BACKGROUND:Scholars are stil looking for ideal bone tissue-engineered scaffolds, and three-dimensional (3D) printing technology is a novel construction method. In the meanwhile, bone extracel ular matrix is becoming a hotspot in osteogenic induction. OBJECTIVE:To construct the polycaprolactone/bone extracel ular matrix scaffold using 3D printing technology and co-culture method, and to detect its osteogenic property. METHODS:216 3D-printed polycaprolactone scaffolds were divided into group A (96 pores, n=72) and group B(48 pores, n=144). Passage 5 bone marrow mesenchymal stem cel s from Sprague-Dawley rats were seeded onto the two kinds of polycaprolactone scaffolds, and the group A was used for alizarin red staining and Masson staining, while the group B for col agen and glycosaminoglycan detection at 1, 2 and 3 weeks of incubation. Afterwards, the scaffolds at 1, 2 and 3 weeks of culture were decel ularized and labeled as groups AE1, AE2, AE3, BE1, BE2 and BE3. Then passage 5 bone marrow mesenchymal stem cel s from Sprague-Dawley rats were seeded onto each scaffold again, and the former three groups underwent alizarin red staining, and the latter three were used for calcium, alkaline phosphatase activity and DNA quantitative analysis at 1, 2 and 3 weeks of culture. RESULTS AND CONCLUSION:Masson staining, glycosaminoglycan and hydroxyproline quantitative analysis showed that the extracel ular matrix on the composite scaffold increased with time. Alkaline phosphatase activity revealed that the composite scaffold had a significantly stronger osteogenic differentiation than the normal polycaprolactone scaffold (P<0.05). Alizarin red staining and calcium quantitative analysis showed that the mineralization of the composite scaffold was more obvious than that of the normal polycaprolactone scaffold (P<0.05), but the total DNA analysis did not differ significantly between scaffolds. These results suggest that the composite scaffold with extracel ular matrix is constructed successful y using the 3D technology and co-culture method and exhibits a better osteoinductivity.

Objective To investigate the mRNA expression of IKB kinase (IKK-α) and interferon-α (IFN-α) in the peripheral blood leukocytes of patients with systemic lupus erythematosus (SLE), and to explore the role of IKK-α in the production of IFN-α in SLE patients. Methods SYBR green dye I based real-time quantitative PCR was used to detect the mRNA expression levels of IKK-α and IFN-α in the peripheral blood leucocytes of SLE patients and healthy controls. Serum levels of IFN-α were measured with ELISA method. Results IKK-α mRNA expression levels in SLE patients were significantly higher than those of normal controls (P<0.05). IKK-α mRNA expression levels in SLE patients with active disease were significantly higher than patients with stable disease (P<0.01). IFN-α mRNA expression level in SLE patients was significantly lower than that of the normal controls (P<0.01). IFN-α mRNA expression levels in SLE patients with active disease were significantly higher than patients with stable disease (P<0.01). Serum levels of IFN-α in SLE patients with active disease was significantly higher than that of the normal controls and patients with stable disease (P<0.05). The anti-dsDNA antibody correlated positively, and complement C3 correlated negatively with serum concentration of IFN-α. IKK-α mRNA expression levels in SLE patients correlated positively with serum concentration of IFN-α. Conclusion IKK-α correlates positively with serum concentration of IFN-α. The IFN-α level is significantly correlated with disease activity, This suggests that IKK-α may play an important role in the pathogenesis of SLE.

Objective To evaluate the bone repair capacity ofpolylactic acid-polyglycolic acid copolymer (PLGA)/collagen type Ⅰ (CoI) microspheres combined with BMSCs after being injected in intertrochanteric bone defect of osteoporotic female rats.Methods Prepared PLGA microspheres.The microspheres were coated with Col.BMSCs of the third passage were cultured with PLGA/CoI microspheres.Forty 3-month-old female SD rats were ovariectomized to establish osteoporotic animal models.The osteoporotic rats were randomly divided into 5 groups,including SHAM group,PBS group,Cell group,MS group and Cell+ MS group.There were 8 rats in each group.Different material was injected into the intertrochanteric bone defect site which was made with electric drill.Four rats of each group were sacrificed at 1 month and 3 months post-operation.The fenora were taken to measure the intertrochanteric bone mineral density (BMD) with DEXA and evaluate trabecular stucture with Micro CT.Results After 7 days of coculture,BMSCs seeded on PLGA/CoI microspheres had nice adherance and proliferation.There was no difference of BMC and BMD among all groups at 1 month post-operation.Tb.Th of Cell+MS group was higher than that of PBS group and MS group at 1 month post-operation.％Tb.Ar of Cell+MS group was higher than that of Cell group and MS group at 1 month post-operation.Tb.Sp of Cell+MS group had a tendence to decrease compared with other groups but there was no statistical difference at 1 month post-operation.After 3 months of operation,the BMC of Cell+MS group had a tendence to increase compared with that of PBS group and MS group but showed no statistical difference.BMD and Tb.Th of Cell+MS group was higher than those of other groups.％Tb.Ar of Cell+MS group was higher than that of SHAM group and PBS group.Tb.Sp of Cell+MS group had a tendence to reduce compared with other groups but showed no statistical difference.Conclusion The bone defect of osteoporotic site can be repaired 1 month after the injection of the PLGA/CoI microspheres combined with BMSCs.The trabecular reconstruction and bone quality of osteoporotic site can be improved 3 months after the injection.

ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)％-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)％-year,P＜0.05] and that of the MTX only group[(5.08±11.10)％-year,P＜0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P＜0.05).The ACR20 response rate of the combined group(80.4％) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1％,P＜0.05) and the MTX group(56.7％,P＜0.01 ).The ACRS0 response rate of the combined group(53.6％) was significantly higher than that of the MTX group(30.8％,P＜0.01 ).The ACR70 response rate of the combined group was 27.7％,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8％) and MTX group (7.7％,P＜0.05or P＜0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9％) was significantly high than that of the MTX group(28.8％,P＜0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.

Objective To evaluate the efficacy and safety profile of a recombinant human tumor necrosis factor receptor: Fc fusion protein in ankylosing spondylitis (AS). Methods This was a multicenter,randomized, double-blind, placebo-controlled trial in the first 6 weeks and then followed by an open-labeled trial in the next 6 weeks. One hundred and forty-three patients of active AS were randomly assigned to receive 25 mg twice-weekly subcutaneous injections of rhTNFR:Fc or placebo for 6 weeks. The primary endpoint was proportion of ASAS20 responders at week 6. The secondary endpoints were the proportion of subjects achieving a BASDAI 20%, BASDAI 50% and BASDAI 70% improvement at week 6. Other secondary endpoints, related to reducing signs and symptoms of AS and improving range of motion and physical function, were evaluated.Results Treatment with rhTNFR:Fc resulted in significant improvement. At 6 weeks, 68% of the 71 patients in the rhTNFR: Fc group had a treatment response, as compared with 28% of those in the placebo group(P＜0.01). Improvements over base-line values for other measures of disease activity were significantly greater in the rhTNFR:Fc group, rhTNFR:Fc was well tolerated, The most frequently treatment related adverse event was injection site reaction. Conclusion rhTNFR:Fc has demonstrated consistent evidence of efficacy and is well tolerated in the treatment of active AS.

Purpose: Whether craniospinal irradiation (CSI) could be replaced by limited-field radiation in non-metastatic bifocal germinoma remains controversial. We addressed the issue based on the data from our series and the literature. Methods: Data from 49 patients diagnosed with non-metastatic bifocal germinoma at our hospital during the last 10 years were collected. The Pediatric Quality of Life Inventory 4.0 was used to evaluate health-related quality of life (HRQOL). Additionally, 81 patients identified from the literature were also analyzed independently. Results: In our cohort, 34 patients had tumors in the sellar/suprasellar (S/SS) plus pineal gland (PG) regions and 15 in the S/SS plus basal ganglia/thalamus (BG/T) regions. The median follow-up period was 52 months (range, 10 to 134 months). Our survival analysis showed that patients treated with CSI (n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS; p=0.540), but better DFS than those treated with focal radiotherapy (FR; n=3, p=0.016). All 81 patients from the literature had tumors in the S/SS+PG regions. Relapses were documented in 4/45 patients treated with FR, 2/17 treated with whole-ventricle irradiation, 0/4 treated with WBRT, and 1/15 treated with CSI. Survival analysis did not reveal DFS differences between the types of radiation field (p=0.785). HRQOL analysis (n=44) in our cohort found that, compared with S/SS+PG germinoma, patients with BG/T involvement had significantly lower scores in social and school domains. However, HRQOL difference between patients treated with CSI and those not treated with CSI was not significant. Conclusion In patients with non-metastatic bifocal germinoma, it is rational that CSI could be replaced by limited-field radiation. HRQOL in patients with BG/T involvement was poorer.

Three-dimensional (3D) printing technology is characterized by "inside-out" stack manufacturing. Compared with conventional technologies, 3D printing has the advantage of personalization and precision. Therefore, the shape and internal structure of the scaffolds made by 3D printing technology are highly biomimetic. Besides, 3D bioprinting can precisely deposit the biomaterials, seeding cells and cytokines at the same time, which is a breakthrough in printing technique and material science. With the development of 3D printing, it will make great contributions to the reconstruction of vertebrae and intervertebral disc in the future.
Biocompatible Materials ; Bioprinting ; Humans ; Intervertebral Disc ; growth & development ; Printing, Three-Dimensional ; Tissue Engineering ; methods ; Tissue Scaffolds

Bone cement-augmented pedicle screw system demonstrates great efficacy in spinal disease treatments. However, the intrinsic drawbacks associated with clinically used polymethylmethacrylate (PMMA) cement demands for new bone cement formulations. On the basis of our previous studies, a novel injectable and biodegradable calcium phosphate-based nanocomposite (CPN) for the augmentation of pedicle screw fixation was systematically evaluated for its surgical feasibility and biomechanical performance by simulated and animal osteoporotic bone models, and the results were compared with those of clinical PMMA cement. ASTM-standard solid foam and open-cell foam models and decalcified sheep vertebra models were employed to evaluate the augmentation effects of CPN on bone tissue and on the cement-injected cannulated pedicle screws (CICPs) placed in osteoporotic bone. Surgical factors in CICPs application, such as injection force, tapping technique, screw diameter, and pedicle screw loosening scenarios, were studied in comparison with those in PMMA. When directly injected to the solid foam model, CPN revealed an identical augmentation effect to that of PMMA, as shown by the similar compressive strengths (0.73 ± 0.04 MPa for CPN group vs. 0.79 ± 0.02 MPa for PMMA group). The average injection force of CPN at approximately 40-50 N was higher than that of PMMA at approximately 20 N. Although both values are acceptable to surgeons, CPN revealed a more consistent injection force pattern than did PMMA. The dispersing and anti-pullout ability of CPN were not affected by the surgical factors of tapping technique and screw diameter. The axial pullout strength of CPN evaluated by the decalcified sheep vertebra model revealed a similar augmentation level as that of PMMA (1351.6 ± 324.2 N for CPN vs. 1459.7 ± 304.4 N for PMMA). The promising results of CPN clearly suggest its potential for replacing PMMA in CICPs augmentation application and the benefits of further study and development for clinical uses.