Calcium sulfate-Cu2+ delivery system improves 3D-Printed calcium silicate artificial bone to repair large bone defects.

There are still limitations in artificial bone materials used in clinical practice, such as difficulty in repairing large bone defects, the mismatch between the degradation rate and tissue growth, difficulty in vascularization, an inability to address bone defects of various shapes, and risk of infection. To solve these problems, our group designed stereolithography (SLA) 3D-printed calcium silicate artificial bone improved by a calcium sulfate-Cu2+ delivery system. SLA technology endows the scaffold with a three-dimensional tunnel structure to induce cell migration to the center of the bone defect. The calcium sulfate-Cu2+ delivery system was introduced to enhance the osteogenic activity of calcium silicate. Rapid degradation of calcium sulfate (CS) induces early osteogenesis in the three-dimensional tunnel structure. Calcium silicate (CSi) which degrades slowly provides mechanical support and promotes bone formation in bone defect sites for a long time. The gradient degradation of these two components is perfectly matched to the rate of repair in large bone defects. On the other hand, the calcium sulfate delivery system can regularly release Cu2+ in the temporal and spatial dimensions, exerting a long-lasting antimicrobial effect and promoting vascular growth. This powerful 3D-printed calcium silicate artificial bone which has rich osteogenic activity is a promising material for treating large bone defects and has excellent potential for clinical application.

Aligned lovastatin-loaded electrospun nanofibers regulate collagen organization and reduce scar formation.

Excessive scar formation caused by cutaneous injury leads to pruritus, pain, contracture, dyskinesia, and unpleasant appearance. Functional wound dressings are designed to accelerate wound healing and reduce scar formation. In this study, we fabricated aligned or random polycaprolactone/silk fibroin electrospun nanofiber membranes with or without lovastatin loading, and then evaluated their scar-inhibitory effects on wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity, and biocompatibility. Furthermore, nanofibers' perpendicular placement to the tension direction of the wound most effectively reduced scar formation (the scar area decreased by 66.9%) and promoted skin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated collagen organization in the early stage of wound healing. Moreover, lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and lovastatin synergistically inhibited mechanical transduction and fibrosis progression, further reducing scar formation. In summary, our study may provide an effective scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients' wounds, and the addition of lovastatin can further inhibit scar formation. STATEMENT OF SIGNIFICANCE: In vivo, cells and collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate scar formation. Electrospun nanofibers' perpendicular placement to the tension direction of the wound most effectively reduces scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and lovastatin could inhibit mechanical transduction and fibrosis progression synergistically, further reducing scar formation. This study proves that combining topographical cues of wound dressing and drugs would be a promising therapy for clinical scar management.

Radial Sponges Facilitate Wound Healing by Promoting Cell Migration and Angiogenesis.

The topographic cues of wound dressings play important roles in regulating cellular behaviors, such as cellular migration and morphology, and are capable of providing a prolonged stimulus for promoting wound healing. However, 3D porous dressings that can guide wound healing from the periphery to the center are poorly studied. Herein, radial sponges with adjustable lamellar spacing and microridge spacing by ice templating are developed to facilitate wound healing. With denser lamellae and microridges, fibroblasts achieve a more orderly arrangement, a larger elongation, and a greater migration rate. Meanwhile, the elongated state enables human umbilical vein endothelial cells to vascularization. The faster healing rate and a higher degree of vascularization based on radial sponges are further demonstrated in full-thickness skin defects in rats. Taken together, radial sponges with the densest lamellae and microridges perform the best in guiding the wound from the periphery to the center of the repair environment. It is believed that the proposed structure here can be combined with various biochemical factors to provide dressings with functions.

Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis.

This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I2 = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I2 = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I2 = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I2 = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I2 = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENTWhat is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women.What do the results of this study add? This systematic review and meta-analysis of data from ten studies (n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls.What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.

Mussel-inspired multifunctional surface through promoting osteogenesis and inhibiting osteoclastogenesis to facilitate bone regeneration.

Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.

Mesh-like electrospun membrane loaded with atorvastatin facilitates cutaneous wound healing by promoting the paracrine function of mesenchymal stem cells.

BACKGROUND: Functional electrospun membranes are promising dressings for promoting wound healing. However, their microstructure and drug loading capacity need further improvements. It is the first time to design a novel mesh-like electrospun fiber loaded with atorvastatin (ATV) and investigated its effects on paracrine secretion by bone marrow-derived mesenchymal stem cells (BMSCs) and wound healing in vivo. METHODS: We fabricated a mesh-like electrospun membrane using a copper mesh receiver. The physical properties of the membranes were evaluated by SEM, FTIR spectroscopy, tensile strength analysis, and contrast angle test. Drug release was measured by plotting concentration as a function of time. We tested the effects of conditioned media (CM) derived from BMSCs on endothelial cell migration and angiogenesis. We used these BMSCs and performed RT-PCR and ELISA to evaluate the expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) genes and proteins, respectively. The involvement of FAK and AKT mechanotransduction pathways in the regulation of BMSC secretion by material surface topography was also investigated. Furthermore, we established a rat model of wound healing, applied ATV-loaded mesh-like membranes (PCL/MAT) seeded with BMSCs on wounds, and assessed their efficacy for promoting wound healing. RESULTS: FTIR spectroscopy revealed successful ATV loading in PCL/MAT. Compared with random electrospun fibers (PCL/R) and mesh-like electrospun fibers without drug load (PCL/M), PCL/MAT induced maximum promotion of human umbilical vein endothelial cell (HUVEC) migration. In the PCL/MAT group, the cell sheet scratches were nearly closed after 24 h. However, the cell sheet scratches remained open in other treatments at the same time point. The PCL/MAT promoted angiogenesis and led to the generation of longer tubes than the other treatments. Finally, the PCL/MAT induced maximum gene expression and protein secretion of VEGF and b-FGF. As for material surface topography effect on BMSCs, FAK and AKT signaling pathways were shown to participate in the modulation of MSC morphology and its paracrine function. In vivo, PCL/MAT seeded with BMSCs significantly accelerated healing and improved neovascularization and collagen reconstruction in the wound area compared to the other treatments. CONCLUSIONS: The mesh-like topography of fibrous scaffolds combined with ATV release creates a unique microenvironment that promotes paracrine secretion of BMSCs, thereby accelerating wound healing. Hence, drug-loaded mesh-like electrospun membranes may be highly efficacious for wound healing and as artificial skin. It is a promising approach to solve the traumatic skin defect and accelerate recovery, which is essential to developing functional materials for future regenerative medicine.

A Self-Assembled Matrix System for Cell-Bioengineering Applications in Different Dimensions, Scales, and Geometries.

Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation-mediated self-assembling mechanism, a biomatrix system optimal for 2D human mesenchymal stromal cell (hMSC) culture and osteogenesis is identified. Its utility for hMSC bioengineering is further demonstrated in coating porous bioactive glass scaffolds and nanoparticle synthesis for esiRNA delivery to knock down the SOX-9 gene with high delivery efficiency. The self-assembled injectable system is further utilized for 3D cell culture, segregated co-culture of hMSC with human umbilical vein endothelial cells (HUVEC) as an angiogenesis model, and 3D bioprinting. Most interestingly, the coating of bioactive glass with the self-assembled biomatrix not only supports the proliferation and osteogenesis of hMSC in the 3D scaffold but also induces the amorphous bioactive glass (BG) scaffold surface to form new apatite crystals resembling bone-shaped plate structures. Thus, the self-assembled biomatrix system can be utilized in various dimensions, scales, and geometries for many different bioengineering applications.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Observational Studies.

The neutrophil-to-lymphocyte ratio (NLR), as an essential systemic inflammation factor, has been widely used as a prognostic indicator in various diseases, such as malignant tumors, cardiovascular disease, and intracranial hemorrhage. An increasing number of studies have believed that NLR is a valuable predictor of prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, these results remain controversial. In the current study, we planned to carry out a systematic review and meta-analysis to investigate the association between NLR and poor outcome, and the occurrence of delayed cerebral ischemia (DCI). We carried out a comprehensive search for published literatures on PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to April 1, 2021. We conducted an assessment of all included studies based on the principles proposed in the Newcastle-Ottawa Quality Assessment Scale (NOS). Poor outcome and the occurrence of DCI were considered as the main outcome measure. We calculated the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) to examine the strength of the association of NLR with poor outcome or the occurrence of DCI. We strictly selected a total of 10 studies comprising 4,989 patients. Nine studies reported the association between NLR and poor outcome, and five studies reported the association between NLR and the occurrence of DCI. The pooled results indicated higher NLR was significantly associated with both poorer outcomes (OR = 1.32, 95%CI 1.11-1.57; P = 0.002, I 2 = 87%), and the occurrence of DCI (OR = 1.72, 95%CI 1.22-2.41; P = 0.002, I 2 = 82%) in aSAH patients. The NLR is a valuable indicator of inflammation to independently predict poor outcome and occurrence of DCI after aSAH, where a higher NLR is significantly associated with poor outcomes and occurrence of DCI. These findings suggest that the NLR can help clinicians evaluate the prognosis and identify potentially severe patients early, which may contribute to better management and improve poor prognosis of aSAH patients.

Adjuvant Corticosteroids With Surgery for Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis.

The use of adjuvant corticosteroids with surgery for chronic subdural hematoma (CSDH) has received considerable attention in recent years. However, there is no conclusive evidence regarding its effectiveness and safety for CSDH. Therefore, we performed a meta-analysis and systematic review to evaluate the effectiveness and safety of corticosteroids as an adjuvant treatment for the treatment of CSDH. We comprehensively searched electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) to identify relevant trials that investigated the efficacy and safety of adjuvant corticosteroids with surgery for CSDH, published from inception until May 2021. Outcome measures included recurrence rate, all-cause mortality, good functional outcome, length of hospitalization, and adverse events. We used the Cochrane risk of bias method to evaluate the quality of randomized controlled trials (RCTs), and the Newcastle Ottawa Scale to evaluate the quality of observational studies. We included nine studies, consisting of three RCTs and six observational studies, that compared corticosteroids as an adjuvant treatment to surgery with surgery alone. Pooled results revealed that the risk of recurrence was significantly reduced in patients who received adjuvant corticosteroids with surgery compared to those who underwent surgery alone (relative risk [RR] = 0.52, 95% confidence interval [CI] = 0.39-0.69, p < 0.00001). However, no statistically significant difference was observed between these groups in all-cause mortality (RR = 0.91, 95% CI = 0.37-2.23, p = 0.83), good functional outcome (RR = 1.03, 95% CI = 0.96-1.10, p = 0.47), length of hospitalization (MD = 0.35, 95% CI = -2.23 to 1.67, p = 0.83), and infection rates (RR = 0.99, 95% CI = 0.64-1.53, p = 0.95). Adjuvant corticosteroids with surgery reduce the risk of recurrence of CDSH, but do not improve the all-cause mortality or functional outcome, as compared to surgery alone. These findings support the use of adjuvant corticosteroids with surgery for CSDH patients. Further high-quality RCTs are required to confirm the efficacy and safety of adjuvant corticosteroids in the treatment of CSDH patients.

Bioinspired Redwood-Like Scaffolds Coordinated by In Situ-Generated Silica-Containing Hybrid Nanocoatings Promote Angiogenesis and Osteogenesis both In Vitro and In Vivo.

Inspired by natural redwood and bone, a biomimetic strategy is presented to develop a highly bioactive redwood-like nanocomposite via radial freeze casting of biocompatible hydrogels followed by the in situ coprecipitation of a Si-containing CaP hybrid nanocoating (SCPN). The engineered material displays radially aligned macrochannels and a porous network structure similar to those of natural redwood. In addition to acting as a mechanical reinforcement, introducing SCPNs into the weak redwood-like scaffold yields not only a nanoroughened surface topography, a low swelling ratio, retarded enzymatic degradation, and enhanced protein absorption abilities but also the sustained sequential release of Si and Ca ions, thereby providing essential biophysical and biochemical cues for effective bone regeneration. Benefiting from the redwood-like structures and bioactive SCPNs, the biomimetic materials create a favorable microenvironment for promoting the initial adhesion, spreading, proliferation, and migration of bone marrow-derived mesenchymal stem cells and human umbilical vein endothelial cells. Furthermore, the in vitro and in vivo data showed that the biocompatible redwood-like scaffold with precipitated SCPN can synergistically promote osteogenesis and angiogenesis in their aligned direction. Collectively, this work presents a novel bioinspired redwood-like material with multifunctional properties that provides new insight into bone defect repair.

Construction and Validation of a Macrophage-Associated Risk Model for Predicting the Prognosis of Osteosarcoma.

BACKGROUND: Osteosarcoma is one of the most common bone tumors among children. Tumor-associated macrophages have been found to interact with tumor cells, secreting a variety of cytokines about tumor growth, metastasis, and prognosis. This study aimed to identify macrophage-associated genes (MAGs) signatures to predict the prognosis of osteosarcoma. METHODS: Totally 384 MAGs were collected from GSEA software C7: immunologic signature gene sets. Differential gene expression (DGE) analysis was performed between normal bone samples and osteosarcoma samples in GSE99671. Kaplan-Meier survival analysis was performed to identify prognostic MAGs in TARGET-OS. Decision curve analysis (DCA), nomogram, receiver operating characteristic (ROC), and survival curve analysis were further used to assess our risk model. All genes from TARGET-OS were used for gene set enrichment analysis (GSEA). Immune infiltration of osteosarcoma sample was calculated using CIBERSORT and ESTIMATE packages. The independent test data set GSE21257 from gene expression omnibus (GEO) was used to validate our risk model. RESULTS: 5 MAGs (MAP3K5, PML, WDR1, BAMBI, and GNPDA2) were screened based on protein-protein interaction (PPI), DGE, and survival analysis. A novel macrophage-associated risk model was constructed to predict a risk score based on multivariate Cox regression analysis. The high-risk group showed a worse prognosis of osteosarcoma (p < 0.001) while the low-risk group had higher immune and stromal scores. The risk score was identified as an independent prognostic factor for osteosarcoma. MAGs model for diagnosis of osteosarcoma had a better net clinical benefit based on DCA. The nomogram and ROC curve also effectively predicted the prognosis of osteosarcoma. Besides, the validation result was consistent with the result of TARGET-OS. CONCLUSIONS: A novel macrophage-associated risk score to differentiate low- and high-risk groups of osteosarcoma was constructed based on integrative bioinformatics analysis. Macrophages might affect the prognosis of osteosarcoma through macrophage differentiation pathways and bring novel sights for the progression and prognosis of osteosarcoma.

Evaluation of Demineralized Bone Matrix Particles Delivered by Alginate Hydrogel for a Bone Graft Substitute: An Animal Experimental Study.

BACKGROUND Our objective was to explore a synthetic alginate hydrogel delivery system for the delivery of demineralized bone matrix (DBM) particles for bone graft substitutes. MATERIAL AND METHODS The physiochemical properties of surface morphology, porosity measurements, in vitro degradation, equilibrium swelling, and mechanical testing of combined DBM powder and alginate in amounts of 0 mg/1 mL, 25 mg/1 mL, 50 mg/1 mL, and 100 mg/1 mL were detected. In vitro cell culture and in vivo studies using Sprague-Dawley rats were performed to evaluate the biocompatibility and osteoinductivity of DBM-alginate (ADBM) composites. RESULTS DBM particles were uniformly scattered in all composites, and macro-scale pores were omnipresent. All composites showed a similar low degradation rate, with approximately 85% of weight remaining after 15 days. As the concentration of DBM particles in composites increased, degradation in collagenase and elastic modulus increased and the pore area and swelling ratio significantly decreased. No cytotoxicity of ADBM or alginate on mesenchymal stem cells (MSCs) was observed. Cell cultivation with ADBM showed greater osteogenic potential, evidenced by the upregulation of alkaline phosphatase and alizarin red staining activity and the mRNA expression level of marker genes RUNX2, OCN, OPN, and collagen I compared with the cells grown in alginate. Evaluation of ectopic bone formation revealed the osteoinductivity of the ADBM composites was significantly greater than that of DBM particles. Osteoinduction of the composites was demonstrated by a cranial defect model study. CONCLUSIONS The delivery of DBM particles using a synthetic alginate hydrogel carrier may be a promising approach in bone tissue engineering for bone defects.

A radial 3D polycaprolactone nanofiber scaffold modified by biomineralization and silk fibroin coating promote bone regeneration in vivo.

The treatment and repair of large bone defects remains a major therapeutic challenge in the clinical setting. Nanofiber scaffolds fabricated via the electrospinning technique have been developed as a universal method for bone regeneration due to their suitable properties. However, traditional two-dimensional (2D) nanofiber mats are usually too dense, which may prevent cell infiltration and growth, thereby restricting their application. Herein, a three-dimensional (3D) polycaprolactone nanofiber scaffold was developed, modified by biomineralization and silk fibroin coating. The scaffold possessed a parallel array of nanofiber surfaces, mimicking the parallel structure of fibrils in natural bone tissue. Furthermore, the fabricated radially or laterally interconnected macrochannels were investigated to elucidate the effect of the scaffold structure on bone regeneration. In vitro studies revealed that the scaffolds could guide cell arrangement and that the radially aligned scaffold demonstrated a stronger ability to promote cell proliferation. In vivo results showed that the radially aligned scaffold could guide tissue arrangement and remodeling and support a significantly faster regeneration rate of bone tissue. Therefore, 3D-mineralized polycaprolactone nanofiber scaffolds with radially interconnected macrochannels and aligned nanofibers are expected to be used in tissue engineering, including in the repair of bone defects, cartilage or other composite tissues.

Efficacy and Safety of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Tranexamic acid has been shown to reduce rebleeding after aneurysmal subarachnoid hemorrhage; however, whether it can reduce mortality and improve clinical outcomes is controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of the tranexamic acid in aneurysmal subarachnoid hemorrhage. We conducted a comprehensive literature search of PubMed, Embase, Web of Science, and Cochrane Library from inception to March 2021 for randomized controlled trials (RCTs) comparing tranexamic acid and placebo in adults with aneurysmal subarachnoid hemorrhage. The risk of bias was evaluated using the Cochrane Handbook, and the quality of evidence was evaluated using the GRADE approach. This meta-analysis included 13 RCTs, involving 2,888 patients. In patients with aneurysmal subarachnoid hemorrhage tranexamic acid had no significant effect on all-cause mortality (RR = 0.96; 95% CI = 0.84-1.10, p = 0.55, I 2 = 44%) or poor functional outcome (RR = 1.04; 95% CI = 0.95-1.15, p = 0.41) compared with the control group. However, risk of rebleeding was significantly lower (RR = 0.59; 95% CI = 0.43-0.80, p = 0.0007, I 2 = 53%). There were no significant differences in other adverse events between tranexamic acid and control treatments, including cerebral ischemia (RR = 1.17; 95% CI = 0.95-1.46, p = 0.15, I 2 = 53%). At present, routine use of tranexamic acid after subarachnoid hemorrhage cannot be recommended. For a patient with subarachnoid hemorrhage, it is essential to obliterate the aneurysm as early as possible. Additional higher-quality studies are needed to further assess the effect of tranexamic acid on patients with subarachnoid hemorrhage.

The minimally invasive endoscopic technique for the treatment of symptomatic benign bone lesions: Preliminary results from a retrospective study.

OBJECTIVE: The present study aimed to evaluate the short-term clinical feasibility and efficacy of the minimally invasive endoscopic technique (MIET) for the treatment of symptomatic benign bone lesions. MATERIALS AND METHODS: This single-institution retrospective study investigated 34 patients with symptomatic benign bone lesions from December 2015 to June 2017. Patients involved in this study presented with definite indications for surgical intervention. All procedures were performed under endoscopic guidance for direct visualization followed by complete curettage of tumor tissue. There were 19 males and 15 females, with a mean age of 33.3 ± 12.7 years (range, 17-68 years). The lesions were located in the upper extremities (20, 58.8%), lower extremities (9, 26.5%) and pelvis (5, 14.7%). Primary outcomes were measured before and after intervention using the visual analog scale (VAS), the Musculoskeletal Tumor Society (MSTS) stage and the 36-item Short-Form Health Survey (SF-36) scoring system. RESULTS: Of the 34 patients included in this study, all completed follow-up examinations, with a mean follow-up duration of 22.4 ± 7.6 months (range, 13-35 months). Significantly improved VAS, MSTS and SF-36 scores were observed at 3 months after the initial treatment (P < 0.001), suggesting enhanced pain relief and improved functional recovery and quality of life following surgery. All procedures were technically successful, with the exception of 3 cases (8.8%) manifesting access site numbness; these patients recovered within the follow-up period through symptomatic treatment alone. Only 2 patients (5.9%; one osteoblastoma and one enchondroma) experienced local recurrence and underwent standard open curettage within the follow-up period. All patients showed functional stability without any major complications. CONCLUSION: The MIET is an effective and safe alternative treatment for symptomatic benign bone lesions. The short-term efficacy of MIET was favorable and associated with improved pain palliation, quality of life and functional recovery.

Biomimetic mineralization of novel hydroxyethyl cellulose/soy protein isolate scaffolds promote bone regeneration in vitro and in vivo.

Although various strategies have been utilized to accelerate bone regeneration in bone tissue engineering (BTE), the treatment and repair of large bone defects remains a clinical challenge worldwide. Inspired by the natural extracellular matrix of bone tissue, organic-inorganic composite scaffolds with three-dimensional (3D) porous structures, sufficient mechanical properties, excellent cytocompatibility, osteoconductivity, and osteogenic potential have received considerable attention within the field of bone engineering. In this work, a novel epichlorohydrin (ECH)-crosslinked hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) porous bi-component scaffold (EHSS) with hydroxyapatite (HAp) functionalization (EHSS/HAp) was constructed for bone defect repair via the combination of lyophilization and in situ biomimetic mineralization. Systematic characterization experiments were performed to assess the morphology, HAp-forming properties, mechanical properties and degradation rate of the scaffold. The results indicated that the prepared scaffolds exhibited an interconnected porous structure, a biomimetic HAp coating on their surfaces, improved mechanical properties in compression and a controllable degradation rate. In particular, semiquantitative analysis showed that the calcium/phosphorus (Ca/P) ratio of EHSS/HAp with 70% SPI content (1.65) was similar to that of natural bone tissue (1.67) according to energy dispersive X-ray spectroscopy analysis. In vitro cell culture experiments indicated that the EHSS/HAp with 70% SPI content showed improved cytocompatibility and was suitable for MC3T3-E1 cell attachment, proliferation and growth. Consistently, in vitro osteogenic differentiation studies showed that EHSS/HAp with 70% SPI content can significantly accelerate the expression of osteogenesis-related genes (Col-1, Runx2, OPN, and OCN) during osteogenic differentiation of MC3T3-E1 cells. Furthermore, when applied to the repair of critical-sized cranial defects in a rat model, EHSS/HAp with 70% SPI was capable of significantly promoting tissue regeneration and integration with native bone tissue. Microscopic computed tomography (micro-CT) results demonstrated that the bone defect site was nearly occupied with newly formed bone at 12 weeks after implantation of EHSS/HAp with 70% SPI content into the defect. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of histological sections further confirmed that EHSS/HAp with 70% SPI markedly promoted new bone formation and maturation. Collectively, our results demonstrate the potential of EHSS/HAp scaffolds with 70% SPI for successful bone defect repair and regeneration.

Use of percutaneous microwave ablation for the treatment of bone tumors: a retrospective study of clinical outcomes in 47 patients.

OBJECTIVE: The present study aimed to evaluate the short-term clinical performance and safety of percutaneous microwave ablation (MWA) techniques for the treatment of bone tumors. METHODS: This single-institution retrospective study investigated 47 cases of bone tumors treated by MWA from June 2015 to June 2018. The study included 26 patients (55.3%) with benign bone tumors and 21 patients (44.7%) with malignant bone tumors. The tumors were located in the spine or sacrum (15, 31.9%), the upper extremities (6, 12.8%), the lower extremities (17, 36.2%) and the pelvis (9, 19.1%). Outcomes regarding clinical efficacy, including pain relief, quality of life, and intervention-related complications, were evaluated before and after MWA using the visual analog scale (VAS) and the 36-item Short-Form Health Survey (SF-36) scoring system. RESULTS: Of the 47 patients included in this study, all of them completed follow-up examinations, with a mean follow-up duration of 4.8 ± 1.6 months (range, 2-9 months). Significantly improved VAS and SF-36 scores were recorded after the initial treatment (P<0.001), suggesting that almost 100% of patients experienced pain relief and an improved quality of life following surgery. No major intervention-related complications (e.g., serious neurovascular injury or infection) occurred during or after the treatment. We recorded only three minor posttreatment complications (6.4%, 3/47), which were related to thermal injury that caused myofasciitis and affected wound healing. CONCLUSION: In our study, the short-term efficacy of MWA was considerably favorable, with a relatively low rate of complications. Our results also showed that MWA was effective for pain relief and improved patients' quality of life, making it a feasible treatment alternative for bone tumors.

PET/CT-guided versus CT-guided percutaneous core biopsies in the diagnosis of bone tumors and tumor-like lesions: which is the better choice?

OBJECTIVE: The present study aimed to evaluate the diagnostic performance and safety of PET/CT-guided percutaneous core bone biopsy and to compare the PET/CT-guided method to conventional CT-guided percutaneous core biopsies to diagnose Chinese patients with bone tumors and tumor-like lesions. METHODS: Data for 97 patients with bone tumors and tumor-like lesions diagnosed by percutaneous core bone biopsy from February 2013 to November 2018 were retrospectively analyzed. The study included 42 cases in the PET/CT group and 55 cases in the CT alone group. The diagnostic performance, cost and complications associated with the intervention were compared between the two groups. All patients were eventually confirmed to have bone tumors and tumor-like lesions according to surgical pathology findings. RESULTS: There were no significant differences in patient characteristics (P > 0.05). For the patients in the PET/CT group, the overall diagnostic yield of the initial biopsies and the diagnostic accuracy derived from the surgically proven cases were both 97.62%, which was significantly higher than the values in the CT group during the same period (P < 0.05). No major biopsy-related complications (e.g., serious bleeding or tumor dissemination) occurred before, during, or after the intervention. Therefore, no significant difference was observed between the two groups with regard to the complication rate (P > 0.05). CONCLUSION: Compared with CT-guided percutaneous bone biopsy, PET/CT-guided percutaneous bone biopsy is an effective and safe alternative with high diagnostic performance in the evaluation of hypermetabolic bone lesions to diagnose bone tumors and tumor-like lesions.

Porous and nonporous silk fibroin (SF) membranes wrapping for Achilles tendon (AT) repair: Which one is a better choice?

Two types of silk fibroin (SF) membranes were developed for tendon repair: porous and nonporous SF membranes. The objective of this study was to compare the efficiency of these two films according to the ability of tendon regeneration using a rat Achilles tendon (AT) rupture suture wrapping model. The in vitro tests were conducted, and theSF membranes were proved to be with ultimate-biodegradability, good-biocompatibility and without toxicity. In vivo, 12 Sprague Dawley rats were used to create a rat AT rupture suture model wrapped by SF membranes. They were randomly divided into six groups. The results revealed that the nonporous SF membrane wrapping group was shown to reduce the inflammatory effect and induce the proliferation of fibroblast-like cells at one week and four weeks post-operatively. After four weeks, the nonporous SF membrane wrapping group exhibited more organized collagen structures and had increased expression of tendon repair proteins. Hence, our nonporous SF membrane improved the efficacy of tendon regeneration by decreasing inflammatory cells, growing fibroblast-like cells, and promoting extracellular matrix production. Nonporous SF membrane can, therefore, be regarded as a better functional membrane for tendon repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 733-740, 2019.