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Electrospun nanofibrous scaffolds providing local delivery of vascular endothelial growth factor (VEGF) have distinctive advantages for vascular tissue engineering. However, more than 90% of VEGF were normally released from scaffolds formed by conventional positive-voltage emulsion electrospinning (PVEES) within the initial 3 days. VEGF molecules bear positive charge. In this investigation, emulsion electrospinning using power supplies of different polarities was studied for producing scaffolds bearing specific electric charge. VEGF-containing poly(lactic-co-glycolic acid) scaffolds with initial potential of −87 and −202 V were formed by negative-voltage emulsion electrospinning (NVEES) at −10 and −20 kV, respectively, which enabled steady and sustained release up to 18 days, exhibiting effective modulation for VEGF release. Compared to VEGF-containing scaffolds formed by PVEES, NVEES-formed scaffolds showed superior performance in promoting endothelial cell functions. [ABSTRACT FROM AUTHOR]

A finite element model of cervical kyphosis was established to analyze the stress of cervical spine under suspensory traction and to explore the mechanism and effect of it. A patient with typical cervical kyphosis (C2-C5) underwent CT scan imaging, and 3D slicer was used to reconstruct the C2 to T2 vertebral bodies. The reconstructed data was imported into Hypermesh 2020 and Abaqus 2017 for meshing and finite element analysis. The changes of the kyphotic angle and the von Mises stress on the annulus fibrosus of each intervertebral disc and ligaments were analyzed under suspensory traction conditions. With the increase of suspensory traction weight, the overall kyphosis of cervical spine showed a decreasing trend. The correction of kyphosis was mainly contributed by the change of kyphotic segments. The kyphotic angle of C2-C5 was corrected from 45° to 13° finally. In cervical intervertebral discs, the stress was concentrated to anterior and posterior part, except for C4-5. The stress of the anterior longitudinal ligament (ALL) decreased from the rostral to the caudal, and the high level von Mises stress of the kyphotic segments appeared at C2-C3, C3-C4, and C4-C5. The roles of the other ligaments were not obvious. The kyphotic angle was significantly reduced by the suspensory traction. Shear effect due to the high von Mises stress in the anterior and posterior parts of annulus fibrosus and the tension on the anterior longitudinal ligament play a role in the correction of cervical kyphosis. [ABSTRACT FROM AUTHOR]

Strontium (Sr) has become increasingly attractive for use in the prevention and treatment of osteoporosis by concomitantly inhibiting bone resorption and enhancing bone formation. Strontium shares similar chemical, physical, and biological characteristics with calcium (Ca), which has been widely used as a dietary supplement in osteoporosis. However, the effects of Sr-Ca coadministration on bone growth and remodeling are yet to be extensively reported. In this study, 18 ovariectomized goats were divided into four groups: three groups of five goats each treated with 100 mg/kg/day Ca, Ca plus 24 mg/kg/day Sr (Ca + 24Sr), or Ca plus 40 mg/kg/day Sr (Ca + 40Sr), and three untreated goats fed low calcium feed. Serum Sr levels increased 6- and 10-fold in the Ca + 24Sr and Ca + 40Sr groups, respectively. Similarly, Sr in the bone increased four- and sixfold in these two groups. Sr-Ca coadministration considerably increased bone mineral apposition rate (MAR). The expression of insulin-like growth factor (IGF)-1 and runt-related transcription factor 2 (Runx2) was significantly upregulated within the Ca + 40Sr treatment group; tumor necrosis factor (TNF)-agr; expression was significantly downregulated in the Ca and Ca + 40Sr groups. The results indicate that Sr-Ca coadministration increases osteogenic gene expression and stimulates new bone formation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 758-762, 2009 [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a 'wear and tear' disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/β‐catenin signalling and its interaction with other signalling pathways, such as transforming growth factor β (TGF‐β), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor κB (NF‐κB), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/β‐catenin signalling in OA pathogenesis and interaction of β‐catenin with other pathways, such as TGF‐β, BMP, Notch, Ihh, NF‐κB, and FGF. Understanding of these novel insights into the interaction of β‐catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR-9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 β (GSK3β), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5-mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3β, ATP8A2, and EIF4EBP1, respectively. [ABSTRACT FROM AUTHOR]

The article focuses on the difference between the impact of strontium-enriched calcium phosphate cement (Sr-CPC) and calcium phosphate cement (CPC) on the healing of soft tissue tendon grafts. Topics discussed include outcomes of surgery with a soft tissue graft tendon in anterior cruciate ligament (ACL) reconstruction, as well as concerns over its long healing time and the anabolic and anticatabolic effects made by strontium on the skeleton system including its role in faster healing.

Background: Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as "cell-free" therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency. Results: In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells. Conclusions: In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The early lung metastasis of osteosarcoma is one of the main factors of poor prognosis. Therefore, searching for new targets and new mechanisms of osteosarcoma metastasis is essential for the prevention and treatment of osteosarcoma. Our previous studies suggested that fatty acid synthase (FASN) was an oncogene and promoted osteosarcoma. In addition, it is reported that the expression of miR-195 was negatively correlated with osteosarcoma. Aberrant DNA methylation can reversely regulate the expression of miRNAs. However, whether miR-195 could target FASN in osteosarcoma and whether ectopic DNA methylation is the upstream regulatory mechanism of miR195 in metastasis of osteosarcoma are not fully studied. The expressions were detected by qPCR and western blot, and methylation level was determined by methylation-specific PCR. Luciferase reporter assay, MTT, wound healing, and Transwell assay were used. We found that the expression of miR-195 was low in osteosarcoma. The methylation of miR-195 was high. miR-195 targeted and decreased the expression of FASN. In osteosarcoma, miR-195 inhibited cell proliferation, cell migration, and invasion. The methylation of miR-195 was related to decreased miR-195, it might promote osteosarcoma [ABSTRACT FROM AUTHOR]

Electrospun fibrous scaffolds attract great attention in tissue engineering owing to their high similarity in architecture to the extracellular matrix (ECM) that support cell attachment and growth in human bodies. Although they have shown superiority in promoting cell attachment and proliferation on their surfaces and hence, hold great promise for the regeneration of body tissues, the research still faces a great challenge of three-dimensional (3D) cell incorporation in electrospun scaffolds to form thick and cell-dense constructs because deep cell infiltration is hard to achieve in conventional electrospun scaffolds that normally have very small diameters of interconnected pores. Such hindrance has severely limited the clinical application of electrospun fibrous scaffolds to repair/regenerate various body tissues, particularly those with complex anatomies. To address this challenge, we have developed a concurrent cell electrospinning and emulsion electrospinning technique for fabricating bioactive bio-hybrid scaffolds with 3D and high-density cell incorporation. Through concurrent electrospinning, cell-encapsulated hydrogel fibers ("cell fibers") and growth factor-containing ultrafine fibers are simultaneously deposited to form two-component scaffolds (i.e., scaffolds composed of two types of fibers) according to the design. With the breakup of cell fibers, live cells with well-preserved cell viability are released in situ inside the scaffolds, resulting in the creation of cell-incorporated bioactive scaffolds with ECM-mimicking fibrous architectures and 3D and high-density incorporation of cells. The growth and functions of incorporated cells in the scaffolds can be enhanced by the released growth factor from the emulsion electrospun fibrous component. The bioactive bio-hybrid scaffolds fabricated via concurrent electrospinning mimic the cell-matrix organization of body tissues and therefore have great potential for regenerating body tissues such as tendon and ligament. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Recent studies have demonstrated new therapeutic strategy using transplantation of mesenchymal stem cells (MSCs), especially bone marrow–derived MSCs (BM-MSCs), to preserve intervertebral disc (IVD) structure and functions. It is important to understand whether and how the MSCs survive and thrive in the hostile microenvironment of the degenerated IVD. Therefore, this review majorly examines how resident disc cells, hypoxia, low nutrition, acidic pH, mechanical loading, endogenous proteinases, and cytokines regulate the behavior of the exogenous MSCs. Purpose: To review and summarize the effect of the microenvironment in biological characteristics of BM-MSCs for IVD regeneration; the presence of endogenous stem cells and the state of the art in the use of BM-MSCs to regenerate the IVD in vivo were also discussed. Study design: Literature review. Methods: MEDLINE electronic database was used to search for articles concerning stem/progenitor cell isolation from the IVD, regulation of the components of microenvironment for MSCs, and MSC-based therapy for IVD degeneration. The search was limited to English language. Results: Stem cells are probably resident in the disc, but exogenous stem cells, especially BM-MSCs, are currently the most popular graft cells for IVD regeneration. The endogenous disc cells and the biochemical and biophysical components in the degenerating disc present a complicated microenvironment to regulate the transplanted BM-MSCs. Although MSCs regenerate the mildly degenerative disc effectively in the experimental and clinical trials, many underlying questions are in need of further investigation. Conclusions: There has been a dramatic improvement in the understanding of potential MSC-based therapy for IVD regeneration. The use of MSCs for IVD degeneration is still at the stage of preclinical and Phase 1 studies. The effects of the disc microenvironment in MSCs survival and function should be closely studied for transferring MSC transplantation from bench to bedside successfully. [Copyright &y& Elsevier]

Selective laser sintering (SLS), a rapid prototyping technology, was investigated for producing bone tissue engineering scaffolds. Completely biodegradable osteoconductive calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) scaffolds were successfully fabricated via SLS using nanocomposite microspheres. In the SLS manufacturing route, the architecture of tissue engineering scaffolds (pore shape, size, interconnectivity, etc.) can be designed and the sintering process can be optimized for obtaining scaffolds with desirable porous structures and mechanical properties. SLS was also shown to be very effective in producing highly complex porous structures using nanocomposite microspheres. To render SLS-formed scaffolds osteoinductive, recombinant human bone morphogenetic protein-2 (rhBMP-2) could be loaded onto the scaffolds. For achieving a controlled release of rhBMP-2 from scaffolds, surface modification of scaffolds by gelatin entrapment and heparin immobilization was needed. The immobilized heparin provided binding affinity for rhBMP-2. Surface modified nanocomposite scaffolds loaded with rhBMP-2 enhanced the proliferation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) and also their alkaline phosphatase activity. In in vivo experiments using a rabbit model, surface modified nanocomposite scaffolds loaded with rhBMP-2 promoted ectopic bone formation, exhibiting their osteoinductivity. The strategy of combining advanced scaffold fabrication, nanocomposite material, and controlled growth factor delivery is promising for bone tissue regeneration. [ABSTRACT FROM AUTHOR]

While electrospinning is an effective technology for producing poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) micrometre-scale fibrous scaffolds for tissue regeneration, electrospinning of PHBV fibrous scaffolds composed of sub-micrometre fibres, surface-porous fibres or nanocomposite fibres is rarely explored. In this study, the average PHBV fibre diameter was successfully reduced to the sub-micrometre scale by dissolving a conductivity-enhancing salt in the polymer solution for electrospinning. Surface-porous fibres were made using a mixture of solvents, and carbonated hydroxyapatite (CHA) nanoparticles were incorporated into the fibres with the aid of an ultrasonic power source. Water contact angle measurements demonstrated that both fibre diameter reduction and CHA incorporation enhanced the wettability of the fibrous scaffolds. Tensile properties of the scaffolds were not undermined by the reduction of fibre diameter and the presence of surface pores. In vitro biological evaluation using a human osteoblast-like cell line (SaOS-2) demonstrated that all types of fibrous scaffolds supported cell attachment, spreading and proliferation. Analysis of cell morphology revealed similar projected cell areas on all types of scaffolds. However, cells on sub-micrometre fibres possessed a lower cell aspect ratio than cells on microfibres. The reduction of fibre diameter to the sub-micrometre scale enhanced cell proliferation after 14 days cell culture, while the incorporation of CHA nanoparticles in microfibres significantly enhanced the alkaline phosphatase activity of SaOS-2 cells. The control of fibre diameter, surface topography and composition is important in developing electrospun PHBV-based scaffolds for specific tissue-engineering applications. [ABSTRACT FROM AUTHOR]

Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) fibrous membranes consisting of parallel-aligned fibers or cross-aligned fibers were fabricated through electrospinning with the help of a rotating cylinder as fiber collector and auxiliary electrodes, and their application as tissue-engineering scaffolds was assessed. First, these membranes were characterized in terms of fiber diameter, spacing between adjacent aligned fibers or interstitial pore diameter, degree of fiber alignment, wettability and tensile properties. Then, human osteoblast-like cells (SaOS-2) were seeded and cultured on these membranes for up to 14 days. The cell morphology and proliferation were evaluated at different cell culture times. Membranes consisting of random fibers or parallel-aligned fibers were obtained when the rotational speed of the cylinder was 500 rpm or 3000 rpm, respectively. A very high rotational speed of 15 000 rpm resulted in the formation of parallel-aligned fibers having low or no spacing between the aligned fibers. Membranes consisting of cross-aligned fibers were made at the rotational speed of 3000 rpm and micrometer-sized fiber spacing was observed in these membranes. The alignment of fibers led to enhanced wettability of fibrous membranes. Tensile testing revealed that the parallel-aligned fibrous membranes were strong in the longitudinal direction but weak in the transverse direction. The cross-aligned fibrous membranes did not exhibit particularly weak tensile properties in any direction. In vitro biological evaluation showed that SaOS-2 cells spread randomly on membranes of random fibers but elongated in membranes of aligned fibers. All membranes supported cell proliferation in spite of the differences in cell morphology. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Background: Low back pain is often associated with increased spinal stiffness which thought to arise from increased muscle activity. Unfortunately, the association between paraspinal muscle activity and paraspinal stiffness, as well as the spatial distribution of this relation, is unknown. The purpose of this investigation was to employ new technological developments to determine the relation between spinal muscle contraction and spinal stiffness over a large region of the lumbar spine. Methods: Thirty-two male subjects performed graded isometric prone right hip extension at four different exertion levels (0%, 10%, 25% and 50% of the maximum voluntary contraction) to induce asymmetric back muscle activity. The corresponding stiffness and muscle activity over bilateral paraspinal lumbar regions was measured by indentation loading and topography surface electromyography, respectively. Paraspinal stiffness and muscle activity were then plotted and their correlation was determined. Findings: Data from this study demonstrated the existence of an asymmetrical gradient in muscle activation and paraspinal stiffness in the lumbar spine during isometric prone right hip extension. The magnitude and scale of the gradient increased with the contraction force. A positive correlation between paraspinal stiffness and paraspinal muscle activity existed irrespective of the hip extension effort (Pearson correlation coefficient, range 0.566–0.782 (P <0.001)). Interpretation: Our results demonstrate the creation of an asymmetrical gradient of muscle activity and paraspinal stiffness during right hip extension. Future studies will determine if alterations in this gradient may possess diagnostic or prognostic value for patients with low back pain. [Copyright &y& Elsevier]

The article determines the effect of posterior spinal fusion on paraspinal muscle by means of electrophysiological and histologic evaluation, using a rabbit model. The results have demonstrated that spinal fusion resultedin atrophy and reduced adjacent paraspinal muscle activity. The article shows that muscular activity was greater in the adjacent regions after spinal fusion, which may indicate muscle hypertrophy.

Abstract: Somatosensory evoked potential (SEP) testing has been widely applied to diagnosis of various neurological disorders. However, SEP recorded using surface electrodes is buried in noises, which makes the signal-to-noise ratio (SNR) very poor. Conventional averaging method usually requires up to thousands of raw SEP input trials to increase the SNR so that an identifiable waveform can be produced for latency and amplitude measurement. In this study, a multi-adaptive filtering (MAF) technique, emerging from the combination of well-developed adaptive noise canceller and adaptive signal enhancer, is introduced for fast and accurate surface SEP extraction. The MAF technique first processes the raw surface recorded SEP by the Canceller with a reference noise channel of background noise for adaptive subtraction before entering the Enhancer. The MAF was verified by filtering simulated SEP signals in which electroencephalography and Gaussian noise of different SNRs were added. It was found that the MAF could effectively suppress the noise and enhance the SEP components such that the SNR of the SEP is improved. Results showed that MAF with 50 input trials could provide similar performance in SEP detection to those extracted by the conventional averaging method with 1000 trials even at an SNR of -20dB. [Copyright &y& Elsevier]

Study Design: The insertion torque and pull-out force after cyclic loading of the bicortical sacral pedicle screw through the S1 endplate were tested using human cadaveric specimens.Objectives: The purpose of this study was to (1) evaluate the effect of cyclic loading on the pull-out force of two different techniques of bicortical sacral pedicle screw fixation and (2) to correlate the pull-out force after cyclic loading with the screw insertion torque.Summary Of Background Data: Biomechanical studies using conventional sacral pedicle screw fixation techniques have demonstrated reduction in stiffness and strength after cyclic loading. Technical difficulties with anterior sacral cortex penetration and frequent screw loosening have been reported in clinical studies. In the authors' center, a new method of sacral pedicle screw fixation bicortically through the S1 endplate has been used successfully in the clinical setting. However, the mechanical stability of this new technique after undergoing cyclic loading has not been documented in the literature.Methods: Seven-millimeter compact Cotrel-Dubousset sacral screws were randomly assigned by side (left vs. right) and inserted bicortically either anteromedially through the anterior sacral cortex or superiorly through the S1 endplate of 17 fresh frozen human sacrum. The tk;4maximum insertion torque for each screw was measured. Cyclic loading from 40 N to 400 N was applied to each screw at a frequency of 2 Hz for 20,000 cycles. Pull-out tests were conducted after completion of the cyclic tests.Results: The mean maximum insertion torque and mean pull-out force following cyclic loading were significantly higher for bicortical fixation through the S1 endplate (mean 3.17 N.m and 1457 N) than bicortical fixation through the anterior sacral cortex (mean 1.98 N.m and 1122 N). Both S1 endplate and anterior cortical fixation techniques demonstrated significant correlations between insertion torque and pull-out force following cyclic loading.Conclusions: In sacral pedicle screw fixation, screw trajectory through the S1 endplate was significantly stronger than screws penetrating the anterior sacral cortex. Insertion torque was a good intraoperative indicator of screw pull-out force after cyclic loading. [ABSTRACT FROM AUTHOR]

Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to methylcellulose (MC) with various feeding ratios using ammonium persulfate and N,N,N′,N′-tetramethyl ethylene diamine as an initiator. FTIR results confirm the formation of PNIPAAm-g-MC copolymers. The temperature responsiveness of copolymer gels was investigated by turbidimetry, dynamic contact angle (DCA), differential scanning calorimetry and dynamic mechanical analysis (DMA). The results indicate that PNIPAAm-g-MC hydrogels are strongly temperature responsive. At lower contents of MC, the lower critical solution temperature (LCST) is decreased, whereas further increasing MC contents raises the LCSTs. It is observed that the phase transition of the hydrogels occurs reversibly within 1 min, and near body temperature, a rigid gel can be generated in a certain range of MC content. What is more, the incorporation of MC prevents the syneresis of copolymer hydrogel. DMA measurement reveals that the storage moduli (E′) of the gels increase upon increasing MC contents, and moreover the values of E′ go up markedly above LCST. The copolymer hydrogels hold a promise as a blood vessel barrier by tuning gelation temperature, gelation time and mechanical strength. [Copyright &y& Elsevier]

A novel biodegradable hydroxyapatite/chitosan-gelatin network (HA/CS-Gel) composite of similar composition to that of normal human bone was prepared as a three-dimensional biomimetic scaffold by phase separation method for bone tissue engineering. Changing the solid content and the compositional variables of the original mixtures allowed control of the porosities and densities of the scaffolds. The HA granules were dispersed uniformly in the organic network with intimate interface contact via pulverizing and ultrasonically treating commercial available HA particles. Scaffolds of 90.6% porosity were used to examine the proliferation and functions of the cells in this three-dimensional microenvironment by culturing neonatal rat caldaria osteoblasts. Histological and immunohistochemical staining and scanning electron microscopy observation indicated that the osteoblasts attached to and proliferated on the scaffolds. Extracellular matrices including collagen I and proteoglycan-like substrate were synthesized, while osteoid and bone-like tissue formed during the culture period. Furthermore, the cell/scaffold constructs had good biomineralization effect after 3 weeks in culture. [Copyright &y& Elsevier]

Homeostasis of bone metabolism is regulated by the central nervous system, and mood disorders such as anxiety are associated with bone metabolism abnormalities, yet our understanding of the central neural circuits regulating bone metabolism is limited. Here, we demonstrate that chronic stress in crewmembers resulted in decreased bone density and elevated anxiety in an isolated habitat mimicking a space station. We then used a mouse model to demonstrate that GABAergic neural circuitry in the ventromedial hypothalamus (VMH) mediates chronic stress-induced bone loss. We show that GABAergic inputs in the dorsomedial VMH arise from a specific group of somatostatin neurons in the posterior region of the bed nucleus of the stria terminalis, which is indispensable for stress-induced bone loss and is able to trigger bone loss in the absence of stressors. In addition, the sympathetic system and glutamatergic neurons in the nucleus tractus solitarius were employed to regulate stress-induced bone loss. Our study has therefore identified the central neural mechanism by which chronic stress-induced mood disorders, such as anxiety, influence bone metabolism. [ABSTRACT FROM AUTHOR]

Screw loosening is a common complication in plate fixation. However, the underlying mechanism is unclear. This study investigated screw loosening mechanisms by finite element analysis (FEA) simulation and clinical X‐ray feature analysis. Two FEA models incorporated bone heterogeneity and orthotropy, representing fracture fixation using dynamic compression plate (DCP) and locking compression plate (LCP), were developed. These models were used to examine the volume of bone exceeding a certain stress value around each screw under physiologically‐relevant loading conditions. These damaged bone was then separated and compared by the axial stress and radial stress of each screw. In addition, features of patients' X‐ray images showing screw loosening were analyzed to validate the loosening features simulated by the models. The FEA study showed that more damaged bone was found at the central two screws which gradually decreased toward the two end screws in all groups. More bone was damaged by the radial stress of each screw than by the axial stress. The radiological analysis of screw loosening showed that bone loss occurred at the screw closest to the fracture line first then subsequent bone loss at the screws further away from the fracture line occurred. This study found that the two screws nearest to the fracture line are more vulnerable to loosening. The radial stress of the screw plays a larger role in screw loosening than the axial stress. Bone resorption triggered by the high radial stress of screws is indicated as the mechanism of screw loosening in the diaphyseal plate fixation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1498–1507, 2019. [ABSTRACT FROM AUTHOR]

[Display omitted] • Asp 8 modification significantly increases targeting ability of EMs. • EM/miR-26a shows enhanced synergetic effects for bone regeneration. • Asp 8 -EM/miR-26a shows good biocompatibility in vitro and in vivo. • Asp 8 -EM/miR-26a promotes bone regeneration in bone defect and osteoporosis models. Mesenchymal stem cell-derived exosomes (MSC-Exos) have shown great potential in the areas of bone regeneration and treatment of age-related diseases. Engineered exosomes can integrate multiple functional components to achieve optimal, targeted therapeutic effects. This study combined large-scale generation, bone-targeting modification, and miR-26a loading for exosome-mimetics (EMs) to construct a cell-free delivery system that promotes bone regeneration with good biocompatibility. EMs were fabricated through sequential extrusion of MSCs and reached a 15-fold production yield compared to conventional exosome secretion. Systemic injection of Asp 8 -EM/miR-26a in mouse models accelerated bone-defect healing and prevented osteoporosis. The underlying mechanism involves miR-26a targeting glycogen synthase kinase-3β (GSK-3β) to induce β-catenin accumulation, thus activating Wnt signaling pathway and promoting bone regeneration. This study provides a feasible and effective strategy for modifying EMs to enhance bone regeneration. [ABSTRACT FROM AUTHOR]

ABSTRACT: A novel computational model of implant migration in trabecular bone was developed using smoothed‐particle hydrodynamics (SPH), and an initial validation was performed via correlation with experimental data. Six fresh‐frozen human cadaveric specimens measuring 10 × 10 × 20 mm were extracted from the proximal femurs of female donors (mean age of 82 years, range 75–90, BV/TV ratios between 17.88% and 30.49%). These specimens were then penetrated under axial loading to a depth of 10 mm with 5 mm diameter cylindrical indenters bearing either flat or sharp/conical tip designs similar to blunt and self‐tapping cancellous screws, assigned in a random manner. SPH models were constructed based on microCT scans (17.33 µm) of the cadaveric specimens. Two initial specimens were used for calibration of material model parameters. The remaining four specimens were then simulated in silico using identical material model parameters. Peak forces varied between 92.0 and 365.0 N in the experiments, and 115.5–352.2 N in the SPH simulations. The concordance correlation coefficient between experimental and simulated pairs was 0.888, with a 95%CI of 0.8832–0.8926, a Pearson ρ (precision) value of 0.9396, and a bias correction factor Cb (accuracy) value of 0.945. Patterns of bone compaction were qualitatively similar; both experimental and simulated flat‐tipped indenters produced dense regions of compacted material adjacent to the advancing face of the indenter, while sharp‐tipped indenters deposited compacted material along their peripheries. Simulations based on SPH can produce accurate predictions of trabecular bone penetration that are useful for characterizing implant performance under high‐strain loading conditions. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1114–1123, 2018. [ABSTRACT FROM AUTHOR]

Purpose: Fresh frozen intervertebral disc allograft transplantation has been reported to be a viable treatment option for advanced degenerative disc diseases, but rapid degeneration of the postoperative allograft was found. Loss of nutrient supply is believed to be the most likely inducer because the disc allografts have to endure in an ischaemic environment until the nutrient pathway is re-established. The aim of this study was to focus on the revascularisation of the disc allograft after transplantation in goats.Methods: Twenty male goats were used in this study. Intervertebral disc allograft transplantation was performed at L4/L5. Groups of five goats were killed at 1.5, 6 and 12 m postoperatively, respectively. The transplanted segments were harvested, fixed, sagittally cut and decalcified for H&E staining and immunochemistry to observe the blood vessel formation at the endplates, anterior outer annulus, posterior outer annulus, inner annulus and the nucleus. The blood vessel density and the sectional vessel area were measured.Results: Blood vessels were first found in the marrow space of the bony endplate and the outer annulus at 1.5 month postoperatively. Then, they were able to penetrate to reach the cartilaginous endplate and the inner annulus after 6 months. Interestingly, the endplate area possessed the most abundant blood vessels, with the highest level of vessel density and area at the final follow-up. None of these newly formed vessels invaded the nucleus during the observation period.Conclusions: Revascularisation of the postoperative disc allograft has been determined, but its pattern was different from that in adult normal discs, suggesting that the typical nutrient diffusion pattern may be affected after transplantation. [ABSTRACT FROM AUTHOR]

Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo. However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo. Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration. [ABSTRACT FROM AUTHOR]

Graphs and tables are presented depicting expression levels of miRNAs in MC3T3-E1 cells and expression changes of the 15 cell adhesion makers of MC3T3-E1 cell.

Purpose: Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model.Methods: Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb's method. The anatomy of the adjacent discs was observed histologically.Results: DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved.Conclusions: Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months. [ABSTRACT FROM AUTHOR]

Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of the Wnt signaling pathways, and β-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from μCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis treatment. The relevant products of miR-375-3p might be developed into molecular drugs in the future. These molecules could be used in translational medicine. [ABSTRACT FROM AUTHOR]

The homeostasis of skeletal tissues requires tight regulation of a variety of signaling pathways, and the onset and progression of skeletal diseases are often caused by signaling abnormalities. MicroRNAs (miRNAs) are short noncoding RNA molecules that have emerged as a new dimension of gene regulation. MiRNAs have been shown to play an important role in the regulation of the differentiation of embryonic and hematopoietic stem cells. However, the role of specific miRNAs and their target genes has not been fully defined in the regulation of mesenchymal stem cells. Runx2 is a key transcription factor controlling MSC differentiation and bone and cartilage function. This article reviews work on Runx2 and miRNA regulation in bone and cartilage diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Transforming growth factor-β (TGF-β) has been demonstrated as a potential therapeutic target in osteoarthritis. However, beneficial effects of TGF-β supplement and inhibition have both been reported, suggesting characterization of the spatiotemporal distribution of TGF-β during the whole time course of osteoarthritis is important. To investigate the activity of TGF-β in osteoarthritis progression, we collected knee joints from Dunkin-Hartley (DH) guinea pigs at 3, 6, 9, and 12-month old ( n = 8), which develop spontaneous osteoarthritis in a manner extraordinarily similar to humans. Via histology and micro-computed tomography (CT) analysis, we found that the joints exhibited gradual cartilage degeneration, subchondral plate sclerosis, and elevated bone remodeling during aging. The degenerating cartilage showed a progressive switch of the expression of phosphorylated Smad2/3 to Smad1/5/8, suggesting dual roles of TGF-β/Smad signaling during chondrocyte terminal differentiation in osteoarthritis progression. In subchondral bone, we found that the locations and age-related changes of osterix+ osteoprogenitors were in parallel with active TGF-β, which implied the excessive osteogenesis may link to the activity of TGF-β. Our study, therefore, suggests an association of cartilage degeneration and excessive bone remodeling with altered TGF-β signaling in osteoarthritis progression of DH guinea pigs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:763-770, 2016. [ABSTRACT FROM AUTHOR]

Poly (d,l-lactic acid) microfibers with tunable nanoporous structure in the superficial layer were fabricated by electrospinning. The density and size of nanopores were controlled by the components of electrospun solvent, which were attributed to the competition between phase separation and solvent evaporation. The nanotopography influenced the mechanical strength, hydrophobicity, and degradation rate of the microfibers. More importantly, it increased the cumulative drug release. The rifampicin loading efficiency was mainly dependent on the drug loading method. This study provided a novel technique to modulate the drug release profiles of PDLLA microfibers by the surface nanotopography. [ABSTRACT FROM AUTHOR]

Antarctic krill chitosan (A-Chitosan) was first evaluated in its hemostatic effect in this study. The prepared A-Chitosan powder showed low level of crystallinity and significantly high water binding capacity as 1293% (w/w). By mice tail amputation model and blood coagulation timing experiment, it is showed that this chitosan accelerated the tail hemostasis by 55% and shortened the blood clotting time by 38%. This efficacy was better than two other commercial chitosans investigated and was corresponding to their water binding capacities. Through examining the effect of chitosan on blood components, it could be found that platelets adhesion was mainly affected by the water binding capacity, and red blood cells aggregation was dependent on their deacetylation degree. The physicochemical properties resulted in better hydration property of chitosan would improve its hemostatic effect. These results suggested that Antarctic krill chitosan is a good candidate for hemostatic application. [ABSTRACT FROM AUTHOR]

Abstract: Piperazine-based polyurethane ureas (P-PUUs) with piperazine (PP) units as the functional ingredients have been designed to explore a novel polymeric biomaterial with the controllable degradation for bone repair in this study. P-PUUs were prepared upon the chain-growth polymerization of poly (d, l -lactic acid) diol (PDLLA diol), 1, 6-hexamethylene diisocyanate (HDI) where PP functioned as the chain extender. The investigation of in vitro degradation of P-PUUs was performed and the mechanical properties of P-PUUs during degradation were calculated. The results revealed that manipulating the ratio of PDLLA diol: HDI: PP could obtain the precise number of PP units (Num(pp)) in P-PUUs which may significantly impact the degradation stability and the degradation rate of P-PUUs. The negative linear correlation between the degradation rate and the Num(pp) of P-PUUs has been proved, suggesting the P-PUUs were endowed with controllable degradation. Such a linear correlation is expected to be applied to bone repair where the specific degradation rate of P-PUUs for the specific bone defect can be precisely predicted once the Num(pp) and the bone repairing period are known. Additionally, P-PUUs with higher Num(pp) exhibited remarkable mechanical properties during degradation which allowed polymers to provide more persistent mechanical support to bone repair. [Copyright &y& Elsevier]

Abstract: The regeneration capacity of the osteoporotic bones is generally lower than that of the normal bones. Current methods of bone defect treatment for osteoporosis are not always satisfactory. Recent studies have shown that the silicate based biomaterials can stimulate osteogenesis and angiogenesis due to the silicon (Si) ions released from the materials, and enhance bone regeneration in vivo. Other studies showed that strontium (Sr) plays a distinct role on inhibiting bone resorption. Based on the hypothesis that the combination of Si and Sr may have synergetic effects on osteoporotic bone regeneration, the porous Sr-substituted calcium silicate (SrCS) ceramic scaffolds combining the functions of Sr and Si elements were developed with the goals to promote osteoporotic bone defect repair. The effects of the ionic extract from SrCS on osteogenic differentiation of bone marrow mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX), angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) were investigated. The in vitro results showed that Sr and Si ions released from SrCS enhanced cell viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteoblast-related genes of rBMSCs-OVX and expression of vascular endothelial growth factor (VEGF) without addition of extra osteogenic and angiogenic reagents. The activation in extracellular signal-related kinases (ERK) and p38 signaling pathways were observed in rBMSCs-OVX cultured in the extract of SrCS, and these effects could be blocked by ERK inhibitor PD98059, and P38 inhibitor SB203580, respectively. Furthermore, the ionic extract of SrCS stimulated HUVECs proliferation, differentiation and angiogenesis process. The in vivo experiments revealed that SrCS dramatically stimulated bone regeneration and angiogenesis in a critical sized OVX calvarial defect model, and the enhanced bone regeneration might be attributed to the modulation of osteogenic differentiation of endogenous mesenchymal stem cells (MSCs) and the inhibition of osteoclastogenesis, accompanying with the promotion of the angiogenic activity of endothelial cells (ECs). [Copyright &y& Elsevier]

Abstract: Degeneration of the intervertebral disc (IVD) is a major spinal disorder that associates with neck and back pain. Recent studies of clinical samples and animal models for IVD degeneration have identified cells with multi-potency in the IVD. However, IVD tissue-specific progenitor cells and their niche components are not clear, although degenerated IVD-derived cells possess in vitro characteristics of mesenchymal stromal cell (MSCs). Here, we firstly identified the tissue-specific intervertebral disc progenitor cells (DPCs) from healthy Rhesus monkey and report the niche components modulated the survival of DPCs under hypoxia. DPCs possess clonogenicity, multipotency and retain differentiation potential after extended expansion in vitro and in vivo. In particular, the nucleus pulposus-derived DPCs are sensitive to low oxygen tension and undergo apoptosis under hypoxic conditions due to their inability to induce/stabilize hypoxia-inducible factors (HIF). The presence of small leucine-rich proteoglycans (SLRP), biglycan or decorin, can reduce the susceptibility of DPCs to hypoxia-induced apoptosis via promoting the activation/stabilization of HIF-1α and HIF-2α. As IVD is avascular, we propose SLRPs are niche components of DPCs in IVD homeostasis, providing new insights in progenitor cell biology and niche factors under a hypoxic microenvironment. [Copyright &y& Elsevier]

Abstract: (Ti, O)/Ti, (Ti, N)/Ti and (Ti, O, N)/Ti composite coatings were fabricated on NiTi shape memory alloy via plasma immersion ion implantation and deposition (PIIID). Surface morphology of samples was investigated using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Cross-sectional morphology indicated that the PIIID-formed coatings were dense and uniform. X-ray diffraction (XRD) was used to characterize the phase composition of samples. X-ray photoelectron spectroscopy (XPS) results showed that the surface of coated NiTi SMA samples was Ni-free. Nanoindentation measurements and pin-on-disc tests were carried out to evaluate mechanical properties and wear resistance of coated NiTi SMA, respectively. For the in vitro biological assessment of the composite coatings in terms of cell morphology and cell viability, osteoblast-like SaOS-2 cells and breast cancer MCF-7 cells were cultured on NiTi SMA samples, respectively. SaOS-2 cells attached and spread better on coated NiTi SMA. Viability of MCF-7 cells showed that the PIIID-formed composite coatings were noncytotoxic and coated samples were more biocompatible than uncoated samples. [Copyright &y& Elsevier]

Abstract: In this investigation, plasma immersion ion implantation and deposition (PIIID) was used to fabricate a (Ti, O, N)/Ti coating on NiTi shape memory alloy (SMA) to improve its long-term biocompatibility and wear resistance. The surface morphology, composition and roughness of uncoated and coated NiTi SMA samples were examined. Energy dispersive X-ray elemental mapping of cross-sections of (Ti, O, N)/Ti coated NiTi SMA revealed that Ni was depleted from the surface of coated samples. No Ni was detected by X-ray photoelectron spectroscopy on the surface of coated samples. Furthermore, three-point bending tests showed that the composite coating could undergo large deformation without cracking or delamination. After 1day cell culture, SaOS-2 cells on coated samples spread better than those on uncoated NiTi SMA samples. The proliferation of SaOS-2 cells on coated samples was significantly higher at day 3 and day 7 of cell culture. [Copyright &y& Elsevier]

Background: Although both single and dual iliac screw techniques are used in spino-pelvic reconstruction following sacrectomy for treating sacral tumors, the basis for choosing between the two techniques for different instability types remains undetermined. The purpose of this study was to evaluate the effects of the extent of sacrectomy on the stability of the lumbo-iliac fixation construct using single and dual iliac screw techniques. Methods: Nine human L2-pelvic specimens were tested for their intact condition simulated by L3–L5 pedicle screw fixation. Sequential partial sacrectomies and L3-iliac fixation using bilateral single and dual iliac screws were conducted on the same specimens as follows: under-S1 sacrectomy+single screw, under-½S1 sacrectomy+single screw, one-side sacroiliac joint resection+single screw, total sacrectomy+single screw, and total sacrectomy+dual screw. Biomechanical testing was performed on a material testing machine for evaluating the stiffness of the L3-iliac fixation construct in compression and torsion. Findings: Single iliac screw technique was found to effectively restore the local stability in under-½S1 sacrectomy. However, it could not provide adequate stability for further resection of one-side sacroiliac joint in torsion and total sacrectomy in compression (P <0.05). On the other hand, dual iliac screw technique could restore the stability to the intact condition after total sacrectomy in both compression and torsion. Interpretation: The single iliac screw technique for L3-iliac fixation could effectively restore the local stability for under-½S1 sacrectomy. However, for instabilities of the under-½S1 sacrectomy with one-side sacroiliac joint resection or total sacrectomy, the dual iliac screw technique should be considered. [Copyright &y& Elsevier]

In vitro studies have demonstrated that strontium (Sr) could increase osteogenic differentiation of bone marrow stromal cells (BMSCs). We investigated the in vivo effect of Sr on BMSCs. Thirty-six female rats were randomly divided into the following groups: sham operated and treated with either vehicle (Sham + Veh) or Sr compound (Sham + Sr) and ovariectomized and treated with either vehicle (OVX + Veh) or Sr compound (OVX + Sr). Vehicle and Sr were orally administrated daily starting immediately after the surgery and continuing for 12 weeks. The anabolic effect of Sr on trabecular bone was determined at the structural and tissue level by microCT and histomorphometry, respectively. Colony formation assays demonstrated that BMSCs exhibited higher osteogenic colony but lower adipogenic colony in Sr-treated versus Veh-treated OVX rats. The mRNA level of osteogenic genes was higher, while the mRNA level of adipogenic genes was lower in BMSCs from Sr-treated versus Veh-treated Sham and OVX rats. The effect of Sr on rat BMSCs was reproducible in human BMSCs. Taken together, this study suggests that the anabolic effect of Sr on normal or osteoporotic bones is associated with increased osteoblastic differentiation of BMSCs. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1208-1214, 2010 [ABSTRACT FROM AUTHOR]

Collagen fibrils are the main structural components of the nucleus pulposus tissue in the intervertebral discs. The structure-property relationship of the nucleus pulposus (NP) tissues is still unclear. We investigated the structure of individual collagen fibrils of the NP and evaluated its correlation with the bulk mechanical properties of the tissue. Collagen fibrils were extracted from the NP of discs retrieved from adolescents during scoliosis correction surgery, and the extracts were confirmed by SDS-PAGE. The diameters of the individual collagen fibrils were measured through atomic force microscopy, and the compressive mechanical properties of the tissues were evaluated by confined compression. The correlations between the nanoscale morphology of the collagen fibrils and the macroscale mechanical properties of the tissues were evaluated by linear regression. The SDS-PAGE results showed that the fibril extracts were largely composed of type II collagen. The mean diameter of the collagen fibrils was 92.1 ± 26.54 nm; the mean swelling pressure and compressive modulus of the tissues were 6.15 ± 4.3 kPa and 1.23 ± 0.7 MPa, respectively. The mean fibril diameter had no linear correlation ( R2 = 0.30) with the swelling pressure of the tissues. However, it had a mild linear correlation with the compressive modulus ( p = 0.023, R2 = 0.68). This is the first study, to our knowledge, to evaluate the nanostructure of the individual collagen fibrils of the nucleus pulposus and its relationship with macroscale mechanical properties of the NP tissues. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:497-502, 2010 [ABSTRACT FROM AUTHOR]

Strontium ralenate is a new anti-osteoporosis agent. The cellular and molecular mechanism underlying the anabolic effect of strontium on bone remains to be elucidated. Osteoblasts, the main bone forming cells are known to be derived from bone marrow mesenchymal stem cells (MSCs). The present study therefore aimed to investigate the possible effects of strontium on MSCs and signaling pathways possibly involved. It was firstly demonstrated that strontium treatment significantly increased osteoblast-related gene expression and alkaline phosphatase (ALP) of osteogenic-differentiating MSCs. Accompanying the enhanced osteogenic differentiation, the increased phosphorylation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 was detected in strontium-treated MSCs. PD98059 and SB203580, selective inhibitors of ERK1/2 kinase and p38, attenuated the effect of strontium on osteogenesis. Furthermore, it was demonstrated that Rat Sarcoma viral oncogene homolog (RAS), an upstream regulator of ERK1/2 and p38, was activated by strontium treatment and siRNA-mediated Ras knockdown inhibited strontium-stimulated expression of osteogenic markers. Finally, the transcriptional activity and phosphorylation level of Runx2 was significantly increased in response to strontium treatment in MSCs. PD98059 and Ras siRNA inhibited the effect of strontium on Runx2 activation. Taken together, these results indicated that strontium can promote osteogenic differentiation of MSCs through activating the Ras/MAPK signaling pathway and the downstream transcription factor Runx2. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bone defects caused by trauma have become increasingly common in aged populations. Clinically, because of the relatively decreased bone healing capacity compared with the youth adults, bone defect repair in the elderly remains challenging. The development of effective biomaterials targeted at bone defects in the elderly is a key component of bone-tissue engineering strategies. However, little attention has been paid to bone regeneration in the elderly. Here, we developed a new scaffold chitosan-Strontium chondroitin sulfate (CH-SrCS) and evaluated its effect on improving bone regeneration. We find that the CH-SrCS scaffold displayed positive effects on downregulation of inflammation and osteoclastogenesis related mRNA expressions while demonstrating a significant increase in the expression level of BMP2. Finally, we show that the bone defects healing effects as assessed using an aged rats' bone defects model. Ultimately, this work also provides insights into the design of effective biomaterials targeted at bone defects in the elderly. • A new scaffold based on chitosan and strontium chondroitin sulfate was developed. • The scaffold facilitated suppressing inflammation and osteoclastogenesis. • The scaffold demonstrated positive effects on improving osteogenesis. • CH-SrCS scaffolds can effectively enhance the bone defect healing of aged rats. [ABSTRACT FROM AUTHOR]

The article discusses a study examining the association between genetic polymorphism in the COL9A2 structural gene and alterations in the mechanical properties of the intervertebral discs that may predispose a person to disc degeneration. Biomechanical studies found that the genetic polymorphism was associated with early deterioration of disc mechanics. In addition, immunohistochemistry was used to confirm the presence of collagen IX in the human disc with scoliosis.

Study Design: Evaluation of a novel, leakage-free vertebroplastic instrumentation by fresh cadaveric studies. Objectives: To compare Vessel-X, a novel percutaneous bone void filling container system, with conventional kyphoplasty in restoring strength, stiffness, and height in experimentally induced vertebral compressive fractures and morphologically determine the cement distribution. Summary Of Background Data: Clinically, both vertebroplasty and kyphoplasty perform well in reinforcement and pain relief. One of the shortcomings, however, is the risk of cement leakage. Vessel-X is a novel bone expander and bone void filler combined instrumentation for vertebral augmentation requiring evaluation. Methods: A total of 28 fresh-frozen vertebral specimens were randomly assigned to 4 groups for testing: unipedicular kyphoplasty, bipedicular kyphoplasty, unipedicular Vessel-X, and bipedicular Vessel-X. Compressive fractures were experimentally created on each vertebra after determining the bone mineral density. Kyphoplasty and Vessel-X were performed using bioactive bone cement (SrHAC) under C-arm fluoroscopy and compared by compression testing to measure the effects of augmentation. Morphologic observations were also performed to determine the cement distribution and vertebral height restoration. Results: There was no significant difference in bone mineral density, initial strength, and stiffness in any of the groups. Furthermore, no significant difference was observed in total cement volume in intragroup comparison within the unipedicular or bipedicular groups. Vessel-X bone filler container could expand well and contain most of the cement. The height restoration ranged from 88.5% to 96.4% in all groups. The augmented strength with unipedicular and bipedicular injections reached 3651.57 N and 4833.73 N, respectively. Stiffness with bipedicular injection was significantly higher than that of unipedicular injection. Conclusion: Vessel-X was comparable to kyphoplasty in restoring the mechanical properties and height of the fractured vertebrae. Interestingly, Vessel-X instrumentation showed considerably less cement leakage and better cement placement in the vertebral body. Therefore, it could be a leakage controllable technique in percutaneous vertebral augmentation. [ABSTRACT FROM AUTHOR]

Abstract: Nickel–titanium shape memory alloy bars were treated by nitrogen plasma immersion ion implantation at 50 and 100 Hz to investigate the effects of pulsing frequencies on the shape recovery ability. The shape recovery of the treated and untreated control samples was assessed using bending tests. It was found that the 50 Hz sample retained the same shape recovery ability similar to the untreated control sample but the 100 Hz sample could not return to the original shape. Immersion tests in simulated body fluids on the bent-and-recovered bars show that the amount of Ni leached from the treated NiTi bars was 18.2% of that of the untreated control samples. The results show that the nitrogen plasma treatment is effective in impeding the out-diffusion of nickel even after extensive shape deformation. [Copyright &y& Elsevier]

Abstract: Human mesenchymal stem cells (hMSCs) have great potential in bone tissue engineering, and hydroxyapatite (HA), a natural component of human hard tissues, is believed to support hMSC growth and osteogenic differentiation. In this study, two types of biomimetic composite materials, chitosan–gelatin (CG) and hydroxyapatite/chitosan–gelatin (HCG), were fabricated and compared to examine the effects of HA on hMSC adhesion and 3-D construct development. The 2-D membranes were prepared to examine the influence of HA on adhesion efficiency of hMSCs, while 3-D porous scaffolds were produced to investigate the effects of HA on material adsorption properties and 3-D hMSC construct development. HA was found to promote protein and calcium ion adsorption of the 3-D porous scaffolds in the complete tissue culture media. HMSCs exhibited higher initial cell adhesion efficiency to 2-D HCG membranes, and maintained higher proliferation rates in the 3-D porous HCG than CG scaffolds with 3.3 times higher final DNA amount in HCG scaffolds over a 35-day period. Colony forming unit-fibroblast (CFU-F) assays showed that higher percentages of cells maintained their progenicity in the 3-D porous HCG scaffolds over the 35-day culture period. Differentiation assays indicated that the multi-lineage differentiation potential of the hMSCs was preserved in both 3-D porous scaffolds. However, higher alkaline phosphate activity was detected in the 3-D porous HCG scaffolds upon osteogenic induction indicating improved osteogenic differentiation potential. The results demonstrate that enhanced protein and calcium ion adsorption properties of HA in the CG polymer network improve initial cell adhesion and long-term growth, favor osteogenic differentiation upon induction, as well as maintain the progenicity of the 3-D hMSC constructs. [Copyright &y& Elsevier]

Abstract: Nickel–titanium shape memory alloys (NiTi) have potential applications as orthopedic implants because of their unique super-elastic properties and shape memory effects. However, the problem of out-diffusion of harmful Ni ions from the alloys during prolonged use inside a human body must be overcome before they can be widely used in orthopedic implants. In this work, we enhance the corrosion resistance of NiTi using carbon plasma immersion ion implantation and deposition (PIII&D). Our corrosion and simulated body fluid tests indicate that either an ion-mixed amorphous carbon coating fabricated by PIII&D or direct carbon PIII can drastically improve the corrosion resistance and block the out-diffusion of Ni from the materials. Results of atomic force microscopy (AFM) indicate that both C2H2-PIII&D and C2H2-PIII do not roughen the original flat surface to an extent that can lead to degradation in corrosion resistance. [Copyright &y& Elsevier]

Abstract: Nickel–titanium shape memory alloys (NiTi) are potentially useful in orthopedic implants due to their super-elasticity and shape memory properties. However, the materials are vulnerable to surface corrosion and the most serious issue is out-diffusion of toxic Ni ions from the substrate into body tissues and fluids. In this paper, we describe our fabrication of TiN barrier layers in NiTi by nitrogen plasma immersion ion implantation followed with vacuum annealing at 450 °C or 600 °C. Our results show that the barrier layer is not only mechanically stronger than the NiTi substrate, but also is effective in impeding the out-diffusion of Ni from the substrate. Among the samples, the 450 °C-annealed TiN barrier layer possesses the highest mechanical strength and best Ni out-diffusion impeding ability. The enhancement can be attributed to the consolidation of the Ti–N layer resulting from optimal diffusion at 450 °C. [Copyright &y& Elsevier]