Bioprinting of a Cell-Laden Conductive Hydrogel Composite.

Bioprinting has gained significant attention for creating biomimetic tissue constructs with potential to be used in biomedical applications such as drug screening or regenerative medicine. Ideally, biomaterials used for three-dimensional (3D) bioprinting should match the mechanical, hydrostatic, bioelectric, and physicochemical properties of the native tissues. However, many materials with these tissue-like properties are not compatible with printing techniques without modifying their compositions. In addition, integration of cell-laden biomaterials with bioprinting methodologies that preserve their physicochemical properties remains a challenge. In this work, a biocompatible conductive hydrogel composed of gelatin methacryloyl (GelMA) and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) was synthesized and bioprinted to form complex, 3D cell-laden structures. The biofabricated conductive hydrogels were formed by an initial cross-linking step of the PEDOT:PSS with bivalent calcium ions and a secondary photopolymerization step with visible light to cross-link the GelMA component. These modifications enabled tuning the mechanical properties of the hydrogels, with Young's moduli ranging from ∼40-150 kPa, as well as tunable conductivity by varying the concentration of PEDOT:PSS. In addition, the hydrogels degraded in vivo with no substantial inflammatory responses as demonstrated by haematoxylin and eosin (H&E) and immunofluorescent staining of subcutaneously implanted samples in Wistar rats. The parameters for forming a slurry of microgel particles to support 3D bioprinting of the engineered cell-laden hydrogel were optimized to form constructs with improved resolution. High cytocompatibility and cell spreading were demonstrated in both wet-spinning and 3D bioprinting of cell-laden hydrogels with the new conductive hydrogel-based bioink and printing methodology. The synergy of an advanced fabrication method and conductive hydrogel presented here is promising for engineering complex conductive and cell-laden structures.

Electroconductive Gelatin Methacryloyl-PEDOT:PSS Composite Hydrogels: Design, Synthesis, and Properties.

Electroconductive hydrogels are used in a wide range of biomedical applications, including electrodes for patient monitoring and electrotherapy, or as biosensors and electrochemical actuators. Approaches to design electroconductive hydrogels are often met with low biocompatibility and biodegradability, limiting their potential applications as biomaterials. In this study, composite hydrogels were prepared from a conducting polymer complex, poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) dispersed within a photo-crosslinkable naturally derived hydrogel, gelatin methacryloyl (GelMA). To determine the impact of PEDOT:PSS loading on physical and microstructural properties and cellular responses, the electrical and mechanical properties, electrical properties, and biocompatibility of hydrogels loaded with 0-0.3% (w/v) PEDOT:PSS were evaluated and compared to GelMA control. Our results indicated that the properties of the hydrogels, such as mechanics, degradation, and swelling, could be tuned by changing the concentration of PEDOT:PSS. In particular, the impedance of hydrogels decreased from 449.0 kOhm for control GelMA to 281.2 and 261.0 kOhm for hydrogels containing 0.1% (w/v) and 0.3% (w/v) PEDOT:PSS at 1 Hz frequency, respectively. In addition, an ex vivo experiment demonstrated that the threshold voltage to stimulate contraction in explanted abdominal tissue connected by the composite hydrogels decreased from 9.3 ± 1.2 V for GelMA to 6.7 ± 1.5 V and 4.0 ± 1.0 V for hydrogels containing 0.1% (w/v) and 0.3% (w/v) PEDOT:PSS, respectively. In vitro studies showed that composite hydrogels containing 0.1% (w/v) PEDOT:PSS supported the viability and spreading of C2C12 myoblasts, comparable to GelMA controls. These results indicate the potential of our composite hydrogel as an electroconductive biomaterial.