Chimeric antigen receptor T cells in the treatment of osteosarcoma (Review).

Osteosarcoma (OS) is a frequently occurring primary bone tumor, mostly affecting children, adolescents and young adults. Before 1970, surgical resection was the main treatment method for OS, but the clinical results were not promising. Subsequently, the advent of chemotherapy has improved the prognosis of patients with OS. However, there is still a high incidence of metastasis or recurrence, and chemotherapy has several side effects, thus making the 5­year survival rate markedly low. Recently, chimeric antigen receptor T (CAR­T) cell therapy represents an alternative immunotherapy approach with significant potential for hematologic malignancies. Nevertheless, the application of CAR­T cells in the treatment of OS faces numerous challenges. The present review focused on the advances in the development of CAR­T cells to improve their clinical efficacy, and discussed ways to overcome the difficulties faced by CAR T­cell therapy for OS.

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30-150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.

Bioactive prosthesis interface compositing variable-stiffness hydrogels regulates stem cells fates to facilitate osseointegration through mechanotransduction.

Fluid hydrogel is proper to be incorporated with rigid porous prosthesis interface, acting as a soft carrier to support cells and therapeutic factors, to enhance osseointegration. In the previous study, we innovatively utilized self-healing supramolecular hydrogel as 3D cell culture platform to incorporate with 3D printed porous titanium alloy scaffold, constructing a novel bioactive interface. However, the concrete relationship and mechanism of hydrogel stiffness influencing cellular behaviors of bone marrow mesenchymal stem cells (BMSCs) within the interface are still inconclusive. Herein, we synthesized a series of supramolecular hydrogels with variable stiffness as extracellular matrix (ECM) to enhance the osseointegration of 3D printed prosthesis interface. BMSCs exposed to stiff hydrogel received massive environmental mechanical stimulations, subsequently transducing biophysical cues into biochemical signal through mechanotransduction process. The mRNA-sequencing analysis revealed that the activated FAK-MAPK pathway played significant roles in promoting osteogenic differentiation, thus contributing to a strong osseointegration. Our work preliminarily demonstrated the relationship of ECM stiffness and osteogenic differentiation trend of BMSCs, and optimized stiffness of hydrogel within a certain range benefitting for osteogenic differentiation and prosthesis interface osseointegration, providing a valuable insight into the development of orthopaedic implants equipped with osteogenic mechanotransduction ability.

Epidemiology and survival of patients with spinal meningiomas: a large retrospective cohort study.

INTRODUCTION: Spinal meningiomas (SMs) are relatively rare central nervous system tumors that usually trigger neurological symptoms. The prevalence of SMs is increasing with the aging of the global population. This study aimed to perform a systematic epidemiologic and survival prognostic analysis of SMs to evaluate their public health impact and to develop a novel method to estimate the overall survival at 3-year, 5-year, and 10-year in patients with SMs. METHODS: Five thousand one hundred fifty eight patients with SMs were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Firstly, descriptive analysis was performed on the epidemiology of SMs. Secondly, these individuals were randomly allocated to the training and validation sets in a ratio of 7:3. Kaplan-Meier method and Cox regression analysis were utilized in the training set to identify independent prognostic factors and to construct a nomogram for survival prognosis. Subsequently, the discriminative power, predictive performance, and clinical utility of the nomogram were evaluated by receiver operating characteristic curve and decision curve analysis. Finally, a mortality risk stratification system and a web-based dynamic nomogram were constructed to quantify the risk of mortality in patients with SMs. RESULTS: The annual age-adjusted incidence rates of SMs increased steadily since 2004, reaching a rate of 0.40 cases per 100 000 population in 2019, with a female-to-male ratio of ~4:1. The age groups of 50-59, 60-69, and 70-79 years old were the most prevalent ages for SMs, accounting for 19.08, 24.93, and 23.32%, respectively. In addition, seven independent prognostic factors were identified to establish a prognostic nomogram for patients with SMs. The decision curve analysis and receiver operating characteristic curve indicated that the nomogram had high clinical utility and favorable accuracy. Moreover, the mortality risk stratification system effectively divided patients into low-risk, middle-risk, and high-risk subgroups. CONCLUSIONS: SMs are relatively rare benign spinal tumors prevalent in the white elderly female population. Clinicians could use the nomogram to personalize the prediction of the overall survival probability of patients with SMs, categorize these patients into different mortality risk subgroups, and develop personalized decision-making plans. Moreover, the web-based dynamic nomogram could help to further promote clinical application and assist clinicians in providing personalized counseling, timely monitoring, and clinical assessment for patients.

Application of advanced biomaterials in photothermal therapy for malignant bone tumors.

Malignant bone tumors are characterized by severe disability rate, mortality rate, and heavy recurrence rate owing to the complex pathogenesis and insidious disease progression, which seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment offering prominent hyperthermal therapeutic effects to enhance the effectiveness of surgical treatment and avoid recurrence. Simultaneously, various advanced biomaterials with photothermal capacity are currently created to address malignant bone tumors, performing distinctive biological functions, including nanomaterials, bioceramics (BC), polymers, and hydrogels et al. Furthermore, PTT-related combination therapeutic strategies can provide more significant curative benefits by reducing drug toxicity, improving tumor-killing efficiency, stimulating anti-cancer immunity, and improving immune sensitivity relative to monotherapy, even in complex tumor microenvironments (TME). This review summarizes the current advanced biomaterials applicable in PTT and relevant combination therapies on malignant bone tumors for the first time. The multiple choices of advanced biomaterials, treatment methods, and new prospects for future research in treating malignant bone tumors with PTT are generalized to provide guidance. Malignant bone tumors seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment enhancing the effectiveness of surgical treatment and avoiding recurrence. In this review, advanced biomaterials applicable in the PTT of malignant bone tumors and their distinctive biological functions are comprehensively summarized for the first time. Simultaneously, multiple PTT-related combination therapeutic strategies are classified to optimize practical clinical issues, contributing to the selection of biomaterials, therapeutic alternatives, and research perspectives for the adjuvant treatment of malignant bone tumors with PTT in the future.

Comprehensive evaluation and advanced modification of polymethylmethacrylate cement in bone tumor treatment.

Bone tumors are invasive diseases with a tendency toward recurrence, disability, and high mortality rates due to their grievous complications. As a commercial polymeric biomaterial, polymethylmethacrylate (PMMA) cement possesses remarkable mechanical properties, injectability, and plasticity and is, therefore, frequently applied in bone tissue engineering. Numerous positive effects in bone tumor treatment have been demonstrated, including biomechanical stabilization, analgesic effects, and tumor recurrence prevention. However, to our knowledge, a comprehensive evaluation of the application of the PMMA cement in bone tumor treatment has not yet been reported. This review comprehensively evaluates the efficiency and complications of the PMMA cement in bone tumor treatment, for the first time, and introduces advanced modification strategies, providing an objective and reliable reference for the application of the PMMA cement in treating bone tumors. We have also summarized the current research on modifications to enhance the anti-tumor efficacy of the PMMA cement, such as drug carriers and magnetic hyperthermia.

Biomaterials-enhanced bioactive agents to efficiently block spinal metastases of cancers.

The spine is the most common site of bone metastases, as 20%-40% of cancer patients suffer from spinal metastases. Treatments for spinal metastases are scarce and palliative, primarily aiming at relieving bone pain and preserving neurological function. The bioactive agents-mediated therapies are the most effective modalities for treating spinal metastases because they achieve systematic and specific tumor regression. However, the clinical applications of some bioactive agents are limited due to the lack of targeting capabilities, severe side effects, and vulnerability of drug resistance. Fortunately, advanced biomaterials have been developed as excipients to enhance these treatments, including chemotherapy, phototherapy, magnetic hyperthermia therapy, and combination therapy, by improving tumor targeting and enabling sustaining and stimuli-responsive release of various therapeutic agents. Herein, the review summarizes the development of biomaterials-mediated bioactive agents for enhanced treatments of spinal metastases and predicts future research trends.

Biomechanical evaluation of a novel individualized zero-profile cage for anterior cervical discectomy and fusion: a finite element analysis.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a standard procedure for treating symptomatic cervical degenerative disease. The cage and plate constructs (CPCs) are widely employed in ACDF to maintain spinal stability and to provide immediate support. However, several instrument-related complications such as dysphagia, cage subsidence, and adjacent segment degeneration have been reported in the previous literature. This study aimed to design a novel individualized zero-profile (NIZP) cage and evaluate its potential to enhance the biomechanical performance between the instrument and the cervical spine. Methods: The intact finite element models of C3-C7 were constructed and validated. A NIZP cage was designed based on the anatomical parameters of the subject's C5/6. The ACDF procedure was simulated and the CPCs and NIZP cage were implanted separately. The range of motion (ROM), intradiscal pressure (IDP), and peak von Mises stresses of annulus fibrosus were compared between the two surgical models after ACDF under four motion conditions. Additionally, the biomechanical performance of the CPCs and NIZP cage were evaluated. Results: Compared with the intact model, the ROM of the surgical segment was significantly decreased for both surgical models under four motion conditions. Additionally, there was an increase in IDP and peak von Mises stress of annulus fibrosus in the adjacent segment. The NIZP cage had a more subtle impact on postoperative IDP and peak von Mises stress of annulus fibrosus in adjacent segments compared to CPCs. Meanwhile, the peak von Mises stresses of the NIZP cage were reduced by 90.0-120.0 MPa, and the average von Mises stresses were reduced by 12.61-17.56 MPa under different motion conditions. Regarding the fixation screws, the peak von Mises stresses in the screws of the NIZP cage increased by 10.0-40.0 MPa and the average von Mises stresses increased by 2.37-10.10 MPa. Conclusion: The NIZP cage could effectively reconstruct spinal stability in ACDF procedure by finite element study. Compared with the CPCs, the NIZP cage had better biomechanical performance, with a lower stress distribution on the cage and a more moderate effect on the adjacent segmental discs. Therefore, the NIZP cage could prevent postoperative dysphagia as well as decrease the risk of subsidence and adjacent disc degeneration following ACDF. In addition, this study could serve as a valuable reference for the development of personalized instruments.

Independent Prognostic Factors and Nomogram Prediction of Cancer-Specific Survival in Postoperative Patients With Spinal Cord Astrocytoma.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Spinal cord astrocytoma (SCA) is a rare central nervous system malignancy that typically requires early surgical intervention. However, the substantial frequency of relapse and bad outcomes limit the surgical advantage for patients. Herein, we aimed to determine the independent prognostic factors of cancer-specific survival (CSS) in post-surgical patients with primary SCA and to develop a new method to estimate the chances of CSS in these patients at 3-, 5- and 10-year. METHODS: A total of 364 postoperative patients with SCA were recruited from the Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validation sets. Univariate and multivariate Cox regression assessments were used to identify independent prognostic indicators. Second, a nomogram was established by integrating these indicators to estimate 3-, 5-, and 10-year CSS in patients with SCA who underwent surgery. Subsequently, the discriminatory power and predictive performance of the nomogram were assessed using the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Finally, a mortality risk stratification system was generated. RESULTS: Age, tumor stage, histological type, and radiotherapy were recognized as potential predictive indicators of CSS for postoperative patients with SCA. The ROC curve and DCA indicate that the nomogram has good accuracy and high clinical utility. Furthermore, the mortality risk stratification system efficiently divides patients into 3 risk subgroups. CONCLUSIONS: The nomogram could accurately anticipate the 3-, 5-, and 10-year percentages of CSS in postoperative patients with SCA. It could assist clinicians with personalized medical counseling, risk stratification management, and clinical decision-making, improving the clinical outcomes of these patients.

Artificial lamina after laminectomy: Progress, applications, and future perspectives.

In clinical practice, laminectomy is a commonly used procedure for spinal decompression in patients suffering from spinal disorders such as ossification of ligamentum flavum, lumbar stenosis, severe spinal fracture, and intraspinal tumors. However, the loss of posterior column bony support, the extensive proliferation of fibroblasts and scar formation after laminectomy, and other complications (such as postoperative epidural fibrosis and iatrogenic instability) may cause new symptoms requiring revision surgery. Implantation of an artificial lamina prosthesis is one of the most important methods to avoid post-laminectomy complications. Artificial lamina is a type of synthetic lamina tissue made of various materials and shapes designed to replace the resected autologous lamina. Artificial laminae can provide a barrier between the dural sac and posterior soft tissues to prevent postoperative epidural fibrosis and paravertebral muscle compression and provide mechanical support to maintain spinal alignment. In this paper, we briefly review the complications of laminectomy and the necessity of artificial lamina, then we review various artificial laminae from clinical practice and laboratory research perspectives. Based on a combination of additive manufacturing technology and finite element analysis for spine surgery, we propose a new designing perspective of artificial lamina for potential use in clinical practice.

Robot-assisted versus navigation-assisted screw placement in spinal vertebrae.

PURPOSE: Both robots and navigation are effective strategies for optimizing screw placement, as compared to freehand placement. However, few studies have compared the accuracy and efficiency of these two techniques. Thus, the purpose of this study is to compare the accuracy and efficiency of robotic and navigation-assisted screw placement in the spinal vertebrae. METHODS: The 24 spine models were divided into a robot- and navigation-assisted groups according to the left and right sides of the pedicle. The C-arm transmits image data simultaneously to the robot and navigates using only one scan. After screw placement, the accuracy of the two techniques were compared using "angular deviation" and "Gertzbein and Robbins scale" in different segments (C1-7, T1-4, T5-8, T9-12, and L1-S1). In addition, operation times were compared between robot- and navigation-assisted groups. RESULTS: Robots and navigation systems can simultaneously assist in screw placement. The robot-assisted group had significantly less angular deviation than the navigation-assisted group from C1 to S1 (p < 0.001). At the C1-7 and T1-4 segments, the robot-assisted group had a higher rate of acceptable screws than the robot-assisted group. However, at the T5-8, T9-12, and L1-S1 segments, no significant difference was found in the incidence of acceptable screws between the two groups. Moreover, robot-assisted screw placement required less operative time than navigation (p < 0.05). CONCLUSION: The robot is more accurate and efficient than navigation in aiding screw placement. In addition, robots and navigation can be combined without increasing the number of fluoroscopic views.

Biomechanical effects of individualized artificial titanium alloy lamina implantation after laminectomy: A finite element analysis.

Background and objectives: Laminectomy is a common surgical procedure in spine surgery. However, disruption of the posterior ligamentous complex of the spine may lead to a range of postoperative complications. Artificial lamina as a kind of bionic implant can well restore the posterior spinal structure. In this study, an individualized artificial titanium alloy lamina was designed to reconstruct the posterior spinal structure after laminectomy and explored its biomechanical effects, which could provide a theoretical basis for the clinical application of the artificial lamina. Methods: Three finite element models were constructed, namely the nonlinear and non-homogeneous intact model of the whole lumbar spine, the lumbar decompression alone surgical model, and the artificial lamina implantation surgical model. The range of motion, intradiscal pressure, and annulus fibrosus peak stress were compared between the three models at the surgical and adjacent segments. The stresses of the artificial lamina and fixation screws were also analyzed for the four movement states. Results: Compared with the intact model, the lumbar decompression alone surgical model showed an increase in range of motion, intradiscal pressure, and annulus fibrosus peak stresses at the surgical segment and adjacent segments under all conditions. The artificial lamina implantation surgical model showed an increase in these measurements only in flexion, increasing by 7.5%-22.5%, 7.6%-17.9%, and 6.4%-19.3%, respectively, over the intact model, while there was little difference under other conditions. The peak stresses in both the screw and the artificial lamina were highest in axial rotation, i. e. 46.53 MPa and 53.84 MPa, respectively. Screw stresses were concentrated on the connection between the screw and the artificial lamina, and artificial lamina stresses were concentrated on the spinous root, around the screw hole, and the contact with the vertebral body. Conclusion: An individualized artificial titanium alloy lamina can effectively reduce the range of motion, intradiscal pressure, and annulus fibrosus stress at the surgical segment and adjacent segments. The application of artificial lamina could better preserve the biomechanical properties of the intact lumbar spine and reduce the risk of adjacent segmental disease.

Advanced strategies for constructing interfacial tissues of bone and tendon/ligament.

Enthesis, the interfacial tissue between a tendon/ligament and bone, exhibits a complex histological transition from soft to hard tissue, which significantly complicates its repair and regeneration after injury. Because traditional surgical treatments for enthesis injury are not satisfactory, tissue engineering has emerged as a strategy for improving treatment success. Rapid advances in enthesis tissue engineering have led to the development of several strategies for promoting enthesis tissue regeneration, including biological scaffolds, cells, growth factors, and biophysical modulation. In this review, we discuss recent advances in enthesis tissue engineering, particularly the use of biological scaffolds, as well as perspectives on the future directions in enthesis tissue engineering.

Biomaterials for Interbody Fusion in Bone Tissue Engineering.

In recent years, interbody fusion cages have played an important role in interbody fusion surgery for treating diseases like disc protrusion and spondylolisthesis. However, traditional cages cannot achieve satisfactory results due to their unreasonable design, poor material biocompatibility, and induced osteogenesis ability, limiting their application. There are currently 3 ways to improve the fusion effect, as follows. First, the interbody fusion cage is designed to facilitate bone ingrowth through the preliminary design. Second, choose interbody fusion cages made of different materials to meet the variable needs of interbody fusion. Finally, complete post-processing steps, such as coating the designed cage, to achieve a suitable osseointegration microstructure, and add other bioactive materials to achieve the most suitable biological microenvironment of bone tissue and improve the fusion effect. The focus of this review is on the design methods of interbody fusion cages, a comparison of the advantages and disadvantages of various materials, the influence of post-processing techniques and additional materials on interbody fusion, and the prospects for the future development of interbody fusion cages.

Multi-input adaptive neural network for automatic detection of cervical vertebral landmarks on X-rays.

Cervical vertebral landmark detection is a significant pre-task for vertebral relative motion parameter measurement, which is helpful for doctors to diagnose cervical spine diseases. Accurate cervical vertebral landmark detection could provide reliable motion parameter measurement results. However, different cervical spines in X-rays with various poses and angles have imposed quite challenges. It is observed that there are similar appearances of vertebral bones in different cervical spine X-rays. For this, to fully use these similar features, a multi-input adaptive U-Net (MultiIA-UNet) focusing on the similar local features between different cervical spine X-rays is put forward to do cervical vertebral landmark detection accurately and effectively. MultiIA-UNet used an improved U-Net structure as backbone network combining with the novel adaptive convolution module to better extract changing global features. At training, MultiIA-UNet applied a multi-input strategy to extract features from random pairs of training data at the same time, and then learned their similar local features through a subspace alignment module. We collected a dataset including 688 cervical spine X-rays to evaluate MultiIA-UNet. The results exhibited that our method demonstrated the state-of-the-art performance (the minimum average point to point error of 12.988 pixels). In addition, we further evaluated the effect of these landmark detection results on cervical motion angle parameter measurement. It showed that our method was capable to obtain more accurate cervical spine motion angle parameters (the minimum symmetric mean absolute percentage is 26.969%). MultiIA-UNet could be an efficient and accurate landmark detection method for doctors to do cervical vertebral motion analysis.

Effects of experimental pain on the cervical spine reposition errors.

BACKGROUND: Healthy subjects showed normal variance of cervical spine reposition errors of approximately 2 degrees. Effects of experimental pain on cervical spine reposition errors were unknown; thus, the purpose of this study was to investigate the effects of experimental pain on cervical spine reposition errors. METHODS: A repeated measured study design was applied. Thirty healthy subjects (12 males) were recruited. Reposition errors were extracted from upright cervical positions before and after cervical flexion movement in healthy subjects before and during experimental neck pain. Cervical spine reposition errors were calculated based on anatomical landmarks of each cervical joint. Reposition errors were extracted in degrees as constant errors and absolute errors for further statistical analysis. Repeated measures analysis of variance (RM-ANOVA) was applied to analyse experimental pain effects on either constant errors or absolute errors of different cervical joints. RESULTS: The cervical spine showed non-significant difference in reposition errors regarding the constant errors (P>0.05) while larger reposition errors regarding the absolute errors during experimental pain compared to before experimental pain (P<0.001). In addition, the pain level joint (C4/C5) and its adjacent joints (C3/C4 and C5/C6) indicated larger reposition errors regarding absolute errors (P=0.035, P=0.329 and P=0.103, respectively). CONCLUSIONS: This study firstly investigated the cervical spine reposition errors in experimental neck pain and further found the joints adjacent to the pain level showed larger errors compared to the distant joints regarding absolute errors. It may imply that the larger reposition errors in specific cervical joint indicate probable injury or pain existed adjacent to the joints.

Incorporation of Bone Morphogenetic Protein-2 and Osteoprotegerin in 3D-Printed Ti6Al4V Scaffolds Enhances Osseointegration Under Osteoporotic Conditions.

Osteoporosis is an age-related metabolic disease that results in limited bone regeneration capacity and excessive osteoclast activity. After arthroplasty in patients with osteoporosis, poor interface osseointegration resulting from insufficient bone regeneration ability often leads to catastrophic complications such as prosthesis displacement and loosening and periprosthetic fractures. In this study, we prepared a thermosensitive hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to promote osteogenesis and osteoprotegerin (OPG) to inhibit excessive osteoclast activity. To construct three-dimensional (3D)-printed composite scaffolds for implantation, a hydrogel loaded with drugs was injected into porous Ti6Al4V scaffolds. The 3D-printed composite scaffolds showed good biocompatibility and sustained release of BMP-2 and OPG for more than 20 days. In vitro experiments indicated that composite scaffolds promoted osteogenic differentiation and reduced the osteoclastic activation simultaneously. Remarkably, immunofluorescence staining, micro-CT, histological, and biomechanical tests demonstrated that the sustained release of both BMP-2 and OPG from composite scaffolds significantly improved bone ingrowth and osseointegration in osteoporotic defects. In conclusion, this study demonstrated that the BMP-2- and OPG-loaded 3D-printed composite scaffolds can potentially promote osseointegration for osteoporotic patients after joint replacement.

MiR-140-5p promotes osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing of mice.

MiR-140-5p is high expressed in normal fracture healing, but its specific role and mechanism in tissue-to-bone healing are rarely reported. Therefore, this study investigated the effects of miR-140-5p on tissue-to-bone healing. Clone formation experiment, flow cytometry, Alizarin Red S Staining and Oil Red O Staining were performed to investigate the biological characteristics of mouse embryonic bone marrow mesenchymal stem cells C3H10T1/2. MiR-140-5p mimic was transfected into osteogenic medium (OS)-treated C3H10T1/2 cells to investigate the effects of miR-140-5p on osteogenic differentiation. MiR-140-5p transgenic mouse model and the transgenic fracture model were established, and the effects of miR-140-5p on osteogenic differentiation, bone mineral density (BMD) and bone mass of bone tissues were detected by haematoxylin and eosin staining and computed tomography scan. The expressions of osteocalcin, differentiation-related genes (Runx2, ALP, Spp1 and Bglap3) and miR-140-5p were determined by quantitative real-time polymerase chain reaction. C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells, and its phenotypes including CD44, CD90.1 and Sca-1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR-140-5p promoted the expressions of differentiation-related genes and calcium deposition of OS-treated C3H10T1/2 cells. MiR-140-5p increased the expression of osteocalcin, BMD and bone mass and promoted bone healing of miR-140-5p-transgenic mice with fracture. MiR-140-5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing in mice. SIGNIFICANCE OF THE STUDY: C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells and its phenotypes including CD44, CD90.1 and Sca-1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR-140-5p promoted the expressions of differentiation-related genes and calcium deposition of osteogenic medium-treated C3H10T1/2 cells. MiR-140-5p increased the expression of osteocalcin and bone mineral density and bone mass and promoted bone healing of miR-140-5p-transgenic mice with fracture. Our results showed that miR-140-5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing in mice, which may be a therapeutic target for treating fractures and promoting bone healing.

Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration.

The injury to the spinal cord is among the most complex fields of medical development. Spinal cord injury (SCI) leads to acute loss of motor and sensory function beneath the injury level and is linked to a dismal prognosis. Currently, while a strategy that could heal the injured spinal cord remains unforeseen, the latest advancements in polymer-mediated approaches demonstrate promising treatment forms to remyelinate or regenerate the axons and to integrate new neural cells in the SCI. Moreover, they possess the capacity to locally deliver synergistic cells, growth factors (GFs) therapies and bioactive substances, which play a critical role in neuroprotection and neuroregeneration. Here, we provide an extensive overview of the SCI characteristics, the pathophysiology of SCI, and strategies and challenges for the treatment of SCI in a review. This review highlights the recent encouraging applications of polymer-based scaffolds in developing the novel SCI therapy.

Downregulation of LINC00707 promotes osteogenic differentiation of human bone marrow­derived mesenchymal stem cells by regulating DKK1 via targeting miR­103a­3p.

Human bone marrow­derived mesenchymal stem cells (HBMSCs) have the potential of multidirectional differentiation and self­renewal, which is important for the formation of human bone. It has been reported that long non­coding RNAs (lncRNAs) serve important roles in HBMSC osteogenic differentiation. The current study aimed to investigate the roles of long intergenic non­protein coding RNA 00707 (LINC00707) and microRNA (miR)­103a­3p in the osteogenic differentiation of HBMSCs. Reverse transcription­quantitative PCR (RT­qPCR) was performed to detect the expression levels of LINC00707, miR­103a­3p and osteogenesis­related genes (Alkaline phosphatase, osteocalcin, osteopontin and RUNX family transcription factor 2) in HBMSCs cultured in proliferation medium (PM) and osteogenic medium (OM). Mineralized matrix deposition was measured using Alizarin Red S staining. The protein expression levels of osteogenesis­related genes were detected by western blotting. The relationships between LINC00707, miR­103a­3p and dickkopf WNT signaling pathway inhibitor 1 (DKK1) were predicted using Starbase and TargetScan7.2, and were further assessed with a dual­luciferase reporter assay. After 21 days of cell culture, the results indicated that expression of LINC00707 was downregulated, and those of miR­103a­3p and osteogenesis­related genes were upregulated in OM­cultured HBMSCs. However, there was no significant difference in the aforementioned gene expression levels in PM­cultured HBMSCs. Small interfering (si)LINC00707 increased the deposition of mineralized matrix and promoted the expression levels of osteogenesis­related proteins. Furthermore, miR­103a­3p was predicted to be a target gene of LINC00707, its expression was significantly upregulated by siLINC00707, while overexpression of miR­103a­3p increased the expression levels of osteogenesis­related proteins. DKK1 was also predicted to be a target gene of miR­103a­3p and could inhibit the expression levels of osteogenesis­related proteins, but such effect of DKK1 could be reversed by the miR­103a­3p mimic. In conclusion, the present results suggested that LINC00707 regulated DKK1 expression by targeting miR­103a­3p to regulate osteogenic differentiation.