Localized delivery of mechano-growth factor E-domain peptide via polymeric microstructures improves cardiac function following myocardial infarction

The Insulin like growth factor-I isoform mechano-growth factor (MGF), is expressed in the heart following myocardial infarction and encodes a unique E-domain region. To examine E-domain function, we delivered a synthetic peptide corresponding to the unique E-domain region of the human MGF (IGF-1Ec) via peptide eluting polymeric microstructures to the heart. The microstructures were made of poly (ethylene glycol) dimethacrylate hydrogel and bioengineered to be the same size as an adult cardiac myocyte (100 × 15 × 15 μm) and with a stiffness of 20 kPa. Peptide eluting microrods and empty microrods were delivered via intramuscular injection following coronary artery ligation in mice. To examine the physiologic consequences, we assessed the impact of peptide delivery on cardiac function and cardiovascular hemodynamics using pressure–volume loops and gene expression by quantitative RT-PCR. A significant decline in both systolic and diastolic function accompanied by pathologic hypertrophy occurred by 2 weeks which decompensated further by 10 weeks post-infarct in the untreated groups. Delivery of the E-domain peptide eluting microrods decreased mortality, ameliorated the decline in hemodynamics, and delayed decompensation. This was associated with the inhibition of pathologic hypertrophy despite increasing vascular impedance. Delivery of the empty microrods had limited effects on hemodynamics and while pathologic hypertrophy persisted there was a decrease in ventricular stiffness. Our data show that cardiac restricted administration of the MGF E-domain peptide using polymeric microstructures may be used to prevent adverse remodeling of the heart and improve function following myocardial infarction.     

Solubilized extracellular matrix from brain and urinary bladder elicits distinct functional and phenotypic responses in macrophages

Extracellular matrix (ECM) derived from a variety of source tissues has been successfully used to facilitate tissue reconstruction. The recent development of solubilized forms of ECM advances the therapeutic potential of these biomaterials. Isolated, soluble components of ECM and matricryptic peptides have been shown to bias macrophages toward a regulatory and constructive (M2-like) phenotype. However, the majority of studies described thus far have utilized anatomically and morphologically similar gastrointestinal derived ECMs (small intestine, esophagus, urinary bladder, etc.) and a small subset of macrophage markers (CD206, CD86, CCR7) to describe them. The present study evaluated the effect of solubilized ECM derived from molecularly diverse source tissues (brain and urinary bladder) upon primary macrophage phenotype and function. Results showed that solubilized urinary bladder ECM (U-ECM) up-regulated macrophage PGE2 secretion and suppressed traditional pro-inflammatory factor secretion, consistent with an M2-like phenotype. The hyaluronic acid (HA) component in solubilized U-ECM played an important role in mediating this response. Brain ECM (B-ECM) elicited a pro-inflammatory (M1-like) macrophage response and contained almost no HA. These findings suggest that the molecular composition of the source tissue ECM plays an important role in influencing macrophage function and phenotype.     

Synthesis,properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of tissue engineering applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental cell research, cell signaling, drug and gene delivery, and bio-sensing.     

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.     

聚乙烯醇水凝胶含水率影响因素的初步研究

目的：研究影响聚乙烯醇（PVA）水凝胶含水率的相关因素。方法：将冷冻干燥后的PVA水凝胶浸泡于模拟体液（SBF）中再溶胀,观察不同分子量,不同循环次数,不同浓度PVA水凝胶随时间的再溶胀规律。结果：以PVA水凝胶的含水率为评价指标,在其他因素相同的条件下：不同分子量水凝胶的含水率：高分子量组＞中分子量组＞低分子量组,差异有显著性（P＜0．05）;冷冻循环1次的PVA水凝胶含水率47％,冷冻循环3次、5次、7次组含水率均大于80％,3组间无显著性差异（P＞0．05）;不同浓度PVA水凝胶的含水率测试结果为：10 wt％组＞15 wt％组＞20 wt％组＞25 wt％组,差异有显著性（P＜0．05）。结论：在本实验条件下,分子量高的PVA水凝胶的含水率较高,PVA浓度高的PVA水凝胶的含水率较低,经3～7次冷冻循环的PVA水凝胶具有高含水率。     

人工晶状体光学材料对后囊膜混浊影响的荟萃分析

目的系统评价不同光学材料人工晶状体对后囊膜混浊的影响。方法通过计算机和手工检索,获得以往发表的相关文献。按照选择标准选取合适的随机对照临床研究进行荟萃(Meta)分析。按照意向性分析原则对纳入文献的相关资料进行提取摘录,并根据Meta分析的统计学方法进行合并分析。以钕:铱铝石榴石(Nd:YAG)激光囊膜切开术为临床治疗终点,以危险差来判定预防效果,选择随机效应模型计算总的治疗效应。结果总计有14个试验纳入Meta分析。疏水性丙烯酸和聚甲基丙烯酸甲酯(PMMA)的合并危险差为-20%(95%CI为-24%～-16%),硅凝胶和PMMA的合并危险差为-8%(95%CI为-15%～-1%),水凝胶和PMMA的合并危险差为10%(05%CI为-9%～29%),硅凝胶和疏水性丙烯酸的合并危险差为4%(95%CI为-1%～8%),水凝胶和疏水性丙烯酸的合并危险差为14%(1%～26%),水凝胶和硅凝胶的合并危险差为23%(95%CI为8%～39%)。结论硅凝胶和疏水性丙烯酸人工晶状体可以预防后囊膜混浊的发生,从而减少Nd:YAG激光囊膜切开术的应用,相反水凝胶人工晶状体不能减少囊膜切开术的应用。     

聚丙烯酰胺水凝胶注入兔体的免疫效应研究

目的　观察注射性聚丙烯酰胺水凝胶 (PAMHG)注入实验兔体的免疫效应。方法　采用间接免疫荧光法或双抗体夹心ELISA法 ,监测PAMHG注入兔体前后T淋巴细胞亚群、NK细胞活性、IL 2和sIL 2R表达水平。结果　PAMHG注入兔体前 ,CD3+ 和CD4 + T淋巴细胞表达水平分别为(17.8± 5 .9) %和 (9.6± 3.5 ) % ;PAMHG注入兔体后 3个月 ,表达水平分别为 (2 4 .3± 5 .6 ) %和 (15 .8± 4 .7) %。注入前后比较有显著差异 (P <0 .0 1)。 3个月后表达水平逐渐下降 ,与术前比较差异无显著意义 (P >0 .0 5 )。PAMHG注入兔体前 ,CD8+ T淋巴细胞表达水平为 (6 .2± 2 .4 ) % ,与注入后 3个月为 (8.5± 4 .2 ) %比较仅略有上升 ,两者比较P >0 .0 5。注入兔体前、后CD4 + CD8+ 比值均在正常范围(1～ 2 )。NK细胞活性仅于注入兔体 1个月为 (2 5 .3± 6 .8) % ,较注入前 (18.0± 9.7) %升高 (P <0 .0 5 ) ,俟后NK细胞活性逐渐下降 ,与注入前比较差异无显著性意义 (P >0 .0 5 )。IL 2和sIL R表达水平于注入兔体前后差异无显著性意义 (P >0 .0 5 )。结论　PAMHG用作软组织填充剂 ,仅在机体内引起短时异物排斥 ,可渐与组织相容 ,不会引起严重免疫功能失调     

Axonal growth within poly (2-hydroxyethyl methacrylate) sponges infiltrated with Schwann cells and implanted into the lesioned rat optic tract

Porous hydrophilic sponges made from 2-hydroxyethyl methacrylate (HEMA) have a number of possible biomedical applications. We have investigated whether these poly(HEMA) hydrogels, when coated with collagen and infiltrated in vitro with cultured Schwann cells, can be implanted into the lesioned optic tract and act as prosthetic bridges to promote axonal regeneration. Nineteen rats (20–21 days old) were given hydrogel/Schwann cell implants. No obvious toxic effects were seen, either to the transplanted glia or in the adjacent host tissue. Schwann cells survived the implantation technique and were immunopositive for the low affinity nerve growth factor receptor, S100 and laminin. Immunohistochemical studies showed that host non-neuronal cells (astrocytes, oligodendroglia and macrophages) migrated into the implanted hydrogels. Astrocytes were the most frequently observed host cell in the polymer bridges. RT97-positive axons were seen in about two thirds of the implants. The axons were closely associated with transplanted Schwann cells and, in some cases, host glia (astrocytes). Individual axons regrowing within the implanted hydrogels could be traced for up to 900 μm, showing that there was continuity in the network of channels within the polymer scaffold. Axons did not appear to be myelinated by either Schwann cells or by migrated host oligodendroglia. In three rats, anterograde tracing with WGA/HRP failed to demonstrate the presence of retinal axons within the hydrogels. The data indicate that poly(HEMA) hydrogels containing Schwann cells have the potential to provide a stable three-dimensional scaffold which is capable of supporting axonal regeneration in the damaged CNS.     

两亲性含IKVAV的肽体内诱导血管生成的研究

目的设计合成含IKVAV的两亲性肽，探讨其体外自组装成三维多孔凝胶及体内诱导血管生成的可行性。方法固相法合成肽．自组装成凝胶，TEM观察凝胶结构。实验组：配制1wt％的肽溶液，pH值为9．0；对照组：配制16．67％的明胶，DH值为7．4。各取1mL，分别注射于大鼠脊柱两侧皮下，术后1周观察全身反应及局部皮肤。2周后取材，固定，常规HE染色及VEGF免疫组织化学染色。结果高效液相频谱仪及质谱仪示肽纯度及分子量分别为95．22％与1438,TEM示凝胶为交织成网状的纳米纤维。术后1周动物存活良好，无全身不良反应，局部皮肤无红肿、无坏死。实验组：1wt％的肽体内自组装成凝胶，血管长入凝胶内部，管腔内可发现红细胞；术后2周，VEGF阳性。对照组：明胶内未发现血管，VEGF阴性。结论本实验合成含IKVAV两亲性肽，在PBS溶液中可自组装成凝胶且体内可诱导新生血管生成。     

Contact lenses can induce stromal thinning

We examined 27 patients who had worn high water content hydrogel contact lenses in one eye only for an average of 62 ± 29 months (mean ± SD). The stroma of the lens-wearing eye was found to be significantly thinner (p < 0.05) than that of the contralateral eye after lens-induced oedema was allowed to subside. Recovery had not occurred after 33 days. We conclude that contact lenses can induce stromal thinning.