Dynamic and biocompatible thermo-responsive magnetic hydrogels that respond to an alternating magnetic field

Abstract Magnetic thermo-responsive hydrogels are a new class of materials that have recently attracted interest in biomedicine due to their ability to change phase upon magnetic stimulation. They have been used for drug release, magnetic hyperthermia treatment, and can potentially be engineered as stimuli-responsive substrates for cell mechanobiology. In this regard, we propose a series of magnetic thermo-responsive nanocomposite substrates that undergo cyclical swelling and de-swelling phases when actuated by an alternating magnetic field in aqueous environment. The synthetized substrates are obtained with a facile and reproducible method from poly-N-isopropylacrylamide and superparamagnetic iron oxide nanoparticles. Their conformation and the temperature-related, magnetic, and biological behaviors were characterized via scanning electron microscopy, swelling ratio analysis, vibrating sample magnetometry, alternating magnetic field stimulation and indirect viability assays. The nanocomposites showed no cytotoxicity with fibroblast cells, and exhibited swelling/de-swelling behavior near physiological temperatures (around 34 °C). Therefore these magnetic thermo-responsive hydrogels are promising materials as stimuli-responsive substrates allowing the study of cell-behavior by changing the hydrogel properties in situ.

[1]  Tomaz Velnar,et al.  The Wound Healing Process: An Overview of the Cellular and Molecular Mechanisms , 2009, The Journal of international medical research.

[2]  John A Timbrell,et al.  In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. , 2006, Toxicology letters.

[3]  T. Aoyagi,et al.  Temperature-Responsive Poly(ɛ-caprolactone) Cell Culture Platform with Dynamically Tunable Nano-Roughness and Elasticity for Control of Myoblast Morphology , 2014, International journal of molecular sciences.

[4]  Todd Hoare,et al.  Injectable superparamagnets: highly elastic and degradable poly(N-isopropylacrylamide)-superparamagnetic iron oxide nanoparticle (SPION) composite hydrogels. , 2013, Biomacromolecules.

[5]  James H Henderson,et al.  Dynamic cell behavior on shape memory polymer substrates. , 2011, Biomaterials.

[6]  M. Ward,et al.  Thermoresponsive Polymers for Biomedical Applications , 2011 .

[7]  Chun-Rong Lin,et al.  Magnetic properties of monodisperse iron oxide nanoparticles , 2006 .

[8]  J. Shumaker-Parry,et al.  Structural study of citrate layers on gold nanoparticles: role of intermolecular interactions in stabilizing nanoparticles. , 2014, Journal of the American Chemical Society.

[9]  Marco Lattuada,et al.  Functionalization of monodisperse magnetic nanoparticles. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[10]  R. Ramanujan,et al.  Magnetic PNIPA hydrogels for hyperthermia applications in cancer therapy , 2007 .

[11]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[12]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[13]  Samantha A. Meenach,et al.  Biocompatibility analysis of magnetic hydrogel nanocomposites based on poly(N-isopropylacrylamide) and iron oxide. , 2009, Journal of biomedical materials research. Part A.

[14]  M. Vázquez,et al.  Magnetic Iron Oxide Nanoparticles in 10−40 nm Range: Composition in Terms of Magnetite/Maghemite Ratio and Effect on the Magnetic Properties , 2011 .

[15]  R. Regmi,et al.  Hyperthermia controlled rapid drug release from thermosensitive magnetic microgels , 2010 .

[16]  Murat Guvendiren,et al.  Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics , 2012, Nature Communications.

[17]  André R. Fajardo,et al.  Natural polymer-based magnetic hydrogels: Potential vectors for remote-controlled drug release. , 2012, Carbohydrate polymers.

[18]  X. Sui,et al.  Probing the collapse dynamics of poly(N-isopropylacrylamide) brushes by AFM: effects of co-nonsolvency and grafting densities. , 2011, Small.

[19]  Kimberly W. Anderson,et al.  Synthesis and characterization of thermoresponsive poly(ethylene glycol)‐based hydrogels and their magnetic nanocomposites , 2010 .

[20]  I. Wilson,et al.  Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. , 2000, European journal of biochemistry.

[21]  Adam J Engler,et al.  Dynamic and reversible surface topography influences cell morphology. , 2013, Journal of biomedical materials research. Part A.

[22]  M. Théry,et al.  Polyacrylamide hydrogel micropatterning. , 2014, Methods in cell biology.

[23]  Shaobing Zhou,et al.  The Control of Mesenchymal Stem Cell Differentiation Using Dynamically Tunable Surface Microgrooves , 2014, Advanced healthcare materials.

[24]  Tian Jian Lu,et al.  Magnetic Hydrogels and Their Potential Biomedical Applications , 2013 .

[25]  C. Brazel Magnetothermally-responsive Nanomaterials: Combining Magnetic Nanostructures and Thermally-Sensitive Polymers for Triggered Drug Release , 2009, Pharmaceutical Research.

[26]  R. Morimoto,et al.  Cells in stress: transcriptional activation of heat shock genes. , 1993, Science.

[27]  Yu-Li Wang,et al.  A photo-modulatable material for probing cellular responses to substrate rigidity. , 2009, Soft matter.

[28]  Neus G. Bastús,et al.  Small Gold Nanoparticles Synthesized with Sodium Citrate and Heavy Water: Insights into the Reaction Mechanism , 2010 .

[29]  Takashi Nakagawa,et al.  Suitability of commercial colloids for magnetic hyperthermia , 2009 .

[30]  Taeghwan Hyeon,et al.  Ultra-large-scale syntheses of monodisperse nanocrystals , 2004, Nature materials.

[31]  N. Satarkar,et al.  Hydrogel nanocomposites as remote-controlled biomaterials. , 2008, Acta biomaterialia.

[32]  M. Marcacci,et al.  A conceptually new type of bio-hybrid scaffold for bone regeneration , 2011, Nanotechnology.

[33]  F. Ludwig,et al.  Size dependent structural and magnetic properties of FeO-Fe3O4 nanoparticles. , 2013, Nanoscale.

[34]  Fernanda F. Rossetti,et al.  Quantitative evaluation of mechanosensing of cells on dynamically tunable hydrogels. , 2011, Journal of the American Chemical Society.

[35]  Hongwei Ma,et al.  Preparation and characterization of sodium alginate/poly(N-isopropylacrylamide)/clay semi-IPN magnetic hydrogels , 2012, Polymer Bulletin.

[36]  S. Dutz,et al.  Magnetic particle hyperthermia: nanoparticle magnetism and materials development for cancer therapy , 2006 .

[37]  I. Chen,et al.  Biomedical nanoparticle carriers with combined thermal and magnetic responses , 2009 .

[38]  C. Cho,et al.  Regulation of cellular morphology using temperature-responsive hydrogel for integrin-mediated mechanical force stimulation. , 2009, Biomaterials.

[39]  J. Overgaard,et al.  Effect of hyperthermia on malignant cells in vivo: A review and a hypothesis , 1977, Cancer.

[40]  Sophie Laurent,et al.  How to quantify iron in an aqueous or biological matrix: a technical note. , 2009, Contrast media & molecular imaging.

[41]  S. Dutz,et al.  Effects of size distribution on hysteresis losses of magnetic nanoparticles for hyperthermia , 2008, Journal of physics. Condensed matter : an Institute of Physics journal.

[42]  A. Gaharwar,et al.  Dual-stimuli responsive PNiPAM microgel achieved via layer-by-layer assembly: magnetic and thermoresponsive. , 2008, Journal of colloid and interface science.

[43]  Paul A. Janmey,et al.  Soft biological materials and their impact on cell function. , 2007, Soft matter.

[44]  Toyoichi Tanaka,et al.  Volume‐phase transitions of ionized N‐isopropylacrylamide gels , 1987 .

[45]  Jeremy M. Rathfon,et al.  Synthesis of thermoresponsive poly(N-isopropylmethacrylamide) and poly(acrylic acid) block copolymers via post-functionalization of poly(N-methacryloxysuccinimide) , 2008 .

[46]  John M. Hoffman,et al.  Shape‐Memory Surface with Dynamically Tunable Nano‐Geometry Activated by Body Heat , 2012, Advanced materials.

[47]  Richard E. Eitel,et al.  Magnetic hydrogel nanocomposites as remote controlled microfluidic valves. , 2009, Lab on a chip.

[48]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[49]  Sébastien Lachaize,et al.  Optimal Size of Nanoparticles for Magnetic Hyperthermia: A Combined Theoretical and Experimental Study , 2011 .

[50]  R. E. Rosensweig,et al.  Heating magnetic fluid with alternating magnetic field , 2002 .

[51]  Bernd Hamm,et al.  Monomer-Coated Very Small Superparamagnetic Iron Oxide Particles as Contrast Medium for Magnetic Resonance Imaging: Preclinical In Vivo Characterization , 2002, Investigative radiology.

[52]  S. K. Srivastava,et al.  Size-dependent structural and magnetic properties of disordered Co2FeAl Heusler alloy nanoparticles , 2019, Journal of Magnetism and Magnetic Materials.

[53]  Cai‐Feng Wang,et al.  Multifunctional Hydrogels with Temperature, Ion, and Magnetocaloric Stimuli-Responsive Performances. , 2016, Macromolecular rapid communications.

[54]  Wendelin Jan Stark,et al.  Crosslinking metal nanoparticles into the polymer backbone of hydrogels enables preparation of soft, magnetic field-driven actuators with muscle-like flexibility. , 2009, Small.

[55]  M. Shamonin,et al.  Ultra-Soft PDMS-Based Magnetoactive Elastomers as Dynamic Cell Culture Substrata , 2013, PloS one.

[56]  Donald E Ingber,et al.  Cell tension, matrix mechanics, and cancer development. , 2005, Cancer cell.

[57]  Alke Petri-Fink,et al.  Particle size distribution measurements of manganese-doped ZnS nanoparticles. , 2009, Analytical chemistry.

[58]  Shaobing Zhou,et al.  Tuning surface micropattern features using a shape memory functional polymer , 2013 .