Biomaterials in droplet-based microfluidics: From structural design to biomedical applications

Droplet-based microfluidics (DBM) affords reproducible control over the breakup of immiscible streams, enabling the on-demand fabrication of well-defined carriers for biomedical use. We first outline droplet-generation techniques, distinguishing passive architectures—in which capillary, viscous, and inertial forces set size and frequency—from active methods that superimpose external fields to refine monodispersity, throughput, and size control. Building on this physical framework, we survey the micro- and nanostructures accessible with DBM—including polymeric nanoparticles and nanogels/microgels, microspheres, core–shell microcapsules, and microfibers—and show how morphology (porosity, shell thickness, network architecture) and spatial composition govern transport, stability, and release. We then examine the biomaterials that endow droplets with function, with emphasis on natural, semi-synthetic, and synthetic hydrogels and on gelation/polymerization routes (ionic, thermal, photo-induced, enzymatic) that are compatible with biological cargo and permit real-time structural control. The applications analysis is intentionally biomaterial-centric. For drug delivery, we relate material choice and crosslinking chemistry to representative release profiles and kinetic models, and we integrate quantitative biocompatibility readouts where available (e.g., LD50, inflammatory signaling) together with in vivo biodistribution and loading efficiency that link carrier design to payload fate. For cell-centric uses, we discuss single-cell encapsulation and droplet-based 3D cultures, highlighting biomaterial-driven morphogenesis, viability, and function, and we outline DBM-enabled bioanalytical platforms (single-molecule detection, single-cell sequencing). By articulating the pathway from droplet-generation techniques, through the resulting micro-/nanostructures and the selected biomaterials, to their biomedical performance, this review provides a coherent design perspective for engineering DBM-fabricated carriers and scaffolds in drug delivery, tissue modeling, and high-throughput bioanalysis.