Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth

Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmprla in the osteoblast lineage with Dmpl-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin （SOST）, a secreted Wnt antagonist, is notably reduced in the Bmprla- deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmprla deletion. Forced expression of human SOST from a Dmpl promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmprla mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compat^a-tent. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmprla deletion, we have generated compound mutants harboring a hyperactive mutation （A214V） in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmprla-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.

Microstructures and properties of cancellous bone of avascular necrosis of femoral heads

The aim of this study is to investigate microscopic structure and characterize cancellous bone of avascular necrosis of the femoral head （ANFH）. The rabbit model of the ANFH is established. The histopathologic features are studied successfully. The differences between the steroidinjection group （S.G.） and the controlled group （C.G.） are examined, including the weight of rabbits, the hematological examination and the three-dimensional stnactures. It is found that the plasma levels of cholesterol （CHO）, high-density lipoprotein （HDL） and low-density lipoprotein （LDL） in S.G. are lower than those in C.G. when the triglyceride （TG） increased in the S.G.; but the bone mineral content （BMC） and the structural model index （SMI） of the organ and tissue decreased significantly in S.G. Three-dimensional structures of the femoral head are obtained using micro-computed tomography （CT） scanning and the mechanical model is established to analyze the influences of these structural changes on the mechanical properties of the cancellous bone.

Ultrasonic backscatter characterization of cancellous bone using a general Nakagami statistical model

The goal of this study is to analyze the statistics of the backscatter signal from bovine cancellous bone using a Nakagami model and to evaluate the feasibility of Nakagami-model parameters for cancellous bone characterization. Ultrasonic backscatter measurements were performed on 24 bovine cancellous bone specimens in vitro and the backscatter signals were compensated for the frequency-dependent attenuation prior to the envelope detection. The statistics of the backscatter envelope were modeled using the Nakagami distribution. Our results reveal that the backscatter envelope mainly followed pre-Rayleigh distributions, and the deviations of the backscatter envelope from Rayleigh distribution decreased with increasing bone density. The Nakagami shape parameter(i.e., m) was significantly correlated with bone densities(R = 0.78–0.81, p < 0.001) and trabecular microstructures(|R| = 0.46–0.78, p < 0.05). The scale parameter(i.e.,?) and signal-to-noise ratio(SNR) also yielded significant correlations with bone density and structural features. Multiple linear regressions showed that bone volume fraction(BV/TV) was the main predictor of the Nakagami parameters,and microstructure produced significantly independent contribution to the prediction of Nakagami distribution parameters,explaining an additional 10.2% of the variance at most. The in vitro study showed that statistical parameters derived with Nakagami model might be useful for cancellous bone characterization, and statistical analysis has potential for ultrasonic backscatter bone evaluation.

An Ultrasonic Backscatter Instrument for Cancellous Bone Evaluation in Neonates

Ultrasonic backscatter technique has shown promise as a noninvasive cancellous bone assessment tool. A novel ultrasonic backscatter bone diagnostic （UBBD） instrument and an in vivo application for neonatal bone evaluation are introduced in this study. The UBBD provides several advantages, including noninvasiveness, non- ionizing radiation, portability, and simplicity. In this study, the backscatter signal could be measured within 5 s using the UBBD. Ultrasonic backscatter measurements were performed on 467 neonates （268 males and 199 females） at the left calcaneus. The backscatter signal was measured at a central frequency of 3.5 MHz. The delay （-/-1） and duration （7-2） of the backscatter signal of interest （SOl） were varied, and the apparent integrated backscatter （AIB）, frequency slope of apparent backscatter （FSAB）, zero frequency intercept of apparent backscatter （FIAB）, and spectral centroid shift （SCS） were calculated. The results showed that the SOl selection had a direct influence on cancellous bone evaluation. The AIB and FIAB were positively correlated with the gestational age （｜R｜ up to 0.45, P 〈 0.001） when -/-1 was short （〈 8 μS）, while negative correlations （｜R｜ up to 0.56, P 〈 0.001） were commonly observed for T1 〉 10 IJS. Moderate positive correlations （IRI up to 0.45, P 〈 0.001） were observed for FSAB and SCS with gestational age when 71 was long （〉 10 μs）. The 7-2 mainly introduced fluctuations in the observed correlation coefficients. The moderate correlations observed with UBBD demonstrate the feasibility of using the backscatter signal to evaluate neonatal bone status. This study also proposes an explicit standard for in vivo SOl selection and neonatal cancellous bone assessment.

Comparative Study on Inorganic Composition and Crystallographic Properties of Cortical and Cancellous Bone

Objective To comparatively investigate the inorganic composition and crystallographic properties of cortical and cancellous bone via thermal treatment under 700 ℃. Methods Thermogravimetric measurement, infrared spectrometer, X-ray diffraction, chemical analysis and X-ray photo-electron spectrometer were used to test the physical and chemical properties of cortical and cancellous bone at room temperature 250 ℃, 450 ℃, and 650 ℃, respectively. Results The process of heat treatment induced an extension in the a-lattice parameter and changes of the c-lattice parameter, and an increase in the crystallinity reflecting lattice rearrangement after release of lattice carbonate and possible lattice water. The mineral content in cortical and cancellous bone was 73.2wt% and 71.5wt%, respectively. For cortical bone, the weight loss was 6.7% at the temperature from 60 ℃ to 250℃, 17.4% from 250 ℃ to 450 ℃, and 2.7% from 450 ℃ to 700 ℃. While the weight loss for the cancellous bone was 5.8%, 19.9%, and 2.8 % at each temperature range, the Ca/P ratio of cortical bone was 1.69 which is higher than the 1.67 of stoichiometric HA due to the B-type CO32- substitution in apatite lattice. The CaJP ratio of cancellous bone was lower than 1.67, suggesting the presence of more calcium deficient apatite. Conclusion The collagen fibers of cortical bone were arrayed more orderly than those of cancellous bone, while their mineralized fibers ollkded similar. The minerals in both cortical and cancellous bone are composed of poorly crystallized nano-size apatite crystals with lattice carbonate and possible lattice water. The process of heat treatment induces a change of the lattice parameter, resulting in lattice rearrangement after the release of lattice carbonate and lattice water and causing an increase in crystal size and crystallinity. This finding is helpful for future biomaterial design, preparation and application.

Bone Regeneration Enhanced by Antigen-Extracted Xenogeneic Cancellous Bone Graft with rhBMP-2 in Rabbits Mandibular Defect Repair

The effects of large piece xenogeneic bone which was separated from healthy pigs as a scaffold on repair of mandibular defect was investigated and the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked with rhBMP-2 in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand Rabbits, and then randomly divided into 4 groups, which was grafted in the mandibular defects with AXCB, AXCB soaked with rhBMP-2, autograft bone, or blank. Equal number of animals from each group was classified into three time points (4, 8, and 12 weeks) after operation for gross pathological observation, hematoxylin and eosin (H & E) staining, radiographic examination, and bone density measurement. H & E staining revealed that the area percentage of bone regeneration in the group of AXCB/rhBMP-2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 when at 4, 8, and 12 weeks, which was better than that of auto bone graft, prompting that the group of AXCB/rhBMP-2 graft had commendable osteogenic effect. And comparing with the AXCB without rhBMP-2, of which the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92, the osteogenic effect of AXCB/rhBMP-2 graft was demonstrated to be much better. In the group of AXCB/rhBMP-2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We concluded that antigen-extracted xenogeneic cancellous bone (AXCB) graft soaked with rhBMP-2 had shown excellent osteogenic effect in repair of bone defects, with good biocompability.

Microstructural Modeling and Multiscale Mechanical Properties Analysis of Cancellous Bone

This paper is devoted to the microstructure geometric modeling and mechanical properties computation of cancellous bone.The microstructure of the cancellous bone determines its mechanical properties and a precise geometric modeling of this structure is important to predict the material properties.Based on the microscopic observation,a new microstructural unit cell model is established by introducing the Schwarz surface in this paper.And this model is very close to the real microstructure and satisfies the main biological characteristics of cancellous bone.By using the unit cell model,the multiscale analysis method is newly applied to predict the mechanical properties of cancellous bone.The effective stiffness parameters are calculated by the up-scaling multi-scale analysis.And the distribution of microscopic stress in cancellous bone is determined through the down-scaling procedure.In addition,the effect of porosity on the stiffness parameters is also investigated.The predictive mechanical properties are in good agreement with the available experimental results,which verifies the applicability of the proposed unit cell model and the validness of the multiscale analysis method to predict the mechanical properties of cancellous bone.

Theoretical Solutions of Dynamic Responses of Cancellous Bone

Human bone may be damaged by impact in the cases of traffic accidents and ship impact. The impact responses of cancellous bone were analyzed based on the two-phase media theory. A direct analytical method is introduced for solving this type of problems. First, flow function and potential function were introduced to decouple the controlling equations. Then direction solving method was used to obtain the solution. The solution is determined by the parameters of a (related with wave speed) and b (related with damping), as well as the boundary conditions. These two parameters a and b determine the propagation speed of the responses along the bone and the attenuation rate. It is shown that the responses: deformation, stress and pressure of the corpus medullae caused by loading, propagate toward the other end when the impact is acted on one end of the bone. The responses are discontinuous during propagate. The discontinuous surface moves with a constant speed. The responses at the cross section increase gradually from the bottom to the top because of the distribution of the loading at the boundary. The solutions can be used as the basis for certification of numerical simulation as well as the design of impact prevention of bone.

Computer-Assisted Surgery for Mandibular Reconstruction Using a Patient-Specific Titanium Mesh Tray and Particulate Cancellous Bone and Marrow

Craniomaxillofacial surgery is difficult due to the complexity of the regional anatomy. Computer-assisted surgery is a promising tool aiming to improve the safety and precision of such surgery. A computer-assisted surgical navigation approach for reconstruction of mandibular defects using a patient-specific titanium mesh tray and particulate cancellous bone and marrow (PCBM) harvested from bilateral anterior ilia is proposed. This case report involves a large multicystic ameloblastoma affecting the right mandible of a 31-year-old male patient. Following detailed clinical examination, radiological interpretation, and histopathological diagnosis, computer-assisted surgical simulation with a virtual 3-dimensional (3-D) model was designed using surgical planning software based on the pre-operative computed tomography data. Long-span segmental resection of the mandible was planned, and the defect was analyzed for reconstruction using a patient-specific reconstruction titanium mesh tray mediated with computer-aided design and manufacturing (CAD/CAM) techniques. During the actual surgery, the ultrasonic bone cutting instrument in the surgeon’s hand was connected to the navigation system to touch an anatomical position on the patient. Therefore, osteotomies were performed finely and smoothly according to the navigation images of the cutting bone line by sequentially moving the instrument. Finally, a CAD/CAM-mediated titanium mesh tray condensed by PCBM was adapted to the remaining mandibular fragments. Six months postoperatively, the patient had a good mandibular configuration and facial contour. Integration of different technologies, such as software planning and 3-D surgical simulation, combined with intraoperative navigation and CAD/CAM techniques, provides safe and precise mandibular reconstruction surgery.

Coherent optical frequency transfer via 972-km fiber link

We demonstrate coherent optical frequency dissemination over a distance of 972 km by cascading two spans where the phase noise is passively compensated for.Instead of employing a phase discriminator and a phase locking loop in the conventional active phase control scheme,the passive phase noise cancellation is realized by feeding double-trip beat-note frequency to the driver of the acoustic optical modulator at the local site.This passive scheme exhibits fine robustness and reliability,making it suitable for long-distance and noisy fiber links.An optical regeneration station is used in the link for signal amplification and cascaded transmission.The phase noise cancellation and transfer instability of the 972-km link is investigated,and transfer instability of 1.1×10^(-19)at 10^(4)s is achieved.This work provides a promising method for realizing optical frequency distribution over thousands of kilometers by using fiber links.

Effect of selected signals of interest on ultrasonic backscattering measurement in cancellous bones

This study examined how the signals of interest （SOI） effect on the backscattering measurement numerically based on 3-D finite-difference time-domain （FDTD） method. High resolution microstructure mappings of bovine cancellous bones provided by micro-CT were used as the input geometry for simulations. Backscatter coefficient （BSC）, integrated backscatter coefficient （IBC） and apparent integrated backscatter （AIB） were calculated with changing the start （L1） and duration （L2） of the SOl. The results demonstrated that BSC and IBC decrease as L1 increases, and AIB decreases more rapidly as L1 increases. The backscattering parameters increase with fluctuations as a function of L2 when L2 is less than 6 mm. However, BSC and IBC change little as L2 continues to increase, while AIB slowly decreases as L2 continues to increase. The results showed how the selections of the SOI effect on the backscattering measurement. An explicit standard for SOl selection was proposed in this study and short L1 （about 1.5 mm） and appropriate L2 （6 mm-12 mm） were recommended for the calculations of backscattering parameters.

Improved the biocompatibility of cancellous bone with compound physicochemical decellularization process

Due to the unique microstructures and components of extracellular matrix(ECM),decellularized scaffolds had been used widely in clinical.The reaction of the host toward decellularized scaffolds depends on their biocompatibility,which should be satisfied before applied in clinical.The aim of this study is to develop a decellularized xenograft material with good biocompatibility for further bone repair,in an effective and gentle method.The existing chemical and physical decellularization techniques including ethylene diamine tetraacetic acid(EDTA),sodium dodecyl sulfate(SDS)and supercritical carbon dioxide(SC-CO2)were combined and modified to decellularize bovine cancellous bone(CB).After decellularization,almost 100%of A-Gal epitopes were removed,the combination of collagen,calcium and phosphate was reserved.The direct and indirect contact with macrophages was used to evaluate the cytotoxicity and immunological response of the materials.Mesenchymal stem cells(MSCs)were used in the in vitro cells’proliferation assay.The decellularized CB was proved has no cytotoxicity(grade 1)and no immunological response(NO,IL-2,IL-6 and TNF-α secretion inhibited),and could support MSCs proliferated continuedly.These results were similar to that of commercial decellularized human bone.This study suggests the potential of using this kind of combine decellularization process to fabricate heterogeneous ECM scaffolds for clinical application.

Comparative Study between Bone Tissue Engineering Scaffolds with Bull and Rat Cancellous Microarchitectures on Tissue Differentiations of Bone Marrow Stromal Cells： A Numerical Investigation

Tissue-engineered bone scaffolds provide temporary mechanical support for bone tissue growth. Mechanical stimuli are transferred to seeded cells through the scaffold structure to promote cell proliferation and differentiation. This paper presents a numerical investigation specifically on bone and cartilage tissue differentiation with the aim to provide a theoretical basis for scaffold design and bone defect repair in clinics. In this study, the scaffold structures were established on the basis of cancellous bone microarchitectures. For finite element simulations, inlet velocity and compressive strain were applied under in vitro culture conditions. The influences of this scaffold mor- phology and macro-level culture conditions on micro-mechanical stimuli at scaffold surfaces were investigated. Correlations between the microarchitectural parameters and the mechanical parameters, as well as the cell differentiation parameters were analyzed. Highly het- erogeneous stress distributions were observed on the scaffolds with irregular morphology. Cell differentiation on the scaffold was more sensitive to the inlet velocity than the axial strain. In addition, cartilage differentiation on the scaffolds with structures comprising more plate-like trabeculae was more pronounced than on those with more rod-like trabeculae. This paper is helpful to gain more insight into the mechanical environments under in vitro culture conditions that approximate the in vivo mechanical environments of Bone Marrow Stromal Ceils （BMSCs）.

The spectrum entropy estimation method for ultrasonic backscattering signal in cancellous bones

In the application of cancellous bone ultrasound diagnosis based on backscattering method, it is of great importance to estimate fast and accurately whether the valid backscattering signal exists in the received signal. We propose a fast estimation method based on spectrum entropy method. With 984 records of adult calcaneus clinical data, we estimate the validity of the backscatter signal using this method. The results of the proposed method and the results of experience-base judgement were compared and analyzed. And two key parameters, the signal range length and the segment number of the spectrum entropy, were analyzed. The results show when the signal range length is 13 I^s and the segment number is 15 20, this method can get the best result （accuracy〉95%, sensitivity〉99%, specificity〉87%）, while taking little calculation time （1.5 ms）. Therefore, this spectrum entropy method can satisfy the accuracy and real-time requirements in the ultrasonic estimation for cancellous bone.

Digital cancellation of multi-band passive inter-modulation based on Wiener-Hammerstein model

Utilizing multi-band and multi-carrier techniques enhances throughput and capacity in Long-Term Evolution(LTE)-Advanced and 5G New Radio(NR)mobile networks.However,these techniques introduce Passive Inter-Modulation(PIM)interference in Frequency-Division Duplexing(FDD)systems.In this paper,a novel multi-band Wiener-Hammerstein model is presented to digitally reconstruct PIM interference signals,thereby achieving effective PIM Cancellation(PIMC)in multi-band scenarios.In the model,transmitted signals are independently processed to simulate Inter-Modulation Distortions(IMDs)and Cross-Modulation Distortions(CMDs).Furthermore,the Finite Impulse Response(FIR)filter,basis function generation,and B-spline function are applied for precise PIM product estimation and generation in multi-band scenarios.Simulations involving 4 carrier components from diverse NR frequency bands at varying transmitting powers validate the feasibility of the model for multi-band PIMC,achieving up to 19 dB in PIMC performance.Compared to other models,this approach offers superior PIMC performance,exceeding them by more than 5 dB in high transmitting power scenarios.Additionally,its lower sampling rate requirement reduces the hardware complexity associated with implementing multi-band PIMC.

Enhanced critical-sized bone defect repair efficiency by combining deproteinized antler cancellous bone and autologous BMSCs

Previously we have demonstrated that calcinated antler cancellous bone（CACB） has great potential for bone defect repair,due to its highly similar composition and architecture to natural extracellular bone matrix.This study is aiming at seeking for an optimal strategy of combined application of CACB and bone marrow mesenchymal stem cells（BMSCs） in bone defect repair.In vitro study demonstrated that CACB promoted the adhesion,spreading and viability of BMSCs.Increased extracellular matrix production and expression of osteogenic markers in BMSCs were observed when seeded on CACB scaffolds.The cells ceased to proliferation in the dual effect of CACB and osteogenic induction at the early stage of incubation.Hence synergistic effect of CACB combined with autologous undifferentiated BMSCs in rabbit mandible critical-sized defect repair was further evaluated.Histological analysis results showed that loading the CACB with autologous BMSCs resulted in enhanced new bone formation and angiogenesis when compared with implanted CACB alone.These findings indicate that the combination of CACB and autologous BMSCs should become potential routes to improve bone repair efficiency

Correction of microwave pulse reflection by digital filters in superconducting quantum circuits

Reducing the control error is vital for high-fidelity digital and analog quantum operations.In superconducting circuits,one disagreeable error arises from the reflection of microwave signals due to impedance mismatch in the control chain.Here,we demonstrate a reflection cancelation method when considering that there are two reflection nodes on the control line.We propose to generate the pre-distortion pulse by passing the envelopes of the microwave signal through digital filters,which enables real-time reflection correction when integrated into the field-programmable gate array(FPGA).We achieve a reduction of single-qubit gate infidelity from 0.67%to 0.11%after eliminating microwave reflection.Real-time correction of microwave reflection paves the way for precise control and manipulation of the qubit state and would ultimately enhance the performance of algorithms and simulations executed on quantum processors.

Quantized Decoders that Maximize Mutual Information for Polar Codes

In this paper,we innovatively associate the mutual information with the frame error rate(FER)performance and propose novel quantized decoders for polar codes.Based on the optimal quantizer of binary-input discrete memoryless channels(BDMCs),the proposed decoders quantize the virtual subchannels of polar codes to maximize mutual information(MMI)between source bits and quantized symbols.The nested structure of polar codes ensures that the MMI quantization can be implemented stage by stage.Simulation results show that the proposed MMI decoders with 4 quantization bits outperform the existing nonuniform quantized decoders that minimize mean-squared error(MMSE)with 4 quantization bits,and yield even better performance than uniform MMI quantized decoders with 5 quantization bits.Furthermore,the proposed 5-bit quantized MMI decoders approach the floating-point decoders with negligible performance loss.

A new adaptive co-site broadband interference cancellation method with auxiliary channel

With the boom of the communication systems on some independent platforms(such as satellites,space stations,airplanes,and vessels),co-site interference is becoming prominent.The adaptive interference cancellation method has been adopted to solve the co-site interference problem.But the broadband interference cancellation performance of traditional Adaptive Co-site Interference Cancellation System(ACICS)with large delay mismatching and antenna sway is relatively poor.This study put forward an Adaptive Co-site Broadband Interference Cancellation System With Two Auxiliary Channels(ACBICS-2A).The system model was established,and the steady state weights and Interference Cancellation Ratio(ICR)were deduced by solving a time-varying differential equation.The relationship of ICR,system gain,modulation factor,interference signal bandwidth and delay mismatching degree was acquired through an in-depth analysis.Compared with traditional adaptive interference cancellation system,the proposed ACBICS-2A can improve broadband interference cancellation ability remarkably with large delay mismatching and antenna sway for the effect of auxiliary channel.The maximum improved ICR is more than 25 dB.Finally,the theoretical and simulation results were verified by experiments.

Off-Grid Compressed Channel Estimation with Parallel Interference Cancellation for Millimeter Wave Massive MIMO

Millimeter wave(mmWave)massive multiple-input multiple-output(MIMO)plays an important role in the fifth-generation(5G)mobile communications and beyond wireless communication systems owing to its potential of high capacity.However,channel estimation has become very challenging due to the use of massive MIMO antenna array.Fortunately,the mmWave channel has strong sparsity in the spatial angle domain,and the compressed sensing technology can be used to convert the original channel matrix into the sparse matrix of discrete angle grid.Thus the high-dimensional channel matrix estimation is transformed into a sparse recovery problem with greatly reduced computational complexity.However,the path angle in the actual scene appears randomly and is unlikely to be completely located on the quantization angle grid,thus leading to the problem of power leakage.Moreover,multiple paths with the random distribution of angles will bring about serious interpath interference and further deteriorate the performance of channel estimation.To address these off-grid issues,we propose a parallel interference cancellation assisted multi-grid matching pursuit(PIC-MGMP)algorithm in this paper.The proposed algorithm consists of three stages,including coarse estimation,refined estimation,and inter-path cyclic iterative inter-ference cancellation.More specifically,the angular resolution can be improved by locally refining the grid to reduce power leakage,while the inter-path interference is eliminated by parallel interference cancellation(PIC),and the two together improve the estimation accuracy.Simulation results show that compared with the traditional orthogonal matching pursuit(OMP)algorithm,the normalized mean square error(NMSE)of the proposed algorithm decreases by over 14dB in the case of 2 paths.