ABSTRACT: Cell-based therapeutics are very promising modalities to address many unmet medical needs, including genetic engineering, drug delivery, and regenerative medicine as well as bioimaging. To enhance the function and improve the efficacy of cell-based therapeutics, a variety of cell surface engineering strategies (genetic engineering and non-genetic engineering) are developed to modify the surface of cells or cell-based therapeutics with some therapeutic molecules, artificial receptors, and multifunctional nanomaterials. In comparison to complicated procedures and potential toxicities associated with genetic engineering, non-genetic engineering strategies have emerged as a powerful and compatible complement to traditional genetic engineering strategies for enhancing the function of cells or cell-based therapeutics. In this review, we will first briefly summarize key non-genetic methodologies including covalent chemical conjugation (surface reactive groups-direct conjugation, and enzymatically mediated and metabolically mediated indirect conjugation) and noncovalent physical bioconjugation (biotinylation, electrostatic interaction, and lipid membrane fusion as well as hydrophobic insertion), which have been developed to engineer the surface of cell-based therapeutics with various materials. Next, we will comprehensively highlight the latest advances in non-genetic cell membrane engineering surrounding different cells or cell-based therapeutics, including whole-cell-based therapeutics, cell membrane-derived therapeutics, and extracellular vesicles. Advances will be focused specifically on cells that are the most popular types in this field, including erythrocytes, platelets, cancer cells, leukocytes, stem cells, and bacteria. Finally, we will end with the challenges, future trends, and our perspectives of this relatively new and fast-developing research field.
