这项工作得到台湾科技部（MOST 104-2221-E-131-010，MOST 105-2622-E-131-001-CC2）的财政支持，部分得到原子分子科学研究所的支持，中央研究院

1.表面改性，水分散磁性纳米粒子，Fe 3 O 4和Fe 3 O 4 -NH 2的合成<ol><li>加入14.02g FeCl 3，8.6g FeCl 2 ·4H 2 O和250mL水加入到500mL烧杯中。 </li><li>连接转子和控制器，进行机械搅拌。将溶液在室温（RT）下以300rpm混合30分钟。 </li><li>在室温下向溶液中加入25mL氢氧化铵（33％），并保持搅拌（300rpm）30分钟。保持烧杯开放。 小心:如果吸入，氢氧化铵会引起鼻部刺激。此步骤必须在适当的通风橱内进行。 </li><li>收集磁性氧化铁（Fe 3 O 4 ），去除机械搅拌。将磁铁放在烧杯下面收集黑色颗粒。 <ol><li> Fe 3 O 4纳米颗粒完全沉淀后，小心除去上清液。不要动摇b在倒出上清液时避免Fe 3 O 4的损失。 </li><li>取出磁铁，并向烧杯中加入50 mL淡水。 </li><li>摇动烧杯重新分散Fe 3 O 4 。重复步骤1.4至1.4.2三次以净化Fe 3 O 4 。 </li></ol></li><li>最后一次洗涤后，将所有的Fe 3 O 4 （10g）转移到100 mL玻璃瓶中。加水至总溶液体积为100mL。大力摇动玻璃瓶直到没有肿块可见。 注意:协议可以在这里暂停。制备Fe 3 O 4纳米颗粒。 </li><li>用氨基硅烷（Fe 3 O 4 -NH 2 ）改变Fe 3 O 4 。 <ol><li>取来自步骤1.5的100mL溶液并转移到1,000mL烧杯中。向烧杯中加入10 mL氨水溶液，90 mL水和900 mL乙醇。 </li><li>使用磁力搅拌棒将溶液混合在一起300 rpm。在室温下向烧杯中滴加500μL（3-氨基丙基）三乙氧基硅烷（APTES），再搅拌12小时。 </li></ol></li><li>如第1.4节所述净化并收集Fe 3 O 4 -NH 2 。 </li><li>将1g Fe 3 O 4 -NH 2 （来自步骤1.7）重新分散在具有20mL水的20mL玻璃瓶中。 注意:协议可以在这里暂停。制备Fe 3 O 4 -NH 2纳米颗粒。 </li></ol> 2.通过热诱导乳液合成有机 - 无机杂化微凝胶<ol><li> 溶液1-1和1-2的制备。 <ol><li>对于溶液1-1，将0.25g PNIPAAm，5mL Fe 3 O 4溶液（来自步骤1.5）和0.2g PEI加入到50mL玻璃瓶中。加入20mL水，并用磁力搅拌棒在300rpm搅拌30分钟。 </li><li>对于溶液1-2，重复步骤2.1.1，但将Fe 3 O 4替代为Fe3 O 4 -NH 2溶液（来自步骤1.8）。 </li></ol></li><li>为了制备溶液2 ，向50mL玻璃瓶中加入0.8g PEI和18.2mL水。使用水浴将溶液加热至70°C 30分钟。准备第二瓶解决方案2 。 </li><li> PNIPAAm / Fe 3 O 4的制备。 <ol><li>使用超声波细胞破碎机超声波（50w），磁力搅拌棒搅拌（300rpm）和水浴以加热溶液2 （70℃）。 </li><li>使用3-mL注射器以1mL / min的速率将溶液1-1滴加到加热的溶液2中。 </li><li>继续超声处理，搅拌和在70℃加热30分钟。 </li><li>将解决方案冷却到RT。从细胞破碎器和水浴中取出溶液。 </li><li>将磁铁靠近玻璃瓶收集微凝胶。 </li><li>取出上清液微小凝胶已经沉淀到玻璃瓶的底部。 </li><li>向玻璃瓶中加入另外25 mL的水，并通过涡旋重新分散微凝胶。该溶液是PNIPAAm / Fe 3 O 4 。 注意:协议可以在这里暂停。 </li></ol></li><li> PNIPAAm / Fe 3 O 4 -NH 2的制备。 <ol><li>使用超声波细胞破碎机超声波（50w），磁力搅拌棒搅拌（300rpm）和水浴以加热溶液2 （70℃）。 </li><li>使用3-mL注射器以1mL / min的速率将溶液1-2滴加到加热的溶液2中。 </li><li>继续超声处理，搅拌和在70℃加热30分钟。 </li><li>将解决方案冷却到RT。从细胞破碎器和水浴中取出溶液。 </li><li>将磁铁靠近玻璃瓶收集微凝胶。 </li><li>一旦微凝胶沉淀，取出上清液。 </li><li>向玻璃瓶中加入另外25 mL的水，并通过涡旋重新分散微凝胶。该溶液是PNIPAAm / Fe 3 O 4 -NH 2 。 注意:协议可以在这里暂停。 </li></ol></li></ol> 3.载有姜黄素的微凝胶（Cur-PNIPAAm / Fe 3 O 4 -NH 2 ）的制备注意:这些步骤必须在黑暗中进行。 <ol><li>将100毫升的Cur和20毫升乙醇加入到20毫升的玻璃瓶中。 </li><li>取2mL的Cur溶液并转移到PNIPAAm / Fe 3 O 4 -NH 2溶液（步骤2.4.7）。以400rpm和室温搅拌过夜。 </li><li>在400rpm和室温下搅拌过夜后，使用磁铁收集PNIPAAm / Fe 3 O 4 -NH 2 ，如步骤2.4.5和2.4.6所述。 </li><li>向玻璃瓶中加入另外25 mL的水，并通过涡旋重新分散微凝胶。这个解决方案是C<html> ur-PNIPAAm / Fe 3 O 4 -NH 2 。 </li></ol>磁性触发药物释放<ol><li>转移10 mL Cur-PNIPAAm / Fe 3 O 4 -NH 2溶液，并加入2 mL水至15 mL离心管中。 </li><li>将离心管放置在线圈的中心，以应用HFMF 20 。在15KHz下应用HFMF 20分钟。 </li><li>取出0.5 mL HFMF溶液，每隔2分钟更换新鲜的0.5 mL水，同时应用HFMF。 </li><li>将取出的溶液转移到1-mL比色杯中。 </li><li>通过UV / Vis在482nm测量吸出的溶液21 。 </li><li>通过使用来自标准校准曲线22的吸收和浓度的关系来确定释放的药物的浓度。 注意:标准校准关系为: <html> s / ftp_upload / 55648 / 55648eq1.jpg"/&gt; 相关系数为0.9993。 </li></ol> 5.磁性微凝胶的表征<ol><li>热重分析仪（TGA） 23 。 <ol><li>测量PNIPAAm / Fe 3 O 4和PNIPAAm / Fe 3 O 4 -NH 2与TGA在空气气氛下的温度的重量损失。 <ol><li>将样品从RT加热至100°C，并在该温度下保持10分钟以消除湿度。以10℃/ min的速度将样品从100℃加热至800℃。称量样品。 </li><li>绘制PNIPAAm / Fe 3 O 4和PNIPAAm / Fe 3 O 4 -NH 2的重量损失与温度的关系。 注意:残渣重量为Fe 3 O 4或Fe 3 O 4 -NH 2 ，而重量为PNIPAAm。 </li></ol></li></ol></li><li> FT-IR"&gt; 24。 <ol><li>干燥10毫克样品与1克KBr在100℃过夜。 </li><li>按照以下步骤（5.2.2.1 - 5.2.2.5）中所述将步骤5.2.1的混合物压成颗粒: <ol><li>使用研钵和研杵将步骤5.2.1中的材料研磨成细粉。 </li><li>将组装的装置（砂浆和杵）放入颗粒压机中。将设备对准印刷机的正中间。 </li><li>泵压机直至达到20,000 psi的压力。让颗粒坐在那个压力下5分钟。 注意:将设备与印刷机的正中间对准，否则样品将从砂浆中分散出来，造成人身伤害。 </li><li>从压机上取出包含颗粒和活塞的模具。 </li><li>将其倒置并泵送活塞以迫使颗粒物流出。 </li></ol></li><li>通过FT-IR在400至4000 cm -1的频率记录样品的FT-IR吸收光谱</sup&gt; 4厘米-1分辨率24 。 </li></ol></li><li> TEM的形态学观察25 。 <ol><li>将样品溶液放在涂有火棉花的铜格栅上，然后在室温或70°C烘箱中干燥过夜。 </li><li>采用TEM图像。 注意:强电子束可能会损坏样品。因此，应尽可能快地拍摄TEM图像。 </li></ol></li><li>聚合物和微凝胶的水分散能力。 <ol><li>为了制备PNIPAAm溶液，将7mg PNIPAAm和7mL水加入到7-mL玻璃瓶中。使用涡流混合溶液，直到没有聚集体。 </li><li>为了制备PNIPAAm / Fe 3 O 4 -NH 2溶液，将0.7mL的PNIPAAm / Fe 3 O 4 -NH 2溶液（步骤2.4.7）转移到7-mL玻璃瓶中并加入6.3mL水。使用涡流混合溶液，直到没有沉淀。 </li><li>准备Cur-PNIPAAm / Fe 3 O 4 -NH 2溶液，将0.7mL的Cur-PNIPAAm / Fe 3 O 4 -NH 2溶液（步骤3.4）转移到7mL玻璃瓶中并加入6.3mL水。使用涡流混合溶液，直到没有沉淀。 </li><li>使用数码相机拍摄解决方案（步骤5.4.1 - 5.4.3）。 </li><li>将溶液放入烘箱中并将温度设定在70°C。等待2小时直到平衡。 </li><li>再来看一下解决方案。为了保持温度，请在1分钟内拍照。避免摇晃玻璃瓶，因为这样可以重新分散沉淀物。 </li></ol></li><li>对于微凝胶的磁集合，将强磁体靠近Cur-PNIPAAm / Fe 3 O 4 -NH 2溶液（步骤5.4.3）。等到微凝胶完全收集，然后拍照。 <ol><li>取出磁铁并旋转微凝胶溶液直到完全分散。再拍一张照片/ LI&gt; </ol></li></ol>

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作者没有什么可以披露的。

制备的最重要步骤在方案第2节中，用于通过热诱导乳液合成磁性微凝胶。 如图2 （TEM图）所示，由于由PNIPAAm（酰胺基），PEI（胺基）之间的强H键而产生的物理交联，微凝胶的球形结构可以保持在RT（低于LCST）和Fe 3 O 4 -NH 2 （胺基）。基于图4的比较，磁性微凝胶在低（25℃）或高（70℃）温度下良好分散。微凝胶也可以由磁体?...

水凝胶是三维（3D）聚合物网络，其不能溶解但可在水溶液中溶胀1 。聚合物网络具有亲水结构域（其可以水合以提供水凝胶结构）和交联构象（其可以防止网络崩溃）。已经研究了制备水凝胶的各种方法，例如乳液聚合，阴离子共聚，相邻聚合物链的交联和反相微乳液聚合2 。通过这些方法引入物理和化学交联以获得结构稳定的水凝胶1,3 。化学交联通常需要连接聚合物的主链或侧链的交联剂的参与。与化学交联相比，物理交联是fabr的更好选择<html>由于这些试剂对于实际应用而言通常是有毒的，因此避免了交联剂的酸化水凝胶。已经研究了几种用于合成物理交联水凝胶的方法，例如用离子相互作用的交联，结晶，两亲嵌段之间的键合或聚合物链上的接枝以及氢键4,5,6,7。 近来，受不同环境条件（ 即温度，pH，光，离子强度和磁场）影响的构象，化学或物理性能变化的刺激敏感性聚合物近来引起了人们的注意，作为控制释放系统的潜在平台，药物输送和抗癌治疗8,9 ，xref"&gt; 10,11,12 ，研究人员正在关注热敏聚合物，其中可以容易地控制固有温度PNIPAAm是一种热敏聚合物，其含有亲水性酰胺基和疏水性异丙基，并且具有较低的临界溶解温度（LCST） 13 。酰胺基和水分子之间的氢键在低温下（低于LCST）提供了PNIPAAm在水溶液中的分散性，而聚合物链之间的氢键在高温（高于LCST）下发生，并且不包括水分子，使得聚合物网络崩溃，关于这种独特的性质，已经出版了许多报道，通过调节聚合物链长度的疏水性和亲水性比例如共聚，接枝或侧链来制备温度触发的自组装水凝胶，制药连锁改造cal平台14,15,16,17 。 磁性材料如铁，钴和镍在过去几十年中也受到越来越多的关注，用于生物化学应用18 。在这些候选物中，由于其稳定性和低毒性，氧化铁被广泛使用。纳米级铁氧化物立即响应于磁场并表现为超顺磁性原子。然而，这样的小颗粒容易聚集;这降低了表面能，因此失去了分散性。为了提高水分散性，接枝或涂层以保护层通常不仅用于分离每个单独的颗粒以获得稳定性，而且还使反应位点进一步官能化。 在这里，我们制造了基于PNIPAAm的磁性微型凝胶作为控制释放系统的药物载体。合成过程如图1所示。代替复杂的共聚和化学交联，采用PNIPAAm的新型温度诱导乳液进行物理交联，得到无需附加表面活性剂或交联剂的微凝胶。这简化了合成并防止了不期望的毒性。在这种简单的制备方案中，合成的微凝胶为磁性氧化铁纳米颗粒和疏水性抗癌药物姜黄素提供了水分散性。 FT-IR，TEM和成像提供了分散和包封的证据。由于嵌入的Fe 3 O 4 -NH 2 ，磁性微凝胶显示出在HFMF下作为控制释放的微器件的潜力。

<table><tbody><tr><td>Poly(N-isopropylacrylamide)</td><td>Polyscience, Inc</td><td>21458-10</td><td>Mw ~40,000</td></tr><tr><td>(3-aminopropyl)trimethoxysilane</td><td>Sigma-Aldrich</td><td>440140</td><td>&gt; 99 %</td></tr><tr><td>Iron(II) chloride tetrahydrate</td><td>Sigma-Aldrich</td><td>44939</td><td>99%</td></tr><tr><td>Iron(III) chloride</td><td>Sigma-Aldrich</td><td>157740</td><td>97%</td></tr><tr><td>Curcumin</td><td>Sigma-Aldrich</td><td>00280590</td><td></td></tr><tr><td>Ammonia hydroxide</td><td>Fisher Chemical</td><td>A/3240/PB15</td><td>35%</td></tr><tr><td>Phosphate Buffered Saline</td><td>Sigma-Aldrich</td><td>806552</td><td>pH 7.4, liquid, sterile-filtered</td></tr><tr><td>Polyethylenimine (PEI)</td><td>Sigma-Aldrich</td><td>P3143</td><td>50 % (w/v) in water</td></tr><tr><td>High-frequency magnetic field (HFMF)</td><td>Lantech Industrial Co., Ltd.,Taiwan</td><td>LT-15-80</td><td>15 kV, 50&amp;ndash;100 kHz</td></tr><tr><td>Ultraviolet-Visible Spectrophotometry</td><td>Thermo Scientific Co.</td><td>Genesys</td><td></td></tr><tr><td>Transmission electron microscopy (TEM)</td><td>JEM-2100</td><td>JEOL</td><td></td></tr><tr><td>Fourier transform infrared spectroscopy (FTIR)</td><td>PerkinElmer</td><td>Spectrum 100</td><td></td></tr><tr><td>Thermogravimetric analyzer</td><td>PerkinElmer</td><td>Pyris 1</td><td></td></tr><tr><td>Ultrasonic cell disruptor</td><td>Hielscher Ultrasonics</td><td>UP50H</td><td></td></tr></tbody></table>

magnetic and thermal-sensitive poly(n-isopropylacrylamide)-based microgels for magnetically triggered controlled release

设计并制造了具有包封的抗癌药物姜黄素（Cur）的磁感和热敏聚（ N-异丙基丙烯酰胺）（PNIPAAm）/ Fe 3 O 4 -NH 2微凝胶用于磁触发释放。通过温度诱导的乳液制备具有球形结构的基于PNIPAAm的磁性微凝胶，然后通过混合PNIPAAm，聚乙烯亚胺（PEI）和Fe 3 O 4 -NH 2磁性纳米粒子进行物理交联。由于其分散性，将Fe 3 O 4 -NH 2纳米颗粒嵌入聚合物基质内。暴露在Fe 3 O 4 -NH 2和PEI表面上的胺基通过与PNIPAAm的酰胺基团物理交联来支撑球形结构。疏水性抗癌药物姜黄素在包封入微凝胶后可以分散在水中。表征微凝胶通过透射电子显微镜（TEM），傅里叶变换红外光谱（FT-IR）和UV-Vis光谱分析。此外，在外部高频磁场（HFMF）下研究了磁触发释放。由于磁感应加热（热疗）效应，将HFMF应用于微凝胶后，观察到姜黄素的显着"爆发"。该手稿描述了Cur-PNIPAAm / Fe 3 O 4 -NH 2包封的姜黄素的磁触发控制释放，其可以潜在地用于肿瘤治疗。

PNIPAAm / PEI / Fe 3 O 4 -NH 2微凝胶的合成示意图如图1所示。应用TGA估计有机化合物相对于整个微凝胶的相对组成。由于只有有机化合物PNIPAAm可以燃烧，因此确定了PNIPAAm和Fe 3 O 4 （或Fe 3 O 4 -NH 2 ）的相对组成，如表1所示。为什么PNIPAAm / Fe 3 O 4 -NH 2微?...

Watch this Scientific Journal Video about Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release at JoVE.com

Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

该手稿描述了通过温度诱导的乳液制备磁性和热敏性微凝胶而没有化学反应。通过混合聚（ N-异丙基丙烯酰胺）（PNIPAAm），聚乙烯亚胺（PEI）和Fe 3 O 4 -NH 2纳米粒子来合成这些敏感微凝胶，用于磁和热触发药物释放的潜在用途。

磁性和热敏性聚（<em&gt;ñ</em基于异丙基丙烯酰胺）的微凝胶用于磁触发控制释放

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

magnetic-thermal-sensitive-poly-n-isopropylacrylamide-based-microgels

Universidad de Cartagena UDEC

Research

JoVE Journal

Bioengineering

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

8.8K 次观看.  National Taiwan University. 该手稿描述了通过温度诱导的乳液制备磁性和热敏性微凝胶而没有化学反应。通过混合聚（ N-异丙基丙烯酰胺）（PNIPAAm），聚乙烯亚胺（PEI）和Fe 3 O 4 -NH 2纳米粒子来合成这些敏感微凝胶，用于磁和热触发药物释放的潜在用途。 

视频: Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

Microwave-assisted Functionalization of Poly(ethylene glycol) and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

One of the main benefits to using poly(ethylene glycol) (PEG) macromers in hydrogel formation is synthetic versatility. The ability to draw from a large variety of PEG molecular weights and configurations (arm number, arm length, and branching pattern) affords researchers tight control over resulting hydrogel structures and properties, including Young&#8217;s modulus and mesh size. This video will illustrate a rapid, efficient, solvent-free, microwave-assisted method to methacrylate PEG precursors into poly(ethylene glycol) dimethacrylate (PEGDM). This synthetic method provides much-needed starting materials for applications in drug delivery and regenerative medicine. The demonstrated method is superior to traditional methacrylation methods as it is significantly faster and simpler, as well as more economical and environmentally friendly, using smaller amounts of reagents and solvents. We will also demonstrate an adaptation of this technique for on-resin methacrylamide functionalization of peptides. This on-resin method allows the N-terminus of peptides to be functionalized with methacrylamide groups prior to deprotection and cleavage from resin. This allows for selective addition of methacrylamide groups to the N-termini of the peptides while amino acids with reactive side groups (e.g.&#160;primary amine of lysine, primary alcohol of serine, secondary alcohols of threonine, and phenol of tyrosine) remain protected, preventing functionalization at multiple sites. This article will detail common analytical methods (proton Nuclear Magnetic Resonance spectroscopy (;H-NMR) and Matrix Assisted Laser Desorption Ionization Time of Flight mass spectrometry (MALDI-ToF)) to assess the efficiency of the functionalizations. Common pitfalls and suggested troubleshooting methods will be addressed, as will modifications of the technique which can be used to further tune macromer functionality and resulting hydrogel physical and chemical properties. Use of synthesized products for the formation of hydrogels for drug delivery and cell-material interaction studies will be demonstrated, with particular attention paid to modifying hydrogel composition to affect mesh size, controlling hydrogel stiffness and drug release.

Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

This video will illustrate a rapid, efficient method to methacrylate poly(ethylene glycol), enabling chain polymerizations and hydrogel synthesis. It will demonstrate how to similarly introduce methacrylamide functionalities into peptides, detail common analytical methods to assess functionalization efficiency, provide suggestions for troubleshooting and advanced modifications, and demonstrate typical hydrogel characterization techniques.

保利的微波辅助功能化（乙二醇）和On-树脂链聚合反应，并形成水凝胶的肽使用

One of the main benefits to using poly(ethylene glycol) (PEG) macromers in hydrogel formation is synthetic versatility. The ability to draw from a large ...

科研

化学

Synthesis of Poly(N-isopropylacrylamide) Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability

Janus microparticles are compartmentalized particles with differing molecular structures and/or functionality on each of their two sides. Because of this unique property, Janus microparticles have been recognized as a new class of materials, thereby attracting a great deal of attention from various research fields. The versatility of these microparticles has been exemplified through their uses as building blocks for self-assembly, electrically responsive actuators, emulsifiers for painting and cosmetics, and carriers for drug delivery. This study introduces a detailed protocol that explicitly describes a synthetic method for designing novel Janus microhydrogels composed of a single base material, poly(N-isopropylacrylamide) (PNIPAAm). Janus microdroplets are firstly generated via a hydrodynamic focusing microfluidic device (HFMD) based on the separation of a supersaturated aqueous NIPAAm monomer solution and subsequently polymerized through exposure to UV irradiation. The resulting Janus microhydrogels were found to be entirely composed of the same base material, featured an easily identifiable compartmentalized morphology, and exhibited anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability. We believe that the proposed method introduces a novel hydrogel platform with the potential for advanced synthesis of multi-functional Janus microhydrogels.

Synthesis of PolyN-isopropylacrylamide Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability

We present a protocol to synthesize Janus microhydrogels composed entirely of the same base material, poly(N-isopropylacrylamide) (PNIPAAm), with a clearly compartmentalized structure base on the phase separation of a supersaturated NIPAAm monomer solution. The synthesized Janus microhydrogels show unique properties such as anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability.

合成聚（<em&gt;ñ</em&gt; -isopropylacrylamide）剑锋Microhydrogels各向异性热响应能力和亲有机/亲水承载能力

Janus microparticles are compartmentalized particles with differing molecular structures and/or functionality on each of their two sides. Because of this ...

Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

X-ray fluoroscopy-guided endovascular procedures have several significant limitations, including difficult catheter navigation and use of ionizing radiation, which can potentially be overcome using a magnetically steerable catheter under MR guidance.
	The main goal of this work is to develop a microcatheter whose tip can be remotely controlled using the magnetic field of the MR scanner. This protocol aims to describe the procedures for applying current to the microcoil-tipped microcatheter to produce consistent and controllable deflections.
	A microcoil was fabricated using laser lathe lithography onto a polyimide-tipped endovascular catheter. In vitro testing was performed in a waterbath and vessel phantom under the guidance of a 1.5-T MR system using steady-state free precession (SSFP) sequencing. Various amounts of current were applied to the coils of the microcatheter to produce measureable tip deflections and navigate in vascular phantoms.
	The development of this device provides a platform for future testing and opportunity to revolutionize the endovascular interventional MRI environment.

Current applied to an endovascular microcatheter with microcoil tip made by laser lathe lithography can achieve controllable deflections under magnetic resonance (MR) guidance, which may improve speed and efficacy of navigation of vasculature during various endovascular procedures.

磁力辅助的远程控制微导管尖端偏转根据磁共振成像

X-ray fluoroscopy-guided  endovascular procedures have several significant limitations, including  difficult catheter navigation and use of ionizing ...

生物工程

Controlled Synthesis and Fluorescence Tracking of Highly Uniform Poly(N-isopropylacrylamide) Microgels

Stimuli-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgels have various prospective practical applications and uses in fundamental research. In this work, we use single particle tracking of fluorescently labeled PNIPAM microgels as a showcase for tuning microgel size by a rapid non-stirred precipitation polymerization procedure. This approach is well suited for prototyping new reaction compositions and conditions or for applications that do not require large amounts of product. Microgel synthesis, particle size and structure determination by dynamic and static light scattering are detailed in the protocol. It is shown that the addition of functional comonomers can have a large influence on the particle nucleation and structure. Single particle tracking by wide-field fluorescence microscopy allows for an investigation of the diffusion of labeled tracer microgels in a concentrated matrix of non-labeled microgels, a system not easily investigated by other methods such as dynamic light scattering.

Controlled Synthesis and Fluorescence Tracking of Highly Uniform PolyN-isopropylacrylamide Microgels

Non-stirred precipitation polymerization provides a rapid, reproducible prototyping approach to the synthesis of stimuli-sensitive poly(N-isopropylacrylamide) microgels of narrow size distribution. In this protocol synthesis, light scattering characterization and single particle fluorescence tracking of these microgels in a wide-field microscopy setup are demonstrated.

可控合成和高度统一聚荧光追踪（<em&gt;ñ</em&gt; -isopropylacrylamide）微凝胶

Stimuli-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgels have various prospective practical applications and uses in fundamental research. In this ...

Characteristics of Precipitation-formed Polyethylene Glycol Microgels Are Controlled by Molecular Weight of Reactants

This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Precipitation reactions offer several advantages over traditional microsphere fabrication techniques. Contrary to emulsion, suspension, and dispersion techniques, microgels formed by precipitation are of uniform shape and size, i.e.&#160;low polydispersity index, without the use of organic solvents or stabilizers. The mild conditions of the precipitation reaction, customizable properties of the microgels, and low viscosity for injections make them applicable for in vivo purposes. Unlike other fabrication techniques, microgel characteristics can be modified by changing the starting polymer molecular weight. Increasing the starting PEG molecular weight increased microgel diameter and swelling ratio. Further modifications are suggested such as encapsulating molecules during microgel crosslinking. Simple adaptations to the PEG microgel building blocks are explored for future applications of microgels as drug delivery vehicles and tissue engineering scaffolds.

This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Increasing the PEG molecular weight increased microgel diameter and swelling ratio. Simple adaptations to the PEG microgel precipitation reaction are explored for future applications of microgels as drug delivery vehicles and tissue engineering scaffolds.

This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Precipitation reactions offer ...

Imaging Denatured Collagen Strands In vivo and Ex vivo via Photo-triggered Hybridization of Caged Collagen Mimetic Peptides

Collagen is a major structural component of the extracellular matrix that supports tissue formation and maintenance. Although collagen remodeling is an integral part of normal tissue renewal, excessive amount of remodeling activity is involved in tumors, arthritis, and many other pathological conditions. During collagen remodeling, the triple helical structure of collagen molecules is disrupted by proteases in the extracellular environment. In addition, collagens present in many histological tissue samples are partially denatured by the fixation and preservation processes. Therefore, these denatured collagen strands can serve as effective targets for biological imaging. We previously developed a caged collagen mimetic peptide (CMP) that can be photo-triggered to hybridize with denatured collagen strands by forming triple helical structure, which is unique to collagens. The overall goals of this procedure are i)&#160;to image denatured collagen strands resulting from normal remodeling activities in vivo, and ii) to visualize collagens in ex vivo tissue sections using the photo-triggered caged CMPs. To achieve effective hybridization and successful in vivo and ex vivo imaging, fluorescently labeled caged CMPs are either photo-activated immediately before intravenous injection, or are directly activated on tissue sections. Normal skeletal collagen remolding in nude mice and collagens in prefixed mouse cornea tissue sections are imaged in this procedure. The imaging method based on the CMP-collagen hybridization technology presented here could lead to deeper understanding of the tissue remodeling process, as well as allow development of new diagnostics for diseases associated with high collagen remodeling activity.

Imaging Denatured Collagen Strands In vivo and Ex vivo via Photo-triggered Hybridization of Caged Collagen Mimetic Peptides

This procedure demonstrates in vivo near IR fluorescence imaging of collagen remodeling activities in mice as well as ex vivo staining of collagens in tissue sections using caged collagen mimetic peptides that can be photo-triggered to hybridize with denatured collagen strands.

成像变性的胶原股<em&gt;在体内</em&gt;和<em&gt;体外</em&gt;通过光引发杂交笼胶原蛋白仿生肽

Collagen is a major structural component of the extracellular matrix that supports tissue formation and maintenance. Although collagen remodeling is an ...

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of smart soft devices for biomedical applications. Although a number of magnetically-responsive drug delivery systems have demonstrated efficacies through either in vitro proof of concept studies or in vivo preclinical applications, their use in clinical settings is still limited by their insufficient biocompatibility or biodegradability. Additionally, many of the existing platforms rely on sophisticated techniques for their fabrications. We recently demonstrated the fabrication of biodegradable, gelatin-based thermo-responsive microgel by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within a three-dimensional gelatin network. In this study, we present a facile method to fabricate a biodegradable drug release platform that enables a magneto-thermally triggered drug release. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and thermo-responsive polymers within gelatin-based colloidal microgels, in conjunction with an alternating magnetic field application system.

We present a facile method to fabricate a biodegradable gelatin-based drug release platform that is magneto-thermally responsive. This was achieved by incorporating superparamagnetic iron oxide nanoparticles and poly(N-isopropylacrylamide-co-acrylamide) within a spherical gelatin micro-network crosslinked by genipin, in conjunction with an alternating magnetic field application system.

交变磁场敏感的混合明胶微凝胶药物控释

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of ...

Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), their ultimate clinical use has been hampered by the lack of biologically-relevant degradation observed for most smart materials. This is particularly true for temperature-responsive hydrogels, which are almost uniformly based on polymers that are functionally non-degradable (e.g., poly(N-isopropylacrylamide) (PNIPAM) or poly(oligoethylene glycol methacrylate) (POEGMA)). As such, to effectively translate the potential of thermoresponsive hydrogels to the challenges of remote-controlled or metabolism-regulated drug delivery, cell scaffolds with tunable cell-material interactions, theranostic materials with the potential for both imaging and drug delivery, and other such applications, a method is required to render the hydrogels (if not fully degradable) at least capable of renal clearance following the required lifetime of the material. To that end, this protocol describes the preparation of hydrolytically-degradable hydrazone-crosslinked hydrogels on multiple length scales based on the reaction between hydrazide and aldehyde-functionalized PNIPAM or POEGMA oligomers with molecular weights below the renal filtration limit. Specifically, methods to fabricate degradable thermoresponsive bulk hydrogels (using a double barrel syringe technique), hydrogel particles (on both the microscale through the use of a microfluidics platform facilitating simultaneous mixing and emulsification of the precursor polymers and the nanoscale through the use of a thermally-driven self-assembly and cross-linking method), and hydrogel nanofibers (using a reactive electrospinning strategy) are described. In each case, hydrogels with temperature-responsive properties similar to those achieved via conventional free radical cross-linking processes can be achieved, but the hydrazone cross-linked network can be degraded over time to re-form the oligomeric precursor polymers and enable clearance. As such, we anticipate these methods (which may be generically applied to any synthetic water-soluble polymer, not just smart materials) will enable easier translation of synthetic smart materials to clinical applications.

Protocols are described for the fabrication of degradable thermoresponsive hydrogels based on hydrazone cross-linking of polymeric oligomers on the bulk scale, microscale, and nanoscale, the latter for preparation of both gel nanoparticles and nanofibers.

通过反应挤出、微流体、自组装和电纺丝制备多长尺度可降解 Thermoresponsive 水凝胶

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), ...

An Additive Manufacturing Technique for the Facile and Rapid Fabrication of Hydrogel-based Micromachines with Magnetically Responsive Components

Polyethylene glycol (PEG)-based hydrogels are biocompatible hydrogels that have been approved for use in humans by the FDA. Typical PEG-based hydrogels have simple monolithic architectures and often function as scaffolding materials for tissue engineering applications. More sophisticated structures typically take a long time to fabricate and do not contain moving components. This protocol describes a photolithography method that allows for facile and rapid microfabrication of PEG structures and devices. This strategy involves an in-house developed fabrication stage that allows for the rapid fabrication of 3D structures by building upwards in a layer-by-layer fashion. Independent moving components can also be aligned and assembled onto support structures to form integrated devices. These independent components are doped with superparamagnetic iron oxide nanoparticles that are sensitive to magnetic actuation. In this manner, the fabricated devices can be actuated using external magnets to yield movement of the components within. Hence, this technique allows for the fabrication of sophisticated MEMS-like devices (micromachines) that are composed entirely out of a biocompatible hydrogel, able to function without an onboard power source, and respond to a contact-less method of actuation. This manuscript describes the fabrication of both the fabrication set-up as well as the step-by-step method for the microfabrication of these hydrogels-based MEMS-like devices.

An additive manufacturing strategy for processing UV-crosslinkable hydrogels has been developed. This strategy allows for the layer-by-layer assembly of microfabricated hydrogel structures as well as the assembly of independent components, yielding integrated devices containing moving components that are responsive to magnetic actuation.

一种简便快速制备磁响应元件的水凝胶基微型机械的添加剂制造技术

Polyethylene glycol (PEG)-based hydrogels are biocompatible hydrogels that have been approved for use in humans by the FDA. Typical PEG-based hydrogels ...

Synthesis of Stimuli-responsive Nanogels using Aqueous One-step Crosslinking and Co-nanopolymerization

Nanogels consisting of crosslinked-polymeric nanoparticles have been developed for the delivery of numerous chemical and biological therapeutics, owing to their versatile bottom-up synthesis and biocompatibility. While various methods have been employed for nanogel synthesis to date, very few have achieved it without the use of harsh organic solvents or high temperatures that can damage the integrity of the biological payload. In contrast, the methodology presented here accomplishes the synthesis of sub-100 nm sized, protein-loaded nanogels using mild reaction conditions. Here, we present a method for the non-covalent encapsulation of protein-based payloads within nano-gels that were synthesized using an aqueous-based, single-step, crosslinking copolymerization technique. In this technique, we initially electrostatically bind a protein-based payload to a cationic quaternary ammonium monomer and simultaneously cross-link and co-polymerize it using ammonium persulfate and N,N,N&#39;,N&#39;-tetramethylethylenediamine to form nanogels that entrap the protein payload. The size and polydispersity index of the nanogels is determined using dynamic light scattering (DLS), while the surface morphology is assessed by transmission electron microscopy (TEM). The mass of protein entrapped within nanogels is determined by calculating the encapsulation efficiency. Furthermore, the controlled-release ability of the nanogels via the gradual degradation of redox-responsive structural elements is also assessed in bioreduction assays. We provide examples of nanoparticle optimization data to demonstrate all caveats of nanogel synthesis and characterization using this technique. In general, uniformly sized nanogels were obtained with an average size of 57 nm and a polydispersity index value of 0.093. A high encapsulation efficiency of 76% was achieved. Furthermore, the nanogels exhibited controlled release of up to 86% of the encapsulated protein by gradual degradation of novel redox-responsive components in the presence of glutathione over 48 h.

Nanogels are an excellent and versatile nanoparticle platform for the delivery of biologics. Stimuli-responsive poly(ethylene) glycol-based polymeric nano-gels, capable of encapsulating protein-based payloads, were synthesized using a one-step cross-linking co-nanopolymerization strategy in aqueous conditions. The optimal fabrication and characterization of these novel nanoparticles are presented here.

使用水性一步交联和共纳米聚合合成刺激响应纳米凝胶

Nanogels consisting of crosslinked-polymeric nanoparticles have been developed for the delivery of numerous chemical and biological therapeutics, owing to ...

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