Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs

Gelatin-based hydrogels are highly desirable biomaterials for use in wound dressing, drug delivery, and extracellular matrix components due to their biocompatibility and biodegradability. However, insufficient and uncontrollable mechanical properties and degradation are the major obstacles to their application in medical materials. Herein, we present a simple but efficient strategy for a novel hydrogel by incorporating the synthetic hydrogel monomer polyethylene glycol diacrylate (PEGDA, offering high mechanical stability) into a biological hydrogel compound (gelatin) to provide stable mechanical properties and biocompatibility at the resulting hybrid hydrogel. In the present work, PEGDA/gelatin hybrid hydrogels were prepared by electron irradiation as a reagent-free crosslinking technology and without using chemical crosslinkers, which carry the risk of releasing toxic byproducts into the material. The viscoelasticity, swelling behavior, thermal stability, and molecular structure of synthesized hybrid hydrogels of different compound ratios and irradiation doses were investigated. Compared with the pure gelatin hydrogel, 21/9 wt./wt. % PEGDA/gelatin hydrogels at 6 kGy exhibited approximately up to 1078% higher storage modulus than a pure gelatin hydrogel, and furthermore, it turned out that the mechanical stability increased with increasing irradiation dose. The chemical structure of the hybrid hydrogels was analyzed by Fourier-transform infrared (FTIR) spectroscopy, and it was confirmed that both compounds, PEGDA and gelatin, were equally present. Scanning electron microscopy images of the samples showed fracture patterns that confirmed the findings of viscoelasticity increasing with gelatin concentration. Infrared microspectroscopy images showed that gelatin and PEGDA polymer fractions were homogeneously mixed and a uniform hybrid material was obtained after electron beam synthesis. In short, this study demonstrates that both the presence of PEGDA improved the material properties of PEGDA/gelatin hybrid hydrogels and the resulting properties are fine-tuned by varying the irradiation dose and PEGDA/gelatin concentration.

Stimuli‐responsive hydrogels with decent electrical properties are a promising class of polymeric materials for a range of technological applications, such as electrical, electrochemical, and biomedical devices. In this paper, thermally responsive and conductive hybrid hydrogels are synthesized by in situ formation of continuous network of conductive polymer hydrogels crosslinked by phytic acid in poly(N‐isopropylacrylamide) matrix. The interpenetrating binary network structure provides the hybrid hydrogels with continuous transporting path for electrons, highly porous microstructure, strong interactions between two hydrogel networks, thus endowing the hybrid hydrogels with a unique combination of high electrical conductivity (up to 0.8 S m−1), high thermoresponsive sensitivity (significant volume change within several seconds), and greatly enhanced mechanical properties. This work demonstrates that the architecture of the filling phase in the hydrogel matrix and design of hybrid hydrogel structure play an important role in determining the performance of the resulting hybrid material. The attractive performance of these hybrid hydrogels is further demonstrated by the developed switcher device which suggests potential applications in stimuli‐responsive electronic devices.

Degradable conductive self-healing hydrogels based on dextran-graft-tetraaniline and N-carboxyethyl chitosan as injectable carriers for myoblast cell therapy and muscle regeneration

Conductive hydrogels are receiving considerable attention because of their important applications, such as flexible wearable electronic, human-machine interfaces, and smart/soft robotics. However, the insufficient mechanical performance and inferior adhesive capability severely hinder the potential applications in such an emerging field. Herein, a highly elastic conductive hydrogel that integrated mechanical robustness, self-adhesiveness, UV-filtering, and stable electrical performance was achieved by the synergistic effect of sulfonated lignin-coated silica nanoparticles (LSNs), polyacrylamide (PAM) chains, and ferric ions (Fe3+). In detail, the dynamic redox reaction was constructed between the catechol groups of LSNs and Fe3+, which could promote the rapid gelation of the acrylamide (AM) monomers in 60 s. The optimized conductive hydrogels containing 1.5 wt % LSNs as the dynamic junction points exhibited the excellent elasticity (<15% hysteresis ratio), high stretchability (∼1100% elongation), and improved mechanical robustness (tensile and compressive strength of ∼180 kPa and ∼480 kPa). Notably, the abundant catechol groups of LSNs endowed the conductive hydrogels with the long-lasting and robust self-adhesion, enabling seamless adhesion to the human skin. Meanwhile, the catechol groups also provided an exceptional UV-blocking capability (∼95.1%) for the conductive hydrogels. The combined advantages of the conductive hydrogels were manifested in flexible sensors for the high-fidelity detection of various mechanical deformations over a wide range of strain (10–200%) with good repeatability and stability. We believed that the designed conductive hydrogels may become a promising candidate material in future flexible wearable electronics for long-term and stable human movements monitoring.

Event Abstract Back to Event PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering Ali Navaei1, Danh Truong1, John Heffernan1, Josh Cutts1, David Brafman1, Rachael Sirianni1, 2, Brent Vernon1 and Mehdi Nikkhah1 1 Arizona State University, School of Biological and Health Systems Engineering, United States 2 Barrow Neurological Institute, Barrow Brain Tumor Research Center, United States Injectable biomaterials offer a non-invasive method to deliver cells into the myocardial infarct region to maintain an adequate level of cellular retention and viability and promote the regeneration process. However, conventional injectable matrices suffer from either low bioactivity or poor mechanical properties. To that extent, in this work we introduced a biohybrid temperature-responsive PNIPAAm-Gelatin-based injectable hydrogel, with excellent bioactivity and mechanical robustness for cardiac tissue engineering. A unique feature of our work was performing extensive in vitro biological analyses to assess the functionalities of cardiomyocytes (CMs) alone and in co-culture with cardiac fibroblasts (CFs) within the hydrogel matrix. The synthesized injectable hydrogel exhibited suitable viscoelastic behavior and adequate water content to properly accommodate the cardiac cells. The encapsulated cells demonstrated a high level of survival and spreading throughout the matrix in both culture groups. A dense network of F-actin fibers illustrated the formation of an intact and three dimensional (3D) cardiac tissue construct within the hydrogel matrix. Furthermore, immunostaining images revealed typical phenotypic characteristics in cardiac cells. Interestingly, the co-culture group exhibited significant improvements in structural organization, cell-cell coupling, genes expression, as well as beating behavior. This study opens a new avenue for extensive in vitro characterizations of injectable matrices, using mono- and co-culture of cardiac cells, prior to in vivo experiments. Keywords: Hydrogel, Regenerative Medicine, MYOCARDIAL TISSUE, Cell functionality Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Biomaterials in constructing tissue substitutes Citation: Navaei A, Truong D, Heffernan J, Cutts J, Brafman D, Sirianni R, Vernon B and Nikkhah M (2016). PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02417 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ali Navaei Danh Truong John Heffernan Josh Cutts David Brafman Rachael Sirianni Brent Vernon Mehdi Nikkhah Google Ali Navaei Danh Truong John Heffernan Josh Cutts David Brafman Rachael Sirianni Brent Vernon Mehdi Nikkhah Google Scholar Ali Navaei Danh Truong John Heffernan Josh Cutts David Brafman Rachael Sirianni Brent Vernon Mehdi Nikkhah PubMed Ali Navaei Danh Truong John Heffernan Josh Cutts David Brafman Rachael Sirianni Brent Vernon Mehdi Nikkhah Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Silicon oxides (SiOx) have been considered to be the likeliest material to substitute graphite anode for lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate working potential plus rich abundance. Nevertheless, the two inherent disadvantages of volume expansion and low electrical conductivity of SiOx have been a main obstacle to its application. Here, SiOx-G/PAA-PANi/graphene composite has been successfully synthesized by in-situ polymerization, in which SiOx-G particles linked together by a graphene-doped polyacrylic acid-polyaniline conductive flexible hydrogel and SiOx-G is encapsulated inside the conductive hydrogel. We demonstrate that SiOx-G/PAA-PANi/graphene composite possesses a discharge-specific capacity of 842.3 mA h g−1 at a current density of 500 mA g−1 after a cycle life of 100 cycles, and a good initial coulombic efficiency (ICE) of 74.77%. The superior performance probably due to the lithium ion transmission rate and the electric conductivity enhanced by the three-dimensional (3D) structured conductive polymer hydrogel.

Electrically conductive hydrogels are highly hydrated 3D networks consisting of a hydrophilic polymer skeleton and electrically conductive materials. Conductive hydrogels have excellent mechanical and electrical properties and have further extensive application prospects in biomedical treatment and other fields. Whereas numerous electrically conductive hydrogels have been fabricated, a set of general principles, that can rationally guide the synthesis of conductive hydrogels using different substances and fabrication methods for various application scenarios, remain a central demand of electrically conductive hydrogels. This paper systematically summarizes the processing, performances, and applications of conductive hydrogels, and discusses the challenges and opportunities in this field. In view of the shortcomings of conductive hydrogels in high electrical conductivity, matchable mechanical properties, as well as integrated devices and machines, it is proposed to synergistically design and process conductive hydrogels with applications in complex surroundings. It is believed that this will present a fresh perspective for the research and development of conductive hydrogels, and further expand the application of conductive hydrogels.

Impact of mesenchymal stem cell-secretome-loaded hydrogel on proliferative and migratory activities of hyperglycemic fibroblasts

Recent advances in cardiac tissue engineering have shown that human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in a three-dimensional (3D) micro-environment exhibit superior physiological characteristics compared with their two-dimensional (2D) counterparts. These 3D cultured hiPSC-CMs have been used for drug testing as well as cardiac repair applications. However, the fabrication of a cardiac scaffold with optimal biomechanical properties and high biocompatibility remains a challenge. In our study, we fabricated an aligned polycaprolactone (PCL)-Gelatin coaxial nanofiber patch using electrospinning. The structural, chemical, and mechanical properties of the patch were assessed by scanning electron microscopy (SEM), immunocytochemistry (ICC), Fourier-transform infrared spectroscopy (FTIR)-spectroscopy, and tensile testing. hiPSC-CMs were cultured on the aligned coaxial patch for 2 weeks and their viability [lactate dehydrogenase (LDH assay)], morphology (SEM, ICC), and functionality [calcium cycling, multielectrode array (MEA)] were assessed. Furthermore, particle image velocimetry (PIV) and MEA were used to evaluate the cardiotoxicity and physiological functionality of the cells in response to cardiac drugs. Nanofibers patches were comprised of highly aligned core-shell fibers with an average diameter of 578 ± 184 nm. Acellular coaxial patches were significantly stiffer than gelatin alone with an ultimate tensile strength of 0.780 ± 0.098 MPa, but exhibited gelatin-like biocompatibility. Furthermore, hiPSC-CMs cultured on the surface of these aligned coaxial patches (3D cultures) were elongated and rod-shaped with well-organized sarcomeres, as observed by the expression of cardiac troponin-T and α-sarcomeric actinin. Additionally, hiPSC-CMs cultured on these coaxial patches formed a functional syncytium evidenced by the expression of connexin-43 (Cx-43) and synchronous calcium transients. Moreover, MEA analysis showed that the hiPSC-CMs cultured on aligned patches showed an improved response to cardiac drugs like Isoproterenol (ISO), Verapamil (VER), and E4031, compared to the corresponding 2D cultures. Overall, our results demonstrated that an aligned, coaxial 3D cardiac patch can be used for culturing of hiPSC-CMs. These biomimetic cardiac patches could further be used as a potential 3D in vitro model for “clinical trials in a dish” and for in vivo cardiac repair applications for treating myocardial infarction.

Repairing infected bone defects is a challenge in the field of orthopedics because of the limited self-healing capacity of bone tissue and the susceptibility of refractory materials to bacterial activity. Innervation is the initiating factor for bone regeneration and plays a key regulatory role in subsequent vascularization, ossification, and mineralization processes. Infection leads to necrosis of local nerve fibers, impeding the repair of infected bone defects. Herein, a biomaterial that can induce skeletal-associated neural network reconstruction and bone regeneration with high antibacterial activity is proposed for the treatment of infected bone defects. A photosensitive conductive hydrogel is prepared by incorporating magnesium-modified black phosphorus (BP@Mg) into gelatin methacrylate (GelMA). The near-infrared irradiation-based photothermal and photodynamic treatment of black phosphorus endows it with strong antibacterial activity, improving the inflammatory microenvironment and reducing bacteria-induced bone tissue damage. The conductive nanosheets and bioactive ions released from BP@Mg synergistically improve the migration and secretion of Schwann cells, promote neurite outgrowth, and facilitate innerved bone regeneration. In an infected skull defect model, the GelMA-BP@Mg hydrogel shows efficient antibacterial activity and promotes bone and CGRP+ nerve fiber regeneration. The phototherapy conductive hydrogel provides a novel strategy based on skeletal-associated innervation for infected bone defect repair.

Microbial fuel cells (MFCs) are promising devices that convert chemical energy into electrical energy via extracellular electron transfer between bacteria and electrodes. However, inefficient extracellular electron transfers and bacteria/electrode interactions often limit their performance. Herein, we demonstrate a hybrid hydrogel assembled by a 2D covalent organic framework (COF) and reduced graphene oxide (rGO) nanosheets as anode materials for MFCs. The 2D COF nanosheets effectively prevent the stacking of rGO nanosheets, resulting in the hybrid hydrogel with a high specific surface area (313.2 m2/g), abundant mesopores and macropores, and high electrical conductivity (492 S/m). The COF material also brings many quinone groups as redox mediators to facilitate electron transfer between bacteria and electrodes. The COF/rGO hybrid hydrogel enhances the growth of Shewanella decolorationis S12 cells, even under the influence of different organic dyes. Dense biofilms are formed on the hybrid hydrogel's surface and inside its macropores, further improving extracellular electron transfers. Assembled MFCs using COF/rGO anodes deliver a maximum power density of 905.1 mW/m2 and can operate for 600 h. They also enable simultaneous power generation and fast organic contamination degradation in electrolytes. This work shows the potential of using 2D nanoarchitectures to promote high-performance MFCs.

Type I collagen hydrogels are of high interest in tissue engineering. With the evolution of 3D bioprinting technologies, a high number of collagen-based scaffolds have been reported for the development of 3D cell cultures. A recent proposal was to mix collagen with silk fibroin derived from Bombyx mori silkworm. Nevertheless, due to the difficulties in the preparation and the characteristics of the protein, several problems such as phase separation and collagen denaturation appear during the procedure. Therefore, the common solution is to diminish the concentration of collagen although in that way the most biologically relevant component is reduced. In this study, we present a new, simple, and effective method to develop a collagen-silk hybrid hydrogel with high collagen concentration and with increased stiffness approaching that of natural tissues, which could be of high interest for the development of cardiac patches for myocardial regeneration and for preconditioning of mesenchymal stem cells (MSCs) to improve their therapeutic potential. Sericin in the silk was preserved by using a physical solubilizing procedure that results in a preserved fibrous structure of type I collagen, as shown by ultrastructural imaging. The macro- and micromechanical properties of the hybrid hydrogels measured by tensile stretch and atomic force microscopy, respectively, showed a more than twofold stiffening than the collagen-only hydrogels. Rheological measurements showed improved printability properties for the developed biomaterial. The suitability of the hydrogels for 3D cell culture was assessed by 3D bioprinting bone marrow-derived MSCs cultured within the scaffolds. The result was a biomaterial with improved printability characteristics that better resembled the mechanical properties of natural soft tissues while preserving biocompatibility owing to the high concentration of collagen. Impact statement In this study, we report the development of silk microfiber-reinforced type I collagen hydrogels for 3D bioprinting and cell culture. In contrast with previously reported studies, a novel physical method allowed the preservation of the silk sericin protein. Hydrogels were stable, showed no phase separation between the biomaterials, and they presented improved printability. An increase between two- and threefold of the multiscale stiffness of the scaffolds was achieved with no need of using additional crosslinkers or complex methods, which could be of high relevance for cardiac patches development and for preconditioning mesenchymal stem cells (MSCs) for therapeutic applications. We demonstrate that bone marrow-derived MSCs can be effectively bioprinted and 3D cultured within the stiffened structures.

Stage-matched conductive hydrogel with pH/ROS/MMP9 triple-responsive salidroside release for post-infarction myocardial repair.

Myocardial infarction (MI) remains one of the leading causes of death globally, necessitating innovative therapeutic strategies for effective repair. Conventional treatment methods such as pharmacotherapy, interventional surgery, and cardiac transplantation, while capable of reducing short-term mortality rates, still face significant challenges in post-MI repair including the restoration of intercellular biological and electrical signaling. This study presents a novel exosome-loaded conductive hydrogel designed to enhance myocardial repair by concurrently improving biological and electrical signals. Adipose-derived stem cell (ADSC) exosomes, encapsulated within a hyaluronic acid-dopamine (HA-DA) hydrogel, were employed to promote angiogenesis and inhibit inflammation. Incorporating black phosphorus (BP) into the hydrogel improved its electrical conductivity, thereby restoring electrical signal transmission in the infarcted myocardium and preventing arrhythmias. In vitro and in vivo experiments demonstrated that the exosome-loaded conductive hydrogel significantly enhanced cardiac function recovery by accelerating angiogenesis, reducing inflammation, and increasing electrical activity between myocardial cells. The hydrogel exhibited excellent biocompatibility, biodegradability, and sustained release of exosomes, ensuring prolonged therapeutic effects. This integrated approach resulted in notable improvements in the left ventricular ejection fraction, reduced fibrosis, and increased neovascularization. The combination of bioactive exosomes and a conductive hydrogel presents a promising therapeutic strategy for myocardial infarction repair.

An electroconductive hydrogel with injectable and self-healing properties accelerates peripheral nerve regeneration and motor functional recovery