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 by reliance on backbone modification or exogenous physicochemical triggers that complicate delivery. Here, we exploit an unavoidable aspect of clinical administration, shear, which is generated during injection through catheters and needles. We introduce SIGMA (Shear-Induced Gelation by Microbead Aggregation), a system composed of gelatin microbeads that remain flowable during injection but rapidly assemble into cohesive hydrogel under confined shear, without exogenous physicochemical triggers such as temperature, pH, light, or chemical crosslinkers. Gelation was tunable by varying flow path length, mixing cycles, particle sizes, or introducing air-liquid interfaces, enabling transitions from a weak dispersion (∼11.3 Pa) to robust gels with storage moduli up to ∼5 kPa and compressive strengths approaching ∼800 kPa. Circular dichroism and gel permeation chromatography revealed shear-induced intermolecular associations without evidence of chain scissions. The platform further enabled post-encapsulation drug loading with tunable release governed by shear-programmed network density. In vitro and in vivo studies confirmed cytocompatibility, biodegradability, systemic safety, and superior submucosal lift compared with saline. Together, SIGMA establishes a mechanically actuated, clinically adaptable hydrogel platform for minimally invasive surgery and localized drug delivery.