3D bioprinting-driven strategies for tissue regeneration and controlled immune modulation

Abstract

Tissue loss, fibrosis-prone repair, and immune-mediated graft failure remain persistent obstacles in regenerative medicine. Within this context, 3D bioprinting is shifting from structure-centric fabrication to a platform for programmed immune modulation. This review synthesizes evidence across materials, architecture, and living components to delineate how bioprinted constructs can steer host responses toward resolution and durable function. We first examine events at the blood–biomaterial interface, including protein corona formation, complement–coagulation crosstalk, and leukocyte recruitment, and map them to tunable parameters, such as chemistry, stiffness, degradability, topography, and pore geometry that direct macrophage and dendritic-cell programs. We compare natural and synthetic bioinks, emphasizing printability windows, batch control, and impurity management as prerequisites for interpretable immunological readouts. We survey stimuli-responsive inks triggered by pH, reactive oxygen species, enzymes, light, or magnetic fields to deliver cytokines, chemokines, and metabolites with temporal precision, and highlight architected lattices and gradients that guide cell trafficking, vascular and lymphatic integration, and mechano-immune conditioning. Cell- and signal-centric strategies include immune–stromal coprinting, extracellular vesicle embedding, membrane cloaking for immune stealth or targeting, and synthetic circuits that sense inflammation and secrete immunoregulatory payloads. Finally, we identify translational bottlenecks and outline opportunities in 4D bioprinting, AI-assisted design, digital twins, and in situ printing. Treating immunity as a primary design variable is essential for predictable, durable, and clinically credible bioprinted therapies.  

 

Keywords

3D bioprinting / Bioinks / Foreign body response / Immunomodulation / Macrophage polarization / Regenerative medicine

Funding

None.

Conflict of Interest

The authors declare they have no competing interests.

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