(624g) Novel Bio-Ionic Liquid Functionalized Conductive Hydrogel for Cardiac Tissue Regeneration

Conducting polymers (CPs) constitute a new generation of organic materials, which exhibit electrical and optical properties that are similar to those of metals and inorganic semiconductors. They also possess the advantageous properties associated with regular polymers, such as ease of synthesis and processability, when compared to metals [1]. CPs are widely used in microelectronics for the manufacture of batteries, photovoltaic devices, light-emitting diodes and electro-chromic displays, as well as in biomedical applications including neural probes and prostheses, and controlled release systems. CPs have also been shown to modulate cellular processes such as cell growth and migration through electrical stimulation (conductivities from 10-4 to 9 S/cm). These properties make CPs and their derivatives remarkably suitable for tissue engineering applications using excitable cell types, including nerve, muscle, and cardiac tissue. However, there are still several technical challenges associated with the use of CPs for tissue engineering applications. The main drawbacks associated with the existing, CP-based biomaterials are: poor polymer-cell interactions due to the absence of cell binding sites, high hydrophobicity, poor solubility and processability, non-biodegradability, as well as the inability to optimize their mechanical properties. Therefore, the synthesis of biomaterials that are both electroactive and biodegradable is highly desirable. Electroconductive properties have been incorporated into biomaterials through the addition of nanomaterials (e.g. silver nanowires, gold nanoparticles, carbon nanotubes (CNTs), and graphene oxide) or conductive polymers (e.g. polyaniline, polypyrole, polythiophene) to the polymeric matrices. However, these approaches suffer from difficult and prolonged processing procedures, harsh reaction conditions, difficulties in the incorporation of nanomaterials into the polymer networks, limited solubility in aqueous media, and cytotoxicity. Therefore, there is an unmet need for the development of biocompatible, biodegradable, and conductive biomaterials, with tunable conductive and physical properties [1].

Here, we introduce a new class of conductive polymer-based biomaterials through conductive bio-ionic liquid (BIL) functionalization of different biopolymers. BIL are low melting organic salts that exhibit several technical advantages, including low volatility, high ionic conductivity and electrochemical stability, and excellent dissolution capabilities. BILs have been previously used as biocompatible and biodegradable materials for various applications such as cancer therapy, multi-responsive drug delivery systems, sensors, batteries, and biomedical implants [2-5]. Functionalization of biopolymers with BIL can provide conductive properties to the polymer networks, while preserving the biological and physical characteristics of the biopolymers. This property makes them unique candidates for various tissue-engineering applications. We performed chemical conjugation of BIL to various synthetic and natural polymers including gelatin, tropoelastin, elastin like polypeptides (ELP), collagen, poly(ethylene glycol) (PEG), hyaluronic acid (HA), poly(glycerol sebacate) polymer (PGS) and combinations of them, in order to generate conductive biomaterials with high biocompatibility and tunable physical and electrical properties. For example, we engineered a novel 3D gelatin-based hydrogel by using a visible light-activated gelatin prepolymer, functionalized with a BIL for heart tissue regeneration. FTIR and NMR analysis confirmed the successful functionalization of BIL to the biopolymer structure. The mechanical and electrical properties of the engineered hydrogel were then optimized to mimic the properties of the native heart tissue. Our in vitro tests confirmed that the engineered conductive scaffolds provide a suitable conductive and mechanical substratum for the culture of cardiac cells. This led to the formation of 3D functional cardiac patches, which can potentially be used for heart tissue regeneration.

References:

[1]- Kaur G , Adhikari R, Cass P , Bown M, Gunatillake P. RSC Adv., 2015, 5, 37553-37567

[2] Brock M, Nickel A-C, Madziar B, Blusztajn JK, & Berse B (2007) Brain Research 1145(0):1-10.

[3] Kumar SSD, Surianarayanan M, Vijayaraghavan R, Mandal AB, & MacFarlane DR (2014) European Journal of Pharmaceutical Sciences 51(0):34-44.

[4] Curto VF, et al. (2014). Physical Chemistry Chemical Physics 16(5):1841-1849.

[5] Dias AMA, et al. (2013) ACS Sustainable Chemistry & Engineering 1(11):1480-1492.