Electrospun materials as potential platforms for bone tissue engineering

Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future.     

Electron transfer kinetics and morphology of cytochrome c at the biomimetic phospholipid layers

Electrochemistry of cytochrome c (cyt c) at biomimetic phospholipid layers was studied in a phosphate buffer solution, which were formed with dilauroyl phosphatidic acid (DLPA, C12:0), dipalmitoyl phosphatidic acid (DPPA, C16:0), distearoyl phosphatidic acid (DSPA, C18:0), and palmitoyl–oleoyl phosphatidic acid (POPA, C16:0–18:1). The lipid-layers formed firstly at the air/water interface were immediately transferred onto the electrode surface using the Langmuir–Blodgett (LB) technique. The electrochemical properties of cyt c at the lipid covered electrodes depended on the orientation, number of layers of phospholipids, tail (or head) group down, and vice versa. Atomic force microscopy (AFM) images of cyt c adsorbed on the POPA monolayer (showing the head group diameter of POPA to be ca. 0.7 nm) formed on highly oriented pyrolytic graphite (HOPG) displayed uniform surface morphology of lipid layer and clumps of aggregated cyt c molecules with a minimum size corresponding to four cyt c molecules. The heterogeneous electron transfer rate constants, k⁰ values, of cyt c were determined to be 1.02 × 10⁻³, 0.98 × 10⁻³, and 0.67 × 10⁻³ cm/s for the lipid monolayer in the tail down orientation (X-type) of POPA, DLPA, and DPPA, and 0.67 × 10⁻³ and 0.50 × 10⁻³ cm/s for the head down orientation (Z-type) of POPA and DLPA monolayers, respectively.     

Bioinspired membrane-based nanomodulators for immunotherapy of autoimmune and infectious diseases

Autoimmune or infectious diseases often instigate the undesirable damages to tissues or organs to trigger immune-related diseases, which involve plenty of immune cells, pathogens and autoantibodies. Nanomedicine has a great potential in modulating immune system. Particularly, biomimetic nanomodulators can be designed for prevention, diagnosis and therapy to achieve a better targeted immunotherapy. With the development of materials science and bioengineering, a wide range of membrane-coated nanomodulators are available. Herein, we summarize recent advancements of bioinspired membrane-coated nanoplatform for systemic protection against immune-related diseases including autoimmune and infectious diseases. We also rethink the challenges or limitations in the progress of the therapeutic nanoplatform, and discuss the further application of the nanomodulators in the view of translational medicine for combating immune-related diseases.     

Enhancing cancer chemo-immunotherapy by biomimetic nanogel with tumor targeting capacity and rapid drug-releasing in tumor microenvironment

In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).     

人工龋树脂牙本质粘接界面拟生态矿化的定量评估

目的 探讨人工龋拟生态再矿化的定量评估方法和效果.方法 通过脱矿/再矿化液的pH 循环法建立人工龋模型,使用全酸蚀粘接剂Single Bond Plus（SB 组）、One-Step（OS 组）和自酸蚀粘接剂Adper Prompt L-Pop（LP 组）进行树脂粘接,在含聚丙烯酸（PAA）和聚乙烯膦酸（PVPA）的模拟体液/硅酸盐水门汀系统中诱导矿化,采用显微计算机X 线断层摄影术（micro CT）定量评估再矿化效果.结果 矿化诱导4 个月后SB 组、OS 组和LP 组样本病损深度均有降低,由矿化前的300 滋m 分别减少至47、53 和87 滋m,矿化率分别为73.76%、81.39%和74.54%.结论 micro CT 是定量评估人工龋树脂牙本质粘接界面矿化程度的一种有效方法.含PAA 和PVPA 的模拟体液/硅酸盐水门汀系统可诱导树脂渗透脱矿牙本质再矿化（P ＜ 0.05）,且不同的粘接剂对人工龋拟生态再矿化效率无显著性影响.     

个体化人工骨双循环系统的仿生制造

目的: 探讨一种从CT图像反求建模, 制造带有双循环系统 (微管循环和微孔循环 ) 的人工骨。方法: 采用狗股骨下段为对象, 应用Medical_Soft软件处理CT数据, 在Surfa cer软件中重构的狗股骨关节面, 并将数据输入Unigraphics软件中设计人工股骨下端三维模具,并且在人工骨模具内部设计立体微管结构。设计完成后生成STL文件并输入快速成型机加工。在模具内灌装磷酸三钙后烧结, 即得到带有双循环系统的人工骨。结果: 采用CT扫描资料建立起来的三维模型, 形态准确, 在这种模型的基础上, 灌装烧结的人工骨具有双循环系统, 微管大小 220 ~250μm,微孔大小 250~300μm, 孔内连接大小 50~100μm。结论: 个体化的人工骨三维模型的建立, 为人工骨的制造打下了良好的基础, 带有双循环系统的人工骨, 可以使生物活性物质 (生长因子、骨细胞 )、组织液渗透入人工骨深部, 缩短血管长入的时间, 从而新骨长入和成骨替代。     

Functional remodeling after vocal fold injury by small intestinal submucosa gel containing hepatocyte growth factor

A biomaterial derived from porcine small intestinal submucosa (SIS) was used in smart drug delivery and tissue remodeling. SIS suspensions were easily formulated by simple mixing with the drug of choice and formed an in situ gel upon injection into tissues, enabling them to act as protein drug depots. This study was conducted to determine whether functional remodeling of an injured vocal fold (VF) could be achieved by hepatocyte growth factor (HGF)-containing SIS in situ-forming gel after VF injury in a rabbit model. To accomplish this, we loaded HGF in SIS suspensions and observed a gradual, sustained release of HGF for at least 21 days in vitro. Evaluation of the in vivo efficacy demonstrated that the HGF and HGF-loaded SIS treated VFs showed improved mucosal healing when compared with the PBS-injected VFs. Histopathological evaluations revealed that treatment with the HGF/SIS group alone successfully ameliorated the deposition of type I collagen and increased synthesis of hyaluronic acids relative to the PBS group at three months post-injury. Functional analyses showed that the HGF/SIS group prevented deterioration of mucosal vibration and induced significant improvement in the mean viscoelastic modulus, but that other groups failed to achieve functional rescue of VF biomechanics. Additionally, the VF oscillation in the HGF/SIS group was superior to that in the HGF group. The results of this study suggest that SIS in situ gel has the potential for use as an HGF delivery carrier for enhancement of wound healing and improvement of functional remodeling following VF injury.     

3-Dimensional spatially organized PEG-based hydrogels for an aortic valve co-culture model

Physiologically relevant in vitro models are needed to study disease progression and to develop and screen potential therapeutic interventions for disease. Heart valve disease, in particular, has no early intervention or non-invasive treatment because there is a lack of understanding the cellular mechanisms which lead to disease. Here, we establish a novel, customizable synthetic hydrogel platform that can be used to study cell–cell interactions and the factors which contribute to valve disease. Spatially localized cell adhesive ligands bound in the scaffold promote cell growth and organization of valve interstitial cells and valve endothelial cells in 3D co-culture. Both cell types maintained phenotypes, homeostatic functions, and produced zonally localized extracellular matrix. This model extends the capabilities of in vitro research by providing a platform to perform direct contact co-culture with cells in their physiologically relevant spatial arrangement.     

国产多孔钽铌合金材料骨结合性能评价

目的: 评价国产多孔钽铌合金材料的骨结合性能。方法: 选取成年新西兰大白兔36只,将多孔钽铌合金植体植入家兔股骨髁部,术后4、8、12周分批处死家兔并取材,通过X线片、硬组织切片、扫描电镜、X线能谱分析、推出试验评价其骨结合性能。采用SPSS19.0软件包对数据进行统计学分析。结果: X线检查未见植体松脱及明显骨吸收影像,随着愈合时间延长,材料周围骨密度增高;硬组织切片甲苯胺蓝染色观察显示,骨组织与多孔钽铌材料呈凹凸嵌合状,随着愈合时间延长,大量骨组织长入材料孔隙内部,4周组材料周围及内部多为类骨质,12周组材料周围及内部骨组织成熟度明显提高;扫描电镜与X线能谱分析显示,随着时间延长,骨组织与材料接触趋于致密,孔隙内骨组织钙磷元素百分含量逐渐增高,Ca/P比值8周组与12周组显著高于4周组（P<0.05）,8周组与12周组之间无明显差异（P>0.05）;推出试验示,4周时平均剪切强度为(8.26±0.75）MPa,12周时增加至(21.04±1.46)MPa,组间比较具有统计学差异（P<0.05）。结论: 国产多孔钽铌合金材料在动物骨内具有优良的骨结合性能,是一种极具潜力的骨组织工程材料。     

The intrinsic pKa values for phosphatidic acid in monolayers deposited on mercury electrodes

The intrinsic K_a values of the phosphate group of phosphatidic acid (PA) in self-organized monolayers deposited on a hanging mercury drop electrode were determined by a novel procedure based on measurements of the differential capacity C of this lipid-coated electrode. In line with the Gouy-Chapman theory, plots of $\text{1}\text{C}$ at constant bulk pH and variable KCl concentration against the reciprocal of the calculated diffuse-layer capacity C_d,0 at zero charge exibit slopes that decrease from an almost unit value to zero as the absolute value of the charge density on the lipid increases from zero to ≈ 2 μC cm^?2. The values so determined are K₁ = 10⁸ M^?1 and K₂ = 10⁴ M^?1. The plots of $\text{1}\text{C}$ against $\text{1}\text{C}{}_{\mathrm{<mtext>d</mtext><mtext>,0</mtext>}}$ for PA exhibit slopes that pass from zero to a maximum value and then again to zero as pH is varied from 7.5 to 1.5, indicating that the charge density of the lipid film passes from slightly negative to slightly positive values over this pH range. An explanation for this anomalous behavior is provided.