Hexapeptide induces M2 macrophage polarization via the JAK1/STAT6 pathway to promote angiogenesis in bone repair.

Angiogenesis is essential for successful bone defect repair. In normal tissue repair, the physiological inflammatory response is the main regulator of angiogenesis through the activity of macrophages and the cytokines secreted by them. In particular, M2 macrophages which secrete high levels of PDGF-BB are typically considered to promote angiogenesis. A hexapeptide [WKYMVm, (Trp-Lys-Tyr-Met-Val-D-Met-NH2)] has been reported to modulate inflammatory activities. However, the underlying mechanisms by which WKYMVm regulates macrophages remain unclear. In this study, the possible involvement by which WKYMVm induces the polarization of macrophages and affects their behaviors was evaluated. In vitro results showed that macrophages were induced to an M2 rather than M1 phenotype and the M2 phenotype was enhanced by WKYMVm through activation of the JAK1/STAT6 signaling pathway. It was also found that WKYMVm played an important role in the PDGF-BB production increase and proangiogenic abilities in M2 macrophages. Consistent with the results in vitro, the elevated M2/M0 ratio induced by WKYMVm enhanced the formation of new blood vessels in a femoral defect mouse model. These findings suggest that WKYMVm could be a promising alternative strategy for angiogenesis in bone repair by inducing M2 macrophage polarization.

The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway.

The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast-related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)-1ß and TNF-α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL- and lipopolysaccharide (LPS)-induced osteoclast differentiation and maturation in vitro and alleviates LPS-induced osteolysis in animal models. WKYMVm down-regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF-kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis.

Underwater target laser polarization suppression scattering detection technology and verification.

The underwater laser polarization detection technology integrates the polarization characteristics of light into the detection and identification of underwater targets. Addressing the challenge of poor accuracy in identifying targets in strong underwater scattering environments, this article proposes an overall scheme for a laser polarization underwater detection device that suppresses scatter using polarized pulse signals. By overcoming key technological barriers in the design of polarization-preserving optical detection systems and utilizing the method of differential amplitude to measure polarization, a laser polarization underwater detection device was developed and underwater polarization detection experiments were conducted, achieving precise detection of underwater targets. The results indicate that the underwater detection device we designed has a root mean square error of less than 5.7% to detect the polarization of the target, demonstrating the accuracy and precision of the underwater detection device.

Shengjihuayu formula ameliorates the oxidative injury in human keratinocytes via blocking JNK/c-Jun/MMPs signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The reactive oxygen species (ROS) surge in the chronic wound tissue of diabetic ulcers (DUs) aggravates the inflammatory response. The oxidative stress state during inflammation will exacerbate inflammation and cause tissue damage, resulting in prolonged wound healing. Shengjihuayu Formula (SJHYF) is a renowned Chinese medicine prescription for treating chronic wounds in diabetic ulcers. Growing clinical evidence has demonstrated that SJHYF exhibits superior therapeutic efficacy and has a favorable safety profile. However, the underlying mechanisms by which SJHYF ameliorates oxidative damage under pathological conditions of DUs remain unclear. OBJECTIVE: To investigate the cytoprotective properties of SJHYF on hydrogen peroxide (H2O2)-induced cell damage in human HaCaT keratinocytes and to explore its potential targets and molecular pathways in treating DUs using RNA-seq. METHODS: HaCaT cells were incubated with H2O2 for 24 h to construct an oxidative stress cell model. Cell viability and proliferation were measured using the MTT and EdU assays, respectively. Cell migration was assessed using the scratch assay, and the fluorescence intensity of ROS was measured using the DCFH-DA probe. The chemical components of SJHYF were analyzed by UPLC-Q-TOF/MS, while the therapeutic effects of SJHYF on H2O2-induced HaCaT cells were analyzed using RNA-Seq. The potential target genes were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). At the same time, the pathway phenotype expression of SJHYF on the protection of H2O2-induced HaCaT cells was explored using Western Blot. RESULTS: The application of SJHY at a concentration of 0.25 mg/mL promoted cell proliferation, cell migration, and reduced ROS production. In addition, SJHYF was detected to have a total of 93 active compounds, including key components such as Galloyl-beta-D-glucose, Danshensu, Procyanidin B2, Catechin, and Alkannin. The RNA-seq analysis identified several core targets namely KRT17, TGM1, JUNB, PRDX5, TXNIP, PRDX1, HSP90AA1, HSP90AB1, HSPA8, and TNF-α. Western blot revealed the presence of the JNK/c-Jun/MMPs pathway and its related transcription factors. CONCLUSION: SJHYF displays significant protective effects on H2O2-induced oxidative cell damage in HaCaT cells via blocking the JNK/c-Jun/MMPs pathway.

Transpedicular closing wedge osteotomy in the treatment of thoracic and lumbar kyphotic deformity with different etiologies.

Transpedicular closing wedge osteotomy (CWO) has become popular in correcting thoracic and lumbar kyphotic deformity (TLKD). Our study aims to evaluate the efficacy of CWO in treating TLKD of different etiologies. CWO was performed on 25 patients with thoracic and lumbar kyphosis, of whom 10 had ankylosing spondylitis, 10 had post-traumatic thoracolumbar fractures, and 5 had tuberculosis. Mean follow-up period was 24 months. Pre- and postoperative kyphotic Cobb angles and the horizontal distance between C7 and S1 in the lateral view were measured. Back pain and disability were assessed by visual analog score (VAS) and oswestry disability index (ODI). Postoperative complications were also recorded. Kyphotic deformity was successfully corrected, and 100% osteotomic site fusion was obtained in all cases. Average operative duration was 255.6 min and blood loss was 1,675.6 ml. Average correction angels were 37.6°. The horizontal distance between C7 and S1 was 88.28 mm before the operation and 20.84 mm after the operation. Pre- and postoperative mean VAS of back pain in all cases was 7.6 and 2.6 respectively. Pre- and postoperative mean ODI was 61.8 and 27.32 receptively. Six complications were registered in six patients. Pedicle subtraction osteotomy is an effective and safe surgical method to correct thoracic and lumbar kyphosis of different etiologies.

Solid polymer electrolytes reinforced with porous polypropylene separators for all-solid-state supercapacitors.

Solid polymer electrolytes (SPEs) encounter the challenge of balancing high ionic conductivity and mechanical strength. Ionic liquids, which are among the contenders to be used in high-performance supercapacitors, have difficulty infiltrating commercial polyolefin separators for combined applications. In this study, a novel SPE involving uniform infiltration in the micropores of commercial polyolefin separators with polyethylene oxide (PEO), lithium salt, and different proportions of added ionic liquid was developed. The composite membranes combining ionic liquid-filled SPE with polypropylene (PP) microporous separators simultaneously achieve excellent mechanical strength and high-ionic conductivity. The low wettability of pure ionic liquids and commercial polyolefin-based separators is addressed. The 70 wt% IL-filled solid electrolyte composite membrane (PLI(70)@PP) exhibits a high ionic conductivity (2.9 × 10-3 S cm-1), low resistance at the electrolyte-electrode interface and excellent mechanical strength (128 MPa) at 25 °C. The all-solid-state supercapacitor using PLI(70)@PP exhibits a specific capacitance of 158 F g-1 at 0.1 A g-1 and stable cycle performance. The proposed method can be performed via high-volume roll-to-roll processing to obtain high-performance all-solid-state supercapacitors (ASSCs) for engineering applications.

Research on the resistance of isoviolanthin to hydrogen peroxide-triggered injury of skin keratinocytes based on Transcriptome sequencing and molecular docking.

Apoptosis of skin keratinocytes is closely associated with skin problems in humans and natural flavonoids have shown excellent biological activity. Hence, the study of flavonoids against human keratinocyte apoptosis has aroused the interest of numerous researchers. In this study, methyl thiazolyl tetrazolium (MTT) assay and Western blots were used to investigate the skin-protective effect of isoviolanthin, a di-C-glycoside derived from Dendrobium officinale, on hydrogen peroxide (H2O2)-triggered apoptosis of skin keratinocytes. Transcriptome sequencing (RNA-Seq) was used to detect the altered expression genes between the model and treatment group and qRT-PCR was used to verify the accuracy of transcriptome sequencing results. Finally, molecular docking was used to observe the binding ability of isoviolanthin to the selected differential genes screened by transcriptome sequencing. Our results found isoviolanthin could probably increase skin keratinocyte viability, by resisting against apoptosis of skin keratinocytes through downregulating the level of p53 for the first time. By comparing transcriptome differences between the model and drug administration groups, a total of 2953 differential expression genes (DEGs) were identified. Enrichment analysis showed that isoviolanthin may regulate these pathways, such as DNA replication, Mismatch repair, RNA polymerase, Fanconi anemia pathway, Cell cycle, p53 signaling pathway. Last, our results found isoviolanthin has a strong affinity for binding to KDM6B, CHAC2, ESCO2, and IPO4, which may be the potential target for treating skin injuries induced by reactive oxide species. The current study confirms isoviolanthin potential as a skin protectant. The findings may serve as a starting point for further research into the mechanism of isoviolanthin protection against skin damage caused by reactive oxide species (e.g., hydrogen peroxide).

Comparison between the antero-posterior and anterior approaches for treating L5-S1 vertebral tuberculosis.

PURPOSE: Both the antero-posterior and anterior approaches have been used for treating L5-S1 vertebral tuberculosis. However, no studies have compared the efficacy of the two methods in treating the disease. METHODS: The antero-posterior (AP group, 14 cases) and anterior (A group, 13 cases) approaches were performed on L5-S1 vertebral tuberculosis cases who were followed up for average of 25 months. Clinical and radiographic data were obtained from and compared between groups. RESULTS: Average operative time, blood loss and pre-operative, post-operative and last follow-up of lumbo-sacral angles for groups AP and A were 497 min vs 190 min, 980 ml vs 410 ml, 22.3° vs 20.6°, 29.8° vs 25.7° and 28.3° vs 23.6°, respectively. Averaged visual analogue scale (VAS) scores in groups AP and A, respectively, were 6.5 vs 6.0 points before surgery and 3.0 vs 2.8 points after surgery. Mean ODI scores were 60.2 vs 63.0 points before and 30.0 vs 28.5 points after the operation for groups AP and A, respectively. Six cases in the AP group and five in the A group who exhibited neurological symptoms recovered to American Spinal Injury Association (ASIA) grade E. The average hospitalisations of groups AP and A lasted for 21 and 15 days, respectively. Bony fusion was achieved in both groups, with an average fusion time of five and four months, respectively. CONCLUSIONS: Both the antero-posterior and anterior approaches can effectively heal L5-S1 vertebral tuberculosis, but the average surgical time, blood loss and hospital stay following the anterior approach are prominently less than those following the antero-posterior approach.

Management of drug-resistant spinal tuberculosis with a combination of surgery and individualised chemotherapy: a retrospective analysis of thirty-five patients.

PURPOSE: Drug-resistant tuberculosis is a major public-health concern globally and can be difficult to manage clinically. Spinal tuberculosis is the most common manifestation of extrapulmonary tuberculosis. However, there have been few reports on the topic of drug-resistant spinal tuberculosis. The aim of this study was to investigate the clinical characteristics and drug susceptibility patterns and the outcomes of management with a combination of surgery and individualised chemotherapy, for drug-resistant spinal tuberculosis. METHODS: We retrospectively analysed 35 patients with drug-resistant tuberculous spondylitis. After surgery, individualised chemotherapy was tailored for each patient according to the drug-resistance profile and previous history of chemotherapy. The patients were followed up clinically and radiologically for an average period of 35.8 months. RESULTS: Among 35 drug-resistant spinal tuberculosis cases, 13 were retreatment cases. Twelve were multi-drug resistant tuberculosis (MDR-TB), and 23 were non-MDR-TB. The patients with MDR-TB and non-MDR-TB had undergone previous chemotherapy for an average of 14.50 ± 2.00 (0-60) months and 4.56 ± 1.54 (0-74) months, respectively. A total of 32 cases underwent open operations, and the other three had percutaneous drainage and local chemotherapy. Patients received individualised chemotherapy for an average of 23.6 months postoperatively. Local recurrence was observed in six patients. Thirty-three patients had been cured at the final follow-up, and the other two were still receiving chemotherapy. CONCLUSIONS: Drug-resistant tuberculous spondylitis is mainly acquired through previous irregular chemotherapy and the spreading of drug-resistant strains. Management with a combination of surgery and individualised chemotherapy is feasible in the treatment of severe complications and the prevention of acquired drug resistance.

The effect of the WKYMVm peptide on promoting mBMSC secretion of exosomes to induce M2 macrophage polarization through the FPR2 pathway.

BACKGROUND: When multicystic vesicles (precursors of exosomes) are formed in cells, there are two results. One is decomposition by lysosomes, and the other is the generation of exosomes that are transported out through the transmembrane. On the other hand, M2 macrophages promote the formation of local vascularization and provide necessary support for the repair of bone defects. To provide a new idea for the treatment of bone defects, the purpose of our study was to investigate the effect of WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2) peptide on the secretion of exosomes from murine bone marrow-derived MSCs (mBMSCs) and the effect of exosomes on the polarization of M2 macrophages. METHODS: The WKYMVm peptide was used to activate the formyl peptide receptor 2 (FPR2) pathway in mBMSCs. First, we used Cell Counting Kit-8 (CCK-8) to detect the cytotoxic effect of WKYMVm peptide on mBMSCs. Second, we used western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of interferon stimulated gene 15 (ISG15) and transcription factor EB (TFEB) in mBMSCs. Then, we detected lysosomal activity using a lysozyme activity assay kit. Third, we used an exosome extraction kit and western blotting to detect the content of exosomes secreted by mBMSCs. Fourth, we used immunofluorescence and western blotting to count the number of polarized M2 macrophages. Finally, we used an inhibitor to block miRNA-146 in exosomes secreted by mBMSCs and counted the number of polarized M2 macrophages. RESULTS: We first found that the WKYMVm peptide had no toxic effect on mBMSCs at a concentration of 1 µmol/L. Second, we found that when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs, ISG15 and TFEB expression was decreased, leading to increased secretion of exosomes. We also found that lysosomal activity was decreased when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs. Third, we demonstrated that exosomes secreted by mBMSCs promote the polarization of M2 macrophages. Moreover, all these effects can be blocked by the WRWWWW (WRW4, H-Trp-Arg-Trp-Trp-Trp-Trp-OH) peptide, an inhibitor of the FPR2 pathway. Finally, we confirmed the effect of miRNA-146 in exosomes secreted by mBMSCs on promoting the polarization of M2 macrophages. CONCLUSION: Our findings demonstrated the potential value of the WKYMVm peptide in promoting the secretion of exosomes by mBMSCs and eventually leading to M2 macrophage polarization. We believe that our study could provide a research basis for the clinical treatment of bone defects.

Therapeutic Effects of Traditional Chinese Exercises on Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

Background: The number of patients with musculoskeletal pain, which seriously affects people's quality of life, has increased. Traditional Chinese exercises are accepted and practiced to strengthen the body. Objective: This study aims to explore the efficacy of traditional Chinese exercises for the treatment of musculoskeletal pain. Methods: A comprehensive search of randomized controlled trials (RCTs) related to traditional Chinese exercises on patients with musculoskeletal pain was completed using PubMed, SinoMed, CNKI, VIP, and Wanfang Med Online databases. All RCTs published until February 2021 were considered. Two researchers independently screened the literature according to the predesigned inclusion and exclusion criteria, and data was extracted and assessed for their risk of bias via the Cochrane collaboration tool. Meta-analysis was performed using RevMan5.2 and Rx64 4.0.2 software. Results: A total of 45 RCT studies with 3178 patients were included. Traditional Chinese exercises were able to effectively alleviate patients with musculoskeletal pain (MD = -1.54, 95% confidence interval (-1.88, -1.19), P < 0.01). Among them, the Yi Jin Jing exercise was superior to other exercises, while Wu Qin Xi showed no significant effects. Besides, traditional Chinese exercises had significant positive effects on the dysfunction and stiffness of the waist and knee joints. Traditional Chinese exercises could effectively relieve the clinical symptoms of patients with musculoskeletal pain. Particularly, the Yi Jin Jing exercise presented the most significant positive effect on pain reduction.

A Modified Surgical Technique of Fovea-Sparing Internal Limiting Membrane Peeling: Continuous Arc-Shaped Foldback Peeling.

PURPOSE: To investigate the efficacy of management of high myopic foveoschisis (MF) with a modified surgical technique of arc-shaped foldback fovea-sparing internal limiting membrane (ILM) peeling. METHODS: A 23-gauge vitrectomy was performed in five patients with high MF. A long strip of ILM was peeled at the temporal side of the central fovea. Next, an ILM forceps was used to grasp the outer side of the ILM flap, and it was moved forward slowly from the outside to the paracentral fovea, followed by folding ILM back in an arc-shaped manner and then removing it. The above operations were repeated, and all ILM flaps were removed from the outside to paracentral fovea until a narrow strip of ILM remained. Finally, the narrow strip of ILM was excised using a vitreous cutter. RESULTS: At the patients' last visits, the foveoschisis almost disappeared completely and the fovea reattached. The central macular thickness statistically decreased from 399.0 ± 96.33 µm preoperatively to 164.60 ± 34.20 µm postoperatively (t = 4.289; P=0.013). The preoperative mean logarithm of the minimum angle of resolution best-corrected visual acuity (1.64 ± 0.65) significantly improved to 0.72 ± 0.18 postoperatively (t = 3.265, P=0.031). The average follow-up time was 11.80 ± 3.35 months (range; 8-16 months). CONCLUSION: The arc-shaped foldback fovea-sparing ILM peeling technique for high MF is safe and effective.

[Three-dimensional printed Ti6Al4V-4Cu alloy promotes osteogenic gene expression through bone immune regulation].

OBJECTIVE: To investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7. METHODS: Ti6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR. RESULTS: Compared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant ( P<0.05). CONCLUSION: 3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.

Dual-Peptide-Functionalized Nanofibrous Scaffolds Recruit Host Endothelial Progenitor Cells for Vasculogenesis to Repair Calvarial Defects.

Vasculogenesis (de novo formation of vessels) induced by endothelial progenitor cells (EPCs) is requisite for vascularized bone regeneration. However, there exist few available options for promoting vasculogenesis within artificial bone grafts except for exogenous EPC transplantation, which suffers from the source of EPC, safety, cost, and time concerns in clinical applications. This study aimed at endogenous EPC recruitment for vascularized bone regeneration by using a bioinspired EPC-induced graft. The EPC-induced graft was created by immobilizing two bioactive peptides, WKYMVm and YIGSR, on the surface of poly(ε-caprolactone) (PCL)/poliglecaprone (PGC) nanofibrous scaffolds via a polyglycolic acid (PGA)-binding peptide sequence. Remarkable immobilization efficacy of WKYMVm and YIGSR peptides and their sustained release (over 14 days) from scaffolds were observed. In vivo and in vitro studies showed robust recruitment of EPCs, which subsequently contributed to early vasculogenesis and ultimate bone regeneration. The dual-peptide-functionalized nanofibrous scaffolds proposed in this study provide a promising therapeutic strategy for vasculogenesis in bone defect repair.

Short segmental pedicle screw fixation combined with percutaneous vertebroplasty in treatment of nonadjacent thoracolumbar fractures.

OBJECTIVE: To evaluate the short-term outcomes of short segmental pedicle screw fixation combined with percutaneous vertebroplasty in treatment of nonadjacent thoracolumbar fractures. METHODS: Twenty patients who suffered from nonadjacent thoracolumbar fractures were treated by short segmental pedicle screw fixation for burst fracture and by percutaneous vertebroplasty for compression fracture. X-rays, CT and MRI scans were conducted using the same protocol before and after surgery and during follow-up. Pre-and post-operative American Spinal Injury Association (ASIA) grades, fusion of fracture sites, visual analog scale (VAS) of back pain, and Oswestry disability index (ODI) were accessed. RESULTS: All patients were followed up for an average period of 12 months. The sagittal profile of the thoracolumbar spine was restored satisfactorily. No patient had neurologic deterioration after surgery, and 9 patients with incomplete lesions improved postoperatively by at least one ASIA grade. The fusion rate was 100%. The average VAS of back pain was 7.6 preoperatively and 3.2 postoperatively. The average ODI was 72.5 preoperatively and 35.5 postoperatively. CONCLUSIONS: Short segmental pedicle screw fixation combined with percutaneous vertebroplasty in treatment of nonadjacent thoracolumbar fractures exhibits such advantages as preserving functional segment units, reliable fixation, good neurologic recovery and early mobilization and, therefore, is suitable for treating nonadjacent thoracolumbar fractures.

Functionalized cell-free scaffolds for bone defect repair inspired by self-healing of bone fractures: A review and new perspectives.

Studies have demonstrated that scaffolds, a component of bone tissue engineering, play an indispensable role in bone repair. However, these scaffolds involving ex-vivo cultivated cells seeded have disadvantages in clinical practice, such as limited autologous cells, time-consuming cell expansion procedures, low survival rate and immune-rejection issues. To overcome these disadvantages, recent focus has been placed on the design of functionalized cell-free scaffolds, instead of cell-seeded scaffolds, that can reduplicate the natural self-healing events of bone fractures, such as inflammation, cell recruitment, vascularization, and osteogenic differentiation. New approaches and applications in tissue engineering and regenerative medicine continue to drive the development of functionalized cell-free scaffolds for bone repair. In this review, the self-healing processes were highlighted, and approaches for the functionalization were summarized. Also, ongoing efforts and breakthroughs in the field of functionalization for bone defect repair were discussed. Finally, a brief summery and new perspectives for functionalization strategies were presented to provide guidelines for further efforts in the design of bioinspired cell-free scaffolds.

[Fabrication of alginate microsphere for controlled release and investigation of its release characteristics in vitro].

This study sought to producte alginate sodium microsphere for controlled release bovine serum albumin(BSA) and to investigate the protein release profile of the BSA-alginate sodium microsphere in vitro, which threw some light on the angiogenesis of tissue engineering bone with vascular endothelial growth factor (VEGF) controlled release under stress. The BSA-alginate sodium microsphere was fabricated with W/O emulsification and ion cross-linking method using alginate sodium. The appearance, microsphere diameter and envelopment rate were detected, and the release characteristics of the BSA-alginate sodium microsphere in vitro was investigated. The alginate microsphere was found to be spherical in shape and evenly distributed. Its mean grain diameter was determined to be 230 +/- 60 microm, carrying capacity 80.3 microg/mg and envelopment rate 61%. Smooth controlled release in BSA-alginate sodium microsphere was shown to last more than 2 weeks. Alginate sodium proved an excellent biodegradable material for protein or polypeptide controlled release. The emulsification and ion cross-linking method was noted to be simple; it was propitious to the structural and functional stablility of protein or polypeptide, thus leading to the prolonged efficacious time of the microsphere.

Retrospective Study of 967 Patients With Spinal Tuberculosis.

China is a country with a high tuberculosis (TB) burden. Spinal TB is one reason for the resurgence of TB in China. The objective of this study was to investigate the clinical and epidemiological features of patients with spinal TB in a teaching hospital of Southwest China. The study group comprised 967 patients with spinal TB who were admitted to the authors' institution from 1999 to 2013. Demographic characteristics, prevalence of symptoms and clinical manifestations, prevalence of multidrug resistance and extensive drug resistance of spinal TB, management and outcome, and incidence of complications were recorded and analyzed. The patients included 473 women and 494 men with a mean age of 35.86±15.68 years. The most common presentation of spinal TB was back pain, followed by night sweats and fever. The thoracic spine was the most commonly involved level, followed by the lumbar spine and cervical spine. The incidence of neurological involvement in spinal TB is 33.3%. Noncontiguous spinal TB was seen in 3.41% of cases. The incidence of concomitant pulmonary TB was 14.37%. A total of 740 patients were successfully treated with surgery and anti-TB drugs. No mortality was related to spinal TB. Spinal TB increased every year from 1999 to 2013 in Southwest China. Back pain is the most common clinical symptom, and the thoracic spine is the vertebral body most often involved. The most commonly used first- and second-line anti-TB drugs are isoniazid and levofloxacin, respectively. [Orthopedics.2016; 39(5):e838-e843.].

Treatment Experiences and Management Outcomes for Skipped Multisegmental Spinal Tuberculosis.

China ranks second among the 22 countries with the highest burden of tuberculosis. The goals of this study were to evaluate the clinical outcomes of treatment of skipped multisegmental spinal tuberculosis and to investigate the selection strategy for the optimal procedure based on focal characteristics. From March 1999 to December 2013, 24 patients with skipped multisegmental spinal tuberculosis were enrolled in this study. Ten patients underwent an anterior procedure (anterior group). Four patients underwent a combined anterior and posterior procedure (combined anterior and posterior group). Ten patients underwent a posterior procedure (posterior group). All patients were evaluated according to clinical presentation and radiographic, computed tomography, and magnetic resonance imaging findings. The focal tissues of all patients underwent drug susceptibility testing. The patients underwent clinical and radiologic follow-up an average of 18.6 months post-operatively. The cohort included 13 male and 11 female patients (age range, 15-69 years). The patients showed significant improvement in deformity and neurologic deficits. All patients had graft union 6 to 12 months postoperatively. No patient had surgical complications. Postoperative recurrence occurred in 1 patient in the combined anterior and posterior group. Two patients had strains that were resistant to at least 1 anti-tuberculosis drug. One patient had multidrug-resistant strains. All 24 patients had achieved cure at final follow-up. This study showed that the 3 procedures can safely and effectively achieve nerve decompression, graft fusion, and kyphosis correction. The procedure should be chosen according to the patient's general condition, focal characteristics, and type of complication, and the surgeon's experience.