Vanillin (4-hydroxy-3-methoxybenzaldehyde) is widely recognized for its aromatic flavor and established pharmacological properties, including antioxidant, antimicrobial, anti-inflammatory, and anticancer effects. While these biological activities underpin its therapeutic potential, recent advances have expanded the application of vanillin into the field of biomaterials. In particular, vanillin’s unique chemical structure enables its use as a multifunctional building block for the development of innovative hydrogels with dynamic covalent bonding, injectability, and self-healing capabilities. Vanillin-based hydrogels have demonstrated promising applications in wound healing, drug delivery, tissue engineering, and antimicrobial platforms, combining structural support with intrinsic bioactivity. These hydrogels benefit from vanillin’s biocompatibility and functional versatility, enhancing mechanical properties and therapeutic efficacy. This review provides an overview of vanillin’s pharmacological effects, with a primary focus on the synthesis, properties, and biomedical applications of vanillin-derived hydrogels. By highlighting recent material innovations and their translational potential, we aim to position vanillin as a valuable natural compound bridging bioactivity and biomaterial science for future clinical and therapeutic advancements.

Metabolic dysfunction-associated steatotic liver disease/nonalcoholic fatty liver disease (MASLD/NAFLD) and rheumatoid arthritis (RA) may share inflammatory mechanisms, although their common cellular basis remains unclear. We integrated bulk transcriptomic datasets (GSE66676 and GSE55235), single-cell RNA-sequencing datasets from murine RA synovium (GSE192504) and NASH liver (GSE129516), disease-association analysis, molecular docking, and in vitro experiments in LPS-stimulated RAW264.7 macrophages. Bulk transcriptomic analysis identified 630 shared differentially expressed genes, including 344 concordantly upregulated genes enriched in immune response, cytokine and chemokine signaling, phagosome, Toll-like receptor signaling, and Fc receptor-mediated phagocytosis; a strict dual-dataset intersection further defined 18 core genes significantly upregulated in both diseases. Immune-signature analysis indicated altered myeloid cell-associated inflammatory activity in both diseases, and several shared genes, including S100A8, S100A9, FCER1G, FCGR3A, LYZ, and MS4A7, correlated positively with monocyte/macrophage-related signatures. Single-cell analysis identified macrophage subsets with high S100a9 expression and elevated shared myeloid inflammatory signature scores in both RA synovium and NASH liver. Triptolide showed favorable predicted binding to the S100A8/A9 complex and reduced LPS-induced inflammatory cytokine secretion and expression of the six-gene signature in RAW264.7 cells, supporting the hypothesis that S100A9-associated inflammatory macrophage activation represents a candidate target for further investigation. These findings support a shared S100A9-positive inflammatory macrophage-associated program in MASLD/NAFLD and RA, and support the hypothesis that the S100A8/A9 complex represents a candidate target for further investigation.