Electroresponsive Silk-Based Biohybrid Composites for Electrochemically Controlled Growth Factor Delivery

Abstract

Stimuli-responsive materials are very attractive candidates for on-demand drug delivery applications. Precise control over therapeutic agents in a local area is particularly enticing to regulate the biological repair process and promote tissue regeneration. Macromolecular therapeutics are difficult to embed for delivery, and achieving controlled release over long-term periods, which is required for tissue repair and regeneration, is challenging. Biohybrid composites incorporating natural biopolymers and electroconductive/active moieties are emerging as functional materials to be used as coatings, implants or scaffolds in regenerative medicine. Here, we report the development of electroresponsive biohybrid composites based on Bombyx mori silkworm fibroin and reduced graphene oxide that are electrostatically loaded with a high-molecular-weight therapeutic (i.e., 26 kDa nerve growth factor-β (NGF-β)). NGF-β-loaded composite films were shown to control the release of the drug over a 10-day period in a pulsatile fashion upon the on/off application of an electrical stimulus. The results shown here pave the way for personalized and biologically responsive scaffolds, coatings and implantable devices to be used in neural tissue engineering applications, and could be translated to other electrically sensitive tissues as well.

Graphene oxide and electroactive reduced graphene oxide-based composite fibrous scaffolds for engineering excitable nerve tissue

“…Recent in silico toxicity screening studies of graphene-containing silk-based materials confirm skin sensitization due to the presence of conjugated dienes in their structures [86], but at much higher loading concentrations (> 10% wt.) than the ones used in the current study.…”

Potential for Chemistry in Multidisciplinary, Interdisciplinary, and Transdisciplinary Teaching Activities in Higher Education

“…ML/AI approaches such as deep learning correlation analysis − can be used to accelerate identification of biological pathways and targets in disease biology, to find potential drug molecules, to understand the biological effects of the compound, and to help design clinical trials to ensure the best outcomes are achieved. Clearly, a multitude of other opportunities exist for inclusion of computational studies in a variety of disciplinary contexts (e.g., agrochemical/drug delivery/design, , catalysis, materials chemistry, medical imaging and analysis, , etc.). Computational chemistry can help engage students learning about important concepts such as kinetics and thermodynamics, molecular descriptors (i.e., constitutional, electronic, physicochemical, topological), stereochemistry, and 3D structures in an interactive virtual learning environment and, moreover, provides various platforms to study intramolecular and intermolecular interactions that can be used for research and development in a safe and cost-effective fashion (e.g., informing the selection of candidates to bind to biological receptors or pharmaceutical carriers for drug delivery, while minimizing resource utilization and exposure to chemicals) .…”

Silk Fibroin: An Ancient Material for Repairing the Injured Nervous System

“…Application of SF surface modification can be further improved once an external stimulus such as electrical stimulation is also introduced. This stimulus can be applied not only to trigger the release of a drug or GF [ 197 ] but also to increase the cellular arrangement and neurite outgrowth. The performance of an electrical stimulus regime to neuronal cells seeded within SF hydrogels [ 198 ] and films [ 64 ] has been found to significantly induce neurite outgrowth and alignment.…”