Design and fabrication of electro conductive photo curable hydrogels for bioelectronic interfacing

Bioelectronic devices interact with cells and tissues, sense electrical activity and modulate cellular behavior through electrical fields. Typically, in vitro devices are based on flat, rigid metal electrodes that are designed for 2D cell models. 3D electrodes, providing physical and biological stimuli, enhance cell-chip coupling creating a more bio-mimetic environment. Topography, and aspect ratio of nano and micro structured surfaces can modulate the interaction with cell membrane affecting also intracellular signaling. Substrate mimicking mechanical properties of the native extracellular matrix (ECM) enhances cell interaction. Natural and synthetic materials such as gelatin and polyethylene glycol diacrylate (PEGDA) can be used to obtain 3D patterned structures at microscale. Challenges in providing electrical and morphological stimuli via these materials persist. The integration of such materials into more complex circuitry requires patterning resolution, flexibility, and control over the geometry to be achieved. To this aim, an innovative approach for the fabrication of conductive 3D structures for cell sensing and stimulation is presented. A conductive hydrogel comprising modified gelatin and PEDOT:PSS will be engineered. Gelatin, modified with methacrylate groups, serves as photo curable material with bioactive features, while PEDOT:PSS acts as the electro conductive element. The obtained blend has been 3D photo-patterned exploiting multiple techniques from drop casting and subsequent UV photopolymerization to two-photon-polymerization (2PP) lithography. The degree of methacrylation (DOM) was assessed by proton nuclear magnetic resonance (1H-NMR). The resulting 3D structures has been characterized by optical microscopy and electrochemical measurements. Finally, biocompatibility assays were carried out with neuronal cells. In this work, GelMA with different DOMs, and GelMA\PEDOT:PSS blends with PEDOT:PSS concentration up to 5%wt were obtained. The presence of PEDOT:PSS reduces the impedance of blends. The obtained blends can be exploited to develop photo cured hydrogels at macro- , meso- and micro-scale. HT-22 cells cultured on GelMA and GelMA\PEDOT:PSS hydrogels showed high viability. The proposed approach offers a promising pathway for creating fully organic and bioactive 3D electrodes with controlled morphology for sensing and stimulating cells and tissues. Such electrodes could find applications in biomedical devices such as implants, probes, and epidermal devices, where flexible, soft, and conductive materials are essential requirements. Also, with constant evolution of micro fluidics technology leading to “on chip” technologies, the integration of a sensing component is crucial to standardization and validation of this techniques.