T cell immunoengineering with advanced biomaterials.

Derfogail Delcassian,Susanne Sattler,Iain E Dunlop

doi:10.1039/c6ib00233a

Abstract

Recent advances in biomaterials design offer the potential to actively control immune cell activation and behaviour. Many human diseases, such as infections, cancer, and autoimmune disorders, are partly mediated by inappropriate or insufficient activation of the immune system. T cells play a central role in the host immune response to these diseases, and so constitute a promising cell type for manipulation. In vivo, T cells are stimulated by antigen presenting cells (APC), therefore to design immunoengineering biomaterials that control T cell behaviour, artificial interfaces that mimic the natural APC-T cell interaction are required. This review draws together research in the design and fabrication of such biomaterial interfaces, and highlights efforts to elucidate key parameters in T cell activation, such as substrate mechanical properties and spatial organization of receptors, illustrating how they can be manipulated by bioengineering approaches to alter T cell function.

Highlights

Biomaterials have been deliberately designed to minimize interactions with the host immune system when implanted
24 This review describes current progress in designing biomimetic structures that direct T cell behaviour
To avoid aberrant immune responses under physiological conditions, in vivo T cell activation is a tightly controlled process, depending on Antigen Presenting Cells (APC) providing antigen-specific signals and co-stimulation, alongside the stimulation provided by the surrounding cytokine milieu[17]

Summary

10 Abstract

Recent advances in biomaterials design offer the potential to actively control immune cell activation and behaviour. This review draws together research in the design and fabrication of such biomaterial interfaces, and highlights efforts to elucidate key parameters in T cell activation, such as substrate mechanical properties and spatial organization of receptors, illustrating how they can be manipulated by bioengineering approaches to alter T cell function. This review describes current progress in designing biomimetic structures that direct T cell behaviour. This new field integrates fundamental research in immune cell biophysics, including receptor nanopatterning and mechanotransduction, together with applied biomaterial design. We comprehensively summarize the current state of the field and advocate a future direction for innovative immunomodulatory biomaterials through the integration of spatial, temporal and mechanical cellular cues in 2- and 3-dimensional therapeutics

31 Introduction

99 Biomaterials for T cell activation

416 Conclusions

Findings

469 References