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Spatiotemporal controlled drug delivery minimizes side-effects and enables therapies that require specific dosing patterns. Conjugated polymers (CP) can be used for electrically controlled drug delivery; however so far, most demonstrations were limited to molecules up to 500 Da. Larger molecules could be incorporated only during the CP polymerization and thus limited to a single delivery. This work harnesses the record volume changes of a glycolated polythiophene p(g3T2) for controlled drug delivery. p(g3T2) undergoes reversible volumetric changes of up to 300% during electrochemical doping, forming pores in the nm-size range, resulting in a conducting hydrogel. p(g3T2)-coated 3D carbon sponges enable controlled loading and release of molecules spanning molecular weights of 800-6000 Da, from simple dyes up to the hormone insulin. Molecules are loaded as a combination of electrostatic interactions with the charged polymer backbone and physical entrapment in the porous matrix. Smaller molecules leak out of the polymer while larger ones could not be loaded effectively. Finally, this work shows the temporally patterned release of molecules with molecular weight of 1300 Da and multiple reloading and release cycles without affecting the on/off ratio.

Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but conventional bioelectronics consist of rigid electrodes fundamentally incompatible with living systems. The difference between static solid-state electronics and dynamic biological matter makes seamless integration of the two challenging. To address this incompatibility, we developed a method to dynamically create soft substrate-free conducting materials within the biological environment. We demonstrate in vivo electrode formation in zebrafish and leech models, using endogenous metabolites to trigger enzymatic polymerization of organic precursors within an injectable gel, thereby forming conducting polymer gels with long-range conductivity. This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo-fabricated electronics within the nervous system., Funding Agencies|European Research Council [834677]; Swedish Research Council [2018-06197, RMX18-0083]; Swedish Foundation for Strategic Research [2021-05231]; Knut and Alice Wallenberg Foundation; Onnesjoe Foundation