Professor Yanan Du's team: Recent review on multiscale biomaterials for bidirectional regulation of immune responses to enhance cell therapy

杜亚楠教授团队：多尺度生物材料双向调节免疫反应以增强细胞治疗最新综述

1. Overview

  In vivo immune responses significantly influence the survival and function of therapeutic cells during cell therapy. Biomaterials, through their bidirectional roles in promoting immune activation or facilitating immune evasion, can be employed to regulate immune responses and thereby improve the efficacy, safety, and sustainability of cell therapies. This review summarizes the design principles and functional roles of biomaterials across multiple spatial scales in supporting immune activation or evasion. In future studies, the physical and chemical properties of biomaterials hold great potential for more precise immunomodulation, further enhancing the outcomes of cell therapy.

2. Background

  Cell therapy has made significant progress in treating refractory diseases such as cardiovascular diseases, neurodegenerative disorders, graft-versus-host disease (GvHD), diabetes, and malignant tumors. However, it still faces several challenges, including immune rejection, cell sourcing, functionality, targeting capability, as well as ethical and safety concerns. Immune activation and immune evasion are two critical processes in cell therapy. Multiscale biomaterials have demonstrated great potential in bidirectional immune modulation, contributing to the enhancement of therapeutic outcomes in cell therapy.

3. Results

  Biomaterials serve as powerful tools in cell engineering, capable of improving the pharmacological properties of therapeutic cells, which are closely linked to cell viability and therapeutic outcomes. From a spatial perspective, biomaterials can be designed in various forms ranging from microscopic to macroscopic scales, targeting single cells, multiple cells, or the tissue level. This review categorizes material engineering into four main strategies: cell surface modification, artificial cells, cell encapsulation, and cell loading within 3D scaffolds, and provides a detailed summary of the specific methods and applications of each approach. Immune activation and immune evasion (cell protection) represent the two primary strategies by which biomaterials modulate immune responses. The review summarizes how biomaterials stimulate (or suppress) endogenous immune cells and discusses specific methods and applications of biomaterial-assisted immune activation (or immune evasion) in the context of cell therapy. Additionally, it explores how multiscale biomaterials regulate different types of immune responses, including type 1 and type 2 immunity.

4. Conclusion

  This review categorizes biomaterial engineering approaches based on spatial dimensions, covering a range from the nanoscale to the centimeter scale. Table 1 in the article presents a comparative overview of these different spatial scales. Research into biomaterials within the field of immunology has revealed their dual functionality: activating endogenous immune cells and enhancing the performance of adoptively transferred therapeutic cells. Immune enhancement primarily targets T cells and macrophages both in vivo and in vitro, leveraging biochemical or physical cues to activate immune phenotypes (refer to Tables 2 and 3 of the review). In contrast, immune evasion support focuses on strategies such as immunosuppression, immune homeostasis regulation, and immune isolation (refer to Table 4 of the review). A comprehensive and systematic understanding of the mechanisms by which biomaterials interact with both therapeutic cells and the host immune system is essential for advancing cell-based therapies.

5. Concluding remarks and future perspectives

  The use of multiscale biomaterials for immune modulation in cell therapy still faces several challenges in clinical applications. Precisely tailoring biomaterials is crucial for effectively regulating immune responses. A deeper understanding of the interactions between biomaterials and the host immune system is essential for optimizing immunomodulatory functions and improving the efficacy of cell-based therapies. Physical properties such as size, shape, and elasticity significantly influence immune responses and represent key areas for future research. Tailored strategies should be developed based on clinical contexts and the characteristics of target tissues. Despite ethical and regulatory challenges, certain biomaterials have already demonstrated potential in clinical applications. Standardization and regulatory oversight are critical to ensuring the safety, efficacy, and reliability of these therapies. Cell therapies enhanced by multiscale immunomodulatory biomaterials hold great promise for advancing the field of biomedicine.

6. Author introduction

Correponding Author  

  Yanan Du is a Professor at the School of Biomedical Engineering, Tsinghua University, and a recipient of the National Natural Science Foundation of China’s Distinguished Young Scholar Award. Her laboratory focuses on the field of microtissue engineering, integrating biomaterials, microfabrication, biophysics, and gene editing technologies to design and regulate the cellular and tissue microenvironment. The research emphasizes the construction of regenerative and fibrotic pathological microenvironments, investigation of cell–matrix interactions, and their translational applications in regenerative medicine.

First Author    

  Jia’nan Zeng is a direct-track Ph.D. student (Class of 2022) at the School of Biomedical Engineering, Tsinghua University. Her research interests include microtissue engineering, microfabrication, stem cell microenvironments, and regenerative medicine.

Co-First Author    

 Yuhong Jin is a Ph.D from the Class of 2018 at the School of Biomedical Engineering, Tsinghua University. Her research focuses on microtissue engineering, artificial cells, and immunomodulatory biomaterials.

DOI: https://doi.org/10.1016/j.engmed.2024.100038