The groundbreaking success of messenger RNA (mRNA) vaccines during the COVID‐19 pandemic has significantly accelerated their application in oncology. This review comprehensively synthesizes the recent advancements in mRNA cancer vaccine development, emphasizing three critical domains: mechanistic innovations, clinical translation, and ongoing challenges. Technologically, advancements in nucleotide modification, lipid nanoparticle (LNP) delivery systems, and AI‐driven neoantigen selection have significantly improved vaccine stability, immunogenicity, and personalization. Clinically, more than 150 trials have demonstrated the synergistic efficacy of mRNA vaccines (e.g., mRNA‐4157/V940, BNT122) in combination with immune checkpoint inhibitors (ICIs), particularly in melanoma, with Phase Ⅲ trials currently underway. Individualized neoantigen vaccines targeting patient‐specific mutations have shown unprecedented response rates (> 50% in certain cohorts), while shared‐antigen vaccines are progressing for high‐incidence cancers. However, several critical challenges remain: (1) overcoming immunosuppressive tumor microenvironments (TME), (2) addressing systemic toxicities and LNP‐related limitations, (3) scaling up cost‐effective personalized manufacturing, and (4) optimizing targeted delivery. Future research directions encompass self‐amplifying mRNA constructs, novel biomaterial vectors, neoadjuvant applications, and multi‐omics integration for next‐generation vaccine development. With rapid industrialization and evolving regulatory frameworks, mRNA vaccines are well‐positioned to revolutionize precision cancer immunotherapy despite persistent translational barriers.

This review synthesizes a decade of advancements in nucleic acid therapeutics for liver diseases, incorporating bibliometric analysis and translational evaluation. The field has evolved from foundational viral vector engineering to precision genome editing and RNA-based modulation, with advancements in CRISPR-Cas9 and innovations in non-viral delivery systems. Our analysis highlights the concentrated research efforts made in metabolic disorders and hepatocellular carcinoma, and reveals an emerging emphasis on multifactorial pathologies. Although clinical milestones highlight important advancements in targeting strategies, significant challenges remain in immune compatibility and preclinical translation. The integration of computational modeling, human-relevant disease models, and combinatorial strategies places nucleic acid therapies in a unique position to tackle the evolving global liver disease burden through mechanism-driven interventions.

Hepatocyte proliferation is essential for recovering liver function after injury. In liver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascular endothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration (LR). Piezo1, a critical mechanosensory ion channel, can detect and convert mechanical forces into chemical signals, importing external stimuli into cells and triggering downstream biological effects. However, the precise role of Piezo1 in VECs, especially in terms of mediating LR, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 in VECs to promote hepatocyte proliferation during the process of LR induced by portal vein ligation in rats. In this LR model, hepatocyte proliferation is mainly distributed in zone 1 and zone 2 of liver lobules at 24–48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermal growth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation. In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantly higher than that in zone 3. The EGFR inhibitor gefitinib inhibits LR by suppressing the proliferation of hepatocytes in the middle zone. These data provide a theoretical basis for the regulation of LR through chemical signals mediated by mechanical stimulation.

The liver is a pivotal organ that maintains internal homeostasis and actively participates in multiple physiological processes. Liver tissue engineering (LTE), by which in vitro biomimetic liver models are constructed, serves as a platform for disease research, drug screening, and cell replacement therapies. 3D bioprinting is used in tissue engineering to create microenvironments that closely mimic authentic tissues with carefully selected functional biomaterials. Ideal functional biomaterials exhibit characteristics such as high biocompatibility, mechanical strength, flexibility, processability, and tunable degradability. Biomaterials can be categorized into natural and synthetic biomaterials, each with its own advantages and limitations, and their combinations serve as a primary source of 3D bioprinting materials. It is noteworthy that the liver decellularized extracellular matrix (dECM), obtained by removing cellular components from tissues, possesses traits such as bioactivity, biocompatibility, and non-immunogenicity, making it a common choice among functional biomaterials. Furthermore, crosslinking of biomaterials significantly impacts the mechanical strength, physicochemical properties, and cellular behavior of the printed structures. This review covers the current utilization of biomaterials in LTE, focusing on natural and synthetic biomaterials as well as the selection and application of crosslinking methods. The aim is to enhance the fidelity of in vitro liver tissue models by providing a comprehensive coverage of functional biomaterials, thereby establishing a versatile platform for tissue-engineered livers.