3D-Printed Bioelectronic Scaffolds: Soft Tissue-Like Hydrogels with Tunable Conductivity for Advanced Tissue Engineering

Tissue engineering aims to develop biomimetic scaffolds that support cellular behavior and provide physiologically relevant environments for cell culture and regenerative medicine. Traditional scaffolds often fail to adequately mimic the native extracellular matrix (ECM), limiting their effectiveness in tissue engineering applications. The advent of 3D printing has enabled precise control over scaffold architecture, facilitating enhanced cell-material interactions. However, integrating electronic functionalities into 3D scaffolds remains an underdeveloped field, despite the potential of bioelectronic interfaces for cellular stimulation, monitoring, and regeneration. A primary challenge in bioelectronic scaffold design is the mechanical mismatch between conventional conducting materials and soft tissues. Most electrically conductive materials, such as metals and silicon-based structures, exhibit stiffness values several orders of magnitude higher than native soft tissues. This discrepancy can alter cell behavior, impairing attachment, proliferation, and differentiation. Additionally, while hydrogels provide an ECM-like environment due to their high water content and mechanical compliance, their electrical conductivity remains insufficient for bioelectronic applications. Efforts to enhance hydrogel conductivity often lead to increased stiffness, compromising biocompatibility.

Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has emerged as a promising conducting polymer due to its high electrical conductivity, biocompatibility, and stability. However, most previous studies focus on 2D film applications, with limited work on 3D scaffolds that retain soft tissue-like properties. Moreover, existing approaches to fabricating PEDOT:PSS hydrogels rely on simple molding techniques that lack the spatial control required for cell culture applications. New research paper published in Advanced Materials Technologies and conducted by Somtochukwu Okafor, Jae Park, Tianran Liu, Anna Goestenkors, Riley Alvarez, Barbar. Semar, Justin Yu, Cayleigh O’Hare, Sandra Montgomery, Lianna C. Friedman, and led by Professor Alexandra Rutz from the Washington University in St. Louis developed a 3D printing strategy for PEDOT:PSS hydrogels that achieves both soft tissue-matching stiffness and high electrical conductivity. By optimizing the printing methodology and post-processing treatments, the researchers aim to create bioelectronic scaffolds suitable for advanced tissue engineering and biointerfacing applications.

The authors employed a novel approach to fabricate PEDOT:PSS hydrogels with controlled mechanical and electrical properties through 3D printing. The researchers developed weak gel inks with low concentrations of PEDOT:PSS and ionic liquids to achieve optimal printability. By employing embedded 3D printing within a sacrificial agarose support medium, they successfully fabricated free-standing hydrogels with interconnected porosity. Post-printing, hydrogels were subjected to controlled crosslinking at elevated temperatures to enhance stability and maintain mechanical integrity. To fine-tune hydrogel properties, post-treatment with solvents and acids, including dimethyl sulfoxide (DMSO), ethanol, acetic acid, and sulfuric acid, was investigated. Acid treatments significantly increased electrical conductivity, with values reaching up to 1891 S/m while maintaining stiffness within the physiological range (6.20–99.8 kPa). X-ray photoelectron spectroscopy (XPS) analysis confirmed that these treatments reduced the PSS-to-PEDOT ratio, leading to enhanced crosslinking and improved conductivity. Furthermore, post-treated hydrogels retained high water content (89.7–99.4%), ensuring cytocompatibility. Long-term stability studies in Dulbecco’s Modified Eagle Medium (DMEM) demonstrated that hydrogel conductivity remained stable after an initial equilibration period of 3–7 days. Scaffolds maintained their structural integrity over 28 days, with no significant mass loss or fragmentation. Chemical analysis suggested that initial conductivity fluctuations were due to media absorption rather than material degradation. In vitro experiments using human dermal fibroblasts confirmed the biocompatibility of the 3D-printed scaffolds. Cells exhibited high attachment efficiency (>74%), viability (>98%), and proliferation over seven days. Microscopy images revealed that fibroblasts penetrated multiple scaffold layers and deposited extracellular matrix, supporting the suitability of these scaffolds for tissue engineering applications.

In conclusion, the research work by Professor Alexandra Rutz and colleagues is a significant advancement in bioelectronic scaffold design by overcoming the longstanding trade-off between electrical conductivity and mechanical compliance. The development of 3D-printed PEDOT:PSS hydrogels with soft tissue-like stiffness enables the integration of bioelectronics into 3D cell culture systems, opening new possibilities for tissue engineering, regenerative medicine, and organ-on-a-chip models. The ability to tune scaffold properties through post-processing treatments allows for customization across different tissue types, enhancing their applicability in various biomedical applications. Beyond in vitro studies, these scaffolds have potential applications in biohybrid devices, implantable electronic interfaces, and electroactive drug delivery systems. By providing a 3D microenvironment with electronic functionalities, these scaffolds could facilitate real-time monitoring and stimulation of cellular activity, improving the efficacy of engineered tissues and therapeutic implants.