SIGMA: Shear-induced gelation by microbead aggregation in tubular flow systems

Injectable hydrogels hold promise for localized drug delivery and regenerative medicine, yet their clinical translation remains limited. An ideal system must combine ease of injection with mechanical robustness, while being biocompatible and practical. However, most reported hydrogels depend on external triggers that complicate delivery and hinder applicability. To address these limitations, we focused on an unavoidable aspect of clinical administration: shear. During injection, confined flow through catheters and needles inevitably generates interfacial shear. We hypothesized that this force could serve as a trigger, inducing protein unfolding, exposing interactive domains, and enabling microbead aggregation into a cohesive hydrogel. This platform, termed SIGMA (Shear-Induced Gelation by Microbead Aggregation), employs gelatin microbeads that remain flowable during injection but rapidly assemble into a gel once shear is applied. Gelation could be tuned by varying path length, mixing cycles, or introducing air–liquid interfaces, shifting the material from a weakly structured dispersion (~11.3 Pa) to robust gels with storage moduli up to ~5 kPa and compressive strengths approaching ~800 kPa. In vivo studies confirmed biocompatibility, complete biodegradation, and superior submucosal lift compared with saline. Together, these results establish SIGMA as a mechanically actuated, reagent-free hydrogel system suitable for minimally invasive surgery and localized drug delivery.