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Smart biomaterials: as active immune modulators to shape pro-regenerative microenvironments.

Wenning Zhang¹, Xianyi Zeng¹, Xikai Deng¹

¹China Unicom Digital Intelligence Medical Technology Co. Ltd., Guangzhou, China.

Frontiers in Cell and Developmental Biology

|October 30, 2025

Summary

Smart biomaterials are shifting from passive to active immune-modulating platforms. These intelligent materials precisely control immune responses for enhanced tissue repair and therapeutic applications.

Keywords:

biomimetic materials immunomodulation macrophage polarization regenerative medicine smart biomaterials

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Area of Science:

Biomaterials Science
Immunology
Regenerative Medicine

Background:

Smart biomaterials have evolved from inert scaffolds to dynamic, immune-modulating systems.
These materials actively shape regenerative microenvironments by responding to biological cues.

Purpose of the Study:

To review the transition of biomaterials from passive to autonomous systems.
To highlight innovations in material responsiveness and their role in regulating immune responses, particularly macrophage polarization.
To discuss applications and future directions in smart biomaterial development for regenerative medicine.

Main Methods:

Review of literature on smart biomaterials, focusing on responsiveness (pH, temperature, enzymatic sensitivity).
Analysis of biomaterial strategies for modulating macrophage polarization in tissue repair.
Examination of applications in cancer immunotherapy, myocardial regeneration, and scar inhibition.

Main Results:

Smart biomaterials demonstrate tunable physicochemical properties and controlled release of immunomodulatory factors.
Macrophage polarization is effectively regulated by biomaterials, influencing tissue repair outcomes.
Therapeutic potential is evident in diverse applications, with ongoing advances in design and modeling.

Conclusions:

Smart biomaterials are enabling precision immune engineering for regenerative medicine.
Challenges in clinical translation include biosafety, scalability, and regulatory hurdles.
Future research will focus on AI-driven design, optogenetic control, and multimodal therapies for advanced disease intervention.