Biomaterial interactions with the immune system

Christopher M. Jewell

Joel H. Collier

The immune system relies on incredible diversity and resiliency to generate, maintain, and resolve responses during injury, infection, and disease. Innate immune functions – while non-specific, have the speed needed to limit early stage infections, to remove cells and tissue debris during wound healing, and to mount responses in the presence of biomedical implants and devices. In contrast, the generation of adaptive immune response requires more time and resources, but enables molecularly-precise responses against specific pathogens such as viruses and bacteria. Miraculously, adaptive responses also generate memory that can provide protection for decades. These mechanisms are also important in many non-infectious disease settings. For example, tumors evade and suppress immune function, while autoimmune diseases such as multiple sclerosis and type 1 diabetes are characterized by the mistaken attack of self-tissue.

Both systems – innate and adaptive – constantly integrate signals and transfer information to ensure resources are conserved when quick non-specific responses suffice, while mounting specific immunity in other cases, or suppressing immune responses in yet other instances. Important immune cues include fragments of pathogens (epitopes or more complex antigens), functional immune proteins such as cytokines, stimulatory adjuvants, and small molecules. The combinations, intervals, concentrations, densities, and locations of these cues in immune cells and tissues collectively determine the specific features of immune responses that develop during disease, vaccination, and immunotherapy. This exquisite sensitivity to spatial and temporal processing positions biomaterials as powerful tools to study and control immunity. Engineered materials seek to control the location and timing of the delivery of combinations of immune cues, while also controlling the release kinetics of mixtures of signals, or the orientation and density of surface-bound cues. Together these strategies provide unique levers for new vaccines and therapies. Additionally, many studies over the past decade have made it clear that biomaterials themselves can activate, suppress, or modulate important immune pathways (e.g., toll-like receptors). From this perspective, biomaterials can play a dual role in vaccination and immunotherapy by serving as carriers of immune signals with their own intrinsic immunogenicity that can be modified by adjusting parameters such as shape, charge, hydrophobicity, or chemical functionality.

Despite the enhanced capabilities biomaterials offer, these components add complexity that can create hurdles in translating exciting technologies to the clinic because of difficulties in characterizing or manufacturing more complicated formulations, or in understanding the mechanisms of action. New insight into the interactions of biomaterials – whether serving as carriers or as active vaccine/immunotherapy components – could help overcome these hurdles and accelerate the clinical translation of emerging vaccines and immunotherapies. Additionally, translation requires an improved understanding of how the properties of various materials impact interactions with specific immune pathways, as well as how altering a design parameter such as release kinetics or biodistribution changes the resulting immune outcome. Such understanding could contribute to generalized metrics or focus areas during clinical assessment.

Toward the goals just described, this special collection of Biomaterials Science centers on the interactions of biomaterials with immune cells and tissues. Several insightful reviews summarize key concepts for readers new to the field. The Green Lab, for example, discusses some of the unique features of vaccines and immunotherapies that are achieved by formulation in nanoparticles or microparticles (DOI: 10.1039/C8BM01285G). In parallel, more than a dozen new primary research articles help push the field's current understanding of these interactions. Some of this work focuses on understanding specific barriers. As one illustration, the Pun Lab used engineered cationic polymers to delve into a problem limiting non-viral gene therapy for T cells: the very poor transfection efficiency of these immune cells (DOI: 10.1039/C8BM01262H). Their work identifies some of the specific differences in the uptake and release processes that occur in T cells compared with those of traditional phagocytic cell targets. This information could inform design of new polymeric vectors for gene therapy in immune cells. Other papers in the collection take a more applied focus, centering on specific targets such as infectious disease or cancer. Along these lines, the Narasimhan Lab formulated different types of nanomaterials (e.g., nanoparticles, micelles, and combinations) for an influenza vaccination in mice (DOI: 10.1039/C8BM01443D). Using a variety of in vivo and in vitro studies – including multi-plexing cytokine analysis – they isolated the contributions of each formulation to the potency and nature of immune response generated. Taken together, the papers in this collection bring new knowledge and exciting ideas to leverage the properties of biomaterials to control immune processes.

As the immune engineering field pushes new technologies toward translation, data sharing and rigor will continue to increase in importance. For example, testing several promising technologies in tandem provides benchmarking, while robustness can be increased by assessing candidate materials across several clinically-relevant animal models, for both sexes, and with in vitro models. Making such data available in an organized, searchable database would also support more rapid and frequent translation of these exciting strategies.

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