Special Issue: Bio‐Interfaces for Immunoengineering
Authors: Weiqiang Chen, Deok‐Ho Kim
Journal: Advanced Healthcare Materials (2019)

Immune system-tissue interactions mediate the success or failure of many clinical treatments. Recently, studies regulating these interactions have shown a dramatic impact on the study of immunity in health and disease and point to the development of therapeutic intervention in the fields of cellular therapy, regenerative, and precision medicine. “Immunoengineering” is an emerging, interdisciplinary research subject that applies immunological principles and engineering tools with methods from molecular, cellular, and biomaterials-based approaches for precisely measuring, modeling and modulating immune responses. Applications include eradicating immune diseases and cancer, improving regenerative medicine and wound-healing responses, circumventing immune-rejection of engineered tissue, and attenuating autoimmune and immunosuppressive disorders. However, realizing this potential requires precise control over the interface between immune function and tissue homeostasis. New understanding of immune-tissue interactions highlights the great potential of modulating immune-tissue bio-interfaces through engineered biomaterials to precisely and selectively regulate immune functions. With innovative engineering techniques and insights into how the immune system interacts with bio-interfaces, more effective therapeutic and diagnostic strategies can be developed. This special issue on “Bio-Interfaces for Immuno-engineering” focuses specifically on emergent research in the fields of cell/molecular immunobiology, biomaterials, microfluidics-based diagnostics and disease modeling, tissue engineering, and mechanobiology. By fostering interactions among renowned and respected experts in these research fields, we hope to bridge the gap between basic science and clinical research to translate immune-based innovations towards the future clinical development of novel immunoengineering strategies. Knowledge regarding the interactions between immune cells and their microenvironment is critical for developing functional biomaterials and bio-interfaces for precisely and selectively regulating immune responses. Liu et al. (see article 201801578) reviewed the extracellular-matrix (ECM) based strategies for designing biomaterials for modulating immune functions. Specifically, Shin et al. discussed the regulation of bone regeneration events, such as osteogenesis, osteoclastogenesis, and inflammation through modulation of biomaterial-mediated immune responses (see article 201801106). Along these lines, Chen et al. (see article 201801234) engineered a biomimetic and photoresponsive hyaluronan hydrogel with tunable ECM adhesion sites for dynamic macrophage phenotype modulation, whereas Spiller et al. (see article 201801451) discussed the intercellular interaction between macrophage and fibroblast in the development of biomaterial-mediated fibrosis. In addition to applying biomaterials as ECM for immunomodulation, Jewell et al. (see article 201801419) discussed the control of interactions between regulatory immune cues, antigens attacked during inflammation, and tissues by using biomaterials as carriers and scaffolds, as well as agents with intrinsic immunomodulatory features. For example, lipid membranes have recently been adapted as drug delivery systems and Moon et al. (see article 201801091) have used dendritic cell membrane vesicles for T cell activation. Artificial antigen presenting cells have been designed by Pun et al. (see article 201801188) for T cell activation by using supported lipid bilayers on various cell-templated silica microparticles. An emerging class of biomaterials have incorporated DNA molecules as structural or bioactive components for modulating immune response. Takayama et al. (see article 201801243) covered the application of a DNA-based biomaterial and its design options for immunoengineering and Lee et al. (see article 201801395) developed self-assembled RNA microspheres for modulating the immune response of macrophages. One of the most exciting directions now in cancer therapy is to develop strategies to reach and modulate immunosuppressive cells. Recent developments in cancer immunotherapy have greatly relied on advances in nanomedicine for targeting and drug delivery strategies. For example, Park et al. have covered the recent advances in polymeric nanomedicines for cancer immunotherapy (see article 201801320). Gu et al. (see article 201801099) summarized the recent advances in combining immune checkpoint blockades with therapies that utilize biomaterials, such as different nanoparticles, for targeting and drug delivery in cancer immunotherapy. Instead of directly targeting cancer cells, Bellamkonda et al. (see article 201801076) successfully constrained the growth of brain tumor by engineering gold nanoparticles to target stromal cells in close vicinity to glioblastoma tumors and activate stromal inflammation. In the work by Gho et al. (see article 201801082), nanovesicles loaded with an anti-inflammatory drug were developed to mitigate outer membrane vesicle-induced systemic inflammatory response syndrome. Vaccine delivery addresses another approach to overcoming the immunological barrier. Woodrow et al. (see article 201801180) emphasized the promise of microneedle-based oral mucosal vaccine delivery to overcome current challenges existing to oral mucosal vaccine delivery. In addition to cancer immunotherapy and immunomodulation strategies utilizing nanomedicine, post-treatment monitoring of immune response in patients is another critical aspect in clinical management. Accurate and sensitive detection of immune response during immunotherapy offers the possibility of adjusting the treatment plan for safe and efficient treatment. Chen et al. (see article 201801478) developed a superparamagnetic Fe3O4/Au core-shell nanoplasmonic sensing array for sensitive and high throughput immunoassay applications. Moreover, a nano-in-micro smart hydrogel composite has been reported by Chen et al. for a rapid and sensitive immunoassay (see article 201801277). In addition to engineering biomaterials and nanomedicines for immune modulation in cancer immunotherapy and other applications, Lab-on-a-Chip and Organ-on-a-Chip technologies (reviewed by Xu et al., see article 201801406), emerging with the development and application of microfluidic and microfabrication in the past three decades, have served to demystify the underlying mechanism of tumor progression and immune evasion by modeling the healthy and diseased tissue microenvironments in vitro and ex vivo. For instance, Teo et al. (see article 201801126) comprehensively introduced the critical immune cell players in the immune microenvironment of lymphoid tissues and the current progress in reverse engineering these microenvironments. Kim et al. (see article 201801332) further extended our vision to the regulatory role of extracellular cues in mechanoregulation of the immune responses from these immune cell players and emphasized the roles of physical cues from the microenvironment for immune mechanobiology. Varghese et al. (see article 201801198) summarized the current development and application of tumor-on-a-chip platforms to interrogate the interactive communications between cancer cell and neighboring cells in tumor progression. Khademhosseini et al. (see article 201801363) also discussed the development of immune organs-on-a-chip systems, such as bone marrow thymus and lymph node, to model disease progression and predict drug-induced responses. Zhang et al. (see article 201801425) developed an integrative Organ-on-a-Chip system to investigate the immune response to external stimulus, which could offer a valuable tool for systematically studying in vitro immune reactions and reveal potential immunological mechanisms. To conclude, this special issue highlights the major achievements of the emerging interdisciplinary field of “Immunoengineering” which applies immunological principles and engineering tools with methods from molecular, cellular, extracellular and biomaterials-based approaches for precisely measuring, modeling and modulating immune responses. With the unremitting efforts of researchers working in this field, it is foreseeable that great breakthroughs will not only deepen our understanding of the fundamental mechanisms in regulating immune response and evasion, but also help develop and provide novel immune interventions and reliable preclinical tumor models that will provide unprecedented benefit in clinical settings. Weiqiang Chen is an Assistant Professor of mechanical and aerospace engineering and biomedical engineering at New York University. He received his Ph.D. in mechanical engineering from the University of Michigan. His research is focused on microfluidics, lab-on-a-chip and organ-on-a-chip systems, biomaterials, and biomanufacturing for new and improved solutions for emerging problems in cancer biology, mechanobiology, immune engineering, and stem cell-based regenerative medicine. Deok-Ho Kim is an Associate Professor in the Department of Bioengineering at the University of Washington. He received his Ph.D. in Biomedical Engineering from Johns Hopkins University School of Medicine. His current research interests cover biomedical materials, tissue engineering, and cell mechanobiology.