Designing lysate-based hydrogels for on-demand therapy

Hydrogels are three-dimensional hydrophilic networks formed via physical or chemical crosslinking. Owing to their structural mimicry of native extracellular matrices and tunable capacity for therapeutic cargo delivery, they have garnered substantial attention in biomedical engineering. Traditional hydrogels primarily function as passive scaffolds for drug encapsulation; however, recent advances have shifted toward integrating bioactive lysates that extract derived from cells or tissues are rich in growth factors, cytokines, and antigenic components to construct dynamic, multifunctional platforms. Lysate-based hydrogels combine the intrinsic bioactivity of lysate-derived factors (e.g., tumor-specific neoantigens or bacteria-derived pathogen-associated molecular patterns) with the spatiotemporal control afforded by hydrogel matrices. This synergy enables precise modulation of the tumor microenvironment, immune priming, and tissue regeneration. In this review, we highlight the emergence of lysate-based hydrogels, which hold significant guiding value for the entire field of bioengineering. This technology represents an innovation in both design concepts and therapeutic strategies, with potential applications across multiple related disciplines. By proposing strategies to exploit underexplored lysate sources (e.g., microbiota-derived components) and integrate stimuli-responsive materials, this work aims to advance lysate-based hydrogels as next-generation platforms for precision oncology, while balancing biological complexity with engineering reproducibility. Key challenges in the development of lysate-based hydrogels include determining the optimal dosage and composition of lysate-derived factors, as well as coordinating their interactions. The presence of multiple factors endows these hydrogels with pluripotent therapeutic effects, but potential crosstalk between factors may limit their efficacy. This area requires further in-depth exploration in future research. • Lysate-based hydrogels represent a paradigm shift in biomedical engineering, bridging biological complexity with engineering reproducibility and inspiring next-generation therapeutic design. • The intrinsic bioactivity of lysates, enriched with diverse growth factors, cytokines, and antigens, enables multifunctional therapeutic outcomes spanning immunotherapy, tissue regeneration, and precision oncology. • The combination of high stability, biocompatibility, and dynamic responsiveness positions lysate-based hydrogels as versatile biomaterials with transformative potential across regenerative medicine, drug delivery, and immunoengineering.