In vivo evaluation of bioactive glass foams associated with platelet-rich plasma in bone defects

The objective of this study was to evaluate the use of bioactive glass foams produced by the sol-gel process, associated or not with platelet-rich plasma (PRP), in the regeneration of bone defects. Mongrel dogs (n = 14) were divided into two groups after having their superior first premolar removed. A small piece of vestibular bone from the alveolus was intentionally removed. The area was filled with bioactive glass foam produced by the sol-gel method. Two groups were tested: group A was the glass foam; group B was the same material associated with PRP, prepared from each animal. The other side of alveolar bone was used as a control group, in which the bone defect did not receive any biomaterial. The thickness of the bone area was measured before and after the intervention. After a period of 60 days implantation, the right and left bones were measured again, and a bone biopsy on both regions was conducted for histological analysis. The findings show an increase of bone thickness for both materials implanted compared to the control group. Group B, implanted with bioactive glass foam associated with PRP, showed a thicker bone area compared to Group A. Histological results indicate bone formation for both materials used. However, the bioactive glass associated with PRP gave rise to a more mature bone formation. These results show that bioactive glass foams processed by a sol-gel method is effective in maintaining the thickness of the alveolar ridge, and the use of PRP associated with the foams improve bone formation.     

Development of a novel functionally graded membrane containing boron‐modified bioactive glass nanoparticles for guided bone regeneration

Barrier membranes are used in periodontal tissue engineering for successful neo‐bone tissue formation and prevention of bacterial colonization. We aimed to prepare and characterize novel 7% boron‐modified bioactive glass (7B‐BG) containing bilayered membrane for this end. We hypothesized that presence of 7B‐BG could promote structural and biological properties of guided bone regeneration (GBR) membrane. Cellulose acetate (CA) layer was prepared by solvent casting, and functionally graded layer of CA/gelatin/BG nanoparticles was prepared by electrospinning. 0B‐BG, and 7B‐BG were synthesized by quick alkali‐mediated sol–gel method and were characterized by scanning electron microscopy (SEM) and Fourier‐transform Raman spectroscopy. Membranes were cross‐linked with glutaraldehyde to preserve their stability. SEM analysis showed the asymmetric nature of membranes consisting of a smooth membrane layer and a rough surface composed of 0B‐BG and 7B‐BG containing nanofibres. 7B‐BG addition increased surface wettability (from 110.5° ± 0.8 to 73.46° ± 7.6) and biodegradability of the membranes. Additionally, a significant increase in Ca–P layer formation was observed in 7B‐BG containing group after 1‐week incubation in stimulated body fluid. 7B‐BG incorporation resulted in a decrease in tensile strength and Young's modulus values. Human dental pulp stem cells showed better attachment, spreading, and proliferation on 7B‐BG containing bilayered membranes. Osteogenic differentiation analysis revealed higher alkaline phosphatase (ALP) enzyme activity of cells (~1.5‐fold), higher intracellular calcium deposition (approximately twofold), and higher calcium deposition revealed by Alizarin red staining on 7B‐BG containing bilayered membranes. Overall, results suggested that functionally graded bilayered membranes hold potential for GBR applications in regenerative dentistry.     

生物活性玻璃联合颈椎椎间融合器在颈椎前路椎间融合中的应用

背景：已有文献报道生物活性玻璃在骨不连、骨折愈合过程中有较佳的临床疗效,但其在脊柱骨融合过程中的效果鲜有报道。 目的：观察生物活性玻璃联合颈椎椎间融合器在颈椎前路椎间融合中应用的安全性和有效性。 方法：回顾性分析68例颈椎前路单节段椎间融合患者资料,全部病例均采用聚醚醚酮材料椎间融合器,其中内填充自体松质骨植骨32例为对照组,采用生物活性玻璃填充36例为实验组。随访观察两组植骨融合、神经功能恢复、椎间隙高度和颈椎生理曲度及伤口并发症等情况。 结果与结论：两组患者的神经功能改善效果相当,均未出现伤口感染及延迟愈合等并发症。治疗3个月时,实验组与对照组骨性融合率分别为94%,97%,组间比较差异无显著性意义;治疗6个月时全部融合。两组随访3,6,12个月时椎间隙高度和颈椎曲度指数均获得良好维持,组间比较差异无显著性意义。提示生物活性玻璃联合颈椎椎间融合器在颈椎前路椎间融合中有良好的临床安全性和有效性。     

The osteogenic response of mesenchymal stromal cells to strontium‐substituted bioactive glasses

Bioactive glasses are known to stimulate bone healing, and the incorporation of strontium has the potential to increase their potency. In this study, calcium oxide in the 45S5 bioactive glass composition was partially (50%, Sr50) or fully (100%, Sr100) substituted with strontium oxide on a molar basis. The effects of the substitution on bioactive glass properties were studied, including density, solubility, and in vitro cytotoxicity. Stimulation of osteogenic differentiation was investigated using mesenchymal stromal cells obtained from rat bone marrow. Strontium substitution resulted in altered physical properties including increased solubility. Statistically significant reductions in cell viability were observed with the addition of bioactive glass powders to culture medium. Specifically, addition of ≥ 13.3 mg/ml of 45S5 bioactive glass or Sr50, or ≥ 6.7 mg/ml of Sr100, resulted in significant inhibition. Real‐time PCR analyses detected the upregulation of genes associated with osteoblastic differentiation in the presence of all bioactive glass compositions. Some genes, including Alpl and Bglap, were further stimulated in the presence of Sr50 and Sr100. It was concluded that strontium‐substituted bioactive glasses promoted osteogenesis in a differentiating bone cell culture model and, therefore, have considerable potential for use as improved bioactive glasses for bone tissue regeneration. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.     

玻璃离子水门汀加入改良纳米羟基磷灰石后的性能

背景：玻璃离子水门汀具有良好的生物稳定性和持久的氟离子释放性,被用于齿科修复领域的材料,但由于其机械强度较低,局限于前牙等受力较小部位的齿科修复。
　　目的：分析加入8%改良型纳米羟基磷灰石后,而至富士IX 玻璃离子水门汀的抗压强度﹑密合度等物理性能。方法：①分别以而至富士IX 玻璃离子水门汀、加入8%改良型纳米羟基磷灰石的而至富士IX 玻璃离子水门汀及超强玻璃离子充填不锈钢圆柱体,采用万能实验机检测各组抗压强度。②分别以而至富士IX 玻璃离子水门汀、加入8%改良型纳米羟基磷灰石的而至富士IX 玻璃离子水门汀及超强玻璃离子充填人离体牙窝洞,观察各组充填体与牙体间的密合度。③分别以而至富士IX 玻璃离子水门汀、加入8%改良型纳米羟基磷灰石的而至富士IX玻璃离子水门汀及超强玻璃离子充填不锈钢矩形试件,采用万能材料测试机检测各组弯曲强度值。
　　结果与结论：加入改良型纳米羟基磷灰石而至富士IX 玻璃离子水门汀填充试件的抗压强度、密合度及弯曲强度均优于其他两组,并且而至富士IX 玻璃离子水门汀填充试件的抗压强度、密合度及弯曲强度均优于超强玻璃离子填充试件组。表明加入8%的改良型纳米羟基磷灰石的而至富士IX 玻璃离子水门汀抗压强度﹑密合度均有提高。     

Effects of chitosan and bioactive glass modifications of knitted and rolled polylactide‐based 96/4 L/D scaffolds on chondrogenic differentiation of adipose stem cells

The performance of biodegradable knitted and rolled 3‐dimensional (3D) polylactide‐based 96/4 scaffolds modified with bioactive glass (BaG) 13‐93, chitosan and both was compared with regard to the viability, proliferation and chondrogenic differentiation of rabbit adipose stem cells (ASCs). Scaffold porosities were determined by micro‐computed tomography (μCT). Water absorption and degradation of scaffolds were studied during 28‐day hydrolysis in Tris‐buffer. Viability, number and differentiation of ASCs in PLA96/4 scaffolds were examined in vitro. The dimensions of the scaffolds were maintained during hydrolysis and mass loss was detected only in the BaG13‐93 containing scaffolds. ASCs adhered and proliferated on each scaffold type. Cell aggregation and expression of chondral matrix components improved in all scaffold types in chondrogenic medium. Signs of hypertrophy were detected in the modified scaffolds but not in the plain PLA96/4 scaffold. Chondrogenic differentiation was most enhanced in the presence of chitosan. These findings indicate that the plain P scaffold provided a good 3D‐matrix for ASC proliferation whereas the addition of chitosan to the PLA96/4 scaffold induced chondrogenic differentiation independent of the medium. Accordingly, a PLA96/4 scaffold modified by chitosan could provide a functional and bioactive basis for tissue‐engineered chondral implants. Copyright © 2012 John Wiley & Sons, Ltd.     

Potential use of craniosynostotic osteoprogenitors and bioactive scaffolds for bone engineering

The cranial bone has a very limited regenerative capability. Patients with craniosynostosis (the premature fusion of cranial sutures, leading to skull abnormalities) often require extensive craniofacial reconstruction and repeated surgery. The possibility of grafting autologous osteoprogenitor cells seeded on bioabsorbable matrices is of great potential for inducing regeneration of craniofacial structure and protecting the brain from external insult. To this purpose we have studied the behaviour of normal and craniosynostotic mouse osteoblast cell lines, and of human primary osteoprogenitors from craniosynostotic patients. We have monitored their ability to grow and differentiate on plastic and on a scaffold composed of bioactive glass and bioabsorbable polymer by live fluorescent labelling and expression of bone differentiation markers. Cells from syndromic patients display a behaviour very similar to that observed in the stable mouse cell line we generated by introducing the human FGFR2-C278F, a mutation found in certain craniosynostosis, into MC3T3 osteblastic cells, indicating that the mutated cell line is a valuable model for studying the cellular response of human craniosynostotic osteoblasts. Both normal and mutated calvarial osteoprogenitors can attach to the bioactive scaffold, although mutated cells display adhesion defects when cultured on plastic. Furthermore, analysis of bone differentiation markers in human osteoblasts shows that the composite mesh, unlike PLGA(80) plates, supports bone differentiation. The ability of the mesh to support homing and differentiation in both normal and mutant osteoprogenitors is important, in view of further developing autologous biohybrids to repair cranial bone deficits also in craniosynostotic patients undergoing extensive reconstructive surgery.     

Characterization and biocompatibility of a fibrous glassy scaffold

Bioactive glasses (BGs) are known for their ability to bond to living bone and cartilage. In general, they are readily available in powder and monolithic forms, which are not ideal for the optimal filling of bone defects with irregular shapes. In this context, the development of BG‐based scaffolds containing flexible fibres is a relevant approach to improve the performance of BGs. This study is aimed at characterizing a new, highly porous, fibrous glassy scaffold and evaluating its in vitro and in vivo biocompatibility. The developed scaffolds were characterized in terms of porosity, mineralization and morphological features. Additionally, fibroblast and osteoblast cells were seeded in contact with extracts of the scaffolds to assess cell proliferation and genotoxicity after 24, 72 and 144 h. Finally, scaffolds were placed subcutaneously in rats for 15, 30 and 60 days. The scaffolds presented interconnected porous structures, and the precursor bioglass could mineralize a hydroxyapatite (HCA) layer in simulated body fluid (SBF) after only 12 h. The biomaterial elicited increased fibroblast and osteoblast cell proliferation, and no DNA damage was observed. The in vivo experiment showed degradation of the biomaterial over time, with soft tissue ingrowth into the degraded area and the presence of multinucleated giant cells around the implant. At day 60, the scaffolds were almost completely degraded and an organized granulation tissue filled the area. The results highlight the potential of this fibrous, glassy material for bone regeneration, due to its bioactive properties, non‐cytotoxicity and biocompatibility. Future investigations should focus on translating these findings to orthotopic applications. Copyright © 2015 John Wiley & Sons, Ltd.     

Adipose‐ and bone marrow‐derived mesenchymal stem cells display different osteogenic differentiation patterns in 3D bioactive glass‐based scaffolds

Mesenchymal stem cells can be isolated from a variety of different sources, each having their own peculiar merits and drawbacks. Although a number of studies have been conducted comparing these stem cells for their osteo‐differentiation ability, these are mostly done in culture plastics. We have selected stem cells from either adipose tissue (ADSCs) or bone marrow (BMSCs) and studied their differentiation ability in highly porous three‐dimensional (3D) 45S5 Bioglass®‐based scaffolds. Equal numbers of cells were seeded onto 5 × 5 × 4 mm³ scaffolds and cultured in vitro, with or without osteo‐induction medium. After 2 and 4 weeks, the cell–scaffold constructs were analysed for cell number, cell spreading, viability, alkaline phosphatase activity and osteogenic gene expression. The scaffolds with ADSCs displayed osteo‐differentiation even without osteo‐induction medium; however, with osteo‐induction medium osteogenic differentiation was further increased. In contrast, the scaffolds with BMSCs showed no osteo‐differentiation without osteo‐induction medium; after application of osteo‐induction medium, osteo‐differentiation was confirmed, although lower than in scaffolds with ADSCs. In general, stem cells in 3D bioactive glass scaffolds differentiated better than cells in culture plastics with respect to their ALP content and osteogenic gene expression. In summary, 45S5 Bioglass‐based scaffolds seeded with ADSCs are well‐suited for possible bone tissue‐engineering applications. Induction of osteogenic differentiation appears unnecessary prior to implantation in this specific setting. Copyright © 2013 John Wiley & Sons, Ltd.     

Low‐melt bioactive glass‐reinforced 3D printing akermanite porous cages with highly improved mechanical properties for lumbar spinal fusion

Although great strides have been made in medical technology, low back/neck pain and intervertebral disc degeneration initiated from disc degenerative disease remains a clinical challenge. Within the field of regenerative medicine therapy, we have sought to improve the biomechanical transformation of spinal fusion procedures conducted using biodegradable porous implants. Specifically, we have focused on developing mechanically strong bioceramic cages for spinal fusion and functional recovery. Herein, we fabricated the akermanite (AKE) ceramic‐based porous cages using low‐melting bioactive glass (BG) and 3D printing technology. The osteogenic cell adhesion on the cages was evaluated in vitro, and the spinal fusion was tested in the intervertebral disc trauma model. The results indicated that incorporation of 15% or 30% BG into AKE (i.e., AKE/BG15 and AKE/BG30) could enhance the compressive strength of bioceramic cages by 2‐ or 5‐fold higher than the pure AKE cages (AKE/BG0). In comparison with porous β‐tricalcium phosphate cages, the surface of AKE/BG15 and AKE/BG30 cages greatly promoted the growth and alkaline phosphatase expression of osteogenic cells. Histological and biomechanical analysis showed that the AKE/BG15 and AKE/BG30 readily stimulated the new bone tissue growth and improved the spinal biomechanics recovery. In the AKE/BG15 and AKE/BG30 cage groups, 4–6 of the rabbits demonstrated a successful fusion. In contrast, only 0–1 of the initial seeded AKE/BG0 and tricalcium phosphate cages resulted in fusion at 12 weeks post‐operatively. In summary, the akermanite‐based cages showed an increased bone regenerative effect within an intervertebral disc trauma model, and thus, provided a promising candidate for improving spinal fusion surgery.     

Bioactive glass containing 90% SiO2 in hard tissue engineering: An in vitro and in vivo characterization study

Bioactive glass has been proved to have many applications in bioengineering due to its bone regenerative properties. In this work, an innovative, highly resorbable bioactive glass containing 90% SiO₂ (BG90) to be used as a bone substitute was developed. The BG90 was synthetized by the sol–gel process with the dry step at room temperature. The biomaterial showed in vitro and in vivo bioactivities even with silica content up to 90%. Moreover, the BG90 presented high porosity and surface area due to its homogenously interconnected porous network. In vitro, it was observed to have high cell viability and marked osteoblastic differentiation of rat bone marrow‐derived cells when in contact with BG90 ion extracts. The BG90 transplantation into rat tibia defects was analysed at 1, 2, 3, 4, 7, and 10 weeks post‐operatively and compared with the defects of negative (no graft) and positive (autogenous bone graft) controls. After 4 weeks of grafting, the BG90 was totally resorbed and induced higher bone formation than did the positive control. Bone morphogenetic protein 2 (BMP‐2) expression at the grafting site peaked at 1 week and decreased similarly after 7 weeks for all groups. Only the BG90 group was still exhibiting BMP‐2 expression in the last experimental time. Our data demonstrated that the BG90 could be an attractive candidate to provide useful approaches in hard‐tissue bioengineering.     

超顺磁性纳米氧化铁颗粒标记胰腺癌细胞的MR分子成像

目的 探讨超顺磁性纳米氧化铁颗粒（SPION）靶向标记胰腺癌细胞（BxPC-3）行MR分子成像的可行性。方法 制备黏蛋白1（MUC1）靶向修饰的探针MUC1-SPION（靶向组）,并以牛血清蛋白（BSA）制备非靶向探针BSA-SPION（非靶向组）。采过噻唑蓝（MTT）法测试不同MUC1-SPION浓度下（铁浓度为0、6.25、12.50、25、50、100、200 μg/ml）的细胞毒性。并分别于铁浓度为50、100、200 μg/ml条件下,对靶向组及对照组与BxPC-3细胞共同孵育2 h后的细胞悬液进行MR成像,测定横向弛豫时间（T2）,计算T2强化率。以普鲁士蓝染色观察靶向探针与细胞结合情况。结果 MTT法细胞毒性实验显示,不同MUC1-SPION浓度下BXPC-3细胞增殖率差异无统计学意义（F=1.74,P=0.183）。铁浓度50、100、200 μg/ml条件下,2组间T2值和T2强化率的差异均有统计学意义（P均<0.05）。普鲁士蓝染色显示靶向组的蓝染颗粒更多。结论 MUC1-SPION对BxPC-3细胞具有良好的靶向性,以SPION靶向标记BxPC-3细胞进行MRI安全、可行。     

经椎弓根内固定附加生物活性玻璃行椎体后外侧融合治疗胸腰椎爆裂骨折

目的探讨经椎弓根内固定附加生物活性玻璃行椎体后外侧融合手术治疗胸腰椎爆裂骨折的临床疗效观察。方法38例胸腰椎爆裂骨折应用后路短节段椎弓根螺钉内固定后,用生物活性玻璃行椎体后外侧融合。结果随访3～16月,脊柱融合效果明显,融合率高达89．5％,椎体后突畸形及高度得到明显的恢复,X线未见一例断钉,断杆,内固定松动现象,无明显脊柱后凸畸形,矫正高度再丢失现象。结论经椎弓根内固定附加生物活性玻璃行椎体后外侧融合手术治疗胸腰椎爆裂骨折疗效显著,方法简单,值得推广。     

Gelatin coating increases in vivo bone formation capacity of three‐dimensional 45S5 bioactive glass‐based crystalline scaffolds

Recent studies have demonstrated that surface characteristics, porosity, and mechanical strength of three‐dimensional 45S5‐type bioactive glass (BG)‐based scaffolds are directly correlated with osteogenic properties. Three‐dimensional BG‐based scaffolds obtained from maritime natural sponges (MNSs) as sacrificial templates exhibit the required morphological properties; however, no in vivo data about the osteogenic features are available. In this study, uncoated (Group A) and gelatin‐coated (Group B) crystalline MNS‐obtained BG‐based scaffolds were evaluated mechanically and seeded with human mesenchymal stem cells prior to subcutaneous implantation in immunodeficient mice. Before implantation and after explantation, micro‐computed tomography scans were conducted, and scaffolds were finally subjected to histomorphometry. Scaffolds of both groups showed bone formation. However, Group B scaffolds performed distinctly better as indicated by a significant increase in scaffold volume (8.95%, p = 0.039) over the implantation period compared with a nonsignificant increase of 5.26% in Group A scaffolds in micro‐computed tomography analysis. Furthermore, percentage bone area was 10.33% (±1.18%) in the Group B scaffolds, which was significantly (p = 0.007) higher compared with the 8.53% (±0.77%) in the Group A scaffolds in histomorphometry. Compressive strength was enhanced significantly by gelatin coating (9 ± 2 vs. 4 ± 1 MPa; p = 0.029). The presence of gelatin on the remnant parts was verified by scanning electron microscopy and X‐ray spectroscopy, demonstrating the coatings' resilience. MNS‐obtained BG‐based scaffolds were thus confirmed to exhibit osteogenic properties in vivo that can significantly be enhanced by gelatin coating.     

In vivo quantification of SPIO nanoparticles for cell labeling based on MR phase gradient images

Along with the development of modern imaging technologies, contrast agents play increasingly important roles in both clinical applications and scientific research. Super‐paramagnetic iron oxide (SPIO) nanoparticles, a negative contrast agent, have been extensively used in magnetic resonance imaging (MRI), such as in vivo labeling and tracking of cells. However, there still remain many challenges, such as in vivo quantification of SPIO nanoparticles. In this work, an MR phase gradient‐based method was proposed to quantify the SPIO nanoparticles. As a calibration, a phantom experiment using known concentrations (10, 25, 50, 100, 150 and 250 µg/ml) of SPIO was first conducted to verify the proposed quantification method. In a following in vivo experiment, C6 glioma cells labeled with SPIO nanoparticles were implanted into flanks of four mice, which were scanned 1–3 days post‐injection for in vivo quantification of SPIO concentration. The results showed that the concentration of SPIO nanoparticles could be determined in both phantom and in vivo experiments using the developed MR phase gradients approach. Copyright © 2014 John Wiley & Sons, Ltd.     

胆固醇合成抑制剂辛伐他汀对K562细胞增殖和凋亡的作用

目的 探讨慢性髓细胞白血病（CML）细胞抗凋亡机制和诱导CML细胞凋亡的有效方法。方法 采用CML细胞株K562体外培养、用^3H-TdR掺入法及DNA末端标记法观察胆固醇合成限速酶3－羟－3－甲基戊二酰辅酶A（HMG－CoA)还原酶抑制剂辛伐他汀对K562细胞增殖及凋亡的作用,以及该制剂联合化疗药物对K562细胞凋亡的影响。结果 辛伐他汀明显抑制562细胞增殖并诱导其凋亡,并能增强K562细胞对化疗药物的敏感性。加入HMG－CoA下游产物甲羟戊酸可完全逆转这种作用。结论 辛伐他汀通过抑制甲羟戊酸代谢途径抑制K562细胞增殖并诱导其凋亡,表明HMG－CoA还原酶抑制剂作为治疗CML的药物具有潜在的应用价值。     

IR780-VPN靶向纳米粒的制备及其对肾母细胞瘤的抑制作用

目的制备同时携带IR780碘化物和硫酸长春新碱（VCR）的聚乳酸-羟基乙酸（PLGA）靶向纳米粒（IR780-VPN）,并观察其在体外对肾母细胞瘤（SK-NEP1）的靶向作用及抗肾母细胞瘤增殖效率。 方法制备IR780-VPN,检测其基本理化特性,培养SK-NEP1细胞作为体外肿瘤细胞模型,研究IR780-VPN的体外靶向性,观察以下6组的体外抗SK-NEP1细胞增殖效率：A组,PBS（对照组）;B组,游离VCR;C组,空白纳米粒（PN）;D组,载VCR纳米粒（VPN）;E组,载IR780纳米粒（IR780-PN）;F组,IR780-VPN。 结果制备出的IR780-VPN平均粒径为（290.82±3.22）nm,粒径的分散指数（PDI）为0.024,平均Zeta电位为（1.16±0.87）mV。用细胞膜绿色荧光探针染色后于倒置荧光显微镜下观察,IR780-VPN大小均匀、形态规则,无聚集、粘连;透射电镜下观察IR780-VPN为球形或类球形,表面光滑,粒径分布均匀。其平均包封率为72.80%,平均载药量为2.80%,平均连靶率为91.30%。体外寻靶实验中可见SK-NEP1细胞表面有大量的IR780-VPN聚集。体外抗SK-NEP1细胞增殖实验证实,在相同药物质量浓度条件下,IR780-VPN组较VCR、VPN组的体外抗肿瘤细胞增殖效率高（P均<0.001）,且游离VCR、VPN、IR780-VPN对SK-NEP1细胞增殖的抑制率具有浓度依赖性,药物质量浓度越大,对细胞的抑制作用越强（F=13254.105、54354.510、1370.059,P均<0.001）;而随着药物质量浓度增加,PN、IR780-PN组的细胞增殖抑制率差异均无统计学意义（P均>0.05）,PBS（对照组）对SK-NEP1细胞增殖的抑制率为（2.83±0.32）%。 结论本实验成功制备了性质稳定的靶向IR780-VPN,对肾母细胞瘤细胞有良好的的靶向性,并提高了体外抗肾母细胞瘤增殖效率,为体内的肿瘤分子靶向研究提供了实验基础。     

Biomaterial and implant induced ossification: in vitro and in vivo findings

Material‐induced ossification is suggested as a suitable approach to heal large bone defects. Fiber‐reinforced composite–bioactive glasses (FRC‐BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC‐BG implant in vivo from the perspective of material‐induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly‐formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC‐BG, we cultured human adipose tissue‐derived mesenchymal stromal cells (AD‐MSCs) in the presence of two different BGs (45S5 and S53P4) and Al₂O₃ control. AD‐MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro‐osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC‐BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC‐BG implant demonstrated material‐induced ossification both in vitro and in vivo.     

PRP19 upregulation inhibits cell proliferation in lung adenocarcinomas by p21-mediated induction of cell cycle arrest

Precursor messenger RNA processing factor 19 (PRP19) is known to be a critical component of the eukaryotic spliceosomal machinery and DNA damage repair system, the deregulation of which leads to many disease conditions. In many human cancers, PRP19 expression is upregulated, but its functional significance and corresponding underlying mechanisms remain to be addressed. Focusing on lung carcinomas, PRP19 upregulation was achieved by plasmid transfection into A549 adenocarcinoma cells. The transfected cells were then subjected to several in vitro and in vivo assays following in situ assessment of the protein in paired clinical lung tissues. We report that PRP19 expression is elevated in lung carcinoma tissues compared to non-tumor tissues. Following its upregulation, PRP19 repressed cell proliferation and tumor growth by upregulating the expression of the cell cycle arrest protein p21.     

火罐疗法辅助治疗毛细支气管炎的临床观察及护理

目的 :探讨火罐疗法辅助治疗毛细支气管炎的作用及护理要点。方法 :将所观察的患儿分为治疗组与对照组。对照组采用传统的治疗方法 ,治疗组在传统治疗的基础上 ,加用火罐疗法 ,在患儿双侧肺俞穴拔罐每日 1次 ,每次 10～ 15min ,2d为一疗程。结果 :治疗组显效率、有效率明显高于对照组 ,差异有显著性意义 (P <0 0 5 )。结论 :火罐疗法能够作为毛细支气管炎的一种辅助疗法 ,能迅速减轻毛细支气管炎的症状