delivery., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Cement injection into osteolytic areas around the cement mantle is a technique for refixation of loose hip implants for patients who cannot undergo standard revision surgery. Preliminary clinical results show the improvement in walking distance, patients' independence and pain relief., Methods: In this study, we use a detailed finite element model to analyze whether cement injection into osteolytic areas contributes to the overall implant stability. We study the effect of various factors, like location and size of osteolytic areas, interface conditions and bone stiffness on bone-cement relative motion., Findings: Presented results demonstrate that the procedure is most effective for the osteolytic areas located in the proximal region of the femur, while factors like a thin layer of residual fibrous tissue around the injected cement, that was not removed during the surgery, combined with reduced bone stiffness reduce the efficiency of the procedure., Interpretation: Cement injection is able to stabilize loosened hip prostheses. However, it is important to remove the fibrous tissue layer completely, as even a thin layer will negatively influence stabilization. We will focus our research efforts on developing fibrous tissue removal techniques in order to optimize this minimally invasive treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Calcium phosphate cement (CPC) can be injected to harden in situ and is promising for dental and craniofacial applications. However, human stem cell attachment to CPC is relatively poor. The objectives of this study were to incorporate biofunctional agents into CPC, and to investigate human umbilical cord mesenchymal stem cell (hUCMSC) seeding on biofunctionalized CPC for osteogenic differentiation for the first time., Methods: Five types of biofunctional agents were used: RGD (Arg-Gly-Asp) peptides, human fibronectin (Fn), fibronectin-like engineered polymer protein (FEPP), extracellular matrix Geltrex, and human platelet concentrate. Five biofunctionalized CPC scaffolds were fabricated: CPC-RGD, CPC-Fn, CPC-FEPP, CPC-Geltrex, and CPC-Platelets. The hUCMSC attachment, proliferation, osteogenic differentiation and mineral synthesis were measured., Results: The hUCMSCs on biofunctionalized CPCs had much better cell attachment, proliferation, actin fiber expression, osteogenic differentiation and mineral synthesis, compared to the traditional CPC control. Cell proliferation was increased by an order of magnitude via incorporation of biofunctional agents in CPC (p<0.05). Mineral synthesis on biofunctionalized CPCs was 3-5 folds of those of control (p<0.05). hUCMSCs differentiated with high alkaline phosphatase, Runx2, osteocalcin, and collagen I gene expressions. Mechanical properties of biofunctionalized CPC matched the reported strength and elastic modulus of cancellous bone., Significance: A new class of biofunctionalized CPCs was developed, including CPC-RGD, CPC-Fn, CPC-FEPP, CPC-Geltrex, and CPC-Platelets. hUCMSCs on biofunctionalized CPCs had cell density, cell proliferation, actin fiber density, and bone mineralization that were dramatically better than those on traditional CPC. Novel biofunctionalized CPC scaffolds with greatly enhanced human stem cell proliferation and differentiation are promising to facilitate bone regeneration in a wide range of dental, craniofacial and orthopedic applications., (Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Calcium phosphate cements (CPC) are well-established materials for the repair of bone defects with excellent biocompatibility and bioactivity. However, brittleness and low flexural/tensile strength so far restrict their application to non-load bearing areas. Reinforcement of CPC with fibers can substantially improve its strength and toughness and has been one major strategy to overcome the present mechanical limitations of CPC. Fiber reinforced calcium phosphate cements (FRCPC) thus bear the potential to facilitate the use of degradable bone substitutes in load bearing applications. This review recapitulates the state of the art of FRCPC research with focus on their mechanical properties and their biological evaluation in vitro and in vivo, including the clinical data that has been generated so far. After an overview on FRCPC constitutes and processing, some general aspects of fracture mechanics of reinforced cementitious composites are introduced, and their importance for the mechanical properties of FRCPC are highlighted. So far, fiber reinforcement leads to a toughness increase of up to two orders of magnitude. FRCPC have extensively been examined in vitro and in vivo with generally good results. While first clinical products focus on the improved performance of FRCPC with regard to secondary processing after injection such as fixation of screws and plates, first animal studies in load bearing applications show improved performance as compared to pure CPCs. Aside of the accomplished results, FRCPC bear a great potential for future development and optimization. Future research will have to focus on the selection and tailoring of FRCPC components, fiber-matrix compatibilization, integral composite design and the adjusted degradation behavior of the composite components to ensure successful long term behavior and make the composites strong enough for application in load bearing defects., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: It has been reported that bone cement correlates with survivorship of cemented total hip replacement. However, little research has been published to investigate the influence of bone cement type on production of fretting wear on the femoral stem., Methods: In the present study, we performed six in vitro wear simulations using the same type of femoral stem (polished Exeter V40™) and three different bone cements (Simplex P, Palacos R, and CMW 3)., Findings: Fretting wear was consistently reproduced on the stem surface and the wear locations compared well with the results of retrieval studies. Selected 3D surface parameters were utilised to quantitatively evaluate fretting wear and no significant difference was identified in terms of fretting wear severity between these simulations. The bone cements were all badly damaged in those sites contacting the fretting wear areas on the femoral stem. Additionally, there were plenty of wear debris present on the cement surface, and the energy dispersive X-ray analysis confirmed that it was just cement particles for Simplex P bone cement, whilst it included metallic particles for Palacos R and CMW 3 bone cements., Interpretation: This preliminary study shed some light on the influence of bone cement type on production of fretting wear on the femoral stem surface but further research is needed to gain a better understanding on this issue., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Cement-in-cement revision hip arthroplasty is an increasingly popular technique to replace a loose femoral stem which retains much of the original cement mantle. However, some concern exists regarding the retention of the existing fatigued and aged cement in such cement-in-cement revisions. This study investigates whether leaving an existing fatigued and aged cement mantle degrades the mechanical performance of a cement-in-cement revision construct., Methods: Primary cement mantles were formed by cementing a polished stem into sections of tubular steel. If in the test group, the mantle underwent conditioning in saline to simulate ageing and was subject to a fatigue of 1 million cycles. If in the control group no such conditioning or fatigue was carried out. The cement-in-cement procedure was then undertaken. Both groups underwent a fatigue of 1 million cycles subsequent to the revision procedure., Findings: Application of a Mann-Whitney test on the recorded subsidence (means: 0.51, 0.46, n=10+10, P=0.496) and inducible displacement (means: 0.38, 0.36, P=0.96) revealed that there was no statistical difference between the groups., Interpretation: This study represents further biomechanical investigation of the mechanical behaviour of cement-in-cement revision constructs. Results suggest that pre-revision fatigue and ageing of the cement may not be deleterious to the mechanical performance of the revision construct. Thus, this study provides biomechanical evidence to back-up recent successes with this useful revision technique., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recently published compression tests on PMMA/bone specimens extracted after vertebral bone augmentation indicated that PMMA/bone composites were not reinforced by the trabecular bone at all. In this study, the reasons for this unexpected behavior should be investigated by using non-linear micro-FE models. Six human vertebral bodies were augmented with either standard or low-modulus PMMA cement and scanned with a HR-pQCT system before and after augmentation. Six cylindrical PMMA/bone specimens were extracted from the augmented region, scanned with a micro-CT system and tested in compression. Four different micro-FE models were generated from these images which showed different bone tissue material behavior (with/without damage), interface behavior (perfect bonding, frictionless contact) and PMMA shrinkage due to polymerization. The non-linear stress-strain curves were compared between the different micro-FE models as well as to the compression tests of the PMMA/bone specimens. Micro-FE models with contact between bone and cement were 20% more compliant compared to those with perfect bonding. PMMA shrinkage damaged the trabecular bone already before mechanical loading, which further reduced the initial stiffness by 24%. Progressing bone damage during compression dominated the non-linear part of the stress-strain curves. The micro-FE models including bone damage and PMMA shrinkage were in good agreement with the compression tests. The results were similar with both cements. In conclusion, the PMMA/bone interface properties as well as the initial bone damage due to PMMA polymerization shrinkage clearly affected the stress-strain behavior of the composite and explained why trabecular bone did not contribute to the stiffness and strength of augmented bone., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Mechanical loosening is the most common cause of revision in unicompartmental knee arthroplasty. We determined the effect of bone lavage on tibial cement penetration and interface temperature with controlled ligament tension forces. We presumed pulsed lavage would allow increased cement penetration compared with syringe lavage., Methods: Cemented unicompartmental knee arthroplasty was performed in 12 pairs of fresh-frozen knees. Lavage was performed using pulsed lavage on one side (A) and syringe lavage on the other (B). Cement penetration pressure, interface temperature, and ligament tension forces were continuously monitored during the operation. Screened radiographs were taken and cement penetration under the tibial plateau was measured., Findings: The pulsed lavage group showed a mean cement penetration area of 187.24 (SD 36.37) mm², whereas 144.29 (SD 35.74) mm(2) was measured in the group with syringe lavage. Cement penetration pressure was 13.29 (SD 8.69) kPa in Group A and 20.21 (SD 7.78) kPa in Group B. Maximum interface temperatures of 46.99°C were observed in Group A and 45.02°C in Group B., Interpretation: Our data showed pulsed lavage cleansing of the cancellous tibial bone substantially improved cement penetration compared with syringe lavage without reaching the temperature threshold for bone necrosis. We recommend the routine use of pulsed lavage to improve long-term fixation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Aseptic tibial component loosening remains a major cause of total knee arthroplasty failure. The cementation technique used to achieve fixation may play a major role in loosening. Despite this, the optimum technique remains unanswered. This study aims to investigate stress and strain distributions in the proximal tibia for full cementation and surface cementation of the Genesis II tibial component., Methods: Principal cortical bone strains were measured experimentally in intact, surface cemented and fully cemented synthetic tibiae using strain gauges. Both axial and 15° flexion loading were considered. Finite element models were used to assess both cortical and cancellous bone stresses and strains. Using a bone remodeling algorithm potential sites of bone formation and resorption were identified post-implantation., Findings: Principal cortical bone strain results demonstrate strong correlations between the experimental and finite element analyses (R(2)≥0.81, RMSE(%)≤17.5%). Higher cortical strains are measured for surface cementation, as full cementation creates a stiffer proximal tibial structure. Simulations reveal that both cementation techniques result in lower cancellous stresses under the baseplate compared to the intact tibia, with greater reductions being computed for full cementation. The surface cementation model displays the closest cancellous stress distribution to the intact model. In addition, bone remodeling simulations predict more extensive bone resorption under the baseplate for full cementation (43%) than for surface cementation (29%)., Interpretation: Full cementation results in greater stress reduction under the tibial baseplate than surface cementation, suggesting that surface cementation will result in less proximal bone resorption, thus reducing the possibility of aseptic loosening., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Biomaterial-associated infections remain a serious complication in orthopaedic surgery. Treatments, including the local use of antibiotic-loaded polymethylmethacrylate (PMMA) bone cement, are not always successful because of multiantibiotic-resistant organisms. In this study, we synthesised a new quaternised chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that contains a series of substitutions of quaternary ammonium and demonstrated that HACC with a 26% degree of substitution (DS; referred to as 26%HACC) had a strong antibacterial activity and simultaneously good biocompatibility with osteogenic cells. We loaded 26%HACC at 20% by weight into PMMA bone cement to investigate whether HACC in PMMA prevents bacterial biofilm formation on the surface of bone cements. Chitosan-loaded PMMA (at the same weight ratio), gentamicin-loaded PMMA and PMMA with no antibiotic were also investigated and compared. Two clinical isolates, Staphylococcus epidermidis 389 and methicillin-resistant S. epidermidis (MRSE287), and two standard strains, S. epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate the bacterial biofilm formation at 6, 12 and 24 h using the spread plate method, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The results showed that 26%HACC-loaded PMMA inhibited biofilm formation on its surface, while the PMMA control and chitosan-loaded PMMA were unable to inhibit biofilm formation. The gentamicin-loaded PMMA decreased the number of viable methicillin-resistant Staphylococcus strains, but its ability to inhibit biofilm formation was lower than 26%HACC-loaded PMMA. Real-time PCR demonstrated that 26%HACC-loaded PMMA markedly downregulated the expression of icaAD, which encodes essential enzymes for polysaccharide intercellular adhesion (PIA) biosynthesis, upregulated the expression level of icaR, which negatively mediates icaAD expression, and also downregulated the expression of MecA, which encodes membrane-bound enzymes known to be penicillin-binding proteins. Our study indicates that 26%HACC-loaded PMMA prevents biofilm formation of Staphylococcus, including antibiotic-resistant strains, on the surface of bone cement, and downregulates the virulence-associated gene expression of antibiotic-resistant staphylococcus, thus providing a promising new strategy for combating implant infections and osteomyelitis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Identifying the critical molecules associated with "biocompatibility" is a grand challenge. Poly(methacrylic acid -co- methyl methacrylate) (MAA) beads improve wound closure and wound vascularity in vivo, but the mechanism of this phenomenon is unknown. We used quantitative real-time PCR to identify the subtle changes in the expression of a small selection of molecules involved in wound healing and angiogenesis in a macrophage-like cell (dTHP-1) treated with the MAA beads (45 mol% methacrylic acid). MAA beads decreased the expression of osteopontin (OPN) compared to poly(methyl methacrylate) (PMMA) and untreated cells, and increased the expression of IL-1β, IL-6 and TNF-α over the 24-96 h of the experiment. Interestingly, molecules associated with angiogenesis, such as bFGF, CXCL12, HIF-1α, PDGF-B, TGF-β and VEGF, were not significantly affected by MAA beads over the course of the study. MAA beads also increased the gene expression of OPN in HUVEC compared to untreated cells, while PMMA beads did not. MAA beads modified the phenotype (gene expression) of dTHP-1 cells in a subtle yet distinct manner that was different than PMMA. It remains to connect the changes in OPN in dTHP-1 (and HUVEC) and other molecules to the enhanced vascularity seen in vivo with this polymer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Bone cements for vertebroplasty must have a much better radiocontrast level than cements for knee or hip arthroplasty. This is generally accomplished by adding a relatively large portion of BaSO(4), although this affects the physical-mechanical and biological properties of the cement. This prompted us to develop an alternative radiopaque cement, on the basis of unique highly radiopaque methacrylic microspheres. These contain iodine in two modalities: (i) covalently linked to the methacrylic polymer, and (ii) as constituent of the stable tetraiodocarborane 8,9,10,12-I(4)-1,2-closo-C(2)B(10)H(8). The total iodine content in these particles exceeded 30% by mass. These radiopaque microspheres as well as the cement made thereof were characterized extensively, e.g., by scanning electron microscopy, X-ray contrast measurements, X-ray photoelectron spectroscopy, measurements of compressive strength, infrared spectroscopy, and solid state (11)B{(1)H} NMR spectroscopy. Furthermore, the new cement was subjected to several biocompatibility tests in vitro. The results show that the new bone cement fulfills all physico-chemical criteria for use in vertebroplasty. Further data on the cement's biocompatibility (in vitro), as well as on the handling parameters and doughviscosity, indicate that this material has a potential to become an alternative to vertebroplasty cements with a high BaSO(4) content. The new cement provides two significant advantages: (i) controlled viscosity in the dough phase, which facilitates precise injection during the vertebroplasty procedure; (ii) excellent structural stability, which precludes leaching of contrast post-implantation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Bone metastases are usually treated by surgical removal, fixation and chemotherapeutic treatment. Bone cement is used to fill the resection voids. The aim of this study was to develop a local drug delivery system using a calcium phosphate cement (CPC) as carrier for chemotherapeutic agents. CPC consisted of alpha-tricalcium phosphate, calcium phosphate dibasic and precipitated hydroxyapatite powders and a 2% Na(2)HPO(4) hardening solution. Scanning electron microscopy (SEM) was used to observe CPC morphology. X-ray diffraction (XRD) was used to follow CPC transformation. The loading/release capacity of the CPC was studied by a bovine serum albumin-loading model. Release/retention was measured by high performance liquid chromatography and X-ray photoelectron spectrometry. For chemotherapeutic loading, paclitaxel (PX) was loaded onto the CPC discs by absorption. Viability of osteosarcoma U2OS and metastatic breast cancer MDA-MB-231 cells was measured by an AlamarBlue assay. Results of SEM and XRD showed changes in CPC due to its transformation. The loading model indicated a high retention behavior by the CPC composition. Cell viability tests indicated a PX minimal lethal dose of 90 μg/ml. PX released from CPC remained active to influence cell viability. In conclusion, this study demonstrated that CPC is a feasible delivery vector for chemotherapeutic agents., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Iliac screw loosening has been a clinical problem in the lumbo-pelvic reconstruction. Although iliac screws are commonly inserted into either upper or lower iliac column, the biomechanical effects of the two fixations and their revision techniques with bone cement remain undetermined. The purpose of this study was to compare the anchoring strengths of the upper and lower iliac screws with and without cement augmentation., Methods: 5 pairs of formalin fixed cadaveric ilia with the bone mineral density values ranged from 0.82 to 0.97 g/cm(2) were adopted in this study. Using screws with 70-mm length and 7.5-mm diameter, 2 conventional iliac screw fixations and their revision techniques with cement augmentation were sequentially established and tested on the same ilium as follows: upper screw, upper cement screw, lower screw, and lower cement screw. Following 2000 cyclic compressive loading of -300 N to -100 N to the screw on a material testing machine, the maximum pull-out strengths were measured and analyzed., Findings: The average pull-out strengths of upper, upper cement, lower, and lower cement screws were 964 N, 1462 N, 1537 N, and 1964 N, respectively. The lower screw showed significantly higher pull-out strength than the upper one (P=0.008). The cement augmentation notably increased the pull-out strengths of both upper and lower screws. The positive correlation between pull-out strength and bone mineral density value was obtained for the 4 fixations., Interpretation: The lower iliac screw technique should be the preferred choice in lumbo-pelvic stabilization surgery; cement augmentation may serve as a useful salvage technique for iliac screw loosening; preoperative evaluation of bone quality is crucial for predicting fixation strength of iliac screw., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Fibronectin (FN) is a ubiquitous extracellular matrix protein (ECM) protein that is organized into fibrillar networks by cells through an integrin-mediated process that involves contractile forces. This assembly allows for the unfolding of the FN molecule, exposing cryptic domains that are not available in the native globular FN structure and activating intracellular signalling complexes. However, organization of FN into a physiological fibrillar network upon adsorption on a material surface has not been observed. Here we demonstrate cell-free, material-induced FN fibrillogenesis into a biological matrix with enhanced cellular activities. We found that simple FN adsorption onto poly(ethyl acrylate) surfaces, but not control polymers, triggered FN organization into a fibrillar network via interactions in the amino-terminal 70 kDa fragment, which is involved in the formation of cell-mediated FN fibrils. Moreover, the material-driven FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules and even type I collagen. Our results demonstrate that molecular assembly of FN can take place at the material interface, giving rise to a physiological protein network similar to fibrillar matrices assembled by cells. This research identifies material surfaces that trigger the organization of extracellular matrix proteins into biological active fibrils and establishes a new paradigm to engineer ECM-mimetic biomaterials., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aseptic loosening at the implant-cement interface is a well-documented cause of failure in joint arthroplasty. Traditionally, the strength of the implant-cement interface is determined using uni-axial normal and shear loading tests. However, during functional loading, the implant fixation sites are loaded under more complex stress conditions. For this purpose, the strength of the implant-cement interface under mixed-mode tensile and shear loading conditions was determined in this study using interface specimens with varying interface roughness. For the lowest roughness value analyzed (R(a)=0.89 μm), the interface strength was 0.40-1.95 MPa at loading angles varying between pure tension and shear, whereas this was 4.90-9.90 MPa for the highest roughness value (R(a)=2.76 μm). The interface strength during pure shear (1.95-9.90 MPa) was substantially higher than during pure tension (0.58-6.67 MPa). Polynomial regression was used to fit a second-order interpolation function through the experimental interface strength data (R²=0.85; p<0.001), relating the interface strength (S [MPa]) to the interface loading angle (α [degrees]) and interface roughness (R(a) [μm]): S(α,R(a))=0.891R²(a)+0.001α²-0.189R(a)-0.064α-0.060. Finally, an interface failure criterion was derived from the interface strength measurements, describing the risk of failure at the implant-cement interface when subjected to a certain tensile and shear stress using only the interface strength in pure tensile and shear direction. The findings presented in this paper can be used in numerical models to simulate loosening at the implant-cement interface., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

In the current study, the effects of different ways to implement the complex micro-mechanical behavior of the cement-bone interface on the fatigue failure of the cement mantle were investigated. In an FEA-model of a cemented hip reconstruction the cement-bone interface was modeled and numerically implemented in four different ways: (I) as infinitely stiff, (II) as infinitely strong with a constant stiffness, (III) a mixed-mode failure response with failure in tension and shear, and (IV) realistic mixed mode behavior obtained from micro-FEA models. Case II, III, and IV were analyzed using data from a stiff and a compliant micro-FEA model and their effects on cement failure were analyzed. The data used for Case IV was derived from experimental specimens that were tested previously. Although the total number of cement cracks was low for all cases, the compliant Case II resulted in twice as many cracks as Case I. All cases caused similar stress distributions at the interface. In all cases, the interface did not display interfacial softening; all stayed the elastic zone. Fatigue failure of the cement mantle resulted in a more favorable stress distribution at the cement-bone interface in terms of less tension and lower shear tractions. We conclude that immediate cement-bone interface failure is not likely to occur, but its local compliancy does affect the formation of cement cracks. This means that at a macro-level the cement-bone interface should be modeled as a compliant layer. However, implementation of interfacial post-yield softening does seems to be necessary., (Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.)

We have developed a technique to directly observe the micromechanics of the stem-cement and cement-bone interfaces of cemented femoral stems under physiologically relevant loading conditions. Thick transverse sections of a stem-cement-femur construct were fixed to the base of a test frame. Ante- and retro-verting torques were applied to the femoral stem by screwing the stem (via a pair of through holes) to an axle, which was turned using a lever arm actuated by the test frame cross-head. The surface of each transverse section was serially digitally imaged during loading. The displacements of the stem, cement and bone were determined using digital image correlation. These data were then used to calculate the relative displacements across the interfaces. This method provides a path to more thorough understanding of load-transfer from femoral stem to femur., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Titanium cermet was successfully synthesized and formed a thin gradient titanium carbide coating on the surface of Ti6Al4V alloy by using a novel sequential carburization under high temperature, while the titanium cermet femoral head was produced. The titanium cermet phase and surface topography were characterized with X-ray diffraction (XRD) and backscattered electron imaging (BSE). And then the wear behavior of titanium cermet femoral head was investigated by using CUMT II artificial joint hip simulator. The surface characterization indicates that carbon effectively diffused into the titanium alloys and formed a hard TiC layer on the Ti6Al4V alloys surface with a micro-porous structure. The artificial hip joint experimental results show that titanium cermet femoral head could not only improve the wear resistance of artificial femoral head, but also decrease the wear of UHMWPE joint cup. In addition, the carburized titanium alloy femoral head could effectively control the UHMWPE debris distribution, and increase the size of UHMWPE debris. All of the results suggest that titanium cermet is a prospective femoral head material in artificial joint.

The goal of this study was to quantify the micromechanics of the cement-bone interface under tensile fatigue loading using finite element analysis (FEA) and to understand the underlying mechanisms that play a role in the fatigue behavior of this interface. Laboratory cement-bone specimens were subjected to a tensile fatigue load, while local displacements and crack growth on the specimen's surface were monitored. FEA models were created from these specimens based upon micro-computed tomography data. To accurately model interfacial gaps at the interface between the bone and cement, a custom-written erosion algorithm was applied to the bone model. A fatigue load was simulated in the FEA models while monitoring the local displacements and crack propagation. The results showed the FEA models were able to capture the general experimental creep damage behavior and creep stages of the interface. Consistent with the experiments, the majority of the deformation took place at the contact interface. Additionally, the FEA models predicted fatigue crack patterns similar to experimental findings. Experimental surface cracks correlated moderately with FEA surface cracks (r(2)=0.43), but did not correlate with the simulated crack volume fraction (r(2)=0.06). Although there was no relationship between experimental surface cracks and experimental creep damage displacement (r(2)=0.07), there was a strong relationship between the FEA crack volume fraction and the FEA creep damage displacement (r(2)=0.76). This study shows the additional value of FEA of the cement-bone interface relative to experimental studies and can therefore be used to optimize its mechanical properties.

This paper reports on the damaging effects of different percentage porosities on the fatigue life of acrylic bone cement as used in the fixation of orthopaedic implants. Both hand-mixed (HM) and vacuum-mixed (VM) specimens containing different levels of porosity were fatigue tested to failure. A negative correlation between porosity level and fatigue life was demonstrated for both techniques. Considerable scatter was present in the data. Using the pore size distributions for HM and VM cement virtual HM and VM specimens were created containing various levels of porosity. Incorporating the effect of pore size and pore clustering quantified previously using the theory of critical distances a fatigue life prediction could be obtained for the virtual specimens. The virtual data agreed strongly with the experimental findings, predicting the correlation and more significantly the scatter in the experimental results. Using the virtual porosity failure model, it was demonstrated that given a constant porosity the fatigue life can vary by over an order of magnitude in both HM and VM cement. This suggests that not only porosity level but pore size distribution is extremely important in controlling the fatigue life of bone cement. It was verified that pore clustering and pore size are the major contributors to failure in HM and VM cement respectively. Furthermore, given the beneficial effects of porosity it has been proposed that an even distribution of small pores would provide an optimal bone cement mantle. Using the virtual model, it was determined that neither technique was capable of achieving such a distribution indicating a need for a new more reliable technique. The TCD based virtual porosity failure model should prove to be a powerful tool in the design of such a technique.

Background: Pedicle screw fixation in a severely osteoporotic spine remains a challenge for orthopedic surgeons. The previous literature does not adequately address the effects of radial holes for cannulated screws with cement injection and pilot hole tapping on the bone/screw interfacial strength., Methods: Specially designed cannulated pedicle screws, with or without radial holes, were installed in tapped and untapped pilot holes and then injected with cement. A uniform synthetic bone (test block) was used to provide a platform for each screw design. Specimens with inserted screws were then tested for axial pullout failure., Findings: (1) Cannulated screws with cement augmentation significantly increased the pullout strength in comparison to solid screws. Additionally, the amount of cement exuded from the cannulated screws increased with an increasing number of radial holes, leading to an increase in the average ultimate pullout strength for cannulated screws with a large number of radial holes. (2) Radiological examination indicated that the cement was exuded from the most proximal holes at the very beginning of its flow path, whereas no cement exudation was found at the remaining distal holes. (3) Cement exudation from the holes of cannulated screws into the open cell of the test block led to a composite (cement/bone) structure at the area of cement exudation. Observations of the failed specimens indicated that failure occurred at the composite/bone interface, while the composite was well bonded to the screws. This implies that the screw/composite interfacial strength was much higher than the composite/bone interfacial strength. (4) Tapping pilot holes decreased the pullout strength of the screws. Generally, larger standard deviations were found for the tapped cases, implying that untapped cases results are more repeatable than tapped cases results., Interpretation: Cannulated pedicle screws with radial holes combined with PMMA cement augmentation but without tapping may be a viable clinical option for achieving fixation in severely osteoporotic bone.

Currently used poly(methyl methacrylate) (PMMA)-based bone cement lacks osteoconductivity and induces osteolysis and implant loosening due to its cellular and tissue-toxicity. A high percentage of revision surgery following the use of bone cement has become a significant universal problem. This study determined whether incorporation of the amino acid derivative N-acetyl cysteine (NAC) in bone cement reduces its cytotoxicity and adds osteoconductivity to the material. Biocompatibility and bioactivity of PMMA-based bone cement with or without 25mm NAC incorporation was examined using rat bone marrow-derived osteoblastic cells. Osteoconductive potential of NAC-incorporated bone cement was determined by microCT bone morphometry and implant biomechanical test in the rat model. Generation of free radicals within the polymerizing bone cement was examined using electron spin resonance spectroscopy. Severely compromised viability and completely suppressed phenotypes of osteoblasts on untreated bone cement were restored to the normal level by NAC incorporation. Bone volume formed around 25mm NAC-incorporated bone cement was threefold greater than that around control bone cement. The strength of bone-bone cement integration was 2.2 times greater for NAC-incorporated bone cement. For NAC-incorporated bone cement, the spike of free radical generation ended within 12h, whereas for control bone cement, a peak level lasted for 6 days and a level greater than half the level of the peak was sustained for 20 days. NAC also increased the level of antioxidant glutathione in osteoblasts. These results suggest that incorporation of NAC in PMMA bone cement detoxifies the material by immediate and effective in situ scavenging of free radicals and increasing intracellular antioxidant reserves, and consequently adds osteoconductivity to the material.

We have developed an injectable bone cement composed of nanocrystalline apatite and crosslinked hyaluronic acid-tyramine conjugates (HA-Tyr). This bone cement was formed via the oxidative coupling of tyramine moieties catalyzed by hydrogen peroxide (H(2)O(2)) and horseradish peroxidase (HRP). The bone cement set within 60s after H(2)O(2) and HRP were added to the apatite/HA-Tyr pastes. The mechanical strength of the apatite/HA-Tyr cement was tuned by varying the apatite loading and H(2)O(2) concentration. This rapid enzyme-mediated setting of our bone cement results in minimal heat release (DeltaH=-11.39 J/g) as compared to conventional bone cements. The crystalline phase and crystallite size (20 nm) of the apatitic phase in our bone cement matched that of trabecular bone. The storage modulus (G'), yield stress (sigma(y)), and compressive stiffness (E(c)) of our bone cement prepared with different apatite loadings and H(2)O(2) concentrations were measured, and optimized at G'=40 MPa, sigma(y)=0.308 MPa and E(c)=2.270 MPa when the cement was formed with 0.4 g/ml of apatite, 0.61 units/ml of HRP and 6.8 mm of H(2)O(2). Our biocompatible bone cement also successfully healed small bone and joint defects in mice within 8 weeks.

An ideal material for maxillofacial vertical bone augmentation procedures should not only be osteoconductive, biocompatible and mechanically strong, but should also be applied using minimally invasive procedures and remain stable with respect to the original bone surfaces. This way, implant exposure and infection might be reduced and good mechanical stability may be achieved. Calcium phosphate cements are proven biocompatible and osteoconductive materials that can be injected using minimally invasive procedures. Among these cements, brushite based cements have the added advantage of being biodegradable in vivo. Therefore, this material has the potential for use in the aforementioned procedures. An in vivo study was performed in rabbits to evaluate the potential use of brushite cements in minimally invasive maxillofacial vertical bone augmentation procedures. In this study, we injected self-setting brushite cements on the subperiosteal bone surface using a minimally invasive tunnelling technique. The cement pastes were stable on the bone surface and hardened soon after they were injected thereby negating the need for additional supports such as membranes or meshes. The animals were sacrificed 8 weeks after the intervention and histological observations revealed signs of successful vertical bone augmentation. Therefore, we have demonstrated a minimally invasive vertical bone augmentation procedure that is an attractive alternative to current surgical procedures in terms of increased simplicity, reduced trauma, and lower cost of surgery.

Strontium-substituted beta-TCP with the general formula Ca((3-x))Sr(x)(PO(4))(2) (0

In order to gain insight into the micro-mechanical behavior of the cement-bone interface, the effect of parametric variations of frictional, morphological and material properties on the mechanical response of the cement-bone interface were analyzed using a finite element approach. Finite element models of a cement-bone interface specimen were created from micro-computed tomography data of a physical specimen that was sectioned from an in vitro cemented total hip arthroplasty. In five models the friction coefficient was varied (mu=0.0; 0.3; 0.7; 1.0 and 3.0), while in one model an ideally bonded interface was assumed. In two models cement interface gaps and an optimal cement penetration were simulated. Finally, the effect of bone cement stiffness variations was simulated (2.0 and 2.5 GPa, relative to the default 3.0 GPa). All models were loaded for a cycle of fully reversible tension-compression. From the simulated stress-displacement curves the interface deformation, stiffness and hysteresis were calculated. The results indicate that in the current model the mechanical properties of the cement-bone interface were caused by frictional phenomena at the shape-closed interlock rather than by adhesive properties of the cement. Our findings furthermore show that in our model maximizing cement penetration improved the micromechanical response of the cement-bone interface stiffness, while interface gaps had a detrimental effect. Relative to the frictional and morphological variations, variations in the cement stiffness had only a modest effect on the micro-mechanical behavior of the cement-bone interface. The current study provides information that may help to better understand the load-transfer mechanisms taking place at the cement-bone interface.

Since calcium phosphate cements were proposed two decades ago, extensive research has been realized to develop and improve their properties. They have proved their efficiency as bone graft substitutes and their ability to incorporate and release drugs. However, to date, all 'resorbable' osteoconductive synthetic biomaterials are in fact simply soluble. In order to investigate a synthetic material capable of inducing osteoclast remodelling post-implantation, a formulation of calcium phosphate cement loaded with a pro-resorptive cytokine (RANKL) was studied. Many prior release studies on calcium phosphates did not confirm that the matrix had no detrimental effect on the molecule to be released during storage prior to use or that bioactivity was maintained during storage. In this report, the stability of our protein was tested after loading onto the cement, and various regimens to improve stability were compared. The presence of trehalose was shown to stabilize the bioactivity of RANKL adsorbed to brushite cement. The reduction of both moisture and oxygen in the storage vessel improved osteoclastogenic potential of the matrix compared with that stored in ambient atmosphere and temperature. No loss in activity was observed over the study period for the loaded matrix stored in dry nitrogen.

Pre-clinical screening of cemented implant systems could be improved by modeling the longer-term response of the implant/cement/bone construct to cyclic loading. We formulated bone cement with degraded fatigue fracture properties (Sub-cement) such that long-term fatigue could be simulated in short-term cadaver tests. Sub-cement was made by adding a chain-transfer agent to standard polymethylmethacrylate (PMMA) cement. This reduced the molecular weight of the inter-bead matrix without changing reaction-rate or handling characteristics. Static mechanical properties were approximately equivalent to normal cement. Over a physiologically reasonable range of stress-intensity factor, fatigue crack propagation rates for Sub-cement were higher by a factor of 25+/-19. When tested in a simplified 2 1/2-D physical model of a stem-cement-bone system, crack growth from the stem was accelerated by a factor of 100. Sub-cement accelerated both crack initiation and growth rate. Sub-cement is now being evaluated in full stem/cement/femur models.

Objectives: Seven million people suffer bone fractures each year in the U.S., and musculoskeletal conditions cost $215 billion/year. The objectives of this study were to develop moldable/injectable, mechanically strong and in situ-hardening calcium phosphate cement (CPC) composite scaffolds for bone regeneration and delivery of osteogenic cells and growth factors., Methods: Tetracalcium phosphate [TTCP: Ca(4)(PO(4))(2)O] and dicalcium phosphate (DCPA: CaHPO(4)) were used to fabricate self-setting calcium phosphate cement. Strong and macroporous scaffolds were developed via absorbable fibers, biopolymer chitosan, and mannitol porogen. Following established protocols, MC3T3-E1 osteoblast-like cells (Riken, Hirosaka, Japan) were cultured on the specimens and inside the CPC composite paste carrier., Results: The scaffold strength was more than doubled via reinforcement (p<0.05). Relationships and predictive models were established between matrix properties, fibers, porosity, and overall composite properties. The cement injectability was increased from about 60% to nearly 100%. Cell attachment and proliferation on the new composite matched those of biocompatible controls. Cells were able to infiltrate into the macropores and anchor to the bone mineral-like nano-apatite crystals. For cell delivery, alginate hydrogel beads protected cells during cement mixing and setting, yielding cell viability measured via the Wst-1 assay that matched the control without CPC (p>0.1). For growth factor delivery, CPC powder:liquid ratio and chitosan content provided the means to tailor the rate of protein release from CPC carrier., Significance: New CPC scaffolds were developed that were strong, tough, macroporous and osteoconductive. They showed promise for injection in minimally invasive surgeries, and in delivering osteogenic cells and osteoinductive growth factors to promote bone regeneration. Potential applications include various dental, craniofacial, and orthopedic reconstructions.

The initial fixation of a cemented hip implant relies on the strength of the interface between the stem, bone cement and adjacent bone. Bone cement is used as grouting material to fix the prosthesis to the bone. The curing process of bone cement is an exothermic reaction where bone cement undergoes volumetric changes that will generate transient stresses resulting in residual stresses once polymerization is completed. However, the precise magnitude of these stresses is still not well documented in the literature. The objective of this study is to develop an experiment for the direct measurement of the transient and residual radial stresses at the stem-cement interface generated during cement polymerization. The idealized femoral-cemented implant consists of a stem placed inside a hollow cylindrical bone filled with bone cement. A sub-miniature load cell is inserted inside the stem to make a direct measurement of the radial compressive forces at the stem-cement interface, which are then converted to radial stresses. A thermocouple measures the temperature evolution during the polymerization process. The results show the evolution of stress generation corresponding to volumetric changes in the cement. The effect of initial temperature of the stem and bone as well as the cement-bone interface condition (adhesion or no adhesion) on residual radial stresses is investigated. A maximum peak temperature of 70 degrees C corresponds to a peak in transient stress during cement curing. Maximum radial residual stresses of 0.6 MPa in compression are measured for the preheated stem.

The goal of the present study was to assess the possibility to change the composition of a calcium phosphate scaffold from a high-temperature phase to a phase only stable at or close to room temperature without macrostructural changes. For that purpose, macroporous beta-TCP scaffolds were converted into alpha-TCP by high-temperature thermal treatment and then dipped into a phosphoric acid solution to obtain a more acidic calcium phosphate phase called monetite or dicalcium phosphate (DCP; CaHPO4). Two different solid-to-liquid ratios (SLR: 0.067 and 0.200g/mL) and three different temperatures (T: 37, 60 and 80 degrees C) were used. The reaction was followed by measuring the change of sample size and weight, by determining the compositional changes by X-ray diffraction (Rietveld analysis), and by looking at the micro- and macrostructural changes by scanning electron microscopy and micro-computed tomography. The results revealed that the transformation proceeded faster at a higher temperature and a higher SLR value but was achieved within a few days in all cases. Morphologically, the porosity decreased by 10%, the pore size distribution became wider and the mean macro pore size was reduced from 0.28 to 0.19mm. The fastest conversion and the highest compressive strength (9MPa) were measured using an incubation temperature of 80 degrees C and an SLR value of 0.2g/mL.