Porous bioelectronic substrates for simple electrochemical conjugation and subsequent, controlled electrochemical release of antisense oligonucleotide drug

Materials and methods that enable selective and controllable conjugation and release of chemical and biological substances are in demand for various applications, such as drug delivery, cell stimulation, and cancer therapy. Stimuli-responsive systems for controlled release and enhanced drug efficacy are of particular interest. We have here developed an electrochemically addressable system for the specific conjugation and release of connexin43 antisense as a wound-healing agent. The system is based on a conducting terpolymer, P(EDOT-co-EDOTSAc-co-EDOTEG), which was coated onto both carbon cloth and highly porous electrospun substrates. We optimized the conducting terpolymer composition and characterized and compared the terpolymer-coated substrates. The conductive terpolymer contains EDOTSAc, which has an acetylthiomethyl group that can be transformed into a “free” thiol. This thiol can undergo reversible oxidation/reduction cycles at moderate potentials (+1.0 and −0.8 V, respectively) to enable electrochemical conjugation and controlled release. The system was able to quickly conjugate (1 min) and release (5 min) a model thiol molecule in a highly controllable manner, which was demonstrated with, and compared between, carbon cloth and electrospun fiber substrates. Furthermore, successful conjugation and release of connexin43 antisense were demonstrated. Overall, this electrochemical system offers a porous and flexible platform with electrochemically stimulated conjugation and release capabilities that holds significant potential for wound dressing applications.