REVIEW article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1640560
Physical Cues in Biomaterials Modulate Macrophage Polarization for Bone Regeneration: A Review
Provisionally accepted
- Nanjing Medical University, Nanjing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Bone regeneration is a complex process governed by inflammation, angiogenesis, and tissue remodeling. Macrophages play central roles by dynamically shifting between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. While biochemical signals have been widely studied, emerging evidence highlights the immunomodulatory potential of physical cues from biomaterials. This review summarizes macrophage functions across bone healing phases and critically examines how physical cues-such as stiffness, topography, pore architecture, hydrophilicity, electromagnetic stimuli, and metal composition-modulate macrophage polarization. We discuss underlying mechanosensing mechanisms, phenotype plasticity, and the dynamic interplay between materials and immune cells. Finally, we highlight current limitations and propose future directions to guide the design of next-generation osteo-immunomodulatory biomaterials.
Keywords: Biomaterials, Bone Regeneration, Macrophage polarization, Tissue Engineering, physical cues, Bone scaffolds
Received: 03 Jun 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Yang, Fang, Zhang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shengnai Zheng, Nanjing Medical University, Nanjing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.