• Systematic analysis of liver fibrosis mechanisms and biomaterial design. • Advanced strategies: exosomes, nanoparticles, nanozymes with clinical cases. • Multifunctional biomaterials for microenvironment reprogramming. • Clinical translation challenges and future development directions. • Next-generation smart materials and interdisciplinary integration. Liver fibrosis (LF) is a central pathological process in the progression of chronic liver disease toward cirrhosis and hepatocellular carcinoma. Currently, there is a lack of effective pharmacological agents capable of reversing liver fibrosis in clinical settings. Although liver transplantation remains the definitive treatment for end-stage disease, it is constrained by several limitations, including donor scarcity, surgical complexity, and immune rejection. In this context, bioengineered materials have emerged as a promising strategy for reversing liver fibrosis, owing to their superior capabilities in targeted delivery, microenvironment regulation, and tissue regeneration. Critically, these materials exert multi-faceted effects rather than targeting a single pathological pathway; they simultaneously intervene in key processes including hepatic stellate cell (HSC) activation, excessive extracellular matrix (ECM) deposition, inflammatory signaling activation, and pathological angiogenesis, thereby enabling precise reconstruction of the liver microenvironment and restoration of function. This review first systematically elaborates the multifaceted pathological mechanisms and key therapeutic targets of liver fibrosis, clarifying the interconnections between different pathological events. It then provides a comprehensive analysis of the categories and design strategies of biomaterials used for liver fibrosis treatment, with an in-depth discussion on the rationale for matching material properties with specific pathological targets. The review highlights the therapeutic mechanisms and application advantages of cutting-edge strategies such as engineered exosomes, biomimetic nanoparticles, and inorganic nanozymes, supplemented with clinical-stage material cases. Finally, it addresses the challenges in clinical translation and potential directions for breakthroughs, aiming to provide a theoretical foundation and technical insights for the development of next-generation anti-fibrotic biomaterials and to facilitate their transition from basic research to clinical application, while also offering valuable references for the treatment of other fibrotic diseases.
Wang et al. (Tue,) studied this question.