Multiscale design of chemically crosslinked dextran hydrogels from bulk scaffolds to microgels and nanofibers

Chemically crosslinked dextran hydrogels (CDHs) offer a tunable platform for biomedical devices and carriers, yet translating crosslinking chemistry into multiscale structure and function remains nontrivial. This review synthesizes design rules that connect epoxide crosslinking (epichlorohydrin, EGDE, BDDE) and process variables to network formation, multiscale morphology, and performance. We first map gelation kinetics via rheology (tan δ invariance at the gel point, viscoelastic exponents) to structural descriptors (fractal dimension, mesh size), showing how temperature, NaOH, and crosslinker/dextran ratios regulate gel point, network compactness, and mechanical robustness. We then establish structure–formulation relationships for bulk CDHs and composites: design-of-experiments reveals NaOH and crosslinker as primary determinants of equilibrium swelling, while incorporation of nano bioglass-ceramic or β‑TCP modulates porosity, non‑linear swelling, mechanics, and apatite-forming bioactivity. At the microscale, inverse W/O emulsification yields spherical CDMs whose size and polydispersity are governed by dispersed-phase viscosity and shear; we integrate screening and full factorial designs with fluid‑mechanical correlations and population balance modeling to predict mean particle size and particle size distribution and to track droplet evolution from break‑up to vitrification. Microfluidic T‑junctions afford monodisperse droplets by tuning viscosity ratio and interfacial tension. At the nanoscale, needleless electrospinning of aqueous dextran produces bead‑free fibers under optimized flow and gap conditions, with post‑spinning glutaraldehyde crosslinking securing aqueous stability. Together, these chemistry‑to‑process guidelines enable purposeful control of CDH architectures—from bulk scaffolds to microgels and nanofibers—for wound care, drug delivery, and tissue engineering.