Name: alternating magnetic field-responsive hybrid gelatin microgels for controlled drug release
Uploaded: 2016-02-13T15:00:00.000+00:00
Duration: 9 min 11 s
Description: Watch this Scientific Journal Video about Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release at JoVE.com

这项研究是由里斯家庭创新奖和美国国立卫生研究院1R01NR015674-01到MK支持。作者感谢何塞普Nayfach（Qteris公司）提供的电磁发电机系统，以及他的技术咨询。作者还感谢焕颜（LCI及物理化学跨学科计划，肯特州立大学），她的技术助理。

注意: 在图1A中示出的制造磁场响应明胶微凝胶的整个过程。 1.准备解决方案及停牌<ol><li>通过在2ml磷酸盐缓冲盐水中溶解20mg的京尼平的制备交联剂京尼平（1％重量/体积）溶液（1×PBS; pH 7.4）中。涡旋该溶液，并发生在50℃水浴2小时以完全溶解该溶液中。 </li><li>由20毫克聚（乙二醇）的聚（丙二醇） -聚（乙二醇）溶解制备表面活性剂溶液（M W = 2900达;称为L64）在200毫升PBS中是在100的浓度PPM。 </li><li>由64.5毫克明胶溶于0.43毫升的PBS制备15％（重量/体积）明胶溶液。涡旋该溶液，将其放在水浴在37℃下 ，直到它到达一个溶胶相，其中所述溶液变成流体。然后，涡明胶溶液2 - 3次，以确保日样品电子同质性。 </li><li> P（NIPAM- 共 -AAm）/的MNP溶液与模型药物（BSA）的制备: <ol><li>分散10.75毫克亲水的MNP的0.43毫升的PBS，然后在MNP悬浮液溶解12.9毫克对的（NIPAM- 共同 -AAm），使其浓度为3％（重量/体积）。的p（NIPAM- 共同 -AAm）浓度的增加，可用于实现微凝胶的增加的消溶胀行为。 </li><li>使用得克萨斯州红共轭牛血清白蛋白（TR-BSA; 男女〜66 kDa的）为模型药物。溶解0.5毫克的TR-BSA中的p（NIPAM- 共同 -AAm）/的MNP的混合物。 </li></ol></li><li>通过增加（0.43毫升）P（NIPAM- 合作 -AAm）混合/的MNP（0.43毫升）到明胶溶液，然后准备明胶/ P（NIPAM- 合作 -AAm）/的MNP / BSA溶液（0.86毫升）的混合物彻底涡他们作出均匀的混合物。因此，聚合物和MNP的浓度成为初始浓度在最终混合物的一半。 </li></ol><ol><li>倒入15毫升硅油[聚二甲基硅氧烷（粘度350 CST）]成一个洁净无菌烧杯中。 </li><li>立即加入明胶/ P（NIPAM- 共 -AAm）/的MNP / BSA溶液（0.86毫升）的预先准备好的含水混合物进硅油，并通过与在900磁性搅拌棒搅拌下乳化于油相中的含水混合物转速，在30℃下 30分钟。 </li></ol> 3.凝胶和微滴转移到水溶液<ol><li>传送从烧杯乳液（〜16ml）中到50毫升管中。 </li><li>冷却该管10分钟，在4℃下，在油中的微滴的凝胶化。 </li><li>装满准备L64溶液（4℃）管可达50 ml和大力摇晃管。它可以是可能的的L64表面活性剂的一部分将是微凝胶内。 </li><li>离心管20分钟为2300 XG在4℃ </li><li> Regularlý检查凝胶粒子的颗粒在管的一侧的存在。如果颗粒不可见，离心以相同的速度和温度20分钟。请继续小心地取出上清液，而不会干扰形成在管的内壁上的沉淀。 </li><li>重复步骤（3.3）至（3.5）一次。每次，将样品转移到新的试管中，以避免任何油滴中微粒凝胶悬浮液中的夹杂物。此步骤后，确保表面活性剂或油滴中不存在的样品悬浮液。然而，重复的分离步骤可导致初始材料的损失。 </li></ol> 4.微凝胶的共价交联<ol><li>加2ml的京尼平溶液（在第1制备的），以凝胶粒子的沉淀并通过涡旋将溶液它们拌匀。 </li><li>很快，在23℃下转移在水浴将悬浮液的管中的德期间发起的共价交联反应（ 如5 - 120分钟）IRED交联时间。 </li><li>交联后，立即被丢弃京尼平的解决方案，在PBS重悬微凝胶，和2,300 XG（4℃）离心管20分钟，除去任何过多的交联剂。如果需要的话，小心翼翼掰开形成颗粒用枪头。该洗涤步骤可重复最多3次，如果京尼平仍然在溶液中剩下的。 </li><li>通过用血球计数的数目弃去上清液并以所希望的密度重悬在PBS中的微粒凝胶（例如，5×10 6微凝胶/ ml）中。 </li><li>对于显微镜观察，加载微粒凝胶悬浮液在载玻片和盖玻片之间的空间和密封用环氧树脂盖玻片的边界。 </li></ol>触发药物释放交变磁场5.应用<ol><li>放置管与在水性介质中微凝胶的期望浓度成磁线圈的腔室。如果需要的话，插入一个光纤温度探头插入管的AMF的应用过程中监视介质的温度变化。 </li><li>在限定的场强（&gt; 5千安/米）和一特定的持续时间施加高频率（&gt; 100千赫）的AMF。以下的AMF的应用，离心机在2,273 xg离心（4℃）并收集上清液量化从微粒凝胶释放到使用分光周围介质的TR-BSA的量20分钟的样品管中。为德克萨斯红的激发和发射波长分别为584纳米和612纳米。 </li></ol>

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The authors have nothing to disclose.

这里所描述的技术演示概念的使用纳米粒子微凝胶杂交的磁热触发药物释放证明。这是通过由京尼平交联的微尺度三维明胶网络内的物理截留的MNP和p（NIPAM- 共 -AAm）链来实现的。磁场响应平台足以响应于远程施加的AMF，这又引发了模型药物，BSA的释放，以产生微粒凝胶内的热量。 A至嵌入两者的MNP和p（NIPAM- 共 -AAm）策略似乎是实现从明胶微凝胶所期望的药物释?...

刺激响应药物输送系统，使响应于内源或外源刺激一个紧密控制的药物递送（例如，温度或pH）已经被广泛地研究作为新型药物递送智能软设备。微尺度水凝胶已被广泛地用作药物递送平台，因为它们赋予可控和持续的药物释放曲线，以及可调的化学和机械性能1-3。特别是，胶体微粒凝胶表现出许多优点，作为药物递送的载体，由于其快速响应外界刺激和合适的可注射到局部组织中以微创方式4。聚（N-异丙基丙烯酰胺）（PNIPAM）或其共聚物已经广泛地在合成热-反应微凝胶通过接枝用的可生物降解/生物相容性的聚合物，包括明胶，壳聚糖，藻酸盐酸或透明质酸PNIPAM通过5,6-，其中在其低临界溶解温度（LCST）PNIPAM的相位转变特性可以用作药物释放7的触发。我们最近证明可生物降解的，基于明胶的热-反应微粒凝胶的制造通过将聚（N- isopropylacrylamide- 共 -丙烯酰胺）[P（NIPAM- 共 -AAm）]链作为三维明胶网络8内的次要组分。明胶/ P（NIPAM- 共 -AAm）微粒凝胶显示出可调谐消溶胀温度增加，这正与牛血清白蛋白（BSA）的释放有关。 在过去的几年里，一直在增加努力，开发出磁响应药物交付平台，可以触发按需时尚9,10药物的释放。为磁响应药物递送平台的合成的基本原理利用超顺磁性纳米颗粒的特性（的MNP）时，他们收到的高频交变磁场（AMF），这将触发一个温度敏感的药物释放产生热量。这适用于在该系统能深定位到组织未来的临床应用的承诺，使得非侵入性和远程控制的药物释放，并可以与热疗治疗和磁共振成像系统10-12被组合。这样的平台包括:（1）的MNP / PNIPAM混合凝胶微粒和13-15（2）宏观水凝胶支架固定结合16-18的MNP。基于PNIPAM-微凝胶平台展示了精细调谐体积相变反应，以磁热刺激。然而，它们仍然依赖于在制造和具有高含量的使用PNIPAM聚合物的复杂和精密的 ​​技术可以潜在细胞毒性，以细胞19，这可能限制了其在体内的应用。宏观支架呈现出相对相比于胶体微粒凝胶LY对外界的刺激反应慢，需要一个微创手术移植。 水包油乳化一直以生产亚毫米或微米尺寸的凝胶颗粒20的标准方法。在该乳液的水 - 油界面，微凝胶颗粒形成球状由于在机械剪切力的水滴的表面能量的最小化。此方法允许产生大量的简单制造过程中水性球形凝胶液滴的，并已成功地采用了用于制造用于药物递送应用21-23基于明胶的微粒凝胶。 这里，我们提出了一个简便的方法通过采用水包油乳化法合成用于药物递送应用magnetothermally响应基于明胶的微粒凝胶。这通过物理地结合的氧化铁的MNP和p（NIPAM- 共同实现-AAM）链作为共价由天然衍生的交联剂京尼平与高频交变磁场（AMF）的应用系统交联的组合，球面微尺度明胶网络中的次要组分。

<table><tbody><tr><td>Gelatin</td><td>Sigma-Aldrich, MO, USA</td><td>G2500</td><td>Gelatin type A, porcine skin</td></tr><tr><td>poly(N-isopropylacrylamide-co-acrylamide)&amp;nbsp;</td><td>Sigma-Aldrich, MO, USA</td><td>738727</td><td>MW = 20,000, LCST = 34 - 38 &amp;#176;C</td></tr><tr><td>Silicone oil</td><td>Sigma-Aldrich, MO, USA</td><td>378372</td><td>Viscosity 350 cSt</td></tr><tr><td>Pluoronic L64</td><td>Sigma-Aldrich, MO, USA</td><td>435449</td><td>poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)</td></tr><tr><td>genipin</td><td>TimTec LLC, DE, USA</td><td>ST080860</td><td>MW = 226.23</td></tr><tr><td>Magnetic nanoparticles (MNPs)</td><td>Micromod Inc, Germany</td><td>79-00-102</td><td>nanomag-D-spio, 100 nm</td></tr><tr><td>TR-BSA</td><td>Life Technologies, NY USA</td><td>A23017</td><td>Albumin from Bovine Serum (BSA), Texas Red conjugate</td></tr></tbody></table>

alternating magnetic field-responsive hybrid gelatin microgels for controlled drug release

磁响应纳米/微工程生物材料，使一个紧密控制的，按需给药已被开发为新的类型的生物医学应用智能软设备。虽然许多磁响应药物递送系统已经证明通过概念研究的或在体内临床前应用中，不是在体外证明功效，其在临床环境中的使用仍然可以通过生物 ​​相容性或生物降解性不足的限制。此外，许多现有的平台依靠自己捏造的尖端技术。我们最近通过物理截留聚（N- isopropylacrylamide- 共 -丙烯酰胺）链作为三维明胶网络中的次要组分表现出生物降解性，基于明胶的热-反应微粒凝胶的制造。在这项研究中，我们提出了一个简便的方法来制造可生物降解的药物释放平台，使磁-Thermally触发药物释放。这是通过结合超顺磁性氧化铁纳米颗粒和热 - 反应聚合物基于明胶的胶体微凝胶内，在结合交变磁场的应用系统来实现的。

当正确地进行协议，所制造的微凝胶应表现出在5微米之间微米至20（图1B 和C）的范围内的充分表征的球形形态和胶体分散直径。任一荧光灯的MNP或荧光的BSA可以用来确认是否的MNP或药物（BSA在这项研究中）的微粒凝胶（图1D）内适当包封。所制作的微凝胶可以稳定且存储在没有任何酶降解剂，包括胶原酶摄氏 4度长达4周。的p?...

Watch this Scientific Journal Video about Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release at JoVE.com

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

交变磁场敏感的混合明胶微凝胶药物控释

我们提出了一个简便的方法来制造可生物降解的明胶释药的平台，磁热响应。这是通过由京尼平交联的球形明胶微网内掺入超顺磁性氧化铁纳米颗粒和聚（N- isopropylacrylamide- 共 -丙烯酰胺），在结合交变磁场的应用系统来实现的。

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

alternating-magnetic-field-responsive-hybrid-gelatin-microgels-for

Universidad de Cartagena UDEC

Research

JoVE Journal

Bioengineering

9.7K 次观看.  Kent State University. 我们提出了一个简便的方法来制造可生物降解的明胶释药的平台，磁热响应。这是通过由京尼平交联的球形明胶微网内掺入超顺磁性氧化铁纳米颗粒和聚（N- isopropylacrylamide- 共 -丙烯酰胺），在结合交变磁场的应用系统来实现的。 

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

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 ...

科研

化学

Generation of Alginate Microspheres for Biomedical Applications

Alginate-based materials have received considerable attention for biomedical applications because of their hydrophilic nature, biocompatibility, and physical architecture. Applications include cell encapsulation, drug delivery, stem cell culture, and tissue engineering scaffolds. In fact, clinical trials are currently being performed in which islets are encapsulated in PLO coated alginate microbeads as a treatment of type I diabetes. However, large numbers of islets are required for efficacy due to poor survival following transplantation. The ability to locally stimulate microvascular network formation around the encapsulated cells may increase their viability through improved transport of oxygen, glucose and other vital nutrients. Fibroblast growth factor-1 (FGF-1) is a naturally occurring growth factor that is able to stimulate blood vessel formation and improve oxygen levels in ischemic tissues. The efficacy of FGF-1 is enhanced when it is delivered in a sustained fashion rather than a single large-bolus administration. The local long-term release of growth factors from islet encapsulation systems could stimulate the growth of blood vessels directly towards the transplanted cells, potentially improving functional graft outcomes. In this article, we outline procedures for the preparation of alginate microspheres for use in biomedical applications. In addition, we describe a method we developed for generating multilayered alginate microbeads. Cells can be encapsulated in the inner alginate core, and angiogenic proteins in the outer alginate layer. The release of proteins from this outer layer would stimulate the formation of local microvascular networks directly towards the transplanted islets.

In the following sections, we outline procedures for the preparation of alginate microspheres for use in biomedical applications. We specifically illustrate a technique for creating multilayered alginate microspheres for the dual purpose of cell and protein encapsulation as a potential treatment for type 1 diabetes.

生物医学应用海藻酸钠微球的一代

Alginate-based materials have received considerable attention for biomedical applications because of their hydrophilic nature, biocompatibility, and ...

医学

An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart

Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the limited access to donor hearts. An example of a treatment to recover the function of the heart consists of the local delivery of drugs and bioactives from a hydrogel. In this paper a method is introduced to formulate and inject a drug-loaded hydrogel non-invasively and side-specific into the pig heart using a long, flexible catheter. The use of 3-D electromechanical mapping and injection via a catheter allows side-specific treatment of the myocardium. To provide a hydrogel compatible with this catheter, a supramolecular hydrogel is used because of the convenient switching from a gel to a solution state using environmental triggers. At basic pH this ureido-pyrimidinone modified poly(ethylene glycol) acts as a Newtonian fluid which can be easily injected, but at physiological pH the solution rapidly switches into a gel. These mild switching conditions allow for the incorporation of bioactive drugs and bioactive species, such as growth factors and exosomes as we present here in both in vitro and in vivo experiments. The in vitro experiments give an on forehand indication of the gel stability and drug release, which allows for tuning of the gel and release properties before the subsequent application in vivo. This combination allows for the optimal tuning of the gel to the used bioactive compounds and species, and the injection system.

Supramolecular hydrogelators based on ureido-pyrimidinones allow full control over the macroscopic gel properties and the sol&#8211;gel switching behavior using pH. Here, we present a protocol for formulating and injecting such a supramolecular hydrogelator via a catheter delivery system for local delivery directly in relevant areas in the pig heart.

可注射药物加载超分子凝胶局部导管注入猪心

Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the ...

生物工程

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and functionalize polymer chains with compounds that are able to improve biocompatibility, mechanical properties, or cell viability allows the design of novel materials to meet new challenges in the biomedical field. With the polymer functionalization strategies, click chemistry is a powerful tool to improve cell-compatibility and drug delivery properties of polymeric devices. Similarly, the fundamental need of biomedicine to use sterile tools to avoid potential adverse-side effects, such as toxicity or contamination of the biological environment, gives rise to increasing interest in the microwave-assisted strategy.
The combination of click chemistry and the microwave-assisted method is suitable to produce biocompatible hydrogels with desired functionalities and improved performances in biomedical applications. This work aims to synthesize RGD-functionalized hydrogels. RGD (arginylglycylaspartic acid) is a tripeptide that can mimic cell adhesion proteins and bind to cell-surface receptors, creating a hospitable microenvironment for cells within the 3D polymeric network of the hydrogels. RGD functionalization occurs through Huisgen 1,3-dipolar cycloaddition. Some PAA carboxyl groups are modified with an alkyne moiety, whereas RGD is functionalized with azido acid as the terminal residue of the peptide sequence. Finally, both products are used in a copper catalyzed click reaction to permanently link the peptide to PAA. This modified polymer is used with carbomer, agarose and polyethylene glycol (PEG) to synthesize a hydrogel matrix. The 3D structure is formed due to an esterification reaction involving carboxyl groups from PAA and carbomer and hydroxyl groups from agarose and PEG through microwave-assisted polycondensation. The efficiency of the gelation mechanism ensures a high degree of RGD functionalization. In addition, the procedure to load therapeutic compounds or biological tools within this functionalized network is very simple and reproducible.

We present a protocol for the synthesis of RGD-functionalized hydrogels as devices for cell and drug delivery. The procedure involves copper catalyzed alkyne-azide cycloaddition (CuAAC) between alkyne-modified polyacrylic acid (PAA) and a RGD-azide derivative. The hydrogels are formed using microwave-assisted polycondensation and their physicochemical properties are investigated.

RGD功能化水凝胶作为治疗应用的工具合成

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and ...

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.), ...

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

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant &#34;burst release&#34; of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

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

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe3O4-NH2 nanoparticles for the potential use in magnetically and thermally triggered drug-release.

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 ...

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 ...

Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications

These methods describe how to formulate injectable, supramolecular polymer-nanoparticle (PNP) hydrogels for&#160;use as biomaterials. PNP hydrogels are composed of two components: hydrophobically modified cellulose as the network polymer and self-assembled core-shell nanoparticles that act as non-covalent cross linkers through dynamic, multivalent interactions. These methods describe both the formation of these self-assembled nanoparticles through nanoprecipitation as well as the formulation and mixing of the two components to form hydrogels with tunable mechanical properties. The use of dynamic light scattering (DLS) and rheology to characterize the quality of the synthesized materials is also detailed. Finally, the utility of these hydrogels for drug delivery, biopharmaceutical stabilization, and cell encapsulation and delivery is demonstrated through in vitro experiments to characterize&#160;drug release, thermal stability, and cell settling and viability. Due to its biocompatibility, injectability, and mild gel formation conditions, this hydrogel system is a readily tunable platform suitable for a range of biomedical applications.

This protocol describes the synthesis and formulation of injectable, supramolecular polymer-nanoparticle (PNP) hydrogel biomaterials. Applications of these materials for drug delivery, biopharmaceutical stabilization, and cell encapsulation and delivery are demonstrated.

用于细胞和药物输送应用的可注射超分子-纳米粒子水凝胶

These methods describe how to formulate injectable, supramolecular polymer-nanoparticle (PNP) hydrogels for&#160;use as biomaterials. PNP hydrogels are ...

Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models

Cell-matrix interactions mediate complex physiological processes through biochemical, mechanical, and geometrical cues, influencing pathological changes and therapeutic responses. Accounting for matrix effects earlier in the drug development pipeline is expected to increase the likelihood of clinical success of novel therapeutics. Biomaterial-based strategies recapitulating specific tissue microenvironments in 3D cell culture exist but integrating these with the 2D culture methods primarily used for drug screening has been challenging. Thus, the protocol presented here details the development of methods for 3D culture within miniaturized biomaterial matrices in a multi-well plate format to facilitate integration with existing drug screening pipelines and conventional assays for cell viability. Since the matrix features critical for preserving clinically relevant phenotypes in cultured cells are expected to be highly tissue- and disease-specific, combinatorial screening of matrix parameters will be necessary to identify appropriate conditions for specific applications. The methods described here use a miniaturized culture format to assess cancer cell responses to orthogonal variation of matrix mechanics and ligand presentation. Specifically, this study demonstrates the use of this platform to investigate the effects of matrix parameters on the responses of patient-derived glioblastoma (GBM) cells to chemotherapy.

The present protocol describes an experimental platform to assess the effects of mechanical and biochemical cues on chemotherapeutic responses of patient-derived glioblastoma cells in 3D matrix-mimetic cultures using a custom-made UV illumination device facilitating high-throughput photocrosslinking of hydrogels with tunable mechanical features.

水凝胶阵列可提高 3D 肿瘤模型中基质成分和治疗药物筛选效果的通量

Cell-matrix interactions mediate complex physiological processes through biochemical, mechanical, and geometrical cues, influencing pathological changes ...

交变磁场敏感的混合明胶微凝胶药物控释

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