Safety assessment, whole genome sequence, and metabolome analysis of Streptococcus thermophilus CICC 20372 for bone cement fermentation.

Bone is a kind of meat processing by-product with high nutritional value but low in calorie, which is a typical food in China and parts of East Asian countries. Microbial fermentation by lactic acid bacteria showed remarkable advantages to increase the absorption of nutrients from bone cement by human body. Streptococcus thermophilus CICC 20372 is proven to be a good starter for bone cement fermentation. No genes encoding virulence traits or virulence factors were found in the genome of S. thermophilus CICC 20372 by a thorough genomic analysis. Its notable absence of antibiotic resistance further solidifies the safety. Furthermore, the genomic analysis identified four types of gene clusters responsible for the synthesis of antimicrobial metabolites. A comparative metabolomic analysis was performed by cultivating the strain in bone cement at 37 °C for 72 h, with the culture in de Man, Rogosa, and Sharpe (MRS) medium as control. Metabolome analysis results highlighted the upregulation of pathways involved in 2-oxocarboxylic acid metabolism, ATP-binding cassette (ABC) transporters, amino acid synthesis, and nucleotide metabolism during bone cement fermentation. S. thermophilus CICC 20372 produces several metabolites with health-promoting function during bone cement fermentation, including indole-3-lactic acid, which is demonstrated ameliorative effects on intestinal inflammation, tumor growth, and gut dysbiosis. In addition, lots of nucleotide and organic acids were accumulated at higher levels, which enriched the fermented bone cement with a variety of nutrients. Collectively, these features endow S. thermophilus CICC 20372 a great potential strain for bone food processing.

Efficacy of Silver Nanoparticles-Loaded Bone Cement against an MRSA Induced-Osteomyelitis in a Rat Model.

Background and Objectives: The purpose of this study was to assess the cytotoxicity and antibacterial effects of AgNP-impregnated Tetracalcium phosphate-dicalcium phosphate dihydrate (TTCP-DCPD). Materials and Methods: Using in vitro experiments, the cytotoxicity of AgNP-impregnated TTCP-DCPD against fibroblasts and osteocytes was assessed in terms of cell viability by water-soluble tetrazolium salt assay. To assess antibacterial effects, a disc diffusion test was used; osteomyelitis was induced first in vivo, by injection of methicillin-resistant Staphylococcus aureus into the tibia of rats. AgNP-impregnated TTCP-DCPD bone cement was then applied at various silver concentrations for 3 or 12 weeks. Antibacterial effects were assessed by culturing and reverse transcription-polymerase chain reaction (RT-PCR). For histological observation, the bone tissues were stained using hematoxylin and eosin. Results: Cell viability was decreased by the impregnated bone cement but did not differ according to AgNP concentration. The diameter of the growth-inhibited zone of MRSA was between 4.1 and 13.3 mm on the disks treated with AgNP, indicating antimicrobial effects. In vivo, the numbers of bacterial colonies were reduced in the 12-week treatment groups compared to the 3-week treatment groups. The groups treated with a higher (10×) dose of AgNP (G2-G5) showed a tendency of lower bacterial colony counts compared to the group without AgNP (G1). The PCR analysis results showed a tendency of decreased bacterial gene expression in the AgNP-impregnated TTCP-DCPD groups (G2-G5) compared to the group without AgNP (G1) at 3 and 12 weeks. In the H&E staining, the degree of inflammation and necrosis of the AgNP-impregnated TTCP-DCPD groups (G2-G5) showed a tendency to be lower at 3 and 12 weeks compared to the control group. Our results suggest that AgNP-impregnated TTCP-DCPD cement has antimicrobial effects. Conclusions: This study indicates that AgNP-impregnated TTCP-DCPD bone cement could be considered to treat osteomyelitis.

Magnesium (Mg2 +), Strontium (Sr2 +), and Zinc (Zn2 +) Co-substituted Bone Cements Based on Nano-hydroxyapatite/Monetite for Bone Regeneration.

New bone cement type that combines Sr2 + /Mg2 + or Sr2 + /Zn2 + co-substituted nano-hydroxyapatite (n-HAs) with calcium phosphate dibasic and chitosan/gelatin polymers was developed to increase adhesion and cellular response. The cements were physicochemically described and tested in vitro using cell cultures. All cements exhibited quite hydrophilic and had high washout resistance. Cement releases Ca2 + , Mg2 + , Sr2 + , and Zn2 + in concentrations that are suitable for osteoblast proliferation and development. All of the cements stimulated cell proliferation in fibroblasts, endothelial cells, and osteoblasts, were non-cytotoxic, and produced apatite. Cements containing co-substituted n-HAs had excellent cytocompatibility, which improved osteoblast adhesion and cell proliferation. These cements had osteoinductive potential, stimulating extracellular matrix (ECM) mineralization and differentiation of MC3T3-E1 cells by increasing ALP and NO production. The ions Ca2 + , Mg2 + , Zn2 + , and Sr2 + appear to cooperate in promoting osteoblast function. The C3 cement (HA-SrMg5%), which was made up of n-HA co-substituted with 5 mol% Sr and 5 mol% Mg, showed exceptional osteoinductive capacity in terms of bone regeneration, indicating that this new bone cement could be a promising material for bone replacement.

Novel Tuning of PMMA Orthopedic Bone Cement Using TBB Initiator: Effect of Bone Cement Extracts on Bioactivity of Osteoblasts and Osteoclasts.

Bone cement containing benzoyl peroxide (BPO) as a polymerization initiator are commonly used to fix orthopedic metal implants. However, toxic complications caused by bone cement are a clinically significant problem. Poly (methyl methacrylate) tri-n-butylborane (PMMA-TBB), a newly developed material containing TBB as a polymerization initiator, was found to be more biocompatible than conventional PMMA-BPO bone cements due to reduced free radical generation during polymerization. However, free radicals might not be the only determinant of cytotoxicity. Here, we evaluated the response and functional phenotypes of cells exposed to extracts derived from different bone cements. Bone cement extracts were prepared from two commercial PMMA-BPO cements and an experimental PMMA-TBB. Rat bone marrow-derived osteoblasts and osteoclasts were cultured in a medium supplemented with bone cement extracts. More osteoblasts survived and attached to the culture dish with PMMA-TBB extract than in the culture with PMMA-BPO extracts. Osteoblast proliferation and differentiation were higher in the culture with PMMA-TBB extract. The number of TRAP-positive multinucleated cells was significantly lower in the culture with PMMA-TBB extract. There was no difference in osteoclast-related gene expression in response to different bone cement extracts. In conclusion, PMMA-TBB extract was less toxic to osteoblasts than PMMA-BPO extracts. Although extracts from the different cement types did not affect osteoclast function, PMMA-TBB extract seemed to reduce osteoclastogenesis, a possible further advantage of PMMA-TBB cement. These implied that the reduced radical generation during polymerization is not the only determinant for the improved biocompatibility of PMMA-TBB and that the post-polymerization chemical elution may also be important.

Nanocomposites drug delivery systems for the healing of bone fractures.

The skeletal system is fundamental for the structure and support of the body consisting of bones, cartilage, and connective tissues. Poor fracture healing is a chief clinical problem leading to disability, extended hospital stays and huge financial liability. Even though most fractures are cured using standard clinical methods, about 10% of fractures are delayed or non-union. Despite decades of progress, the bone-targeted delivery system is still restricted due to the distinctive anatomical bone features. Recently, various novel nanocomposite systems have been designed for the cell-specific targeting of bone, enhancing drug solubility, improving drug stability and inhibiting drug degradation so that it can reach its target site without being removed in the systemic circulation. Such targeting systems could consist of biological compounds i.e. bone marrow stem cells (BMSc), growth factors, RNAi, parathyroid hormone or synthetic compounds, i.e. bisphosphonates (BPs) and calcium phosphate cement. Hydrogels and nanoparticles are also being employed for fracture healing. In this review, we discussed the normal mechanism of bone healing and all the possible drug delivery systems being employed for the healing of the bone fracture.

In vivo resorption of injectable apatitic calcium phosphate cements: Critical role of the intergranular microstructure.

The in vivo resorption rate of two injectable apatitic calcium phosphate cements used in clinics (Graftys® HBS and NORIAN®) was compared, using a good laboratory practice (GLP) study based on an animal model of critical-sized bone defect. To rationalize the markedly different biological properties observed for both cements, key physical features were investigated, including permeability and water-accessible porosity, total porosity measured by mercury intrusion and gravimetry, and microstructure. Due to a different concept for creating porosity between the two cements investigated in this study, a markedly different microstructural arrangement of apatite crystals was observed in the intergranular space, which was found to significantly influence both the mechanical strength and in vivo degradation of the two calcium phosphate cements.

Composition control in biphasic silicate microspheres on stimulating new bone regeneration and repair of osteoporotic femoral bone defect.

Application of bioactive materials as synthetic bone graft substitutes in regenerative medicine has seen great evolution over the past decades in treating challengeable bone defects. However, balancing the preparation conditions and biological performances of inorganic biomaterials remain a great challenge, especially when there is lack of biomaterial design on how to control component distribution and how pathological bone responds to the biomaterial stimulations and osteogenesis. Here, our objective is to develop yolk-shell Ca-silicate microspheres and to investigate the potential biological performances to overcome the limitations in repair of osteoporotic bone defects. The introduction of ß-calcium silicate (CaSiO3 ) or mesoporous bioactive glass (MBG) into self-curing ß-dicalcium silicate (Ca2 SiO4 ) cement shell to form spherical granules (CaSiO3 @Ca2 SiO4 , MBG@Ca2 SiO4 ) was to retain the physicochemical property and/or microstructure of each component for optimizing bioactive ion release that could maximize osteostimulation in osteoporosis. We report a scalable shape-controlled mild fabrication protocol to yield the yolk-shell granules, endowing to different phases in yolk layer and interconnected macropore networks in the closely packed granule scaffolds. This unique heterostructure preparation is governed by coaxially aligned bilayer nozzle, inorganic powders and biocompatible binders. Extensive in vitro and in vivo evaluation showed that the CaSiO3 @Ca2 SiO4 and MBG@Ca2 SiO4 granules exhibited many superior properties such as controllable ion release, improved biodegradation and enhanced osteogenic capability in comparison with the pure Ca2 SiO4 @Ca2 SiO4 , thereby opening new mild-condition approach in fabricating osteogenesis-tailored silicate biomaterials for bone regenerative medicine, especially for efficient reconstruction of challenging pathological bone defects.

Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for Postimplantation Refilling.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination antibiotic PMMA composite system composed of rifampicin-filled ß-cyclodextrin (ß-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through zone of inhibition, drug activity, antibiotic release, and refilling, as well as mechanical studies. Our combination antibiotic PMMA composite system achieved up to an 8-fold increase in the duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for load-bearing applications (e.g., bone cement), our composites are certainly amenable for a variety of nonload-bearing applications (e.g., antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).

Influence of bone density on morphologic cement penetration in minimally invasive tibial unicompartmental knee arthroplasty: an in vitro cadaver study.

BACKGROUND: Unicompartmental knee arthroplasty is an established treatment option for anteromedial osteoarthritis. However, large registry studies report higher rates of aseptic loosening compared to total knee arthroplasty. The objective of this study was to assess the impact of bone density on morphological cement penetration. Moreover, an alternative regional bone density measuring technique was validated against the established bone mineral density assessment. METHODS: Components were implanted on the medial side of 18 fresh-frozen cadaver knees using a minimally invasive approach. Bone density has been quantified prior to implantation using Hounsfield units and bone mineral density. Morphological cement penetration has been assessed in different areas and was correlated with local bone density. FINDINGS: A highly significant correlation between Hounsfield units and trabecular bone mineral density was detected (r = 0.93; P < 0.0001), and local bone density was significantly increased in the anterior and posterior area (P = 0.0003). The mean cement penetration depth was 1.5 (SD 0.5 mm), and cement intrusion into trabecular bone was interrupted in 31.8% (SD 23.7%) of the bone-cement interface. Bone density was correlated significantly negative with penetration depth (r = - 0.31; P = 0.023) and positive with interruptions of horizontal interdigitating (r = + 0.33; P = 0.014). Cement penetration around the anchoring peg was not significantly correlated with bone density. INTERPRETATION: Areas with high bone density were characterized by significantly lower penetration depths and significantly higher areas without cement penetration. Anchoring pegs facilitate cement intrusion mechanically. Regional quantification of bone density using Hounsfield units is a simple but valuable extension to the established determination of bone mineral density.

The chitosan/tri-calcium phosphate bio-composite bone cement promotes better osteo-integration: an in vitro and in vivo study.

BACKGROUND: Polymethylmethacrylate bone cement has a variety of applications in orthopedic surgery, but it also has some shortcomings such as high heat generation during polymerization and poor integration with bone tissue. In this study, a bio-composite bone cement composed of tri-calcium phosphate and chitosan as additives to acrylic bone cement was developed. Our hypothesis is that this new bio-composite bone cement has a better osteo-integration than pure polymethyl methacrylate cement. METHODS: Physiological composition, i.e., 65 wt% inorganic and 35 wt% organic components, of tri-calcium phosphate and chitosan contents was selected as degradable additives to replace acrylic bone cement. A series of properties such as exothermic temperature changes, setting time, bio-mechanical characteristics, degradation behaviors, and in vitro cytotoxicity were examined. Preliminary in vivo animal study was also performed. RESULTS: The results showed that the bio-composite bone cement exhibited lower curing temperature, longer setting time, higher weight loss and porosity after degradation, lower compressive Young's modulus, and ultimate compressive strength as compared with those of pure polymethyl methacrylate cement. Cell proliferation tests demonstrated that the bio-composite bone cement was non-cytotoxic, and the in vivo tests revealed that was more osteo-conductive. CONCLUSIONS: The results indicated that the modified chitosan/tri-calcium phosphate/polymethyl methacrylate bio-composites bone cement could be degraded gradually and create rougher surfaces that would be beneficial to cell adherence and growth. This new bio-composite bone cement has potential in clinical application. Our future studies will focus on long-term implantation to investigate the stability of the bio-composite bone cement in long-term implantation.

Factors Associated with Perioperative Serum Calcium Levels in Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fracture: A Prospective Clinical Study.

BACKGROUND Long-term hypocalcemia can result in osteoporotic vertebral compression fracture (OVCF). Transient paralysis and tetraplegia due to hypocalcemia is a rare but severe complication after kyphoplasty. The aims of this prospective clinical study were to investigate the clinical factors associated with serum calcium levels in patients undergoing percutaneous kyphoplasty (PKP). MATERIAL AND METHODS Sixty-eight patients with OVCF were clinically evaluated before and after PKP. Serum calcium was measured before surgery and 24 hours after surgery. Clinical information included the time between vertebral fracture and surgery, the number of involved vertebral bodies, the dose of bone cement required during surgery, and bone mineral density. Correlation coefficient and simple linear regression analysis were performed to identify the clinical factors associated with serum calcium levels. RESULTS Peri-operative serum calcium levels were significantly and positively associated with the dose of bone cement required during PKP and the number of affected vertebral bodies. There was a significant and negative correlation between the time from vertebral fracture to surgery and bone mineral density, which were shown by linear regression analysis to have a predictive value of 5.8% and 47.3%, respectively. CONCLUSIONS For patients undergoing PKP, the amount of bone cement required and the number of affected vertebral bodies were associated with low serum calcium levels. Surgeons should be aware of the importance of measuring and monitoring serum calcium levels in this patient group.

Tricalcium silicate/graphene oxide bone cement with photothermal properties for tumor ablation.

Bone cements have been used in the clinical setting to fill bone defects resulting from bone tumors. However, traditional bone cements do not have the function to kill tumor cells. This study develops a new type of tricalcium silicate (CS) based functional bone cement with excellent photothermal performance for the minimally invasive therapy of bone defects as well as bone tumors. Graphene oxide (GO) was introduced into the CS cement by co-precipitation of CS particles with GO nanosheets to form a CS/GO composite material based on charge interactions between the CS and GO. The incorporation of GO enhanced the self-setting properties of CS and endowed the cement with excellent photothermal performance with the irradiation of near-infrared light. Besides this, the temperature of the composite cement could be regulated by adjusting the laser power and the GO content, where the rising temperature significantly inhibited the growth of subcutaneous tumor tissue in vivo. In addition, the hydration process and development of the early compressive strength of the composite cement could be modulated based on its photothermal performance. Moreover, the CS/GO composite cement retained the bioactivity of CS to promote cell proliferation and the alkaline phosphate activity of MC3T3-E1. Therefore, the CS/GO composite cement holds great promise as a new type of functional bone cement with photothermal performance for bone tumor therapy and bone defect repair.

Antibiotics release from cement spacers used for two-stage treatment of implant-associated infections after total joint arthroplasty.

Two-stage revision arthroplasty is the treatment of choice for periprosthetic infection, a serious complication after knee or hip arthroplasty. Our prospective clinical trial aimed to investigate the concentrations of gentamicin and vancomycin in wound exudate and tissue in two-stage revision arthroplasty. Wound exudate and periprosthetic membrane samples were collected from 18 patients (10 hip and eight knee patients), who were due for two-stage treatment after a periprosthetic joint infection. Samples were taken during insertion of antibiotic-impregnated spacers and after their removal. The concentrations of gentamicin and vancomycin in wound exudates and adjacent tissue were analyzed using high-performance liquid chromatography mass spectrometry. Average time period of spacer implantation was 13.6 weeks (9.3-22.6 weeks). The concentration of vancomycin in wound exudate decreased from a median of 43.28 µg/mL (0.28-261.22) after implantation to 0.46 µg/mL (0.13-37.47) after the removal of the spacer. In the adjacent tissue, vancomycin concentration was mainly undetectable prior to spacer implantation (0.003 µg/g [0.003-0.261]) and increased to 0.318 µg/g [0.024-484.16] at the time of spacer removal. This was also observed for gentamicin in the tissue of patients who previously had cement-free implants (0.008 µg/g [0.008-0.087] vs. 0.164 µg/g [0.048-71.75]) while in the tissue of patients with previously cemented prosthesis, baseline concentration was already high (8.451 µg/g [0.152-42.926]). Despite the rapid decrease in antibiotics release from spacer cement observed in vitro, in vivo antibiotics are much longer detectable, especially in the adjacent soft tissue. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published By Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2019. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1587-1597, 2019.

Effect of setting atmosphere on apatite cement resorption: An in vitro and in vivo study.

OBJECTIVES: The aim of this present study was to investigate the effect of setting atmosphere on replacement of apatite cement with new bone both in vitro and in vivo. MATERIAL AND METHODS: Apatite cement consisting of an equimolar mixture of tetracalcium phosphate and anhydrous dicalcium phosphate was mixed with distilled water and allowed to set at 37 °C and 100% relative humidity under 0%, 5%, and 100% CO2 atmospheres. X-Ray diffraction and Fourier Transform Infrared Spectroscopy were employed to confirm the carbonate apatite formation. Micro-CT and histological evaluation was made at 1 and 6 month(s) using twelve 10-week-old specific-pathogen-free male Wistar rats. RESULTS: B-type carbonate apatite was found when the apatite cement was set under 100% CO2 and 5% CO2. More carbonate apatite was formed in the case of 100% CO2 when compared with 5% CO2, and none was formed under 0% CO2. Interestingly, unreacted tetracalcium phosphate was significant when apatite cement was set under 0% CO2, indicating the formation of Ca-deficient hydroxyapatite. When a bone defect of rat tibia was reconstructed in these conditions of apatite cement and sintered hydroxyapatite, replacement of the apatite cement was confirmed 6 months after implantation, whereas no replacement was observed in the case of sintered hydroxyapatite. The amount of replacement of apatite cement with bone was greater, on the order of 100% CO2 and 5% CO2, followed by 0% CO2. CONCLUSION: The results obtained in the present study demonstrated that setting atmosphere clearly plays an important role in the replacement of set apatite cement with bone.

Injectable chelate-setting hydroxyapatite cement prepared by using chitosan solution: Fabrication, material properties, biocompatibility, and osteoconductivity.

An injectable chelate-setting hydroxyapatite cement (IP6-HAp), formed by chelate-bonding capability of inositol phosphate (IP6), was developed. The effects of ball-milling duration of starting HAp powder and IP6 concentration on the material properties such as injectability and mechanical strength of the cement were examined. The cement powder was prepared by ball-milling the as-synthesized HAp powder for 5 min using ZrO2 beads with a diameter of 10 mm, followed by another 60 min with ZrO2 beads with a diameter of 2 mm, and thereafter surface-modified with 5000 ppm of IP6 solution. Injectable cement was then fabricated with this HAp powder and 2.5 mass% chitosan as a mixing solution, with a setting time of 36.3 ± 4.7 min and a compressive strength of 19.0 ± 2.1 MPa. The IP6-HAp cements prepared with chitosan showed favorable biocompatibility in vitro using an osteoblast cell model, and osteoconductivity in vivo using a pig tibia model.

Biomechanical analysis of stiffness and fracture displacement after using PMMA-augmented sacroiliac screw fixation for sacrum fractures.

Cement augmentation of pedicle screws is the gold standard for the stabilization of osteoporotic fractures of the spine. In-screw cement augmentation, in which cement is injected through the cannula, is another option for fracture stabilization of fragility fractures of the sacrum. However, biomechanical superiority of this technique compared to conventional sacroiliac screw fixation has not been tested. The present study compares the stability of cement-augmented and non-cement-augmented sacroiliac screw fixation in osteoporotic sacrum fractures under cyclic loading. Eight human donor pelvises with intact ligaments and 5th lumbar vertebra were dissected. A vertical shear fracture was created as a combination of a sacrum fracture and cutting of the symphysis. Both sides were tested in a single-limb-stance setup with 10,000 loading cycles applied. Stiffness of the pelvis and displacement of the fracture were measured using a hydraulic testing machine and a 3D image correlation system. The augmented screw fixation failed in two of eight pelvises, and the non-augmented screws failed in three of eight pelvises. CT scans showed no leakage of cement. In-screw polymethylmethacrylate (PMMA) augmentation showed no advantage based on measured displacement of the sacrum fractures or stiffness for sacroiliac screw fixation of fragility fractures of the sacrum.

[Biomechanical and biocompatible enhancement of reinforced calcium phosphate cement via RGD peptide grafted chitosan nanofibers].

Objective: To analysis the biomechanical and biocompatible properties of calcium phosphate cement (CPC) enhanced by chitosan short nanofibers(CSNF) and Arg-Gly-Asp (RGD). Methods: Chitosan nanofibers were prepared by electrospinning, and cut into short fibers by high speed dispersion. CPC with calcium phosphorus ratio of 1.5:1 was prepared by Biocement D method. The composition and structure of CPC, CSNF, RGD modified CSNF (CSNF-RGD), CSNF enhanced CPC (CPC-CSNF), RGD modified CPC-CSNF (CPC-CSNF-RGD) were observed by infrared spectrum, X-ray diffraction (XRD) and scan electron microscopy (SEM). The mechanical properties were measured by universal mechanical testing instrument. The adhesion and proliferation of MC3T3 cells were assessed using immunofluorescence staining and MTT method. Results: The distribution of CSNF in the scaffold was homogeneous, and the porous structure between the nanofibers was observed by SEM. The infrared spectrum showed the characteristic peaks at 1633 nm and 1585 nm, indicating that RGD was successfully grafted on chitosan nanofibers. The XRD pattern showed that the bone cement had a certain curability. The stain-stress test showed that break strengths were (17.74±0.54) MPa for CPC-CSNF and (16.67±0.56) MPa for CPCP-CSNF-RGD, both were higher than that of CPC(all P<0.05). The immunofluorescence staining and MTT results indicated that MC3T3 cells grew better on CPC-CSNF-RGD after 240 min of culture(all P<0.05). Conclusion: CSNF-RGD can improve the biomechanical property and biocompatibility of CPC, indicating its potential application in bone tissue repair.

Quantitative study on Vancomycin release from cement in 3 different formulations: preliminary results and antimicrobial activity.

The purpose of this study is to investigate the best preparation method of the cement powder mixture, solvent and antibiotic in order to obtain the greatest amount of antibiotic in the joint for the longest time as possible. At time T0 the three samples, packed in a sterile environment in different formulations, were placed in sterile tubes, adding to each one 5 ml of saline phosphate buffer solution (PBS) and put in a stove at 37°C for 24 h. A sample of PBS without cement (T control) was also created. Qualitative and quantitative assessment of the incubated liquid with cement was performed along with biochemical analysis with High Performance Liquid Chromatography (HPLC). The analysis of the raw data demonstrated that at T1 there was a prevalence of antibiotic release from sample , compared to sample 2 and 3. This difference was maintained until the T20; from T21 the antibiotic release gradually leveled in 3 samples. The elution of the antibiotic remained detectable up to T60. Our work shows that the sample preparation is decisive on the quantity of released antibiotic. These results are confirmed by microbiological tests. It is useful to know the actual kinetics of antibiotics in articulation. Further studies are necessary to determine the effectiveness of antibiotic against micro-organisms and how long it acts.

A novel, multi-barrier, drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model.

This article discloses the development of an effective and versatile technology to prepare a novel antibiotics-loaded biodegradable composite bone cement to treat methicillin-resistant Staphylococcal (MRSA) osteomyelitis and reports its detail in vitro characterization, drug loading efficiency, physico-mechanical properties, drug elution in simulated body fluid (SBF) and human plasma, merits and demerits over poly-methyl methacrylate (PMMA) cement. Chronic osteomyelitis in rabbit tibia (42) was induced by MRSA and composite cement was implanted to evaluate its safety and efficacy over PMMA cement and parenteral treated animals with histopathology, radiographs, bone/plasma drugs concentration, and SEM for 90days. The composite cement showed higher setting time, degradability, pH rise, injectability, in vitro drug elution but lesser mechanical strength than PMMA cement. Antibiotics release from cement beads was faster in SBF than plasma. Further, in vivo antibiotics elution from composite (42days) showed effective concentration against MRSA without eliciting drug-toxicity. Platelets activation by composite was an extraordinary feature. The in vivo studies also proved the superiority of composite cement than other treatment methods in terms of faster infection control and osteosynthesis. Based particularly on drug elution and in vivo results, this newly developed cement can successfully be used in clinical cases of chronic osteomyelitis.