Guidance of neural regeneration on the biomimetic nanostructured matrix

Biomimetic materials are used for creating microsystems to control cell growth spatially and elicit specific cellular responses by combining complex biomolecules with nanostructured surfaces. Intercellular cell-to-cell and cell-to-extracellular matrix (ECM) interactions in biomimetic materials have demonstrated potential in the development of drug discovery platforms and regeneration medicine. In this study, we developed a biomimetic nanostructured matrix by using various ECM molecular layers to create a biomimetic and biocompatible environment for realizing neuronal guidance in neural regeneration medicine. Silicon-based substrates possessing nanostructures were modified using different ECM proteins and peptides to develop a biomimetic and biocompatible environment for studying neural behaviors in adhesion, proliferation, and differentiation. The substrates were flat glass, flat silicon wafers (FWs), and nanorod-structured wafers prepared using wet etching. The three substrates were then functionalized using laminin-1 peptide, PA22-2-contained active isoleucine-lysine-valine-alanine-valine (IKVAV) peptide, and poly-d-lysine (PDL), separately. When PC12 cells were cultured and differentiated on the modified substrates, the cells were able to elongate the neurites on the glass and FW, which was coated with three types of peptide. More differentiated neurons were observed on the nanorod-structured wafers coated with laminin than on those coated with IKVAV or PDL. For achieving directional guidance of neurite outgrowth, substrates exhibiting a grating pattern of nanorods were partially collapsed by the pulling force of water, leaving few nanorods, which support the net form of laminin on the surface. Furthermore, we fabricated the topological nanostructure-patterned wafer coated with laminin and successfully manipulated the extension and direction of neurites by using more than 80 μm of a single soma. This approach demonstrates potential as a facile and efficient method for guiding the direction of single axons and for enhancing neurite outgrowth in studies on nerve regenerative medicine.     

醒脑开窍针法联合仿生物电刺激治疗脑卒中后吞咽障碍的疗效观察

目的：探讨醒脑开窍针法联合仿生物电刺激治疗脑卒中后吞咽障碍的临床疗效。方法：将80例伴有吞咽障碍的脑卒后患者随机分为对照组和治疗组,在使用无差别的神经科药物治疗基础上,对照组单纯给予普通针刺治疗,治疗组给予醒脑开窍针法联合仿生物电刺激治疗。治疗结束后评估患者的吞咽障碍改善情况,评价临床疗效。结果：治疗结束后治疗组总有效率明显高于对照组（P＜0．05）,醒脑开窍针法联合仿生物电刺激治疗对脑卒中后吞咽障碍的改善情况与对照组比较有统计学差异。结论：醒脑开窍针法联合仿生物电刺激治疗对脑卒中后吞咽障碍具有明显的改善作用。     

Fabrication and mechanical properties of biomimetic nacre-like ceramic/polymer composites for chairside CAD/CAM dental restorations

ObjectiveTo fabricate and characterise a novel chairside CAD/CAM composite dental materials. These composites have a nacre-like anisotropic microstructure, consisting of highly aligned ceramic scaffolds infiltrated with polymer.MethodBi-directional freeze casting of alumina ceramic suspension was used to fabricate highly aligned ceramic scaffolds that were subsequently uniaxially pressed to control the ceramic volume fraction and then infiltrated with UDMA/TEGDMA polymer. The produced composites were subjected to mechanical testing, namely three-point bending, hardness and fracture toughness tests.ResultsNovel biomimetic ceramic/polymer composites (BCPCs) were fabricated with nacre-like brick and mortar anisotropic microstructure. The mechanical properties were dependent on the ceramic volume fraction. The 70 vol% BCPC had sufficient flexural strength (135.08–145.77 MPa), stiffness (57.75–61.22 GPa) and hardness (3.07–3.36 GPa) and showed remarkable fracture resistance with K_IC value of (2.54 MPa m^1/2).SignificantNovel biomimetic ceramic/polymer composites show great potential as the next generation of CAD/CAM dental materials, as they closely resemble the combined mechanical properties of dentine and enamel.     

Biomimetic bone-like composites fabricated through an automated alternate soaking process

Hydroxyapatite–gelatin composites have been proposed as suitable scaffolds for bone and dentin tissue regeneration. There is considerable interest in producing these scaffolds using biomimetic methods due to their low energy costs and potential to create composites similar to the tissues they are intended to replace. Here an existing process used to coat a surface with hydroxyapatite under near physiological conditions, the alternate soaking process, is modified and automated using an inexpensive “off the shelf” robotics kit. The process is initially used to precipitate calcium phosphate coatings. Then, in contrast to previous utilizations of the alternate soaking process, gelatin was added directly to the solutions in order to co-precipitate hydroxyapatite–gelatin composites. Samples were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and nanoindentation. Calcium phosphate coatings formed by the alternate soaking process exhibited different calcium to phosphate ratios, with correspondingly distinct structural morphologies. The coatings demonstrated an interconnected structure with measurable mechanical properties, even though they were 95% porous. In contrast, hydroxyapatite–gelatin composite coatings over 2 mm thick could be formed with little visible porosity. The hydroxyapatite–gelatin composites demonstrate a composition and mechanical properties similar to those of cortical bone.     

Guiding the morphogenesis of dissociated newborn mouse retinal cells and hES cell-derived retinal cells by soft lithography-patterned microchannel PLGA scaffolds

Embryonic stem (ES) cell-derived photoreceptors are a promising cell source for enhanced in vitro models of retinal degenerative diseases, but the more differentiated characteristics of retinal cells do not typically develop in dissociated cell cultures. Therefore, we have reconstructed organized retinal tissue by seeding dissociated cells into an array of aligned units that more faithfully mimics the retina. We solvent-processed poly(lactic-co-glycolic acid) (PLGA) into a microchannel scaffold format to achieve this geometric constraint. We compared the effect of PLGA concentration on channel morphology and, along with other culture conditions, on the infiltration of dissociated newborn mouse retinal cells into the channels. Culturing scaffolds at the gas-liquid interface with low serum media increased infiltrated rod photoreceptor viability 18-fold over submerged, high serum cultures when evaluated after seven days. Rod photoreceptors and Müller glia aligned processes parallel to the microchannel walls. Otx2+ and Pax6+ subpopulations recapitulated lamination behavior. Further, we constructed scaffold/retinal pigment epithelium (RPE) co-cultures and observed rods extending rhodopsin-positive processes toward RPE cells, mimicking normal rod polarization and morphology. Finally, human embryonic stem cell-derived photoreceptors exhibited infiltration and morphological characteristics similar to mouse retinal cells inside the scaffolds. These findings constitute an important advance in generating tissue-level retinal models from dissociated cells for use as drug screening platforms and in regenerative medicine.     

A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms,and future perspectives

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems, respectively. And the current challenges and prospects of each strategy are discussed. In addition, we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.     

钛表面TiO2纳米管仿生修饰对成骨细胞骨功能基因表达的影响

目的:钛种植体表面制备TiO₂纳米管并在其表面仿生构建钙磷涂层,探索该涂层对成骨细胞骨功能基因表达的影响。方法:采用阳极氧化法在钛基底表面制备TiO₂纳米管,并进行碱热处理后在其表面构建仿生钙磷涂层,扫描电镜观察其表面结构的改变,能谱分析其表面化学成分的改变,采用实时定量PCR检测成骨细胞在其表面骨相关基因表达差异。结果:仿生处理可以在TiO₂纳米管表面制备出纳米絮状的钙磷涂层,该涂层可以提高碱性磷酸酶和骨钙蛋白基因的表达(P<0.05)。结论:TiO₂纳米管仿生修饰更有利于成骨细胞的碱性磷酸酶和骨钙蛋白的基因表达。     

Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study

Objectives

Sleep, which comprises of rapid eye movement (REM) and non-REM stages 1–3 (N1–N3), is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function. The principal sedative drugs produce electroencephalogram beta oscillations, which have been associated with neurocognitive dysfunction. Pharmacological induction of altered arousal states that neurophysiologically approximate natural sleep, termed biomimetic sleep, may eliminate drug-induced neurocognitive dysfunction.

仿生物电刺激治疗对薄型子宫内膜不孕症患者再妊娠的有效性及安全性

目的 探究仿生物电刺激治疗薄型子宫内膜不孕症患者后再次妊娠的有效性及对胚胎的安全性。方法 采用前瞻性非随机对照研究选取本院2020年1月—2021年3月诊断为薄型子宫内膜不孕症的72例患者为研究对象,根据患者治疗意愿选择芬吗通治疗组(对照组)和电刺激阴道+穴位(中极、关元、足三里、三阴交、太冲、肾俞)联合芬吗通组(观察组),每组各36例,治疗时间为3个排卵周期,比较两组治疗前后的盆底肌肌力、子宫内膜容受性、再妊娠及孕产结局等临床数据。结果 治疗后,观察组患者盆底肌肌力,子宫内膜容受性,再妊娠率均有改善,盆底肌I类肌纤维及Ⅱ类肌纤维肌力有明显提升,且子宫动脉血流RI值较观察组显著降低(均P<0.05),再妊娠率高于对照组,差异具有统计学意义(P<0.05);两组子宫内膜厚度及A型子宫内膜形态比例均有所增加但差异不明显(P>0.05),两组无创产前检测、剖宫产率、产时出血量、胎儿Apgar评分无明显差异(P>0.05)。两组治疗期间无严重不良反应,妊娠期主要并发症为妊娠期糖尿病。结论 薄型子宫内膜不孕症患者盆底肌肌力差,联合穴位、药物阴道电刺激能够促进盆腔血液循环,...