An Oral Biodegradable Spiny Milli-Ball Robot for Targeted Intestinal Delivery of Biologics with Delayed Onset and Sustained Action.

Oral delivery of biologics offers a noninvasive alternative to repeated injections for treating intestinal and systemic diseases, yet it remains challenged by poor gastric protection, limited intestinal targeting, and uncontrolled payload release timing. Conventional passive delivery systems fail to coordinate targeted localization with delayed onset and sustained action, while most ingestible robotic systems rely on non-degradable materials and lack integrated biologic delivery functions. Here, we present an oral biodegradable spiny milli-ball robot for targeted intestinal delivery of biologics with temporally regulated release. The spiny milli-ball robot integrates a magnetic actuation skeleton for controllable locomotion and precise positioning, a core-shell microneedle array for protected payload loading and mucosal penetration, and pH-responsive biodegradable materials for gastric shielding and intestinal activation. Fabricated via 3D-printing-assisted micromolding, the robot exhibits robust mechanical properties for tissue insertion and adaptive locomotion in complex intestinal environments. In vitro characterizations confirm pH-triggered delayed release, negligible gastric leakage, tunable payload capacity, and excellent biocompatibility. In vivo porcine studies validate magnetic-guided intestinal targeting, effective mucosal insertion, and delayed-onset sustained insulin delivery with reduced early-phase exposure compared to subcutaneous injection. This work establishes a biodegradable ingestible robotic platform that unites active intestinal targeting, tissue engagement, and programmed payload release, addressing critical unmet needs for oral biologic delivery.