Review Articles

Synthetic gene circuits can endow cells with therapeutic functions. This Review discusses synthetic macromolecular systems, encompassing transcriptional, translational and post-translational mechanisms, that conditionally regulate protein expression and activity in response to specific internal or external stimuli, and their role in enhancing the therapeutic efficacy and safety of engineered cell therapies.

Microbial bioelectronic sensors offer rapid and cost-effective chemical monitoring by generating electrical signals. However, deploying such sensors in the field remains challenging. This Review proposes interdisciplinary solutions and integrates advances in chassis selection, genetic modification, material engineering and device fabrication.

Biomaterials can be designed to be injectable in a minimally invasive manner for the treatment of various conditions. This Review outlines design considerations for injectable biomaterials for different delivery routes, highlighting preclinical and clinical applications of injectable biomaterials.

Projection-based 3D bioprinting has the highest resolution/time for manufacturing ratio among all 3D printing technologies. This Review discusses the main components of projection-based 3D bioprinting and summarizes the necessary steps and challenges to improve bioprinting resolution.

Microbial catalysts must partition incoming substrate between synthesis of biomass and synthesis of a desired product. Two-stage bioprocesses can accommodate this tradeoff to maximize process productivity by temporal separation of growth and production phases. This Review discusses the challenges of maintaining a high metabolic activity during the production phase.

Volumetric compression is a pervasive phenomenon in the human body, manifesting during development, limb movement, digestion, tumorigenesis and injury. This Review provides an in-depth discussion of emerging engineering methods centred on volumetric compression, including foundational rationales, design principles and illustrative applications.

To overcome the immune rejection issue in allogeneic cell transplants, various genetic engineering strategies have been developed. This Review explores these advances and discusses challenges in evading immune responses, as well as considerations for clinical development.

This Review explores the principles and applications of cell purification technologies, with a particular emphasis on their clinical relevance for pluripotent stem-cell-based therapies. The authors discuss current technologies and emerging state-of-the-art approaches that promise even greater potential.

Degenerative retinal dystrophies, such as retinitis pigmentosa and age-related macular degeneration, lead to blindness owing to the progressive damage of retinal photoreceptors. This Review discusses nanotechnology-based treatment approaches for vision restoration.

Nanozymes are nanomaterials that exert biocatalytic functions within biological systems. This Review discusses the design criteria and mechanisms of nanozymes for in vivo applications to treat different pathological disorders.

Drug delivery systems can be integrated with cell therapies to improve the efficacy and safety of therapeutic cells. This Review discusses the design of nanoscale, microscale and macroscale drug delivery systems for precise cell modulation, targeted cell and cargo delivery and cell protection.

Nanoparticles, such as gold nanoparticles and magnetic ferrite nanoparticles, can be applied in biosensors for disease detection. This Review discusses the design of nanoparticles for clinical diagnostics, focusing on their optimization and device construction for the detection of nucleic acids, proteins and small molecules.

Cell engineering by synthetic biology typically relies on synthetic gene constructs that compete with the host cell for intracellular resources. This Review discusses how such resource competition can impact mammalian cell engineering and outlines strategies for how to mitigate cellular burden using circuit-centric and host-centric approaches.

Microbial nanowires are attractive materials for the fabrication of electronic devices because they are sustainably produced and can be genetically reengineered for a broad range of functionalities. Guberman-Pfeffer and colleagues describe novel devices and mass production strategies that have been demonstrated and outline the optimization strategies required for their commercialization.

Organoids and organs-on-chips aim to improve drug testing and disease modelling, but each has limitations. This Review discusses the integration of these systems to improve cellular hierarchy, structural fidelity, reproducibility, throughput, scale-up and efficiency to improve translational outcomes.

Photodynamic therapy allows the local destruction of diseased cells and tissues by light. This Review examines how photodynamic therapy and priming can be engineered for the treatment of localized, regional and distant cancer, from photosensitizer engineering to photonic devices and clinical translation.

Cells can be engineered to modify their function and behaviour for therapeutic and diagnostic applications. This Review discusses biological, genetic and materials-based engineering approaches for both mammalian and bacterial cells, outlining key design strategies and applications of engineered cell products.

Polysaccharides possess immune-activating or immune-regulatory functions and can thus be applied as immunomodulators. This Review discusses engineering approaches for the design of polysaccharides for vaccine, immunoadjuvant, immune-modulation and drug-delivery applications.

Soft bioelectronic devices are made from polymer-based and hybrid electronic materials that form natural interfaces with the human body. In this Review, the authors present recent developments in soft bioelectronic sensors and actuators, and discuss system-level integration for wearable and implantable medical applications.

Brain-on-a-chip models, mimicking brain physiology, hold promise for developing treatments for neurological disorders. This Review discusses the engineering challenges and opportunities for these devices, including the integration of 3D cell cultures and electrodes and scaffold engineering strategies.