Development of Electrically Conductive Double‐Network Hydrogels via One‐Step Facile Strategy for Cardiac Tissue Engineering

Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of electrical conductivity of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one‐step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chemical crosslinked poly(thiophene‐3‐acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo‐crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mechanical, and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its conductivity (≈10−4 S cm−1) falls in the range of reported conductivities for native myocardium tissue. To assess their biological activity, the brown adipose‐derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without electrical stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, electrical stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.

[1]  Boguang Yang,et al.  RoY peptide-modified chitosan-based hydrogel to improve angiogenesis and cardiac repair under hypoxia. , 2015, ACS applied materials & interfaces.

[2]  Lele Peng,et al.  Conductive “Smart” Hybrid Hydrogels with PNIPAM and Nanostructured Conductive Polymers , 2015 .

[3]  Guorui Jin,et al.  The electrically conductive scaffold as the skeleton of stem cell niche in regenerative medicine. , 2014, Materials science & engineering. C, Materials for biological applications.

[4]  E. Alsberg,et al.  Improved conduction and increased cell retention in healed MI using mesenchymal stem cells suspended in alginate hydrogel , 2014, Journal of Interventional Cardiac Electrophysiology.

[5]  Boguang Yang,et al.  A PNIPAAm-based thermosensitive hydrogel containing SWCNTs for stem cell transplantation in myocardial repair. , 2014, Biomaterials.

[6]  A. Boccaccini,et al.  Development and characterization of novel electrically conductive PANI-PGS composites for cardiac tissue engineering applications. , 2014, Acta biomaterialia.

[7]  Hai-bin Wang,et al.  Promotion of cardiac differentiation of brown adipose derived stem cells by chitosan hydrogel for repair after myocardial infarction. , 2014, Biomaterials.

[8]  P. Ma,et al.  In situ forming biodegradable electroactive hydrogels , 2014 .

[9]  A. Haverich,et al.  Engineering cardiac muscle: new ways to refurbish old hearts? , 2014, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[10]  Changyong Wang,et al.  A chitosan-glutathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocytes. , 2013, Biomaterials.

[11]  F. Watt,et al.  Monodisperse collagen-gelatin beads as potential platforms for 3D cell culturing. , 2013, Journal of materials chemistry. B.

[12]  Gulden Camci-Unal,et al.  Synthesis and characterization of hybrid hyaluronic acid-gelatin hydrogels. , 2013, Biomacromolecules.

[13]  A. Khademhosseini,et al.  Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. , 2013, ACS nano.

[14]  S. Kundu,et al.  Silk sericin/polyacrylamide in situ forming hydrogels for dermal reconstruction. , 2012, Biomaterials.

[15]  W. Blau,et al.  The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to MSCs. , 2012, Biomaterials.

[16]  Joselito M. Razal,et al.  Electrically Conductive, Tough Hydrogels with pH Sensitivity , 2012 .

[17]  Elise M. Stewart,et al.  A Single Component Conducting Polymer Hydrogel as a Scaffold for Tissue Engineering , 2012 .

[18]  Bappaditya Roy,et al.  Self-sustaining, fluorescent and semi-conducting co-assembled organogel of Fmoc protected phenylalanine with aromatic amines , 2012 .

[19]  Y. Osada,et al.  Electro‐conductive double‐network hydrogels , 2012 .

[20]  Shyh‐Chyang Luo,et al.  Oligoethylene-glycol-functionalized polyoxythiophenes for cell engineering: syntheses, characterizations, and cell compatibilities. , 2012, ACS applied materials & interfaces.

[21]  S. Pedron,et al.  Stimuli Responsive Delivery Vehicles for Cardiac Microtissue Transplantation , 2011 .

[22]  Changyou Gao,et al.  Biological hydrogel synthesized from hyaluronic acid, gelatin and chondroitin sulfate by click chemistry. , 2011, Acta biomaterialia.

[23]  A. Kirschning,et al.  Preparation and Evaluation of Hydrogel-Composites from Methacrylated Hyaluronic Acid, Alginate, and Gelatin for Tissue Engineering , 2011, The International journal of artificial organs.

[24]  R. Das,et al.  Spectroscopic, microscopic and first rheological investigations in charge-transfer interaction induced organogels , 2010 .

[25]  Nicola Elvassore,et al.  Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. , 2009, Experimental cell research.

[26]  S. Omata,et al.  Improvement of hydrogelation abilities and handling of photocurable gelatin-based crosslinking materials. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[27]  Prashanthan Sanders,et al.  Fractionated atrial electrograms during sinus rhythm: relationship to age, voltage, and conduction velocity. , 2009, Heart rhythm.

[28]  V. Barron,et al.  Carbon nanotubes and mesenchymal stem cells: biocompatibility, proliferation and differentiation. , 2008, Nano letters.

[29]  J. Ying,et al.  Poly(3,4-ethylenedioxythiophene) (PEDOT) nanobiointerfaces: thin, ultrasmooth, and functionalized PEDOT films with in vitro and in vivo biocompatibility. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[30]  Eric D. Adler,et al.  Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population , 2008, Nature.

[31]  Ling Wei,et al.  Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. , 2008, The Journal of thoracic and cardiovascular surgery.

[32]  Tal Dvir,et al.  Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes cardiac tissue assembly. , 2007, Tissue engineering.

[33]  Christine E. Schmidt,et al.  Conducting polymers in biomedical engineering , 2007 .

[34]  N. Fukuda,et al.  Cardiac progenitor cells in brown adipose tissue repaired damaged myocardium. , 2006, Biochemical and biophysical research communications.

[35]  M. Wartenberg,et al.  Reactive oxygen species as signaling molecules in cardiovascular differentiation of embryonic stem cells and tumor-induced angiogenesis. , 2005, Antioxidants & redox signaling.

[36]  Yoshihito Osada,et al.  High Mechanical Strength Double‐Network Hydrogel with Bacterial Cellulose , 2004 .

[37]  J. Ingwall,et al.  Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts , 2003, Nature Medicine.

[38]  T. Kurokawa,et al.  Double‐Network Hydrogels with Extremely High Mechanical Strength , 2003 .

[39]  A D McCulloch,et al.  Myocardial Mechanics and Collagen Structure in the Osteogenesis Imperfecta Murine (oim) , 2000, Circulation research.

[40]  Yoshihito Osada,et al.  Environmental responses of polythiophene hydrogels , 2000 .

[41]  J. Hescheler,et al.  Effects of electrical fields on cardiomyocyte differentiation of embryonic stem cells , 1999, Journal of cellular biochemistry.

[42]  Yoshihito Osada,et al.  Titration Behavior and Spectral Transitions of Water-Soluble Polythiophene Carboxylic Acids , 1999 .

[43]  K. Yoshino,et al.  Instability of conducting polymer, poly(3-alkylthiophene) gel with solvent, temperature and doping and effect of alkyl chain length , 1989 .

[44]  K. Rayner,et al.  Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction. , 2015, Biomaterials.

[45]  Yen Chang,et al.  Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating. , 2013, Biomaterials.