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Cells execute remarkable functions using biopolymers synthesized from natural building blocks. Engineering cells to leverage the vast array of synthesizable abiotic polymers could provide enhanced or entirely new cellular functions. Here we discuss the applications of in situ-synthesized abiotic polymers in three distinct domains: intracellular polymerization, cell-surface polymerization and extracellular polymerization. These advances have led to novel applications in various areas, such as cancer therapy, cell imaging, cellular activity manipulation, cell protection and electrode assembly. Examples of these synthetic approaches can be applied across all domains of life, ranging from microbes and cultured mammalian cells to plants and animals. Finally, we discuss challenges and future opportunities in this emerging field, which could enable new synthetic approaches to influence biological processes and functions. 

Cell type-specific interfaces within living animals will be invaluable for achieving communication with identifiable cells over the long term, enabling applications across many scientific and medical fields. However, biological tissues exhibit complex and dynamic organization properties that pose serious challenges for chronic cell-specific interfacing. A new technology, combining chemistry and molecular biology, has emerged to address this challenge: genetically targeted chemical assembly (GTCA), in which specific cells are genetically programmed (even in wild-type or non-transgenic animals, including mammals) to chemically construct non-biological structures. Here, we discuss recent progress in genetically targeted construction of materials and outline opportunities that may expand the GTCA toolbox, including specific chemical processes involving novel monomers, catalysts and reaction regimes both de cellula (from the cell) and ad cellula (towards the cell); different GTCA-compatible reaction conditions with a focus on light-based patterning; and potential applications of GTCA in research and clinical settings. 

Genetically engineered neurons express membrane-bound enzymes that can catalyze oxidative polymerization on the cell surface. 

The ability to record, stimulate, and modify brains of living animals would unlock numerous research opportunities and create potential clinical interventions, but it is difficult to interface with a living neural network without damaging it. We previously reported a novel approach to building neural interfaces, namely: genetically programming cells to build artificial structures to modify the electrical properties of neurons in situ, which opens up the possibility of modifying neural circuits in living animals without surgery. However, the spatiotemporal resolution, efficiency, and biocompatibility of this approach were still limited and lacked selectivity on cell membrane. Here, we demonstrate an approach using genetically-targeted photosensitizers to instruct living cells to synthesize functional materials directly on the plasma membrane under the control of light. Polymers synthesized by this approach were selectively deposited on the membrane of targeted live neurons. This platform can be readily extended to incorporate a broad range of light-controlled reactions onto specific cells, which may enable researchers to grow seamless, dynamic interfaces directly in living animals. 

Multicellular biological systems, most notably living neural networks, exhibit highly complex physical organization properties that pose challenges for building cell-specific and biocompatible interfaces. We developed a novel approach to genetically program cells to chemically assemble artificial structures that modify the electrical properties of neurons in situ, opening up the possibility of minimally-invasive cell-specific interfaces with neural circuits in living animals. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed material. Here, we report a method with significantly improved molecular construct properties, which expresses highly localized enzymes targeted to the plasma membrane of primary neurons with minimal intracellular retention. Polymers synthesized in situ by this approach form dense clusters on the targeted cell membrane, and neurons remain viable after polymerization. This platform can be readily extended to incorporate a broad range of materials onto the surface membranes of specific cells within complex tissues, using chemistry that may further enable the next generation of interfaces with living biological systems. 

Owing to their excellent mechanical flexibility, mixed-conducting electrical property, and extraordinary chemical turnability, conjugated polymers have been demonstrated to be an ideal bioelectronic interface to deliver therapeutic effect in many different chronic diseases. This review article summarizes the latest advances in implantable electronics using conjugated polymers as electroactive materials and identifies remaining challenges and opportunities for developing electronic medicine. Examples of conjugated polymer-based bioelectronic devices are selectively reviewed in human clinical studies or animal studies with the potential for clinical adoption. The unique properties of conjugated polymers are highlighted and exemplified as potential solutions to address the specific challenges in electronic medicine.