Dynamic immunomodulatory nanoarchitectonics: Rewiring tissue regenerative microenvironment via intelligent regulation
image: This schematic illustration shows how different classes of biomaterials—including synthetic biomaterials, natural biomaterials, and other engineered bio-platforms—modulate the immune microenvironment to promote tissue repair across multiple organs. The diagram highlights representative regenerative processes such as bone tissue regeneration, wound healing, heart repair, nerve repair, and cell-behavior regulation. By engaging immune pathways, these biomaterials guide host–material interactions and support functional tissue remodeling.
Credit: Nano Research, Tsinghua University Press
Understanding and reshaping the interaction between immune cells and damaged tissues is central to the future of regenerative medicine. Injuries to the skin, nerves, myocardium, and bone all trigger complex immune cascades that decide whether the body heals effectively or progresses toward chronic inflammation and fibrosis. A new review led by Haohua Yuan and colleagues from Tianjin University provides an in-depth overview of how emerging nano-engineered biomaterials can dynamically modulate immune activity to create a microenvironment favorable for tissue regeneration.
The team summarizes recent progress in immunomodulatory nanoarchitectonics—engineered nanosystems designed to direct immune behavior at injured sites—highlighting how their physical and biochemical properties can be programmed to guide the transition from inflammation to repair. This evolving toolkit allows biomaterials to move beyond passive structural support and instead act as active regulators of innate and adaptive immune processes. These developments have opened new opportunities for improving outcomes in acute injuries, chronic wounds, and complex degenerative conditions.
The authors published their review in Nano Research on November 27, 2025.
“In this review, we outline how nanoscale biomaterials can serve as intelligent regulators of immune activity, orchestrating a shift toward a pro-regenerative microenvironment,” said Bin Zheng, senior author of the paper and a professor at Tianjin Medical University. “By understanding how immune cells respond to material cues—such as stiffness, topography, charge, degradability, and ligand presentation—we can design biomaterials that actively promote healing rather than simply integrate into tissue.”
The review describes how macrophages, T cells, neutrophils, dendritic cells, and platelets contribute to wound healing, and how their functions can be precisely tuned through engineered materials. For instance, nanoscale adjustments in stiffness or surface chemistry can shift macrophages from a pro-inflammatory M1 state to a pro-repair M2 state, while engineered hydrogels and nanocarriers can promote regulatory T-cell aggregation to prevent excessive inflammation. These immune-directing strategies help drive angiogenesis, collagen remodeling, and functional tissue regeneration.
The team also summarizes advances in controlled release systems using hydrogels, microspheres, and bioactive scaffolds that deliver cytokines, growth factors, or immune-modulating molecules in a temporally synchronized manner. “One of the most exciting directions is the development of biomaterials that respond to the wound microenvironment in real time,” noted Bowen Li, co-first author from Tianjin Medical University. “Responsive nanosystems can sense inflammation, hypoxia, or oxidative stress and modulate their release behavior accordingly, greatly improving the precision of regenerative therapies.”
In addition to biochemical cues, the authors emphasize the importance of biophysical regulation. Microstructured architectures, porous networks, and spatially graded geometries can influence immune-cell migration and stem-cell recruitment while serving as scaffolds for new vessel formation and extracellular matrix deposition. These synergistic interactions enable biomaterials to act as immunological “conductors,” coordinating multiple repair pathways simultaneously.
Looking forward, the researchers highlight several challenges that must be addressed before the widespread clinical translation of immunomodulatory materials. These include safety concerns associated with long-term degradation, patient-to-patient variability in immune responses, and manufacturing hurdles for complex nano-engineered systems. Despite these barriers, the team is optimistic. “Immunomodulatory nanoarchitectures offer a powerful strategy for next-generation regenerative therapies,” said Zheng. “By integrating materials science, immunology, and clinical medicine, we can move closer to personalized and highly effective solutions for tissue repair.”
Other contributors include Huahao Yuan, Bowen Li, Xuefei Shao, Yanguo Xi, Shixiang Cheng, and Aifeng Liu from Tianjin University, Tianjin Medical University, Cangzhou Central Hospital, and Wannan Medical College.
This work was supported by the National Natural Science Foundation of China (Nos. 32271400 and 324B2045), the Tianjin Natural Science Foundation (No. 25JCJQJC00210), Key Projects of the Institutes of Brain Science, Wannan Medical College (No. KF2024004), Fund Project of Central Guidance for Local Scientific and Technological Development (No. 246Z7726G), Open Project of the State Key Laboratory of Neurology and Oncology Drug Development (No. SKLSIM-F-2024112), and the China Foundation for Youth Entrepreneurship and Employment.
About the Authors
Dr. Bin Zheng is a full professor and doctoral supervisor at Tianjin Medical University, China. His research focuses on biomaterials, immunomodulation, tissue regeneration, and biosafety technologies. Over the past several years, he has published more than 50 SCI papers as corresponding author in leading international journals, including Nature Materials, Nature Communications, Med, Cell Biomaterials, and Advanced Materials. He has served as principal investigator for two sub-projects of the Ministry of Science and Technology’s Key Program on “Biosafety Key Technologies,” as well as projects supported by the National Natural Science Foundation of China (General Program and Young Program), the Military Biosafety Research Special Fund, major projects in Tianjin, and more than ten industry-funded projects.
Homepage: https://www.x-mol.com/groups/zhengbin
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.