Advanced hydrogels for pancreatic fistula prevention, management and treatment: requirements, advances, and prospects

Pancreatic fistula (PF) is a common complication following pancreatic injury, inflammation, surgery, or endoscopic procedures, with no effective clinical treatment available to date. Physical sealing and repair are the most direct and effective strategies for PF management, with smart hydrogels emerging as potential executors of this strategy. Research on hydrogel materials for preventing PF has grown rapidly but remains in its infancy. The challenge lies in the customized design requirements for pancreatic hydrogels, due to the high ionic strength, high protease load, and alkalinity of the PF microenvironment, in addition to basic requirements for tissue adhesion and degradation. Based on differences in the physical isolation modes of preventing PF hydrogel materials, they can be categorized into "hydrogel patches" (adhesive repair and sealing) and "hydrogel plugs" (injectable plug and sealing). Herein, the pathological characteristics of PF and the customized requirements for preventing PF hydrogels are summarized. A comprehensive review and discussion of the advances in anti-PF hydrogels under the "patch" and "plug" strategies are provided, highlighting their prospects. We envision that PF prevention hydrogel materials will play a crucial role in postoperative PF treatment and hope to provide new perspectives for the design and preparation of advanced PF prevention materials.