Amelogenin-inspired peptide, calcium phosphate solution, fluoride and their synergistic effect on enamel biomimetic remineralization: an in vitro pH-cycling model.

BACKGROUND: Several methods were introduced for enamel biomimetic remineralization that utilize a biomimetic analogue to interact and absorb bioavailable calcium and phosphate ions and induce crystal nucleation on demineralized enamel. Amelogenin is the most predominant enamel matrix protein that is involved in enamel biomineralization. It plays a major role in developing the enamel's hierarchical microstructure. Therefore, this study was conducted to evaluate the ability of an amelogenin-inspired peptide to promote the remineralization potential of fluoride and a supersaturated calcium phosphate solution in treating artificially induced enamel carious lesions under pH-cycling regimen. METHODS: Fifty enamel slices were prepared with a window (4*4 mm2 ) on the surface. Five samples were set as control healthy enamel and 45 samples were subjected to demineralization for 3 days. Another 5 samples were set as control demineralized enamel and 40 enamel samples were assigned into 8 experimental groups (n=5) (P/I, P/II, P/III, P/AS, NP/I, NP/II, NP/III and NP/AS) according to peptide treatment (peptide P or non-peptide NP) and remineralizing solution used (I; calcium phosphate solution, II; calcium phosphate fluoride solution, III; fluoride solution and AS; artificial saliva). Samples were then subjected to demineralization/remineralization cycles for 9 days. Samples in all experimental groups were evaluated using Raman spectroscopy for mineral content recovery percentage, microhardness and nanoindentation as healthy, demineralized enamel and after pH-cycling. Data were statistically analysed using two-way repeated measures Anova followed by Bonferroni-corrected post hoc test for pairwise multiple comparisons between groups. Statistical significance was set at p= 0.05. Additionally, XRD, FESEM and EDXS were used for crystal orientation, surface morphology and elemental analysis after pH-cycling. RESULTS: Nanocrystals clumped in a directional manner were detected in peptide-treated groups. P/II showed the highest significant mean values in mineral content recovery (63.31%), microhardness (268.81±6.52 VHN), elastic modulus (88.74±2.71 GPa), nanohardness (3.08±0.59 GPa) and the best crystal orientation with I002/I300 (1.87±0.08). CONCLUSION: Despite pH changes, the tested peptide was capable of remineralizing enamel with ordered crystals. Moreover, the supplementary use of calcium phosphate fluoride solution with peptide granted an enhancement in enamel mechanical properties after remineralization.

Effects of rhBMP-2-loaded hydroxyapatite granules/beta-tricalcium phosphate hydrogel (HA/ß-TCP/hydrogel) composite on a rat model of caudal intervertebral fusion.

The effects and inflammation-related side effects of bone morphogenetic protein (BMP)-2 on posterior lumbar interbody fusion are controversial. One of the potential causes for the inconsistent results is the uncontrolled release of BMP-2 from the collagen carrier. Therefore, BMP delivery systems that support effective bone regeneration while attenuating the side effects are strongly sought for. We developed NOVOSIS putty (NP), a novel composite material of hydroxyapatite (HA), beta-tricalcium phosphate (ß-TCP)/hydrogel, and BMP-2, which can sustainably release BMP-2 over 2 weeks. This study was aimed at comparing the effects and side effects of NP and collagen sponge (CS) containing BMP-2 using a rat caudal intervertebral fusion model. The fusion rates of NP with low and high doses of BMP-2 were significantly higher than those of an iliac bone (IB) graft, but those of CS with low and high doses of BMP-2 were not different from those of the IB graft. Furthermore, the incidences of ectopic bone formation and soft tissue swelling were significantly lower in the NP group than in the CS group. The HA/ß-TCP/hydrogel carrier enabled superior bone induction with low-dose BMP-2 and decreased the incidence of side effects caused by high-dose BMP-2 vis-à-vis the collagen carrier.

BMSC seeding in different scaffold incorporation with hyperbaric oxygen treats seawater-immersed bony defect.

INTRODUCTION: The experiment was undertaken to estimate the effect of BMSC seeding in different scaffold incorporation with HBO on the repair of a seawater-immersed bone defect. And future compared n-HA/PLGA with ß-TCP/PLGA as a scaffold in treatment effect of the seawater-immersed bone defect. METHODS: Sixty New Zealand White rabbits with standard seawater defect in radius were randomly divided into group A (implant with nothing), group B (implanted with autogenous bone), group C (implanted with n-HA/PLGA/BMSCs), and group D (implanted with ß-TCP/PLGA/BMSCs). After the implant, each rabbit receives HBO treatment at 2.4 ATA 100% oxygen for 120 min/day for 2 weeks. Radiograph, histological, and biomechanical examinations were used to analyze osteogenesis. RESULT: X-ray analysis shows that n-HA/PLGA/BMSCs and ß-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was larger than that in group D or group A and close to group B (P < 0.05). After 12 weeks, in group A, the defect without scaffold shows a loose connect tissue filled in the areas. The medullary canal in group B was recanalized. Defects in groups C and D show a larger number of woven bone formation. The new woven bone formation in defect areas in group C was larger than that in group D. The mechanical examination revealed ultimate strength at 12 weeks was group D > group C > group B > group A (P < 0.05). CONCLUSION: Scaffolds of n-HA/PLGA and ß-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater-immersed bone defect, and n-HA/PLGA was more excellent than ß-TCP/PLGA.

The effect of calcium sulfate/calcium phosphate composite for the treatment of chronic osteomyelitis compared with calcium sulfate.

BACKGROUND: Treatment of chronic osteomyelitis often requires surgical debridement in combination with bone defect reconstruction and antibiotics administration. We aimed at investigating and evaluating the effect of antibiotic-loaded absorbable calcium sulfate/calcium phosphate (CS/CP) composite as bone substitute in the treatment of chronic osteomyelitis compared with CS. METHODS: A retrospective study of 31 consecutive patients with chronic osteomyelitis from one medical center was conducted. The treatment involved thorough debridement, antibiotic loaded bone substitutes filling (group A: CS/CP, 21 patients, group B: CS, 10 patients), laboratory and radiographic examination, and culture-specific systemic antibiotic treatment guided by a multidisciplinary team. New bone formation property and resorption kinetics were analyzed through X-ray and CT scan qualitatively and quantitatively. Anti-infection effect was mainly analyzed by postoperative laboratory examination and healing of wound. RESULTS: The average follow-up in each group was 61.3 and 86.7 weeks, respectively. In group A (CS/ CP), no patient had recurrent infection at 17 months after surgery, 1 case had delayed wound healing and healed after dressing change. In group B (CS), 2 patients had recurrent infection at 18 weeks after surgery, and were managed after further surgical treatment, 3 cases had delayed wound healing and healed after dressing change. The infection in the two groups was mainly caused by staphylococcus aureus. The average percentage of new bone formation was 20.5%, 43.7%, 75.2% at 1, 3, and 6 months in group A and 15.4%, 32.2%, 49.7% at 1, 3, and 6 months in group B after operation (P=0.001 at 1 month, P=0.025 at 3 months, P=0.000 at 6 months). The average percentage of resorption was 23.7%, 56.4%, 81.2% at 1, 3, and 6 months in group A and 47.1%, 96.2%, 100% at 1, 3, and 6 months in group B after operation (P=0.000 at 1 month, P=0.000 at 3 months, P=0.000 at 6 months). There was difference in infection recurrence (P=0.034). CONCLUSIONS: Our preliminary results proved that compared with CS, this novel antibiotic-impregnated CS/CP composite acted as superior scaffold for bone formation with a lower rate of infection recurrence, when choosing bone substitutes in the treatment of chronic osteomyelitis.

Supplementation with 45S5 Bioactive Glass Reduces In Vivo Resorption of the ß-Tricalcium-Phosphate-Based Bone Substitute Material Vitoss.

Compared to other materials such as 45S5 bioactive glass (BG), ß-tricalcium phosphate (ß-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of ß-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of ß-TCP/45S5-BG composite bone substitute materials.

Inherent Chemotherapeutic Anti-Cancer Effects of Low-Dimensional Nanomaterials.

Low-dimensional nanomaterials (LDNs) are receiving increasing attention in cancer therapy owing to their unique properties, especially the large surface area-to-volume ratio. LDNs such as metallic nanoparticles (NPs), hydroxyapatite NPs, graphene derivatives, and black phosphorus (BP) nanosheets have been proposed for drug delivery, photothermal/photodynamic therapies, and multimodal theranostic treatments. The therapeutic effectiveness is mainly based on the physical characteristics of LDNs, but their inherent bioactivity has not been fully capitalized. In this Minireview, recent advances in the anti-cancer effects of various types of LDNs with inherent chemotherapeutic bioactivity are described and the bioactivity mechanisms are discussed on the cellular and molecular levels. BP, one of the newest and exciting members of the LDN family, is highlighted owing to the excellent inherent bioactivity, selectivity, and biocompatibility in cancer therapy. LDNs and related derivatives possess inherent bioactivity and selective chemotherapeutic effects suggesting large potential as nanostructured anti-cancer agents in cancer therapy.

Recombinant Human Platelet-Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB/ß-TCP)-Collagen Matrix as an Alternative to Autograft.

BACKGROUND: Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (ß-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/ß-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. METHODS: Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/ß-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/ß-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. RESULTS: In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/ß-TCP-collagen to autograft. Safety-related outcomes were equivalent. CONCLUSION: PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/ß-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. LEVEL OF EVIDENCE: Level I, prospective randomized study.

Biomechanical evaluation of calcium phosphate-based nanocomposite versus polymethylmethacrylate cement for percutaneous kyphoplasty.

BACKGROUND CONTEXT: Polymethylmethacrylate (PMMA) is the most commonly used filling material when performing percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures. However, there are some inherent and unavoidable drawbacks with the clinical use of PMMA. PMMA bone cement tends to leak during injection, which can lead to injury of the spinal nerves and spinal cord. Moreover, the mechanical strength of PMMA-augmented vertebral bodies is extraordinary and this high level of mechanical strength might predispose to adjacent vertebral fractures. A novel biodegradable calcium phosphate-based nanocomposite (CPN) for PKP augmentation has recently been developed to potentially avoid these issues. PURPOSE: By comparison with PMMA, the leakage characteristics, biomechanical properties, and dispersion of CPN were evaluated when used for PKP. STUDY DESIGN: Biomechanical evaluation and studies on the dispersion and anti-leakage properties of CPN and PMMA cements were performed and compared using cadaveric vertebral fracture model, sheep vertebral fracture model, and simulated rigid foam model. METHODS: Sheep vertebral bodies were decalcified by ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) to simulate osteoporosis in vitro. After compression to create wedge-shaped fractures using a self-designed fracture creation tool, human cadaveric vertebrae and decalcified sheep vertebrae were augmented by PKP. In addition, three L5 vertebral bodies from human cadavers were used in a contrast vertebroplasty (VP) augmentation experiment. Occurrence of cement leakage was observed and compared between CPN and PMMA during the process of vertebral augmentation. Open-cell rigid foam model (Sawbones#1522-507) was used to create a simulated leakage model for the evaluation of the leakage characteristics of CPN and PMMA with different viscosities. The augmentation effects of CPN and PMMA were evaluated in human cadaveric and decalcified sheep vertebral models and then compared to the results from solid rigid foam model (Sawbones#1522-23). The dispersion abilities of CPN and PMMA were evaluated via three methods as follows. The dispersion volume and dispersion ratio were calculated by three-dimensional reconstruction using human vertebral body CT scans; the ratio of cement area to injection volume was calculated from three-dimensional sections of micro-CT scans of a sheep vertebra; and the micro-CT images of cement dispersion in open-cell rigid foam model (Sawbones#1522-507) were compared between CPN and PMMA. This study was funded by the National Natural Science Foundation of China (No. 81622032, 190,000 dollars and No. 51672184, 90,600 dollars), Principal Project of Natural Science Research of Jiangsu Higher Education Institutions (No. 17KJA180011, 22,000 dollars), and Jiangsu Innovation and Entrepreneurship Program (146,000 dollars). RESULTS: There was no significant difference in vertebral height between CPN and PMMA during PKP augmentation and both cements restored the vertebral height after augmentation. In PKP augmentation experiment, posterior wall cement leakage occurred in 75% of human vertebrae augmented with PMMA; however, no leakage occurred in human vertebrae augmented with CPN. Anterior leakage occurred in all vertebrae augmented by PMMA, while in only 75% of vertebra augmented by CPN. Furthermore, CPN and PMMA had completely different leakage patterns in the simulated rigid foam model whether administered at the same injection speed or under the same injection force, suggesting that CPN has anti-leakage characteristics. The augmentation in human cadaveric vertebrae was lower with CPN compared to PMMA (1,668±816 N vs. 2,212±813 N, p=.459, respectively), but this difference was not significant. The augmentation force in sheep vertebral bodies reached 1,393±433 N when augmented with PMMA, but 1,108±284 N when augmented with CPN. The dispersion of CPN was better, and the dispersion volume and ratio were greater, with CPN than with PMMA. Imaging of the open-cell rigid foam model showed completely different dispersion modes for CPN and PMMA. After injection, the PMMA cement formed a contracted clump in the open-cell rigid foam model. However, the CPN cement extended many antennae outward, appearing to spread to the surrounding area. The surface areas of the CPN cement blocks with different liquid-to-solid ratios were significantly larger than the surface area of the PMMA cement in the open-cell rigid foam model (p<.05). CONCLUSIONS: CPN has anti-leakage properties, which might be related to its high viscosity and viscoplasticity. CPN had a slightly lower augmentation force than PMMA when used in cadaveric vertebrae, decalcified sheep vertebrae, and in the standard rigid foam model. However, CPN diffused more easily into cancellous bone than did PMMA and encapsulated bone tissue during the dispersion process. The excellent dispersion of CPN generated better interdigitation with cancellous bone, which may be why the augmentation effect of CPN is similar to that of PMMA. CLINICAL SIGNIFICANCE: Biodegradable CPN is a potential alternative to PMMA cement in PKP surgery, in which CPN is likely to reduce the cement leakage during the surgery and avoid the post-surgery complications caused by excessive strengths and nondegradability of PMMA cement.

Single-center, consecutive series study of the use of a novel platelet-rich fibrin matrix (PRFM) and beta-tricalcium phosphate in posterolateral lumbar fusion.

PURPOSE: To evaluate the radiographic and clinical outcomes of the combination of platelet-rich fibrin matrix (PRFM) with beta-tricalcium phosphate (ß-TCP) and bone marrow aspirate (BMA) as a graft alternative in posterolateral lumbar fusion procedures. METHODS: Researchers evaluated 50 consecutive patients undergoing one-level to three-level posterolateral lumbar fusion procedures, resulting in a total of 66 operated levels. The primary outcome was evidence of radiographic fusion at 1-year follow-up, assessed by three independent evaluators using the Lenke scoring system. Secondary outcomes included back and leg VAS scores, incidence of reoperations and complications, return-to-work status, and opioid use. RESULTS: At 1-year follow-up, radiographic fusion was observed in 92.4% (61/66) of operated levels. There was significant improvement in VAS scores for both back and leg pain (p < 0.05). Compared to baseline figures, the number of patients using opioid analgesics at 12-months decreased by 38%. The majority (31/50) of patients were retired, yet 68% of employed patients (n = 19) were able to return to work. No surgical site infections were noted, and no revision surgery at the operated level was required. CONCLUSIONS: This is the first report to analyze the combination of PRFM with ß-TCP and BMA for PLF procedures. Our results indicate a rate of fusion similar to those reported using iliac crest bone graft (ICBG), while avoiding donor site morbidity related to ICBG harvesting such as hematoma, pain, and infection. These slides can be retrieved under Electronic Supplementary Material.

Protection Against Discolouration by Two Over-the Counter Desensitising Products.

PURPOSE: To determine in vitro the protection potential against discolouration of two OTC (over-the-counter) desensitising products on enamel and dentin in comparison to a standard toothpaste and water by means of a spectrophotometer. MATERIALS AND METHODS: A total of 96 samples of bovine enamel-dentin complex and 48 of bovine dentin were alternatively immersed in red wine, tea, coffee or water after having been treated by a sodium monofluorophosphate- and calcium phosphate-based product (Curodont Protect), an amine fluoride-based toothpaste (Elmex Red), a stannous chloride-based toothpaste (Elmex Protection Erosion) or distilled water (negative control). Initial (T0) and final colour (T1, after 4 weeks of immersion in staining solutions) of each specimen were assessed by a spectrophotometer. Statistical analysis was done by means of repeated measures ANOVA followed by Fisher's LSD post-hoc test. Differences between T0 and T1 were considered stastistically significant at p ≤ 0.05. RESULTS: When enamel samples were measured over a black background, ΔE00 values (T0-T1) varied from 2.2 (SD 0.7) for amine fluoride-based product/water to 53.9 (SD 7.6) for amine fluoride-based-product/red wine. When dentin samples were measured over a black background, ΔE00 values (T0-T1) varied from 5.4 (SD 0.9) stannous chloride based product/water to 61.6 (SD 3.7) amine fluoride-based product/red wine. CONCLUSION: Specifically, the application of the sodium monofluorophosphate was able to statistically significantly (p ≤ 0.05) reduce discolouration induced by the staining solutions tested only on the enamel-dentin complex, while distilled water and the stannous fluoride-based product were able to statistically significantly (p ≤ 0.05) reduce discolouration induced by the staining solutions tested in pure dentin samples.

CaP Coating and Low-Level Laser Therapy to Stimulate Early Bone Formation and Improve Fixation of Rough Threaded Implants.

PURPOSE: This study aimed to compare in vivo osteogenesis on rough threaded dental implants with and without calcium phosphate (CaP) coating deposition, alone or in association with low-level laser therapy (LLLT) by gallium aluminum arsenide. MATERIAL AND METHODS: Four groups were studied: G1: implant; G2: implant + CaP coating; G3: implant + LLLT; and G4: implant + CaP coating + LLLT. LLLT was applied for 7 days at the surgical site before and after placing the implant. Topographic characterization was performed before surgery using scanning electron microscopy and energy dispersion spectrophotometry. Bone-implant contact (BIC) was measured after 1, 2, and 6 weeks and reverse torque after 6 weeks. In short periods, G2, G3, and G4 showed significantly greater BIC than G1 (P < 0.05), but no difference in BIC was observed at 6 weeks. However, the values for the removal torque test at 6 weeks were higher in G2 and G4 (P < 0.05). CONCLUSION: Both CaP coating alone and using LLLT induce cellular stimulation and improve BIC in short-term healing, resulting in higher implant fixation, and should be considered in clinical practice due to their low cost and high effectiveness.

Calcium Phosphate Cement Paste Injection as a Fiducial Marker of Cervical Cancer.

BACKGROUND/AIM: Calcium phosphate cement (CPC) is used to fill bone voids in dental, orthopedic, and craniofacial applications. This study evaluated CPC marker as an injectable non-metallic fiducial marker. MATERIALS AND METHODS: Six patients received 3-5 injections of CPC paste placed at a depth of 10 mm into tumors of the cervix before treatment planning CT (TPCT). Patients were treated with external-beam radiotherapy (EBRT) and high-dose rate brachytherapy (BT). We investigated marker visibility on cone-beam CT (CBCT), T2-weighted MRI, and interfraction of the marker motion for cervical cancer patients. RESULTS: Of a total of 22 visible CPC markers at TPCT, 17 CPC markers were visible on the first CBCT. Excluding one patient, all markers were visible on CBCT during EBRT. Of 16 visible CPC markers on CBCT, 13 CPC markers were visible on the magnetic resonance imaging (MRI) obtained before BT. For CPC marker centroid movement, the mean-of-means/systematic variation/random variation were 0.2/0.4/1.4, -1.6/5.1/4.1, and -3.4/2.1/2.8 mm for the left-right, dorsal-ventral, and cranial-caudal directions, respectively. CONCLUSION: This is the first report of a CPC marker injected into tumors of the cervix. It can be visualized on CBCT and MRI with reductions in marker loss and artifacts.

Long-term Follow-up of the Use of a Synthetic Bone Graft Composite in the Surgical Management of Primary Bone Tumors.

The surgical management of benign and benign aggressive bone tumors typically involves intralesional curettage and reconstruction of the resulting defect with cement or bone graft material. At the authors' institution, an injectable synthetic calcium sulfate-calcium phosphate composite is now the standard graft material for these cases. This study reports the long-term follow-up, specifically the stability of bone regeneration, for the use of the synthetic graft material for oncologic reconstruction. Fourteen patients who underwent intralesional curettage of a primary bone tumor followed by cavitary reconstruction with synthetic graft material who had at least 4-year follow-up were identified from an institutional orthopedic oncology database. Clinical outcome data, focusing on long-term clinical and radiographic features of the reconstruction, were extracted from electronic and paper medical records. Seven females and 7 males were included (mean age at surgery, 28.1 years; range, 13-64 years). Follow-up ranged from 50 to 105 months (mean, 68 months). Most surgical reconstructions were done for the lower limb (n=11), and giant cell tumor of bone was the most common tumor treated. The mean amount of synthetic graft material used was 18.6 cm3. Complete radiographic resorption and new bone incorporation was observed within the first year, and bone remodeling was complete in all patients. Bone remodeling remained stable throughout the longer-term follow-up (ie, up to 9 years). The use of an injectable synthetic calcium sulfate-calcium phosphate composite is a viable option in the reconstruction of cavitary bone defects following intralesional curettage of primary benign bone tumors. This reconstruction technique was safe, with no long-term complications, and led to complete radiographic resorption and new bone incorporation with long-lasting stability. [Orthopedics. 2018; 41(6):e868-e875.].

Comparative study of adjuvants for allergen-specific immunotherapy in a murine model.

AIM: To compare the immunological and clinical changes induced by allergen-specific immunotherapy (AIT) using different adjuvants. MATERIALS & METHODS: Olea europaea pollen-sensitized mice were treated with olea plus aluminum hydroxide, calcium phosphate, monophosphoryl lipid A (MPL) or immunostimulatory sequences (ISS). RESULTS: Aluminum hydroxide seems to drive initially to a Th2-type response. Bacteria-derived adjuvants (MPL and ISS) skew the immune response toward Th1 and Treg pathways. Specific-IgE production was lower after AIT with MPL and ISS. Moreover, IgG2a production significantly increased in ISS-treated mice. Bacteria-derived adjuvants also improved the Th1 cytokine response due to IFN-γ higher secretion. In addition, they improved bronchial hyper-reactivity and lung inflammation. CONCLUSION: Bacteria-derived adjuvants may enhance the efficacy of AIT.

Is vertebral body stenting in combination with CaP cement superior to kyphoplasty?

PURPOSE: In the evolution of the minimally invasive treatment of vertebral compression fractures, vertebral body stenting (VBS) was developed to reduce intraoperative and secondary loss of vertebral height. Particularly in combination with the usage of biodegradable cement, the influence of VBS on the rate of intraoperative complications and long-term outcome is unclear. The purpose of this study was to investigate the differences between balloon kyphoplasty (BKP) and VBS regarding their long-term clinical and radiological outcome in combination with calcium phosphate (CaP) application instead of polymethyl methacrylate (PMMA). METHODS: This retrospective study included 49 patients with fresh mono-segmental thoracolumbar fractures without neurological signs treated with VBS or BKP and CaP cement (Calcibone). The outcome was evaluated with the visual analogue pain scale (VAS), the Oswestry disability score (ODI), and radiologically assessed. RESULTS: In the course of the radiological follow-up, the VBS group showed statistically significant less vertebral height loss than the BKP group. However, with respect to VAS and ODI scores there were no statistically significant differences between the VBS and BKP group in the clinical follow-up. The rate of cement leakage was comparable in both groups. CONCLUSIONS: Both techniques facilitated good clinical results in combination with absorbable cement augmentation. In particular, the VBS enabled us to benefit from the advantages of the resorbable isothermic CaP cement with an improved radiological outcome in the long term compared to BKP. However, there was a mentionable loss of reduction in the follow-up in both groups compared to previously published data with PMMA cement. These slides can be retrieved under Electronic Supplementary Material.

Emergent nanotherapies in microcrystal-induced arthritis.

The anti-inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine how nanoparticles modulate the inflammatory pathways that characterize the most prevalent forms of microcrystal-induced arthritis, including gout, pseudogout, and BCP-induced arthritis. The nanoparticles of chitosan-coated calcium phosphate, uricase, aceclofenac, and gold have been investigated in crystal-inducedarthritis. The most important results of the studies outlined in this review show that nanoparticles can inhibit the expression and the release of some pro-inflammatory mediators and proteolytic enzymes, and the activity of different transcriptional factors in vitro, as well as decrease the uric acid levels in several studies of in vitro and in vivo models of gout, which show interesting results in terms of decreasing the amount of crystals and tissue damage, respectively. In view of their multiple beneficial effects, nanoparticles can be considered a valuable therapy that contributes to the pharmacological treatment in crystalinduced arthritis.

Improvement of physical properties of calcium phosphate cement by elastin-like polypeptide supplementation.

Calcium phosphate cements (CPCs) are synthetic bioactive cements widely used as hard tissue substitutes. Critical limitations of use include their poor mechanical properties and poor anti-washout behaviour. To address those limitations, we combined CPC with genetically engineered elastin-like polypeptides (ELPs). We investigated the effect of the ELPs on the physical properties and biocompatibility of CPC by testing ELP/CPC composites with various liquid/powder ratios. Our results show that the addition of ELPs improved the mechanical properties of the CPC, including the microhardness, compressive strength, and washout resistance. The biocompatibility of ELP/CPC composites was also comparable to that of the CPC alone. However, supplementing CPC with ELPs functionalized with octaglutamate as a hydroxyapatite binding peptide increased the setting time of the cement. With further design and modification of our biomolecules and composites, our research will lead to products with diverse applications in biology and medicine.

Implantation of an empty polyetheretherketone cage in anterior cervical discectomy and fusion: a prospective randomised controlled study with 2 years follow-up.

PURPOSE: To compare the clinical outcomes, radiographic results and fusion rate of ACDF between empty PEEK cages and PEEK cages packed with ß-tricalcium phosphate. METHODS: Forty-five patients were prospectively enrolled with cervical degenerative disc disease who requiring ACDF with a PEEK cage. 23 patients were randomised to the study group (empty cages) and 22 patients were in the control group (cages filled with ß-tricalcium phosphate). Both patient groups were fixed with a cervical locking plate. A CT scan was performed 12 months postoperatively and 24 months if not confirmed fused at 12 months to evaluate the status of fusion. Clinical status was evaluated using the Japanese Orthopaedic Association (JOA) score, the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS). RESULTS: 46 levels (97.88%) in the study group and 44 levels (97.77%) in the control group were confirmed as fused at 24 months. There was no significant difference between the fusion rates observed in the study and control groups (p = 0.82). There was no significant difference in JOA, ODI, or VAS scores at 24 months follow-up. The results showed that the members of the non-fusion group tended to be older than the individuals in the fusion group at 12 months, but was not significant in statistics. CONCLUSIONS: Similar fusion rates and clinical outcomes were achieved when using ACDF with PEEK cages and instrumentation, regardless of whether the cage was filled with bone substitute at 24 months follow-up. Fusion rates improved over time and are comparable between both groups. These slides can be retrieved under Electronic Supplementary material.

Hyperthermia effect and antibacterial efficacy of Fe3+ /Co2+ co-substitutions in ß-Ca3 (PO4 )2 for bone cancer and defect therapy.

The combined effect of cobalt and iron substitutions in ß-Ca3 (PO4 )2 as a potent material for application in hyperthermia and as a bone substitute is presented. Structural analysis reveals the preferential accommodation of Co2+ and Fe3+ at the Ca2+ (5) sites of ß-Ca3 (PO4 )2 until the limit of ∼10 mol % and, thereafter, prefer Ca2+ (4) lattice sites. Occupancy of both the Co2+ and Fe3+ ions induces a significant contraction of the ß-Ca3 (PO4 )2 unit cell. The Co2+ /Fe3+ co-substitutions in ß-Ca3 (PO4 )2 display magnetic characteristics that enhances hyperthermia effect. In addition, the presence of Co2+ in ß-Ca3 (PO4 )2 enunciates pronounced antibacterial efficacy against tested microorganisms. Nevertheless, the enhanced level of Co2+ in ß-Ca3 (PO4 )2 results to induce significant toxicity. The biocompatibility of the synthesized thermoseeds is verified from the hemolytic tests and cytotoxicity test performed on human sarcoma cell line MG-63. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1317-1328, 2018.

Basic research and clinical application of beta-tricalcium phosphate (ß-TCP).

The mechanism of bone substitute resorption involves two processes: solution-mediated and cell-mediated disintegration. In our previous animal studies, the main resorption process of beta-tricalcium phosphate (ß-TCP) was considered to be cell-mediated disintegration by TRAP-positive cells. Thus, osteoclast-mediated resorption of ß-TCP is important for enabling bone formation. We also report the results of treatment with ß-TCP graft in patients since 1989. Two to three weeks after implantation, resorption of ß-TCP occurred from the periphery, and then continued toward the center over time. Complete or nearly complete bone healing was achieved in most cases within a few years and was dependent upon the amount of implanted material, the patient's age, and the type of bone (cortical or cancellous). We have previously reported that an injectable complex of ß-TCP granules and collagen supplemented with rhFGF-2 enabled cortical bone regeneration of rabbit tibiae. Based on the experimental results, we applied this technique to the patients with femoral and humeral fractures in elderly patients, and obtained bone union.