Regenerating the diseased tissue is one of the foremost concerns for the millions of patients who suffer from tissue damage each year. Local delivery of cell-laden hydrogels offers an attractive approach for tissue repair. However, due to the typical macroscopic size of these cell constructs, the encapsulated cells often suffer from poor nutrient exchange. These issues can be mitigated by incorporating cells into microscopic hydrogels, or microgels, whose large surface-to-volume ratio promotes efficient mass transport and enhanced cell-matrix interactions. Using microfluidic technology, monodisperse cell-laden microgels with tunable sizes can be generated in a high-throughput manner, making them useful building blocks that can be assembled into tissue constructs with spatially controlled physicochemical properties. In this review, we examine microfluidics-generated cell-laden microgels for tissue regeneration applications. We provide a brief overview of the common biomaterials, gelation mechanisms, and microfluidic device designs that are used to generate these microgels, and summarize the most recent works on how they are applied to tissue regeneration. Finally, we discuss future applications of microfluidic cell-laden microgels as well as existing challenges that should be resolved to stimulate their clinical application.

Spatial structuring is important for the maintenance of natural ecological systems 1 , 2 . Many microbial communities, including the gut microbiome, display intricate spatial organization 3 – 9 . Mapping the biogeography of bacteria can shed light on interactions that underlie community functions 10 – 12 , but existing methods cannot accommodate hundreds of species found in natural microbiomes 13 – 17 . Here we describe m et a genomic p lot-sampling by seq uencing (MaP-Seq), a culture-independent method to characterize the spatial organization of a microbiome at micron-scale resolution. Intact microbiome samples are immobilized in a gel matrix and cryo-fractured into particles. Neighboring microbial taxa in the particles are then identified by droplet-based encapsulation, barcoded 16S rRNA amplification and deep sequencing. Analysis of three regions of the mouse intestine revealed heterogeneous microbial distributions with positive and negative co-associations between specific taxa. We identified robust associations between Bacteroidales taxa in all gut compartments and showed that phylogenetically clustered local regions of bacteria were associated with a dietary perturbation. Spatial metagenomics could be used to study microbial biogeography in complex habitats.

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CRISPR/Cas9 technology enables targeted gene editing; yet, the efficiency and specificity remain unsatisfactory, particularly for the nonvirally delivered, plasmid‐based CRISPR/Cas9 system. To tackle this, a self‐assembled micelle is developed and evaluated for human papillomavirus (HPV) E7 oncogene disruption. The optimized micelle enables effective delivery of Cas9 plasmid with a transient transgene expression profile, benefiting the specificity of Cas9 recognition. Furthermore, the feasibility of using the micelle is explored for another nucleic acid‐guided nuclease system, Natronobacterium gregoryi Argonaute (NgAgo). Both systems are tested in vitro and in vivo to evaluate their therapeutic potential. Cas9‐mediated E7 knockout leads to significant inhibition of HPV‐induced cancerous activity both in vitro and in vivo, while NgAgo does not show significant E7 inhibition on the xenograft mouse model. Collectively, this micelle represents an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine‐based therapeutics.

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To advance emulsion droplet technology, we synthesize functional derivatives of Pluronic F127 that can simultaneously act as surfactants and as reactive sites for droplet surface decoration. The amine-, carboxyl-, N-hydroxysuccinimide ester-, maleimide- and biotin-terminated Pluronic F127 allows ligand immobilization on single-emulsion or double-emulsion droplets via electrostatic adsorption, covalent conjugation or site-specific avidin-biotin interaction.

Malignant spinal tumors, categorized into primary and metastatic ones, are one of the most serious diseases due to their high morbidity and mortality rates. Common primary spinal tumors include chordoma, chondrosarcoma, osteosarcoma, Ewing’s sarcoma, and multiple myeloma. Spinal malignancies are not only locally invasive and destructive to adjacent structures, such as bone, neural, and vascular structures, but also disruptive to distant organs (e.g., lung). Current treatments for spinal malignancies, including wide resection, radiotherapy, and chemotherapy, have made significant progress like improving patients’ quality of life. Among them, chemotherapy plays an important role, but its potential for clinical application is limited by severe side effects and drug resistance. To ameliorate the current situation, various polymer nanoparticles have been developed as promising excipients to facilitate the effective treatment of spinal malignancies by utilizing their potent advantages, for example, targeting, stimuli response, and synergetic effect. This review overviews the development of polymer nanoparticles for antineoplastic delivery in the treatment of spinal malignancies and discusses future prospects of polymer nanoparticle-based treatment methods.

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