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Introduction: The translation of signals between the human body and biomedical implants is a critical challenge in advancing tissue engineering, regenerative medicine, and diagnostics. Minimizing the inherent differences between neural biological components and synthetic interfaces, particularly in stiffness, biocompatibility, and cellular cues, is crucial for effective neural interfaces1. In this regard, Electroactive hydrogels (EAHs) are promising due to their biomimetic properties: elastic networks, high water content, and electroactive behavior1. These materials can better replicate the mechanical, electrical, and biological properties of the native extracellular matrix1-3. Given the electroactive nature of neural tissue, interfaces interacting with this activity are of greatest importance. This work addresses the need for a mechanically stable, printable, and electroactive soft interface for neural applications1. Its objectives include developing such a material and evaluating its efficiency in interacting with growth factors and modulating neural cell behavior through electrical stimulation to enhance proliferation3 and differentiation2. Successful interfaces could significantly advance our understanding of cellular responses to electrical stimulation, improve tissue repair, and lead to innovative therapeutic and drug delivery systems.
Methods: An electroactive hydrogel composite was fabricated using Gelatin Methacryloyl (GelMA) as the hydrogel matrix and graphene oxide (GO) as the conductive nanofiller. In vitro studies were conducted using neural cells, cultured on the electroactive hydrogel interface. These cultures were subjected to various electrical stimulation protocols to assess cell proliferation and differentiation. The interaction of specific growth factors with the electroactive hydrogel was also investigated, including encapsulation and release characteristics, and the influence of electrical stimulation on growth factor delivery and cellular response. Electrochemical impedance spectroscopy was used to evaluate the electroactivity of the composite hydrogel. Rheological properties were assessed to confirm printability and shape fidelity.
Results: Incorporation of graphene oxide into GelMA significantly enhanced electroactivity, evidenced by reduced impedance and increased charge injection capacity. GO also improved GelMA's rheological properties, enabling the development of an electrically active bioink with high-fidelity 3D printing. The electroactive hydrogel, combined with electrical stimulation, modulated neural cell behavior, enhancing proliferation and potentially differentiation of neuronal cells. GO in GelMA positively influenced cell viability and metabolic activity. The study also demonstrated successful growth factor encapsulation and controlled release, with the hydrogel and electrical stimulation affecting growth factor efficacy on neural cells.
Discussion: These findings highlight the potential of mechanically stable, printable, and electroactive GelMA/GO hydrogels for neural interfaces. The ability to modulate neural cell behavior through the combined effects of electroactive material, electrical stimulation, and controlled growth factor delivery offers advantages over traditional methods. Also, the printable electroactive hydrogels enable biofabrication of complex 3D neural interfaces with customized functionalities, potentially improving in vivo integration in future. This advancement is promising for a variety of neural tissue engineering applications, such as spinal cord injury repair and drug delivery.
References: 1) Xavier Mendes, A. et al. ACS Biomaterials Science & Engineering 2021, 7, (6), 2279-2295. 2) Xavier Mendes, A.et al. ACS Applied Bio Materials 2024, 7, (6), 4175-4192. 3) Xavier Mendes, A.et al. J Mater Chem B 2023, 11, 581-593
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