Search

The osteoporotic bone defect caused by excessive activity of osteoclasts has posed a challenge for public healthcare. However, most existing bioinert bone cement fails to effectively regulate the pathological bone microenvironment and reconstruct bone homeostasis in the presence of osteoclast overactivity and osteoblast suppression. Herein, inspired by natural bone tissue, an in-situ modulation system for osteoporotic bone regeneration is developed by fabricating an injectable double-crosslinked PEGylated poly(glycerol sebacate) (PEGS)/calcium phosphate cement (CPC) loaded with sodium alendronate (ALN) (PEGS/CPC@ALN) adhesive bone cement. By incorporating ALN, the organic-inorganic interconnection within PEGS/CPC@ALN results in a 100 % increase in compression modulus and energy dissipation efficiency. Additionally, PEGS/CPC@ALN effectively adheres to the bone by bonding with amine and calcium ions present on the bone surface. Moreover, this in-situ regulation system comprehensively mitigates excessive bone resorption through the buffering effect of CPC to improve the acidic microenvironment of osteoporotic bone and the release of ALN to inhibit hyperactive osteoclasts, and facilitates stem cell proliferation and differentiation into osteoblasts through calcium ion release. Overall, the PEGS/CPC@ALN effectively regulates the pathological microenvironment of osteoporosis while promoting bone regeneration through synergistic effects of drugs and materials, thereby improving bone homeostasis and enabling minimally invasive treatment for osteoporotic defects.

Vertebral compression fractures are one of the most severe clinical consequences of osteoporosis and the most common fragility fracture afflicting 570 and 1070 out of 100,000 men and women worldwide, respectively. Vertebroplasty (VP), a minimally invasive surgical procedure that involves the percutaneous injection of bone cement, is one of the most efficacious methods to stabilise osteoporotic vertebral compression fractures. However, postoperative fracture has been observed in up to 30% of patients following VP. Therefore, this study aims to investigate the effect of different injectable bone cement formulations on the stress distribution within the vertebrae and intervertebral discs due to VP and consequently recommend the optimal cement formulation. To achieve this, a 3D finite element (FE) model of the T11‐L1 vertebral body was developed from computed tomography scan data of the spine. Osteoporotic bone was modeled by reducing the Young's modulus by 20% in the cortical bone and 74% in cancellous bone. The FE model was subjected to different physiological movements, such as extension, flexion, bending, and compression. The osteoporotic model caused a reduction in the average von Mises stress compared with the normal model in the T12 cancellous bone and an increment in the average von Mises stress value at the T12 cortical bone. The effects of VP using different formulations of a novel injectable bone cement were modeled by replacing a region of T12 cancellous bone with the materials. Due to the injection of the bone cement at the T12 vertebra, the average von Mises stresses on cancellous bone increased and slightly decreased on the cortical bone under all loading conditions. The novel class of bone cements investigated herein demonstrated an effective restoration of stress distribution to physiological levels within treated vertebrae, which could offer a potential superior alternative for VP surgery as their anti‐osteoclastogenic properties could further enhance the appeal of their fracture treatment and may contribute to improved patient recovery and long‐term well‐being. [ABSTRACT FROM AUTHOR]

Background: As a class of promising bone augmentation materials, bone cements have attracted particular attention. Due to various limitations, the current bone cements are still imperfect. In this study, an injectable pH neutral bioactive bone cement (PSC/CSC) was developed by mixing phosphosilicate bioactive glass (PSC) and α-calcium sulfate hemihydrate (CSH), with the goal of optimizing bone defects repairs. Methods: A range of compositions (PSC/CSC: 10P/90C, 30P/70C, 50P/50C) were developed and their physicochemical properties evaluated. Their bone regeneration ability was compared to those of two widely used bone cements as controls (calcium phosphate cement (CPC) and Genex®) in rabbit femoral condyle bone defect models for 4, 8 and 12 weeks. Based on physicochemical properties and in vivo bone regeneration ability, the PSC/CSC exhibited the best outcomes was selected. Then, in vitro, the effects of selected PSC/CSC, CPC and Genex® extracts on MC3T3-E1 cell proliferation, migration and osteogenesis as well as angiogenesis of HUVECs were examined. Results: Based on physicochemical properties, the 30P/70C formula exhibited suitable operability and compressive strength (3.5 ± 0.3 MPa), which fulfilled the requirements for cancellous bone substitutes. In vivo, findings from micro-CT and histological analyses showed that the 30P/70C formula better promoted bone regeneration, compared to 10P/90C, 50P/50C, CPC and Genex®. Hence, 30P/70C was selected as the ideal PSC-based cement. In vitro, the 30P/70C extracts showed better promotion of cell viability, alkaline phosphatase (ALP) activity, calcium mineral deposition, mRNA and protein expression levels of osteogenesis in MC3T3-E1 cells, further supporting its superiority. Meanwhile, the 30P/70C extracts also showed better stimulation of HUVECs proliferation and angiogenesis. Conclusion: The new composite cement, 30P/70C, is a favorable bioactive glass-based bone cement with suitable operability, compressive strength and bone regeneration ability. The translational potential of this article: Clinically, treatment of large bone defects is still a major challenge for orthopaedic trauma. We showed that 30P/70C has the potential to be clinically used as an injectable cement for rapid bone repairs and reconstruction of critical sized bone defects.

There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery. Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo. However, the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined. In this study, bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr (0 mol% to 12 mol% SrO) were created and evaluated in vitro and in vivo. The setting time of the cement increased with Sr substitution of the glass. Upon immersion in PBS, the cement degraded and converted more slowly to HA (hydroxyapatite) with increasing Sr substitution. The released Sr2+ modulated the proliferation, differentiation, and mineralization of hBMSCs (human bone marrow mesenchymal stem cells) in vitro. Osteogenic characteristics were optimally enhanced with cement (designated BG6Sr) composed of particles substituted with 6mol% SrO. When implanted in rabbit femoral condyle defects, BG6Sr cement supported better peri-implant bone formation and bone-implant contact, comparing to cements substituted with 0mol% or 9mol% SrO. The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs. These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.

Background: The most common type of fracture of the lateral tibial plateau is the Schatzker type II split-depressed fracture. Minimally invasive surgery using balloon reduction appears to be very promising compared to the gold standard using a bone tamp. This surgery aims to have the best reduction and stabilization to benefit from an early passive and active rehabilitation to avoid stiffening and muscle wasting. Using a balloon for fracture reduction has allowed the use of semi-liquid Injectable Bone Cement (IBC) fillers. These fillers can be phosphocalcic or polymethyl methacrylate (PMMA). The latest recommendations on these IBCs in spinal surgery increasingly rule out phosphocalcic fillers because of their low mechanical strength.Questions/purposes: 1) What is the mechanical influence of IBC filling (PMMA) regarding the split and depression components of a Schatzker type II fracture? 2) What is the mechanical influence of osteosynthesis regarding the split and depression components of a Schatzker type II fracture with or without PMMA filing in three different kinds of percutaneous fixations?Methods: This biomechanical study was performed on 36 fresh frozen tibia/fibula specimens. Six groups were formed according to the type of percutaneous osteosynthesis or possible PMMA filling. Mechanical strength tests were carried out using a Unicompartmental Knee prosthesis and displacement components were measured on either side of the separation on the anterolateral facet by optical method.Results: We found a significant difference between cementless and cemented osteosynthesis for depression fracture stabilization (difference −507.56N with 95% confidence interval [−904.17; −110.94] (p-value = 0.026)). The differences between the different types of osteosynthesis were not significant (p-value = 0.58). There was a significant difference between osteosynthesis without cement and osteosynthesis with cement on separation (difference −477.72N [−878.52; −76.93] (p-value = 0.03)). The differences between the different types of fixations were not significant regarding separation (p-value = 0.99).Conclusion: PMMA cement significantly improves primary stability, regardless of the type of osteosynthesis for a Schatzker type II plateau fracture. Filling with PMMA cement during tuberoplasty seems to be a very promising strategy in association with percutaneous osteosynthesis to allow rapid recovery after surgery.

This study aimed to evaluate the effectiveness of a novel calcitonin-loaded calcium phosphate composite bone cement in vitro and in vivo. The novel composite bone cements were composed of NuROs injectable bone graft substitute, type I collagen, and/or salmon calcitonin. The setting time, porosity, wettability, compressive strength, compressive modulus, and crystallographic structures of cement specimens were determined. Degradation rate, calcitonin release rate, and osteoinductivity were assessed in vitro. In addition, osteogenic effect was examined in a rabbit model of femoral defect. The results revealed that addition of collagen/calcitonin did not substantially alter physical properties and degradation rate of bone cement specimens. Calcitonin was released into culture medium in a two-phase manner. Osteogenic effect of conditioned medium derived from calcitonin containing bone cement was observed. Finally, de novo bone growth and bone mineralization across the bone defect area were observed in rabbits after implantation of composite bone cement specimens. In conclusion, this novel calcitonin-loaded composite calcium phosphate bone cement exhibits biocompatibility, bioresorbability, osteoinductivity, and osteoconductivity, which may be suitable for clinical use. [ABSTRACT FROM AUTHOR]

In this study a premixed strontium-containing calcium phosphate bone cement for the application in osteoporotic bone defects has been developed and characterised regarding its material and in vitro properties as well as minimally invasive applicability in balloon kyphoplasty. Strontium was introduced into the cement by substitution of one precursor component, CaCO 3 , with its strontium analogue, SrCO 3 . Using a biocompatible oil phase as carrier liquid, a cement paste that only set upon contact with aqueous environment was obtained. Strontium modification resulted in an increased strength of set cements and radiographic contrast; and the cements released biologically relevant doses of Sr 2+ -ions that were shown to enhance osteoprogenitor cell proliferation and osteogenic differentiation. Finally, applicability of strontium-containing cement pastes in balloon kyphoplasty was demonstrated in a human cadaver spine procedure. The cement developed in this study may therefore be well suited for minimally invasive, osteoporosis-related bone defect treatment. Statement of Significance Strontium-releasing calcium phosphate bone cements are promising materials for the clinical regeneration of osteoporosis-related bone defects since they have been shown to stimulate bone formation and at the same time limit osteoclastic bone resorption. Today clinical practice favours minimally invasive surgical techniques, e.g. for vertebral fracture treatment, posing special demands on such cements. We have therefore developed a premixed, strontium-releasing bone cement with enhanced mechanical properties and high radiographic visibility that releases biologically relevant strontium concentrations and thus stimulates cells of the osteogenic lineage. In a pilot experiment we also exemplify its excellent suitability for minimally invasive balloon kyphoplasty procedures. [ABSTRACT FROM AUTHOR]

Despite its common usage in vertebral augmentation procedures (VAPs), shortcomings of commercial polymethylmethacrylate (PMMA) still remain. Accordingly, injectable and biodegradable composite cements, which are composed of poly(propylene fumarate)/α-tricalcium/hydroxyapatite (PPF/α-TCP/HAP) and PPF/tetracalcium phosphate/dicalcium phosphate (PPF/TtCP/DCP), were developed. A porcine model was used and cylindrical holes in critical size were created at the center of the lateral cortex of vertebral bodies of the lumbar spine. A fixed volume of testing materials and PMMA were randomly injected into the defects. Results showed that both composite groups had a comparable radiolucency as PMMA but a significantly lower setting temperature. Histological inspections revealed new bone formation and remodeling along the border of the two composite cements. New bone substitution and irregular sclerotic bone mantles were found along the composite cements but not in the PMMA group. Radiological and histological changes were observed in the two composite groups and these modifications were diminished along the block boundaries. These findings imply gradual substitution of decomposed composite by new bone formation, which could not be found around the PMMA block. Comparing PPF/α-TCP/HAP with the PPF/TtCP/DCP cement block, smaller particles that were spreading out were observed in the TtCP/DCP group, which represents rapid degradability. In conclusion, the composite cements have advantages such as a low setting temperature, radio-opacity, biodegradability, and osteoconductivity. The injectable PPF/calcium phosphate ceramic composite has the potential to be used in VAPs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2232-2243, 2017. [ABSTRACT FROM AUTHOR]

An ultrasound through-transmission method to monitor the setting process of injectable calcium phosphate bone cements in body fluids is presented. This method can be used to determine the acoustic properties of the bone cement as it sets, which are linked to its material properties and provide some information about changes occurring within the cement. The development of the methodology of ultrasonic testing and execution of velocity measurements of the longitudinal and transverse waves using the through-transmission method made it possible to determine the material constants of samples during the setting and hardening process of an injectable cement paste in physiological fluids (i.e. the Young's modulus (E), the Poisson ratio (ν) and the shear modulus (G)), and to determine the degree of anisotropy of wave velocity in the samples. A strong advantage of the proposed method is that it is non-destructive, and the same sample can be used to monitor the whole process of the cement setting. The testing was performed on premixed and injectable calcium phosphate (CPC)/chitosan blend, where glycerol was used as a liquid phase. Comparisons between ultrasonic velocity and empirical tests such as compressive strength, porosity measurement, FTIR, SEM and XRD analysis at different days of immersion in Ringer's solutions showed that the ultrasonic velocity can be very useful to provide in situ information about changes occurring within the cement. [ABSTRACT FROM AUTHOR]

There is a need for synthetic biomaterials to reconstruct bone defects using minimal invasive surgery. In this study, the preparation, bioactivity and setting mechanism of an injectable cement composed of borate bioactive glass particles and a chitosan solution was evaluated as a function of varying solid to liquid (SL) ratio. As the SL ratio increased from 1.0 g/ml to 2.5 g/ml, the injectability and initial setting time decreased from 97 ± 1% to 84 ± 10% and from 16.9 ± 0.9 min to 3.0 ± 0.5 min, respectively, while the compressive strength of the cement increased from 8 ± 2 MPa to 31 ± 2 MPa. The cement maintained its cohesiveness in a vigorously stirred aqueous medium. When immersed in phosphate-buffered saline, the glass phase reacted and converted to hydroxyapatite. The setting mechanism of the cement appeared to involve a combination of processes, such as the sol–gel transition of the chitosan solution, formation of an interlocked interface between the converted glass surface and the chitosan, and bonding between the converted glass surface and the functional groups of the chitosan. By controlling the reaction between the glass particles and the chitosan solution, injectable cements can be created with the requisite workability, degradation, strength and bioactivity for bone repair applications. [ABSTRACT FROM AUTHOR]

The injectability of Portland cement (PC) with several citrate additives was investigated for use in clinical applications such as vertebroplasty (stabilization of a fractured vertebra with bone cement) using a syringe. A 2-wt % addition of sodium or potassium citrate with PC significantly improved cement injectability, decreased cement setting times from over 2 h to below 25 min, while increasing the compressive strength to a maximum of 125 MPa. Zeta-potential measurements indicated that the citrate anion was binding to one or more of the positively charged species causing charged repulsion between cement particles which dispersed aggregates and caused the liquefying effect of the anion. Analysis of the hydrating phases of PC indicated that the early strength producing PC phase (ettringite) developed within the first 2 h of setting following addition of the citrate anion, while this did not occur in the control cement (PC only). Within 24 h ettringite developed in PC as well as calcium-silicate-hydrate (C-S-H), the major setting phase of PC, whereas cements containing citrate did not develop this phase. The evidence suggested that in the presence of citrate the cements limited water supply appeared to be utilized for ettringite formation, producing the early strength of the citrate cements. The present study has demonstrated that it is possible to modify PC with citrate to both improve the injectability and crucially reduce the setting times of PC while improving the strength of the cement. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1799-1808, 2014. [ABSTRACT FROM AUTHOR]

Injectable bone cements (IBCs) are biocompatible materials that can be used as bone defect fillers in maxillofacial surgeries and in orthopedic fracture treatment in order to augment weakened bone due to osteoporosis. Current clinically available IBCs, such as polymethylmethacrylate and calcium phosphate cement, have certain advantages; however, they possess several drawbacks that prevent them from gaining universal acceptance. New gel-based injectable materials have also been developed, but these are too mechanically weak for load-bearing applications. Recent research has focused on improving various injectable materials using nanomaterials in order to render them suitable for bone tissue regeneration. This article outlines the requirements of IBCs, the advantages and limitations of currently available IBCs and the state-of-the-art developments that have demonstrated the effects of nanomaterials within injectable systems. [ABSTRACT FROM AUTHOR]

Abstract: Osteonecrosis of the femoral head commonly occurs when the blood supply to bone was disrupted. The general treatment for early stages of necrosis in the femoral head is core decompression. However, the long-term outcome of this operation is usually compromised due to collapse of the necrotic bone. In this study, poly(propylene fumarate) (PPF) and calcium phosphate cement (CPC) were combined to provide appropriate mechanical strength after core-decompressed femoral heads and offer the properties of osteoconductivity. Effects of different ratios of CPC to PPF on mechanical and cytotoxicity were investigated. Results show that bone cement is less cytotoxic with the C/P ratio raise, and the increment of the CPC proportion also strengthens the mechanical strength, reduces the crosslinking temperature and diminishes excessive swelling of the cement. With addition of ginsenoside Rg1 the bone cement composite can also offer angiogenic effect. The drug release profiles were analyzed and the angiogenecity of released Rg1 was confirmed by the assay of tube formation in human umbilical vein endothelial cells (HUVECs). In summary, the newly developed angiogenic bone cement composite possesses remarkable development potential for application to treating osteonecrosis of the femoral head. [Copyright &y& Elsevier]

Quick setting and poor injectability due to liquid–solid phase separation have limited the clinical use of brushite and monetite cements. The presence of certain ions in the cement during the setting reaction moderate the setting time and properties of the cement. This study reports the preparation of injectable bone cement by using biphasic calcium phosphate (BCP) extracted from femur lamb bone by calcination at 1450 °C. EDX analysis infers the presence of Mg and Na ions as trace elements in BCP. X-ray diffraction patterns of the prepared cement confirmed the formation of brushite (DCPD) along with monetite (DCPA) as a minor phase. DCPA phase diminished gradually with a decrease in powder to liquid ratio (PLR). Initial and final setting time of 5.3 ± 0.5 and 14.67 ± 0.5 min respectively are obtained and within the acceptable recommended range for orthopedic applications. Exceptional injectability of ≈90% is achieved for all prepared bone cement samples. A decrease in compressive strength was observed with increase in the liquid phase of the cement, which is attributed to the higher degree of porosity in the set cement. Immersion of bone cement in simulated body fluid (SBF) for up to 7 days resulted in the formation of apatite layer on the surface of cement with Ca/P ratio 1.71, which enhanced the compressive strength from 2.88 to 9.15 MPa. The results demonstrate that bone cement produced from BCP extracted from femur lamb bone can be considered as potential bone substitute for regeneration and repair of bone defects. [ABSTRACT FROM AUTHOR]

Minimally invasive surgery will be gradually applied to the surgical treatment of bone tumors. One of the difficulties in the minimally invasive treatment of bone tumors is the lack of injectable materials that can be used to treat tumor-induced bone defects. Therefore, it is imperative to develop an injectable bone filler that can not only be injected into the defect site by minimally invasive methods to provide strong support and repair bone tissue but also inactivate residual tumor cells around the defect. To achieve this aim, in our study, for the first time, we doped Fe 3 O 4 /graphene oxide (GO) nanocomposites into α-tricalcium phosphate (α-TCP)/calcium sulfate (CS) biphasic bone cement to prepare an injectable magnetic bone cement (α-TCP/CS/Fe 3 O 4 /GO, αCFG), which can be applied in bone tumor minimally invasive surgery and fit ideally even if the area is irregular. The magnetothermal performance of the αCFG bone cement could be well adjusted by altering the content of Fe 3 O 4 /GO nanocomposites and the magnetic field parameters, but a 10 wt % Fe 3 O 4 /GO content formed the most stable bone cement with excellent magnetothermal performance. The αCFG bone cement not only promotes bone regeneration but also exhibits enhanced tumor treatment effects. Such multifunctional bone cement could provide a promising clinical strategy for the minimally invasive treatment of tumor-induced bone destruction.

The development of a new generation of injectable bone cements that are bioactive and have enhanced osteogenic capacity for rapid osseointegration is receiving considerable interest. In this study, a novel injectable cement (designated Sr-BBG) composed of strontium-doped borate bioactive glass particles and a chitosan-based bonding phase was prepared and evaluated in vitro and in vivo. The bioactive glass provided the benefits of bioactivity, conversion to hydroxyapatite, and the ability to stimulate osteogenesis, while the chitosan provided a cohesive biocompatible and biodegradable bonding phase. The Sr-BBG cement showed the ability to set in situ (initial setting time = 11.6 ± 1.2 min) and a compressive strength of 19 ± 1 MPa. The Sr-BBG cement enhanced the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro when compared to a similar cement (BBG) composed of chitosan-bonded borate bioactive glass particles without Sr. Microcomputed tomography and histology of critical-sized rabbit femoral condyle defects implanted with the cements showed the osteogenic capacity of the Sr-BBG cement. New bone was observed at different distances from the Sr-BBG implants within eight weeks. The bone-implant contact index was significantly higher for the Sr-BBG implant than it was for the BBG implant. Together, the results indicate that this Sr-BBG cement is a promising implant for healing irregularly shaped bone defects using minimally invasive surgery.