Granular materials for biomedical applications: structural design, functional properties, advanced manufacturing and clinical application

This is the authors' abstract. We don't add key points for this paper.

Granular materials, comprising discrete macro/micro-particles exhibiting both solid- and fluid-like behaviors, have emerged as a transformative class of biomaterials owing to their tunable multiscale architectures and stimuli-responsive dynamics. Unlike bulk materials, their jamming-to-flow transition and shear-thinning behavior enable minimally invasive delivery through injection or spraying. These unique features drive transformative applications in biomedical area: (1) Tissue engineering and cell encapsulation leverage injectable granular scaffolds that endow porosity for nutrient diffusion and cell migration; (2) 3D bioprinting employs granular suspensions as self-supportive bioinks or self-healing matrices to stabilize fragile bioinks; (3) Drug delivery utilizes their modular feature for payload release with enhanced spatiotemporal precision; (4) Immunotherapy exploits engineered granular materials as synthetic antigen-presenting platforms to direct immune cell activation in vitro and in vivo. Key challenges in the application of granular materials include scalable monodisperse production of particles with designed microstructure, collective property prediction emerging from inter-particle interactions, expansion of their biomedical applications and translation of these materials to clinical practice. Emerging computational models and biohybrid designs promise advances in applying granular materials in organ-on-chip systems and adaptive medical implants. This review highlights the mechanistic synergy between granular physics and biomedical requirements, proposing a roadmap for designing next-generation therapeutic biomaterials.