Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation.

Annulus fibrosus (AF) defect is an important cause of disc re-herniation after discectomy. The self-regeneration ability of the AF is limited, and AF repair is always hindered by the inflammatory microenvironment after injury. Hydrogels represent one of the most promising materials for AF tissue engineering strategies. However, currently available commercial hydrogels cannot withstand the harsh mechanical load within intervertebral disc. In the present study, an innovative triple cross-linked oxidized hyaluronic acid (OHA)-dopamine (DA)- polyacrylamide (PAM) composite hydrogel, modified with collagen mimetic peptide (CMP) and supplied with transforming growth factor beta 1 (TGF-ß1) (OHA-DA-PAM/CMP/TGF-ß1 hydrogel) was developed for AF regeneration. The hydrogel exhibited robust mechanical strength, strong bioadhesion, and significant self-healing capabilities. Modified with collagen mimetic peptide, the hydrogel exhibited extracellular-matrix-mimicking properties and sustained the AF cell phenotype. The sustained release of TGF-ß1 from the hydrogel was pivotal in recruiting AF cells and promoting extracellular matrix production. Furthermore, the composite hydrogel attenuated LPS-induced inflammatory response and promote ECM synthesis in AF cells via suppressing NFκB/NLRP3 pathway. In vivo, the composite hydrogel successfully sealed AF defects and alleviated intervertebral disk degeneration in a rat tail AF defect model. Histological evaluation showed that the hydrogel integrated well with host tissue and facilitated AF repair. The strategy of recruiting endogenous cells and providing an extracellular-matrix-mimicking and anti-inflammatory microenvironment using the mechanically tough composite OHA-DA-PAM/CMP/TGF-ß1 hydrogel may be applicable for AF defect repair in the clinic. STATEMENT OF SIGNIFICANCE: Annulus fibrosus (AF) repair is challenging due to its limited self-regenerative capacity and post-injury inflammation. In this study, a mechanically tough and highly bioadhesive triple cross-linked composite hydrogel, modified with collagen mimetic peptide (CMP) and supplemented with transforming growth factor beta 1 (TGF-ß1), was developed to facilitate AF regeneration. The sustained release of TGF-ß1 enhanced AF cell recruitment, while both TGF-ß1 and CMP could modulate the microenvironment to promote AF cell proliferation and ECM synthesis. In vivo, this composite hydrogel effectively promoted the AF repair and mitigated the intervertebral disc degeneration. This research indicates the clinical potential of the OHA-DA-PAM/CMP/TGF-ß1 composite hydrogel for repairing AF defects.

Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR-124/CILP/TGF-ß.

Immuno-inflammation is highly associated with anabolic and catabolic dysregulation of the extracellular matrix (ECM) in the nucleus pulposus (NP), which dramatically propels intervertebral disc degeneration (IVDD). With the characteristics of tissue remodeling and regeneration, M2c macrophages have attracted great attention in research on immune modulation that rebuilds degenerated tissues. Therefore, we first demonstrated the facilitating effects of M2c macrophages on ECM anabolism of the NP in vitro. We subsequently found that exosomes from M2c macrophages (M2c-Exoss) mediated their metabolic rebalancing effects on the ECM. To determine whether M2c-Exoss served as positive agents protecting the ECM in IVDD, we constructed an M2c-Exos-loaded hyaluronic acid hydrogel (M2c-Exos@HA hydrogel) and implanted it into the degenerated caudal disc of rats. The results of MRI and histological staining indicated that the M2c-Exos@HA hydrogel alleviated IVDD in vivo in the long term. To elucidate the underlying molecular mechanism, we performed 4D label-free proteomics to screen dysregulated proteins in NPs treated with M2c-Exoss. Cartilage intermediate layer protein (CILP) was the key protein responsible for the rebalancing effects of M2c-Exoss on ECM metabolism in the NP. With prediction and verification using luciferase assays and rescue experiments, miR-124-3p was identified as the upstream regulator in M2c-Exoss that regulated CILP and consequently enhanced the activity of the TGF-ß/smad3 pathway. In conclusion, we demonstrated ameliorating effects of M2c-Exoss on the imbalance of ECM metabolism in IVDD via the miR-124/CILP/TGF-ß regulatory axis, which provides a promising theoretical basis for the application of M2c macrophages and their exosomes in the treatment of IVDD.

Metal-organic frameworks functionalized biomaterials for promoting bone repair.

Bone defects induced by bone trauma, tumors and osteoarthritis greatly affect the life quality and health of patients. The biomaterials with numerous advantages are becoming the most preferred options for repairing bone defects and treating orthopedic diseases. However, their repairing effects remains unsatisfactory, especially in bone defects suffering from tumor, inflammation, and/or bacterial infection. There are several strategies to functionalize biomaterials, but a more general and efficient method is essential for accomplishing the functionalization of biomaterials. Possessing high specific surface, high porosity, controlled degradability and variable composition, metal-organic frameworks (MOFs) materials are inherently advantageous for functionalizing biomaterials, with tremendous improvements having been achieved. This review summarizes recent progresses in MOFs functionalized biomaterials for promoting bone repair and therapeutic effects. In specific, by utilizing various properties of diverse MOFs materials, integrated MOFs functionalized biomaterials achieve enhanced bone regeneration, antibacterial, anti-inflammatory and anti-tumor functions. Finally, the summary and prospects of on the development of MOFs-functionalized biomaterials for promoting bone repair were discussed.

Clinical and imaging outcomes of self-locking stand-alone cages and anterior cage-with-plate in three-level anterior cervical discectomy and fusion: a retrospective comparative study.

BACKGROUND: Anterior cervical discectomy and fusion has been considered standard management for cervical myelopathy and radiculopathy. However, the option of using self-locking stand-alone cages or cage-with-plate in three-level anterior cervical discectomy and fusion still remains controversial. The aim of this study was to evaluate the clinical and imaging outcomes of the two procedures in multilevel anterior cervical discectomy and fusion. METHODS: Sixty-seven patients who underwent three-level anterior cervical discectomy and fusion were enrolled in this study, of which 31 patients underwent surgery using self-locking stand-alone cages (group cage) and 36 patients using cage-with-plate (group plate). For the evaluation of clinical outcomes, modified Japanese Orthopedic Association scores, visual analogue scale for neck pain, neck disability index, Odom's criteria and dysphagia status were measured. Imaging outcomes were evaluated by cervical sagittal angle, fusion segmental Cobb's angle, fusion segmental height, range of motion, cage subsidence rate, fusion rate and adjacent segment degeneration. Statistical analyses were performed using the SPSS software (version 19.0). RESULTS: Both groups showed improvement in modified Japanese Orthopedic Association scores, visual analogue scale for neck pain and neck disability index, after surgery, and there was no significant difference between the groups. The occurrence rate of dysphagia is significantly lower in the group cage compared with the group plate (p < 0.05). The postoperative cervical sagittal angle, fusion segmental Cobb's angle, fusion segmental height and cage subsidence rate in the group plate were significantly superior to that in the group cage (p < 0.05). However, the rate of adjacent segment degeneration was significantly lower in the group cage compared with the group plate (p < 0.05). Both groups showed no significant difference in terms of fusion rate (p > 0.05). CONCLUSIONS: The self-locking stand-alone cages are effective, reliable and safe in anterior cervical discectomy and fusion for the treatment of cervical myelopathy and radiculopathy. Self-locking stand-alone cages showed a significantly lower rate of dysphagia and adjacent segment degeneration, while anterior cervical cage-with-plate could provide stronger postoperative stability and maintain better cervical spine alignment.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Metal-Organic Framework Functionalized Bioceramic Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration.

Osteoarthritis (OA) is a degenerative disease that often causes cartilage lesions and even osteochondral damage. Osteochondral defects induced by OA are accompanied by an inflammatory arthrosis microenvironment with overproduced reactive oxygen species (ROS), resulting in the exacerbation of defects and difficulty regenerating osteochondral tissues. Therefore, it is urgently needed to develop osteochondral scaffolds that can not only promote the integrated regeneration of cartilage and subchondral bone, but also possess ROS-scavenging ability to protect tissues from oxidative stress. Herein, zinc-cobalt bimetallic organic framework (Zn/Co-MOF) functionalized bioceramic scaffolds are designed for repairing osteochondral defects under OA environment. By functionalizing Zn/Co-MOF on the 3D-printed beta-tricalcium phosphate (ß-TCP) scaffolds, the Zn/Co-MOF functionalized ß-TCP (MOF-TCP) scaffolds with broad-spectrum ROS-scavenging ability are successfully developed. Benefiting from its catalytic active sites and degradation products, Zn/Co-MOF endows the scaffolds with excellent antioxidative and anti-inflammatory properties to protect cells from ROS invasion, as well as dual-bioactivities of simultaneously inducing osteogenic and chondrogenic differentiation in vitro. Furthermore, in vivo results confirm that MOF-TCP scaffolds accelerate the integrated regeneration of cartilage and subchondral bone in severe osteochondral defects. This study offers a promising strategy for treating defects induced by OA as well as other inflammatory diseases.

Oblique lateral interbody fusion stand-alone vs. combined with percutaneous pedicle screw fixation in the treatment of discogenic low back pain.

Objective: Oblique lateral interbody fusion (OLIF) has unique advantages in the treatment of discogenic low back pain (DBP). However, there are few studies in this area, and no established standard for additional posterior internal fixation. The purpose of this study was to investigate the efficacy of OLIF stand-alone vs. combined with percutaneous pedicle screw fixation (PPSF) in the treatment of DBP. Methods: This retrospective case-control study included forty patients. All patients were diagnosed with DBP by discography and discoblock. Perioperative parameters (surgery duration, blood loss, and muscle damage), complications, Visual analog scale (VAS), and Oswestry Disability Index (ODI) were assessed. Imaging data including cage subsidence, cage retropulsion, fusion rate, and adjacent spondylosis degeneration (ASD) were analyzed. Results: There were 23 patients in the OLIF stand-alone group and 17 patients in the OLIF + PPSF group. The mean surgery duration, blood loss, and muscle damage in the OLIF stand-alone group were significantly better than those in the OLIF + PPSF group (P < 0.05). However, there was no significant difference in the average hospitalization time between the two groups (P > 0.05). There was no significant difference in the VAS and ODI scores between the two groups before surgery (P > 0.05), and VAS and ODI scores significantly improved after surgery (P < 0.05). The VAS and ODI scores in the OLIF stand-alone group were significantly better than those in the OLIF + PPSF group at 1 month (P < 0.05), While there was no significant difference between the two groups at 12 months and last follow up (P > 0.05). At the last follow-up, there was no significant difference in cage subsidence, fusion rate, ASD and complication rate between the two groups (P > 0.05). Conclusion: OLIF stand-alone and OLIF + PPSF are both safe and effective in the treatment of DBP, and there is no significant difference in the long-term clinical and radiological outcomes. OLIF stand-alone has the advantages of surgery duration, blood loss, muscle damage, and early clinical effect. More clinical data are needed to confirm the effect of OLIF stand-alone on cage subsidence and ASD. This study provides a basis for the clinical application of standard DBP treatment with OLIF.

Diagnosis and treatment of left ureteral injury as a rare complication of oblique lumbar interbody fusion surgery: a case report and literature review.

BACKGROUND: Oblique lumbar interbody fusion (OLIF) surgery has been performed as a minimally invasive lateral lumbar fusion technique in recent years. Reports of operative complications of OLIF are limited, and there are fewer reports of ureteral injuries. CASE PRESENTATION: A 62-year-old Chinese woman diagnosed with "lumbar spondylolisthesis (L4 forward slip, I degree)" underwent OLIF treatment. The surgical decompression process was smooth, and the cage was successfully placed. After the expansion sleeve of OLIF was removed, clear liquid continuous outflow from the peritoneum was found. The patient was diagnosed with a ureteral injury. The urological surgeon expanded the original incision, and left ureteral injury anastomosis and ureteral stent implantation were performed. The patient was changed to the prone position and a percutaneous pedicle screw was placed in the corresponding vertebral body. The patient was indwelled with a catheter for 2 weeks, and regular oral administration of levofloxacin to prevent urinary tract infection. After 2 months, the double J tube was removed using a cystoscope. One year after surgery, the symptoms of lumbar back were significantly improved, and there were no urinary system symptoms. However, the patient needed an annual left ureter and kidney B-ultrasound. CONCLUSION: Ureteral injury is a rare complication and is easily missed in OLIF surgery. If the diagnosis is missed, the consequences can be serious. Patients should undergo catheterization before the operation and hematuria should be observed during the operation. We emphasize the careful use of surgical instruments to prevent intraoperative complications. In addition, after withdrawing the leaf in the operation, it is necessary to carefully observe whether a clear liquid continues to leak. If ureteral injury is found, one-stage ureteral injury repair operation should be performed to prevent ureteral stricture.

Galectin-1 deletion in mice causes bone loss via impaired osteogenic differentiation potential of BMSCs.

Bone formation is dependent on the osteoblasts which are differentiated from bone marrow stromal cells (BMSCs). In addition to potent proliferation, self-renewal, and pluripotent differentiation, BMSCs have been extensively studied due to their low immunogenicity and immunomodulatory effects. Recently, galectin-1 (Gal-1) has been proposed as a potent mediator of immunomodulatory properties of BMSCs. Previous study demonstrated that Gal-1 showed age-related decline in mice serum and serum Gal-1 was positively associated with bone mass in mice. The current study makes attempts to elucidate the functional role of Gal-1 in skeletal system by investigating the regulation of Gal-1 expression during BMSCs osteogenic differentiation and the molecular mechanisms underlying the effects of Gal-1 on BMSCs osteogenic differentiation. In Gal-1 null (-/-) mice, bone loss was observed due to bone formation attenuation. In in vitro experiments, Gal-1 supported the osteogenic differentiation of BMSCs by binding to CD146 to activate Lrp5 expression and Wnt/ß-catenin signaling pathway. Meanwhile, there was positive feedback regulation via Wnt/ß-catenin signaling to maintain Gal-1 high-level expression during osteogenic differentiation of BMSCs. More importantly, Gal-1 down-regulation in BMSCs and attenuation of osteogenic differentiation potential of BMSCs were observed in aged mice compared with young mice. Gal-1 over-expression could enhance osteogenic differentiation potential of aged BMSCs. Our study will benefit not only for deeper insights into the functional role of Gal-1 but also for finding new targets to modulate BMSCs osteogenic differentiation.

Neuroprotective Effects of Curcumin against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Cultured Primary Rat Astrocyte by Improving Mitochondrial Function and Regulating the ERK Signaling Pathway.

Objectives: Curcumin (Cur) is a natural polyphenol isolated from turmeric and has potent anti-inflammatory and antioxidant activities. This study aimed to explore the effects and possible mechanisms of curcumin on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in cultured rat astrocyte primary cells. Methods: After screening for effective doses, the cultured rat astrocyte primary cells were divided into three groups: control, OGD/R, and OGD/R + curcumin (10 µM, 20 µM, and 40 µM). Cell viability was detected using CCK8 assays. The level of malondialdehyde and superoxide dismutase activity was determined using commercial kits. The endothelial nitric oxide synthase and adenosine triphosphate concentrations were determined by enzyme-linked immunosorbent assay. The mRNA levels of the inflammatory indexes interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1ß were evaluated by quantitative reverse-transcription polymerase chain reaction. Annexin V-fluorescein isothiocyanate/propidium iodide was used to detect apoptosis. JC-1 was used to assess the mitochondrial membrane potential. The protein expression of apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), and cleaved caspase 3), mitochondria-related proteins (dynamin-related protein 1 (DRP1), phosphorylated DRP1 (p-DRP1), and mitofusin 2), and essential proteins of the extracellular signal-regulated kinase (ERK) signaling pathway (ERK1/2, p-ERK1/2) were analyzed by western blot. Results: Our data indicated that curcumin reversed OGD/R-induced cell viability loss, oxidative stress, inflammatory cytokine production, and cell apoptosis in a dose-dependent manner. Furthermore, curcumin attenuated OGD/R-induced mitochondrial dysfunction and ERK1/2 phosphorylation in a dose-dependent manner. Conclusions: Curcumin protected against OGD/R-induced injury in rat astrocyte primary cells through improving mitochondrial function and regulating the ERK signaling pathway.

Morphology of Herniated Disc as a Predictor for Outcomes of Posterior Percutaneous Full-endoscopic Cervical Discectomy in Treating Cervical Spondylotic Radiculopathy.

OBJECTIVE: To quantitively characterize the morphology of cervical disc herniation (CDH) causing cervical spondylotic radiculopathy (CSR) and investigate whether the morphological features of CDH are associated with clinical outcomes in CSR patients treated by posterior percutaneous full-endoscopic cervical discectomy (PPECD). METHODS: This is a single-center retrospective study. Eighty-seven PPECD-treated patients meeting the inclusion criteria were included between May 2017 and May 2019. Based on preoperative T2-weighted magnetic resonance imaging (MRI), we designed and measured six morphological parameters of CDH for all patients to reflect its relative position to cervical spinal cord and protruding degree: DC-SC distance from the center of disc (DC) and the center of spinal cord (SC); DC-DP distance from the center of cervical disc (DC) to the peak of herniation (DP); internal diameter of the disc; axial length of CDH; central angle of CDH formed by central axes of CDH and spinal cord; the modified index of CDH. We recorded general information, neck disability index (NDI) scores, visual analog scale (VAS) scores of neck and arm of all patients preoperatively and postoperatively at 1-year follow-up. The association of preoperative general variables and morphological parameters with clinical outcomes were explored by utilizing logistic regression and receiver operating characteristic curve (ROC) analysis. RESULTS: The preoperative neck-VAS, arm-VAS, and NDI were significantly decreased after PPECD and remained at a low value at follow-up. In regards to the morphological parameters of CDH, the mean value of DC-SC distance, DC-DP distance, internal diameter of the disc, axial length of CDH, central angle of CDH, and modified index of CDH were 1.61 ± 0.30 cm, 1.66 ± 0.32cm, 1.04 ± 0.21 cm, 0.63 ± 0.19cm, 39.38° ± 11.94°, and 0.39 ± 0.24, respectively. For patients grouped by difference in the recovery rate of NDI and arm-VAS (excellent improved group, EI; and limited improved group, LI), there were no differences in the age, gender, surgical segments, and morphological parameters, except for the central angle of CDH. According to binary logistic regression analysis, only the preoperative central angle of CDH was significantly associated with postoperative NDI recovery (odds ratio: 0.873; 95% confidence interval: 0.819-0.931, P = 0.002). ROC analysis showed the optimal cut-off value of the central angle of CDH for predicting the postoperative improvement of functional outcomes is 33.788°. CONCLUSION: Preoperative morphology of CDH is related to the outcomes of CSR patients after PPECD. Patients with a large central angle of CDH (>33.788°) have more likelihood of ameliorating neurological symptoms of CSR. There is the potential to select the central angle of CDH as a predictor for outcomes of PPECD in treating CSR.

Marine-Derived Collagen as Biomaterials for Human Health.

Collagen is a kind of biocompatible protein material, which is widely used in medical tissue engineering, drug delivery, cosmetics, food and other fields. Because of its wide source, low extraction cost and good physical and chemical properties, it has attracted the attention of many researchers in recent years. However, the application of collagen derived from terrestrial organisms is limited due to the existence of diseases, religious beliefs and other problems. Therefore, exploring a wider range of sources of collagen has become one of the main topics for researchers. Marine-derived collagen (MDC) stands out because it comes from a variety of sources and avoids issues such as religion. On the one hand, this paper summarized the sources, extraction methods and characteristics of MDC, and on the other hand, it summarized the application of MDC in the above fields. And on the basis of the review, we found that MDC can not only be extracted from marine organisms, but also from the wastes of some marine organisms, such as fish scales. This makes further use of seafood resources and increases the application prospect of MDC.

Recent Trends in the Development of Bone Regenerative Biomaterials.

The goal of a biomaterial is to support the bone tissue regeneration process at the defect site and eventually degrade in situ and get replaced with the newly generated bone tissue. Biomaterials that enhance bone regeneration have a wealth of potential clinical applications from the treatment of non-union fractures to spinal fusion. The use of bone regenerative biomaterials from bioceramics and polymeric components to support bone cell and tissue growth is a longstanding area of interest. Recently, various forms of bone repair materials such as hydrogel, nanofiber scaffolds, and 3D printing composite scaffolds are emerging. Current challenges include the engineering of biomaterials that can match both the mechanical and biological context of bone tissue matrix and support the vascularization of large tissue constructs. Biomaterials with new levels of biofunctionality that attempt to recreate nanoscale topographical, biofactor, and gene delivery cues from the extracellular environment are emerging as interesting candidate bone regenerative biomaterials. This review has been sculptured around a case-by-case basis of current research that is being undertaken in the field of bone regeneration engineering. We will highlight the current progress in the development of physicochemical properties and applications of bone defect repair materials and their perspectives in bone regeneration.

Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a promising treatment. Injectable ECM hydrogels have good biological activity and in-situ gelatinization. However, its biomechanics and stability are insufficient to provide adequate mechanical support for intervertebral discs and to maintain the long-term differential stimulus for seeded stem cells. In our study, we developed genipin cross-linked decellularized nucleus pulposus hydrogel (GDH) as delivery system. We evaluated the mechanical properties, stability, biocompatibility, and differentiation induction of GDH cross-linked with different concentrations of genipin in vitro. The GDH-loaded adipose-derived mesenchymal stem cells (ADSCs) (GDHA) were injected into the rat degenerated coccygeal intervertebral disc. The effect of intervertebral disc regeneration in vivo was evaluated. The results showed that GDH with 0.02% of genipin had similar elastic modulus to human nucleus pulposus, good biocompatibility, and inducibility of expressing NP-related genes. In vivo studies showed that GDHA improved the survival of ADSCs and improved the intervertebral height, MRI index, and histological grading score. In conclusion, GDH, as an outstanding bio-hydrogel cell delivery system, has the therapeutic potential for retarding IDD.

Vesselplasty for the treatment of osteoporotic vertebral compression fractures with peripheral wall damage: a retrospective study.

STUDY DESIGN: A retrospective study. OBJECTIVE: The clinical efficacy of vertebroplasty and kyphoplasty treating osteoporotic vertebral compression fractures (OVCF) has been widely recognized in recent years. However, there are also disadvantages of bone cement leakage (BCL), limited correction of kyphosis and recovery of vertebral height. Nowadays, in view of these shortcomings, vesselplasty has been widely used in clinical practice. The objective of this study is to assess its clinical effect and application value for the treatment of OVCF with peripheral wall damage. METHODS: 62 patients (70 vertebrae) treated for OVCF with peripheral wall damage using vesselplasty retrospectively reviewed. The data collection included operation time, volume of bone cement, relevant surgical complications, visual analog scale (VAS), Oswestry disability index (ODI), vertebral body height and kyphosis Cobb angle. RESULTS: The volume of bone cement was 3-8 (5.3 ± 1.3) ml. There were 3 vertebrae of BCL (4.3%). VAS and ODI at different time points after operation were decreased compared with before operation (all p < 0.05). There were no statistical differences between VAS or ODI at different postoperative time points (p > 0.05). Vertebral body height and Cobb angle at different time points after operation were improved compared with before operation (all p < 0.05). There were no statistical differences between vertebral body height or Cobb angle at different postoperative time points (all p > 0.05). CONCLUSIONS: Vesselplasty may reduce the risk of BCL and better control the dispersion of bone cement in the treatment of OVCF. It relieves pain, restores vertebral body height and corrects kyphosis, especially in OVCF with peripheral wall damage. Therefore, vesselplasty is safe and worthy of clinical application.

Osteopontin sequence modified mesoporous calcium silicate scaffolds to promote angiogenesis in bone tissue regeneration.

Sufficient blood supply remains the key issue to be addressed for an optimal performance of implanted bone tissue engineering scaffolds. Host vessel invasion is limited to a depth of only several hundred micrometers from the scaffold/host interface. In this study, an osteopontin sequenced polypeptide SVVYGLR was grafted into/onto mesoporous calcium silicate (MCS) and then 3D-printed into scaffolds. The peptide motifs can be accessed on the scaffold surfaces and released as well. In vitro studies of human umbilical vein endothelial cells (HUVECs) indicated enhanced cell adhesion and vascular-like structure formation on MCS-SVVYGLR scaffolds. At the same time, human bone marrow stromal cells (hBMSCs) showed enhanced osteogenic differentiation capability and higher expression levels of angiogenic genes and proteins as well. The results of in vivo radial defect repair tests of rabbits showed that more tubular vessels formed throughout the whole MCS-SVVYGLR scaffolds, and therefore, a more homogeneous new bone formation pattern was obtained on MCS-SVVYGLR scaffolds instead of a peripheral bone growth pattern on pure MCS scaffolds by Micro-CT and tissue staining techniques over 3 months. Relative gene and protein expressions in PI3K/AKT and ERK1/2 pathways suggested that the SVVYGLR motif on the MCS scaffold surface could initiate the PI3K/AKT signaling pathway and up-regulate ERK1/2 expression, which positively stimulated VEGF expression, to improve angiogenesis.

An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells.

In contrast to the early acting bone morphogenetic protein 2, bone morphogenetic protein 7 (BMP7) plays a decisive role mainly in the late stages of bone formation. To overcome deactivation and degradation of expensive BMP7, we designed a novel long-acting BMP7 release system based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) nanoparticles to enable the induction of osteogenic differentiation in human adipose mesenchymal stem cells (ADSCs). In order to improve the encapsulation efficiency of BMP7 and avoid damage by organic solvents, BMP7 was modified and protected using the biosurfactant soybean lecithin. In an in vitro test, BMP7-soybean lecithin-P34HB nanoparticles (BMP7-SPNPs) showed a short initial burst of BMP7 release during the first 24h, followed by a steady increase to a cumulative 80% release in 20days. Compared with the rapid release of control P34HB nanoparticles without soybean phospholipids loaded with BMP7 without soybean lecithin, BMP7-SPNPs significantly reduced the initial burst of BMP7 release and stabilized the content of BMP7 to allow long-term osteogenic differentiation during the late phase of bone development. Human ADSCs treated with BMP7-SPNPs showed higher alkaline phosphatase activity and higher expression levels of genetic markers of osteogenic differentiation compared with the control group. Thus, the results indicate that BMP7-SPNPs can be used as a rapid and long-acting BMP7 delivery system for osteogenic differentiation.

Removal of calcified lumbar disc herniation with endoscopic-matched ultrasonic osteotome - Our preliminary experience.

Objective: To evaluate the clinical efficacy, practicability, and safety of an ultrasonic osteotome for percutaneous transforaminal endoscopic discectomy (PTED) in patients with calcified lumbar disc herniation (CLDH).Methods: A total of 25 CLDH patients who underwent PTED at our department between December 2017 and August 2018 were analyzed retrospectively. Post-operative lumbar spine CT was used to evaluate residual calcification. Efficacy was evaluated by pre- and post-operative with the pain visual analog scale (VAS), Oswestry disability index (ODI), and the Modified MacNab Scale; the incidence of intra- and postoperative complications was also analyzed.Results: All procedures were successfully completed and none of the patients was lost to follow-up. Postoperative CT verified the successful removal of calcified protrusions. VAS and ODI scores improved significantly after surgery. Based on the Modified MacNab scale, >90% patients achieved good or excellent outcomes. There were no complications such as dural tear and infection. Seven patients had varying degrees of postoperative dysesthesia. One patient experienced recurrence of herniation within 1 week after operation; successful recovery was achieved after repeat PTED.Conclusions: Use of this ultrasonic osteotome for PTED facilitated effective removal of calcified disc protrusion, relieved nerve compression, and protected the adjacent neurovascular tissues. The instrument may help expand the indications for endoscopic surgery and avoid open surgery for some CLDH patients.

Preliminary studies on the anti-osteoporosis activity of Baohuoside I.

The aim of the present study was to investigate the anti-osteoporotic activity of Baohuoside I, an active component of Herba Epimedii. Effects of Baohuoside I on the differentiation of BMSCs and the formation of adipocytes were evaluated using alkaline phosphatase staining and methylene blue staining method, respectively. Osteoporosis model was established in ovariectomized rats prior to the measurement of the serum SOD and MDA levels as well as the expression of inflammatory cytokines protein in the rats' tissues after treatment with Baohuoside I using ELISA assay kits. The estrogen-like effect of Baohuoside I was also measured on HeLa cells. The positive rates of ALP staining in Baohuoside I groups were significantly higher (p < 0.01) compared with the normal group, with no obvious adipocyte formation observed in the groups that received Baohuoside I treatments. The levels of inflammatory markers (IL-1ß, TNF-α, IL-6 and IL-8) in the treated groups were significantly lower (p < 0.05) than in the model group. Likewise, the treated groups exhibited a significantly higher (p < 0.05) serum levels of MDA compared with the model group, while SOD levels were markedly lower (p < 0.05) in a dose-dependent fashion. Baohuoside I showed no estrogen-like effect on HeLa cells upon treatment with the drug. Collectively, these results indicated that the anti-osteoporotic activity of Baohuoside I could be related to the induction of BMSCs differentiation into osteoblasts coupled with the inhibition of adipocyte formation, regulation of immune functions, and antioxidant activity.

Effect of needle diameter, type and volume of contrast agent on intervertebral disc degeneration in rats with discography.

PURPOSE: Discography can increase disc degeneration, but the influence of different discography variables on the degeneration of discs has not been reported. The aim of this study was to investigate the effects of discography variables of needle diameter, type of contrast agent and volume of contrast agent on disc degeneration. METHODS: Three separate experiments examined needle diameter, and type and volume of contrast agent. Coccygeal discs (Co7-10) adult male rats were used. X-rays were used to detect the disc height degeneration index at 1, 2 and 4 weeks after the procedure. MRI was used to study the changes in the disc structure and the signal intensity of IVD 2 and 4 weeks after the procedure. Disc water content and histology were measured at 4 weeks after the procedure. RESULTS: A 21-g needle significantly increased disc degeneration when compared with the 30-g needle as detected by X-ray, MRI, disc water content and histology (P < 0.05). Two microlitres of iodine significantly decreased the disc MRI signal and water content at 4 weeks compared with the same volume of normal saline (P < 0.05). Three microlitres of iodine significantly increased disc degeneration when compared with 2 µl iodine, as detected by X-ray, MRI, disc water content and histology at 4 weeks (P < 0.05). CONCLUSION: To reduce disc degeneration after discography, it may be best to choose a smaller needle size, minimize the use of contrast agent and use non-ionic contrast agents with osmotic pressure similar to the intervertebral disc. These slides can be retrieved under Electronic Supplementary Material.